Criteria for approximating certain microgravity flow boiling characteristics in Earth gravity.
The forces governing flow boiling, aside from system pressure, are buoyancy, liquid momentum, interfacial surface tensions, and liquid viscosity. Guidance for approximating certain aspects of the flow boiling process in microgravity can be obtained in Earth gravity research by the imposition of a liquid velocity parallel to a flat heater surface in the inverted position, horizontal, or nearly horizontal, by having buoyancy hold the heated liquid and vapor formed close to the heater surface. Bounds on the velocities of interest are obtained from several dimensionless numbers: a two-phase Richardson number, a two-phase Weber number, and a Bond number. For the fluid used in the experimental work here, liquid velocities in the range U = 5-10cm/sec are judged to be critical for changes in behavior of the flow boiling process. Experimental results are presented for flow boiling heat transfer, concentrating on orientations that provide the largest reductions in buoyancy parallel to the heater surface, varying +/-5 degrees from facing horizontal downward. Results are presented for velocity, orientation, and subcooling effects on nucleation, dryout, and heat transfer. Two different heater surfaces were used: a thin gold film on a polished quartz substrate, acting as a heater and resistance thermometer, and a gold-plated copper heater. Both transient and steady measurements of surface heat flux and superheat were made with the quartz heater; only steady measurements were possible with the copper heater. R-113 was the fluid used; the velocity varied over the interval 4-16cm/sec; bulk liquid subcooling varied over 2-20 degrees C; heat flux varied over 4-8W/cm(2).


Dispersal probability distributions and the wave-front speed problem.
The speed and width of front solutions to reaction-dispersal models are analyzed both analytically and numerically. We perform our analysis for Laplace and Gaussian distribution kernels, both for delayed and nondelayed models. The results are discussed in terms of the characteristic parameters of the models.


Primary Shoulder Hemiarthroplasty: What Can Be Learned From 359 Cases That Were Surgically Revised?
Primary shoulder hemiarthroplasty is used to address a range of glenohumeral disorders, including fracture, arthritis, avascular necrosis, and capsulorrhaphy arthropathy; some patients with hemiarthroplasties undergo revision surgery for persistent pain or residual shoulder dysfunction. The literature does not clarify the features of the hemiarthroplasties having repeat surgery in a way that can guide surgeons' efforts to minimize the need for revision. To help address this gap, we analyzed the characteristics of patients from our region for whom we performed surgical revision of a prior humeral hemiarthroplasty QUESTIONS/PURPOSES: (1) What are the common characteristics of shoulder hemiarthroplasties having a revision? (2) What are the common characteristics of the subset of revised shoulder hemiarthroplasties that were performed for fracture? (3) What are characteristics of the subset of all revised hemiarthroplasties that were associated with glenoid bone erosion? Data for 983 patients for whom we performed a surgical revision of any type of shoulder arthroplasty between January 1991 and January 2017 were identified in our longitudinally maintained institutional arthroplasty revision database. In each case, revision had been elected by shared patient and surgeon decision-making after consideration of the disorder, degree of compromised comfort and function, treatment alternatives, and the risks of surgery. Of these 983 patients, 359 (37%) had a revision of a prior primary hemiarthroplasty; these patients were the subjects of this investigation. In this group of patients, we investigated the patient demographics, shoulder characteristics, prerevision radiographic findings, and findings at revision surgery. No patients were excluded. The patients having revision of primary hemiarthroplasties had severe loss of self-assessed shoulder comfort and function, with Simple Shoulder Test (SST) scores averaging 2.2 ± 2.2 of the maximum score of 12. The majority of these patients (81%) were women. The medical records of these 359 patients were abstracted to determine the diagnosis for the index primary hemiarthroplasty, clinical characteristics before surgery, and findings at surgical revision. One hundred twelve of the arthroplasties had been performed for fracture-related diagnoses; a subgroup analysis was performed on these patients. Two hundred seventy-three of the 359 patients (76%) had plain radiographs performed within 3 months before revision surgery that were adequate for assessing the radiographic characteristics of the glenoid, humerus, humeral component, and glenohumeral relationships; a subgroup analysis was performed on these patients. The degree of glenoid erosion was measured by a single observer in accordance with established criteria: Grade 1 is no erosion, Grade 2 is erosion limited to subchondral bone, Grade 3 is moderate erosion with medialization, and Grade 4 is medialization beyond the coracoid base. Some patients were included in both of these subgroups. Common characteristics of the revised hemiarthroplasties included female sex (81%), rotator cuff (89 of 359; 25%) or subscapularis (81 of 359; 23%) failure, problems related to prior fracture (154 of 359; 43%), glenoid erosion 125 of 359; 35%), and component malposition (89 of 359; 25%). Hemiarthroplasties performed for fracture-related problems often were associated with tuberosity malunion or nonunion (58 of 79; 73%) and decentering of the humeral component on the glenoid surface (45 of 71; 63%). Major erosion of the bony glenoid (Grade 3 or 4) was more common in decentered hemiarthroplasties (42 of 102; 41%) than for centered hemiarthroplasties (36 of 146; 25%) (Fisher's exact p = 0.008) and more common for hemiarthroplasties positioned in valgus (28 of 50; 56%) than for those positioned in neutral or varus (40 of 188; 21%) (Fishers' exact p < 0.0001). These findings suggest that some revisions of primary hemiarthroplasties may be avoided by surgical techniques directed at centering the prosthetic humeral articular surface on the glenoid concavity using proper humeral component positioning and soft tissue balance, by avoiding valgus positioning of the humeral component, and by managing glenoid disorders with a primary glenohumeral arthroplasty rather than a hemiarthroplasty alone. When durable security of the subscapularis, rotator cuff, and tuberosities is in question, the surgeon may consider a reverse total shoulder arthroplasty. Level III, therapeutic study.


Genetic architecture of parallel pelvic reduction in ninespine sticklebacks.
Teleost fish genomes are known to be evolving faster than those of other vertebrate taxa. Thus, fish are suited to address the extent to which the same vs. different genes are responsible for similar phenotypic changes in rapidly evolving genomes of evolutionary independent lineages. To gain insights into the genetic basis and evolutionary processes behind parallel phenotypic changes within and between species, we identified the genomic regions involved in pelvic reduction in Northern European ninespine sticklebacks (Pungitius pungitius) and compared them to those of North American ninespine and threespine sticklebacks (Gasterosteus aculeatus). To this end, we conducted quantitative trait locus (QTL) mapping using 283 F2 progeny from an interpopulation cross. Phenotypic analyses indicated that pelvic reduction is a recessive trait and is inherited in a simple Mendelian fashion. Significant QTL for pelvic spine and girdle lengths were identified in the region of the Pituitary homeobox transcription factor 1 (Pitx1) gene, also responsible for pelvic reduction in threespine sticklebacks. The fact that no QTL was observed in the region identified in the mapping study of North American ninespine sticklebacks suggests that an alternative QTL for pelvic reduction has emerged in this species within the past 1.6 million years after the split between Northern European and North American populations. In general, our study provides empirical support for the view that alternative genetic mechanisms that lead to similar phenotypes can evolve over short evolutionary time scales.


What we have learned from ribosome structures.
The determination of the high-resolution structures of ribosomal subunits in the year 2000 and of the entire ribosome a few years later are revolutionizing our understanding of the role of the ribosome in translation. In the present article, I summarize the main contributions from our laboratory to this worldwide effort. These include the determination of the structure of the 30S ribosomal subunit and its complexes with antibiotics, the role of the 30S subunit in decoding, and the high-resolution structure of the entire 70S ribosome complexed with mRNA and tRNA.


Fine structure of the human synovial lining cell in osteoarthritis: its prominent cytoskeleton.
The cytoskeleton of the human osteoarthritic synovial lining cell (SLC) consists of an extensive number of vimentin intermediate filaments (IFs) in addition to microfilaments and microtubules. The IFs are especially prevalent in the SLC processes, but are commonly seen in a paranuclear arrangement. Processes, ending in numerous microvilli and blebs, project into the joint space. Scanning electron microscopy (SEM) further reveals the processes that may parallel the synovium surface for a short distance. IFs extend to the termination of such Numerous pinocytotic vesicles and extensive rough endoplasmic reticulum (rER) are characteristic of the type B cells. Lysosomes and long microvilli identify the type A cell. Punctate adherens, gap junctions, and cilia are the cell membrane specializations of the osteoarthritis (OA) synovium. A comparison with synovium from rheumatoid arthritis (RA) patients is made in order to assess the effect o this inflammatory disease on the SLC cytoskeleton, cell type relationship, and cell arrangement. The prominent cytoskeleton appears to play an important role in the architecture of the synovium. Our findings are further presented in the form of a drawing which in some aspects could describe the morphology of the normal synovium.


Soil pathogen-aphid interactions under differences in soil organic matter and mineral fertilizer.
There is increasing evidence showing that microbes can influence plant-insect interactions. In addition, various studies have shown that aboveground pathogens can alter the interactions between plants and insects. However, little is known about the role of soil-borne pathogens in plant-insect interactions. It is also not known how environmental conditions, that steer the performance of soil-borne pathogens, might influence these microbe-plant-insect interactions. Here, we studied effects of the soil-borne pathogen Rhizoctonia solani on aphids (Sitobion avenae) using wheat (Triticum aestivum) as a host. In a greenhouse experiment, we tested how different levels of soil organic matter (SOM) and fertilizer addition influence the interactions between plants and aphids. To examine the influence of the existing soil microbiome on the pathogen effects, we used both unsterilized field soil and sterilized field soil. In unsterilized soil with low SOM content, R. solani addition had a negative effect on aphid biomass, whereas it enhanced aphid biomass in soil with high SOM content. In sterilized soil, however, aphid biomass was enhanced by R. solani addition and by high SOM content. Plant biomass was enhanced by fertilizer addition, but only when SOM content was low, or in the absence of R. solani. We conclude that belowground pathogens influence aphid performance and that the effect of soil pathogens on aphids can be more positive in the absence of a soil microbiome. This implies that experiments studying the effect of pathogens under sterile conditions might not represent realistic interactions. Moreover, pathogen-plant-aphid interactions can be more positive for aphids under high SOM conditions. We recommend that soil conditions should be taken into account in the study of microbe-plant-insect interactions.


Evaluation of the effects of human leukocyte IFN-alpha on the immune response to the HBV vaccine in healthy unvaccinated individuals.
HBV vaccine needs 3 injections over 6 months to induce immunity. Thus, the use of adjuvants capable of inducing earlier immune protection would be highly desirable. Most adjuvants may act by inducing cytokines, and among them, type I interferons (IFNs), deserve a special attention in view of the potent immunomostimulatory activity observed in mouse models and on dendritic cell functions. The aim of the present trial was to evaluate the effects of IFN-alpha administered as an adjuvant of HBV vaccine in healthy unvaccinated individuals. No significant enhancing effect on the antibody response was observed, in spite of an early and transient upregulation of costimulatory molecule expression on peripheral blood mononuclear cells, which may be suggestive of an IFN-mediated activation of antigen presenting cells. We conclude that, under the conditions used in this trial, natural IFN-alpha does not act as an adjuvant of the HBV vaccine in healthy unvaccinated individuals.


Transforming growth factor-beta potently inhibits the viability-promoting activity of stem cell factor and other cytokines and induces apoptosis of primitive murine hematopoietic progenitor cells.
In contrast with the extensively characterized effects of transforming growth factor-beta (TGF-beta) on proliferation and differentiation of hematopoietic progenitors, little is known about the effects of TGF-beta on viability of normal hematopoietic progenitors. In the present report, we demonstrate that TGF-beta potently counteracts hematopoietic growth factor (HGF)-induced survival of individually cultured primitive Lin-Sca-1+ bone marrow progenitors. Specifically, 74% of single Lin-Sca-1+ cells cultured for 40 hours in the presence of stem cell factor (SCF) survived, whereas only 16% survived in the presence of SCF plus TGF-beta. Similarly, the enhanced survival of primitive hematopoietic progenitors in response to granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1, IL-6, or IL-11 was also potently opposed by TGF-beta. Furthermore, it is demonstrated that neutralization of endogenous TGF-beta present in the cultures enhances survival of Lin-Sca-1+ progenitors in the absence, as well as in the presence, of HGFs such as SCF and IL-6. The reduced HGF-induced survival of primitive hematopoietic progenitors in the presence of TGF-beta was associated with increased apoptosis, as detected by an in situ terminal deoxynucleotidyl transferase (TdT) assay. After 16 hours of incubation in the absence of HGFs, 61% +/- 6% of the hematopoietic progenitors had DNA strand breaks characteristic of apoptosis. The presence of SCF reduced the frequency of apoptic cells to 27% +/- 5%, whereas 55% +/- 3% of the cells had signs of apoptosis in the presence of SCF plus TGF-beta.


Microbial ecology of arsenic-mobilizing Cambodian sediments: lithological controls uncovered by stable-isotope probing.
Microbially mediated arsenic release from Holocene and Pleistocene Cambodian aquifer sediments was investigated using microcosm experiments and substrate amendments. In the Holocene sediment, the metabolically active bacteria, including arsenate-respiring bacteria, were determined by DNA stable-isotope probing. After incubation with (13) C-acetate and (13) C-lactate, active bacterial community in the Holocene sediment was dominated by different Geobacter spp.-related 16S rRNA sequences. Substrate addition also resulted in the enrichment of sequences related to the arsenate-respiring Sulfurospirillum spp. (13) C-acetate selected for ArrA related to Geobacter spp. whereas (13) C-lactate selected for ArrA which were not closely related to any cultivated organism. Incubation of the Pleistocene sediment with lactate favoured a 16S rRNA-phylotype related to the sulphate-reducing Desulfovibrio oxamicus DSM1925, whereas the ArrA sequences clustered with environmental sequences distinct from those identified in the Holocene sediment. Whereas limited As(III) release was observed in Pleistocene sediment after lactate addition, no arsenic mobilization occurred from Holocene sediments, probably because of the initial reduced state of As, as determined by X-ray Absorption Near Edge Structure. Our findings demonstrate that in the presence of reactive organic carbon, As(III) mobilization can occur in Pleistocene sediments, having implications for future strategies that aim to reduce arsenic contamination in drinking waters by using aquifers containing Pleistocene sediments.


Hair and cancer chemotherapy: consequences and nursing care--a literature study.
Hair is a body appendage that throughout history has been a symbol of the social, cultural and political climate, in addition to connoting religious affiliation. Hair loss on the other hand has been associated with a loss of attractiveness, individuality, a state of disgrace and illness, in addition to the ageing process, death and a loss of sexuality. One of the most common side-effects of chemotherapy is hair loss (alopecia). Alopecia can range from sporadic thinning of the hair to complete baldness. Several factors may contribute to the severity of hair loss including drug, dose and schedule as well as hair care practices. Prevention of alopecia has been a focus in the medical and nursing literature since the late 1960s. Mechanical, physical and biological measures have been used with varying success. The goal of prevention is primarily the reduction of patient distress caused by chemotherapy-induced alopecia. Patient reactions to alopecia vary and may be dependent on the individual importance of hair, prognosis, degree of expected hair loss, the amount of information and preparation given, and physical and psychological coping mechanisms. Nurses play an important role in assisting the patient to cope with alopecia by giving the needed information and teaching self-care strategies to minimize alopecia, cope with alopecia, and protect the skin and eyes following alopecia. These interventions are aimed at helping the patient move through a potentially devastating experience to a renewed sense of well-being.


Acute kidney injury in non-severe pneumonia is associated with an increased immune response and lower survival.
While sepsis is a leading cause of acute kidney injury in critically ill patients, the relationship between immune response and acute kidney injury in less severely ill patients with infection is not known. Here we studied the epidemiology, 1-year mortality, and immune response associated with acute kidney injury in 1836 hospitalized patients with community-acquired severe and non-severe pneumonia. Acute kidney injury developed in 631 patients of whom 329 had severe and 302 had non-severe sepsis. Depending on the subgroup classification, 16-25% of the patients with non-severe pneumonia also developed acute kidney injury. In general, patients with acute kidney injury were older, had more comorbidity, and had higher biomarker concentrations (interleukin-6, tumor necrosis factor, D-dimer) even among patients without severe sepsis. The risk of death associated with acute kidney injury varied when assessed by Gray's survival model and after adjusting for differences in age, gender, ethnicity, and comorbidity. This risk was significantly higher immediately after hospitalization but gradually fell over time in the overall cohort and in those with non-severe pneumonia. A significantly higher risk of death (hazard ratio 1.29) was also present in those never admitted to an intensive care unit. Hence acute kidney injury is common even among patients with non-severe pneumonia and is associated with higher immune response and an increased risk of death.


Benzyl 3-[(E)-(furan-2-yl)methyl-idene]-2-methyldithio-carbazate.
In the title compound, C(14)H(14)N(2)OS(2), the furan ring exhibits rotational disorder over two orientations, with an occupancy ratio of 0.508 (7):0.492 (7). The furan and phenyl rings form dihedral angles of 8.2 (6) (major occupancy component), 14.8 (6) (minor occupancy component) and 73.65 (9)°, respectively, with the central residue (C(4)N(2)S(2)), indicating a twisted conformation for the mol-ecule. The methyl group and the thione S atom are syn and the conformation about the imine bond is E. In the crystal, C-H⋯π inter-actions involving the phenyl ring are observed.


Work-related risk factors for the incidence and recurrence of shoulder and neck complaints among nursing-home and elderly-care workers.
This study assessed the differences and similarities in the incidence and recurrence of shoulder and neck complaints with respect to work-related physical, psychosocial, and personal risk factors. A prospective cohort study was carried out among 769 workers of nursing homes and homes for the elderly. At baseline, a questionnaire was used to collect data on personal characteristics, physical workload, psychosocial workload, and the presence of shoulder and neck complaints. After 1 and 2 years, follow-up data were collected on shoulder and neck complaints. Generalized estimation equations were used for analyzing risk factors for the participants with at least one follow-up measurement available (N=556, 72%). In the multivariate model, adjusted for age and gender, obesity [odds ratio (OR) 2.12, 95% confidence interval (95%CI) 1.23-3.65] was related to the incidence of shoulder complaints. The incidence of neck complaints was increased for obesity (OR 1.81, 95% CI 1.07-3.05), work in awkward postures (OR 1.76, 95% CI 1.11-2.78), and poor or fair general health (OR 1.53, 95% CI 1.02-2.31). The recurrence of both shoulder and neck complaints was associated with chronic complaints at baseline (shoulder: OR 1.91, 95% 1.36-2.67; neck: OR 1.71, 95% 1.14-2.55) but not with work-related risk factors. The results suggest that there are differences in risk factors for the incidence and recurrence of shoulder and neck complaints.


Aggregation and mobility of membrane proteins interplay with local lipid order in the plasma membrane of T cells.
To disentangle the elusive lipid-protein interactions in T-cell activation, we investigate how externally imposed variations in mobility of key membrane proteins (T-cell receptor [TCR], kinase Lck, and phosphatase CD45) affect the local lipid order and protein colocalisation. Using spectral imaging with polarity-sensitive membrane probes in model membranes and live Jurkat T cells, we find that partial immobilisation of proteins (including TCR) by aggregation or ligand binding changes their preference towards a more ordered lipid environment, which can recruit Lck. Our data suggest that the cellular membrane is poised to modulate the frequency of protein encounters upon alterations of their mobility, for example in ligand binding, which offers new mechanistic insight into the involvement of lipid-mediated interactions in membrane-hosted signalling events.


[Efficiency of influenza vaccination in the working population in Spain].
Influenza is a major cause of morbidity and mortality worldwide. Currently, licensed influenza vaccines are safe and effective. Any intervention aimed at reducing the burden of illness is worth analyzing from a clinical and economic perspective. To assess the costs and benefits of an influenza vaccination program in the Spanish working population. A theoretical model of costs and benefits in terms of productivity savings was developed to compare 2 strategies (vaccination and non-vaccination) in 2 cohorts of 1,000 workers each. The time horizon was 1 year and the study's perspective was societal. epidemiological and clinical data on the incidence of influenza and the effectiveness of the vaccine. Data on the use of direct and indirect resources were obtained from an expert panel of 5 experts in preventive medicine, microbiology, occupational health, and health economics. Unit costs (euros 2003) were extracted from local databases. A sensitivity analysis was performed with the data on incidence, effectiveness, and work absenteeism due to influenza. In the base case scenario, influenza vaccine saved 35 Euros per worker, of which 88% were savings in work loss days avoided. Threshold values in the sensitivity analysis were 6% for the incidence of influenza and 1.5 days for absence from work, above which the vaccine leads to net savings. Influenza vaccination in the Spanish working population might result in net resource savings to society at large.


Evaluation of the Auditory Pathway in Traffic Policemen.
Traffic policemen working at heavy traffic junctions are continuously exposed to high level of noise and its health consequences. To assess the hearing pathway in traffic policemen by means of brainstem evoked response audiometry (BERA), mid-latency response (MLR), and slow vertex response (SVR). In this observational comparative study, BERA, MLR, and SVR were tested in 35 male traffic policemen with field posting of more than 3 years. 35 age-matched men working in our college served as controls. Increase in the latencies of waves I and III of BERA, and IPL I-III were observed. Compared to controls, the MLR and SVR waves showed no significant changes in studied policemen. We found that chronic exposure of traffic policemen to noise resulted in delayed conduction in peripheral part of the auditory pathway, ie, auditory nerve up to the level of superior olivary nucleus; no impairment was observed at the level of sub-cortical, cortical, or the association areas.


Fate of heterotrophic microbes in pelagic habitats: focus on populations.
Major biogeochemical processes in the water columns of lakes and oceans are related to the activities of heterotrophic microbes, e.g., the mineralization of organic carbon from photosynthesis and allochthonous influx or its transport to the higher trophic levels. During the last 15 years, cultivation-independent molecular techniques have substantially contributed to our understanding of the diversity of the microbial communities in different aquatic systems. In parallel, the complexity of aquatic habitats at a microscale has inspired research on the ecophysiological properties of uncultured microorganisms that thrive in a continuum of dissolved to particulate organic matter. One possibility to link these two aspects is to adopt a"Gleasonian" perspective, i.e., to study aquatic microbial assemblages in situ at the population level rather than looking at microbial community structure, diversity, or function as a whole. This review compiles current knowledge about the role and fate of different populations of heterotrophic picoplankton in marine and inland waters. Specifically, we focus on a growing suite of techniques that link the analysis of bacterial identity with growth, morphology, and various physiological activities at the level of single cells. An overview is given of the potential and limitations of methodological approaches, and factors that might control the population sizes of different microbes in pelagic habitats are discussed.


Experimental and Computational Study on Motor Control and Recovery After Stroke: Toward a Constructive Loop Between Experimental and Virtual Embodied Neuroscience.
Being able to replicate real experiments with computational simulations is a unique opportunity to refine and validate models with experimental data and redesign the experiments based on simulations. However, since it is technically demanding to model all components of an experiment, traditional approaches to modeling reduce the experimental setups as much as possible. In this study, our goal is to replicate all the relevant features of an experiment on motor control and motor rehabilitation after stroke. To this aim, we propose an approach that allows continuous integration of new experimental data into a computational modeling framework. First, results show that we could reproduce experimental object displacement with high accuracy via the simulated embodiment in the virtual world by feeding a spinal cord model with experimental registration of the cortical activity. Second, by using computational models of multiple granularities, our preliminary results show the possibility of simulating several features of the brain after stroke, from the local alteration in neuronal activity to long-range connectivity remodeling. Finally, strategies are proposed to merge the two pipelines. We further suggest that additional models could be integrated into the framework thanks to the versatility of the proposed approach, thus allowing many researchers to achieve continuously improved experimental design.


Effects of daily versus weekly testing and pre-training on the assessment of neurologic impairment following diffuse traumatic brain injury in rats.
A number of test paradigms have been used to determine acute and chronic motor and cognitive deficits after experimental traumatic brain injury (TBI). Some involve daily testing of either trained or untrained animals whereas others utilize periodic testing over extended time periods. Which test paradigm is the most appropriate for the assessment of motor and cognitive deficits is, however, unclear. In the current study, we have used both daily and weekly testing in trained and untrained animals to ascertain which assessment protocol is most suited for the detection of functional deficits after diffuse TBI in rats. Animals were subjected to severe injury using the impact-acceleration model of diffuse TBI. An equal number of animals were also prepared surgically but not subject to injury (shams). The rotarod device and the Barnes Maze were used for motor and cognitive assessment respectively, with half of the animals being pre-trained on each test for 10 days prior to injury. The open field test was used to assess spontaneous exploratory activity (stress). Following injury, animals were assessed for neurologic deficits either on a daily basis (for 10 days) or a weekly basis (for 4 weeks). In trained animals, the greatest differences in neurologic outcome between injured and sham animals were observed early after injury. In contrast, in untrained animals, greatest differences between injured and sham animals were observed at later time points. Pre-injury training did not improve the rate of cognitive recover, or the rate of motor recovery in the weekly test paradigm, but did improve the rate of motor recovery in the daily assessment paradigm. Daily assessment promoted rapid functional recovery whereas weekly assessments did not significantly affect outcome in injured animals over the 4-week assessment period. Spontaneous exploratory activity was decreased after TBI and was not influenced by task exposure. These studies demonstrate that the functional assessment paradigm needs to be considered when quantifying functional deficits following diffuse TBI in rats.


Better Prescribing Project: a randomized controlled trial of the impact of case-based educational modules and personal prescribing feedback on prescribing for hypertension in primary care.
The purpose of this study was to assess the impacts of individualized prescribing feedback and interactive small group education aimed at encouraging evidence-based prescribing in family/general practice. A two-by-two factorial randomized controlled trial was carried out involving 200 family physicians in British Columbia, Canada. The physicians met monthly in 28 peer learning groups within the Practice-Based Small Group (PBSG) learning programme. Personalized prescribing feedback related to hypertension was provided through 'prescribing portraits' which graphically displayed comparative rates of individual and peer group prescribing, together with a concise guide for evidence-based prescribing. A case-based educational module, containing the same evidence-based message, was discussed in small groups. Groups were matched and randomized into four arms of seven groups each: control (n = 56), prescribing portrait only (n = 48), educational module only (n = 47), both portrait and module (n = 49). The main outcome measure was changes in 'prescribing preferences' to new patients among those medications used to treat hypertension (i.e. probability that a patient would receive the evidence-based medication as first-line therapy). Using data from the provincial pharmacy registry (PharmaNet), prescribing preferences for antihypertensive agents were determined for all groups for a 6 month period before and after the interventions, based on 4394 patients receiving a first-line antihypertensive. Significant absolute increases in prescribing preference for thiazides were documented for both the module +0.068 (confidence interval [CI] 0.022-0.115) and the portrait +0.065 (CI 0.018-0.111). Preference in the group receiving both module and portrait increased by +0.115 (CI 0.040-0.189). Evidence-based educational interventions combining personalized prescribing feedback with interactive group discussion can lead to modest but meaningful changes in physician prescribing. Clear messages, proper trial design and sensitive outcomes are necessary to demonstrate these changes.


Auto-transplantation of whole rat ovary in different transplantation sites.
This study was carried out to assess the different ovarian transplantation sites after short-time autografting. Female rats were randomized into five groups, with six rats in each group, including control (intact), cervical subcutaneous transplanted (CST), back subcutaneous transplanted (BST), subfascial transplanted (SFT) and intramuscular transplanted (IMT) groups. In all experimental groups, the right ovary was removed and transplanted into different sites. After three weeks, ovaries were removed for morphology assessment, follicular counting and the rates of corpus luteum (CL) and cyst formation. Transplanted ovaries in BST and SFT groups were full of cysts and did not have sufficient numbers of intact follicles and were excluded from experiments. In IMT and CST groups, re-anastomosis, follicular development and good homogeneity of the stromal tissue were seen. However, the difference in intact antral follicles between CST (7.92 ± 0.02%) and CST-Op (opposite ovary of CST group) (30.99 ± 0.03%) was significant as well as the difference between CST (7.92 ± 0.02%) and control (10.08 ± 0.01%) groups. In addition, the number of intact primordial follicles in the CST-Op (16.58 ± 0.02%) group was significantly less than that of the control (40.40 ± 0.03%) group. Interestingly, the number of CL was significantly increased in the CST-Op (11.71 ± 0.01%) and IMT-Op (9.16 ± 0.02%) groups compared to the control and experimental groups. Although both intramuscular and subcutaneous sites effectively preserved ovarian follicles after three weeks, cervical subcutaneous site was better suited for auto-transplantation in rat.


Symptom distress, coping style and biological variables as predictors of survival after bone marrow transplantation.
Psychological assessments made at the time of bone marrow transplantation (BMT) were examined in 31 patients at 1-2 years posttransplantation and factors associated with survival were explored. Psychological assessments were carried out soon after admission to hospital for the BMT and about 3-4 weeks later. Cox regression survival analysis revealed that an interactive biopsychological model could explain survival status. Shorter survival was associated with mismatched marrow grafts (p = 0.04), prior experience with chemoradiotherapy (p-0.02), disease stage (p = 0.04), higher symptom distress during BMT (p = 0.008), less hopefulness (p = 0.005), and more acceptance of the situation (p = 0.02). These psychological/psychosomatic and personality characteristics may act directly by interacting with immune function or indirectly by leading to other behaviors known to affect survival in cancer patients. Enhancing more effective coping strategies and altering high symptom-related distress during BMT seem important means not only for improving psychosocial adjustment (quality of life), as has been shown in the literature, but also for increasing survival (quantity of life).


Glucose 6 phosphate dehydrogenase deficiency: A single-center experience.
This study aims to evaluate the demographic information, clinical and laboratory findings of patients with glucose 6 phosphate dehydrogenase deficiency. We collected data by reviewing files and electronic records of 65 patients with glucose 6 phosphate dehydrogenase deficiency under the age of 18 years who were followed up in our clinic between 2007 and 2019. Demographic, clinical, and laboratory features, family history, complications of the disease, and history of splenectomy and cholecystectomy were evaluated. Mean, standard deviation, and median values were used when descriptive analyses were presented. The age of diagnosis ranged between 1-192 months and the median age of diagnosis was two months. Fifty-nine patients (90.7%) were boys and six (9.2%) were girls. The mean value of glucose 6 phosphate dehydrogenase enzyme on admission was 1,9±1,4 U/g of hemoglobin (Hb). Family history was pesent in 40% of patients in whom information was avaliable. The most common presentation was prolonged jaundice and the most common physical finding was jaundice. Splenomegaly was detected in none of the patients. Cholelithiasis was present in one of 21 patients who were evaluated with ultrasonography. None of the patients required splenectomy, cholecystectomy, and regular erythrocyte transfusion during follow-up. As G6PD variants with chronic hemolysis are not usually seen in Turkey, patients who required splenectomy, cholecystectomy, and regular erythrocyte transfusion were not detected. Although glucose 6 phosphate dehydrogenase deficiency is more common in males, it can also be seen in girls. In Turkey, glucose 6 phosphate dehydrogenase deficiency should be considered in patients presenting with prolonged jaundice.


Valproate-induced liver injury: modulation by the omega-3 fatty acid DHA proposes a novel anticonvulsant regimen.
The polyunsaturated, ω-3 fatty acid, docosahexaenoic acid (DHA), claims diverse cytoprotective potentials, although via largely undefined triggers. Thus, we currently first tested the ability of DHA to ameliorate valproate (VPA)-evoked hepatotoxicity, to modulate its anticonvulsant effects, then sought the cellular and molecular basis of such actions. Lastly, we also verified whether DHA may kinetically alter plasma levels/clearance rate of VPA. VPA (500 mg/kg orally for 14 days in rats) evoked prominent hepatotoxicity that appeared as a marked rise (2- to 4-fold) in serum hepatic enzymes (γ-glutamyl transferase [γ-GT], alanine aminotransferase [ALT], and alkaline phosphatase [ALP]), increased hepatic lipid peroxide (LPO) and tumor necrosis factor-alpha (TNFα) levels, as well as myeloperoxidase (MPO) activity (3- to 5-fold), lowering of serum albumin (40 %), and depletion of liver reduced-glutathione (GSH, 35 %). Likewise, histopathologic examination revealed hepatocellular degeneration, replacement by inflammatory cells, focal pericentral necrosis, and micro/macrovesicular steatosis. Concurrent treatment with DHA (250 mg/kg) markedly blunted the elevated levels of liver enzymes, lipid peroxides, TNFα, and MPO activity, while raising serum albumin and hepatic GSH levels. DHA also alleviated most of the cytologic insults linked to VPA. Besides, in a pentylenetetrazole (PTZ) mouse convulsion model, DHA (250 mg/kg) markedly increased the latency in convulsion evoked by VPA, beyond their individual responses. Lastly, pharmacokinetic studies revealed that joint DHA administration did not alter serum VPA concentrations. DHA substantially ameliorated liver injury induced by VPA, while also markedly boosted its pharmacologic effects. DHA manipulated definite cellular machinery to curb liver oxidative stress and inflammation, without affecting VPA plasma levels. Collectively, these protective and synergy profiles for DHA propose a superior VPA-drug combination regimen.


Need for the Development of a Specific Regulatory Framework for Evaluation of Mobile Health Apps in Peru: Systematic Search on App Stores and Content Analysis.
In Peru, there is an increase in the creation of mobile health (mHealth) apps; however, this situation could present problems related to the quality of information these apps share, data security and privacy, usability, and effectiveness, as there is no specific local regulation about their creation and use. The objective of this study was to review mHealth apps created, uploaded, or used in Peru, and perform an analysis of the national regulatory framework that could be applied to evaluate whether there is a need to develop and implement a specific regulation to these apps. A total of 3 reviews were performed. First, we reviewed information about Peruvian mHealth apps created up to May 2019 from scientific publications, news, government communications, and virtual stores, and evaluated their purpose, creator, and the available evidence of their usability and effectiveness. The second review was carried out by taking a sample of the 10 most commonly used mHealth apps in Peru (regardless of the country of creation), to evaluate the information they collect and classify them according to the possible risks that they could present in terms of security and privacy. In addition, we evaluated whether they refer to or endorse the information they provided. Finally, in the third review, we searched for Peruvian standards related to electronic health (eHealth) that involve information technology that can be applied to regulate these apps. A total of 66 apps meeting our inclusion criteria were identified; of these, 47% (n=31) belonged to government agencies and 47% (n=31) were designed for administrative purposes (private and government agencies). There was no evidence about the usability or effectiveness of any of these apps. Concerning the 10 most commonly used mHealth apps in Peru, about the half of them gathered user information that could be leaked, changed, or lost, thus posing a great harm to their users or to their related patients. In addition, 6/10 (60%) of these apps did not mention the source of the information they provided. Among the Peruvian norms, the Law on the Protection of Personal Data, Law on Medical Devices, and administrative directives on standards and criteria for health information systems have some regulations that could be applied to these apps; however, these do not fully cover all aspects concerning the evaluation of security and privacy of data, quality of provided information, and evidence of an app's usability and effectiveness. Because many Peruvian mHealth apps have issues related to security and privacy of data, quality of information provided, and lack of available evidence of their usability and effectiveness, there is an urgent need to develop a regulatory framework based on existing medical device and health information system norms in order to promote the evaluation and regulation of all the aforesaid aspects, including the creation of a national repository for these apps that describes all these characteristics.


Effect of target controlled propofol infusion versus intermittent boluses during oesophagogastroduodenoscopy: a randomized controlled trial.
Propofol is administered as intermittent boluses to achieve deep sedation to facilitate oesophagogastroduodenoscopy. Target controlled infusion (TCI) can be employed for this purpose. 176 adults were randomly allocated into two groups of 88 patients. Control group: Received an initial bolus of propofol 1mg/kg, with repeat boluses of 0.25mg/kg. Intervention group: Received an initial target effect-site concentration of 4mcg/ml, followed by maintenance target effect-site concentration of 2.5mcg/ml, titrated by 0.5mcg/ml from baseline infusion rate as needed. Oxygen saturation, blood pressure and heart rate were evaluated immediately before administering the sedative and at 2.50, 5.00, 7.50 and 10.00 minutes. Oxygen desaturation below 90% in both study groups was recorded. Sedation starting time, stopping time, waking up time and overall duration of time to recovery of participants in each study arm was recorded. More hypoxic episodes were observed in the intermittent bolus group with statistically significant association between control and the incidence of hypoxia: Chi square test, p=0.037. There were more hypotensive episodes in the TCI group but not achieving statistical significance: Chi square test for association X2(1) = 0.962, p=0.327.The time to recovery between the two groups was comparable, with 18.84 ± 10.76 minutes in the bolus group and 19.72 ± 9.27 minutes in the TCI group; no statistically significant difference was shown: Student's t-test, p=0.0564. TCI of propofol was associated with fewer episodes of hypoxia compared to intermittent bolus administration. Similar hemodynamic profiles and comparable time to recovery were demonstrated by these two sedation techniques.


Prospective evaluation of contrast-enhanced ultrasound of breast BI-RADS 3-5 lesions.
To determine the benefit of contrast-enhanced ultrasound (CEUS) in the assessment of breast lesions. A standardized contrast-enhanced ultrasound was performed in 230 breast lesions classified as BI-RADS category 3 to 5. All lesions were subjected to qualitative and quantitative analysis. MVI (MicroVascular Imaging) technique was used to derive qualitative analysis parameters; blood perfusion of the lesions was assessed (perfusion homogeneity, type of vascularization, enhancement degree). Quantitative analysis was conducted to estimate perfusion changes in the lesions within drawn regions of interest (ROI); parameters TTP (time to peak), PI (peak intensity), WIS (wash in slope), AUC (area under curve) were obtained from time intensity (TI) curves. Acquired data were statistically analyzed to assess the ability of each parameter to differentiate between malignant and benign lesions. The combination of parameters was also evaluated for the possibility of increasing the overall diagnostic accuracy. Biological nature of the lesions was verified by a pathologist. Benign lesions without histopathological verification (BI-RADS 3) were followed up for at least 24 months. Out of 230 lesions, 146 (64%) were benign, 67 (29%) were malignant, 17 (7%) lesions were eliminated. Malignant tumors showed statistically significantly lower TTP parameters (sensitivity 77.6%, specificity 52.7%) and higher WIS values (sensitivity 74.6%, specificity 66.4%) than benign tumors. Enhancement degree also proved to be statistically well discriminating as 55.2% of malignant lesions had a rich vascularity (sensitivity 89.6% and specificity 48.6%). The combination of quantitative analysis parameters (TTP, WIS) with enhancement degree did not result in higher accuracy in distinguishing between malignant and benign breast lesions. We have demonstrated that contrast-enhanced breast ultrasound has the potential to distinguish between malignant and benign lesions. In particular, this method could help to differentiate lesions BI-RADS category 3 and 4 and thus reduce the number of core-cut biopsies performed in benign lesions. Qualitative analysis, despite its subjective element, appeared to be more beneficial. A combination of quantitative and qualitative analysis did not increase the predictive capability of CEUS.


High-salt diet blunts renal autoregulation by a reactive oxygen species-dependent mechanism.
High dietary salt is common in Western countries and is an important contributor to increased cardiovascular disease. Autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) is an essential function of the renal microcirculation that could be affected by excessive dietary salt. High salt (HS) increases renal ROS generation partly by the enzyme NADPH oxidase. We hypothesized that a HS diet would impair autoregulation via NADPH oxidase-dependent ROS generation. The role of NADPH-dependent ROS production on the blunted autoregulatory response with a HS diet was assessed in vitro and in vivo using the blood-perfused juxtamedullary nephron preparation and anesthetized rats, respectively. The increase in renal lipid peroxidation and p67(phox) expression induced by HS was prevented by apocynin treatment. Control afferent arterioles exhibited normal autoregulatory behavior in response to acute increases in renal perfusion pressure, whereas arterioles from HS rats exhibited a blunted response. Autoregulatory behavior in HS rats was restored in vitro by acute exposure to the NADPH oxidase inhibitor apocynin. At the whole kidney level, in vivo experiments showed that both RBF and GFR declined in HS rats when left kidney renal perfusion pressure was reduced from ambient to 95 mmHg, whereas control rats maintained stable GFR and RBF consistent with efficient autoregulatory behavior. Apocynin treatment improved in vivo autoregulatory behavior in HS rats and had no detectable effect in normal salt diet-fed rats. These data support the hypothesis that impaired renal autoregulatory behavior in rats fed a HS diet is mediated by NADPH oxidase-derived ROS.


Patient, community and clinician perceptions of the quality of life associated with diabetes mellitus.
A study was undertaken to assess the quality of life of patients with type 1 and type 2 diabetes mellitus and to ascertain whether clinicians and non-diabetic respondents from the general public have similar views of the impact of diabetes upon health-related quality of life. Time tradeoff utility values were generated from a standardized time-tradeoff questionnaire. Three hundred and fifty-two individuals with type 1 or type 2 diabetes mellitus, 157 non-diabetic participants from the general public (community), and 61 health care clinicians participated in the study. The mean utility score for diabetic patients was 0.889 and the median utility score was 1.000. The mean utility score for clinicians was 0.861, with a median value of 0.894, while the respective mean and median scores for the general public were 0.919 and 0.953. There was a significant difference between the distribution of the means of scores of clinicians and patients as well as between clinicians and the general public. There was no significant difference between the utility scores of patients and the general public. Within the group of diabetic patients, there was no significant difference in utility scores between type 1 and type 2 diabetics. Clinicians tended to overemphasize the impact that diabetes mellitus has on health related quality of life, while the non-diabetic publics' utility values are more closely correlated with those of diabetics themselves. We conclude that there is a significant difference in how clinicians, diabetics and the general public perceive the effect diabetes has upon quality of life.


The Epidemiology of Incident Fracture from Cradle to Senescence.
To reduce the burden of fracture, not only does bone fragility need to be addressed, but also injury prevention. Thus, fracture epidemiology irrespective of degree of trauma is informative. We aimed to determine age-and-sex-specific fracture incidence rates for the Barwon Statistical Division, Australia, 2006-2007. Using radiology reports, incident fractures were identified for 5342 males and 4512 females, with incidence of 210.4 (95 % CI 204.8, 216.2) and 160.0 (155.3, 164.7)/10,000/year, respectively. In females, spine (clinical vertebral), hip (proximal femoral) and distal forearm fractures demonstrated a pattern of stable incidence through early adult life, with an exponential increase beginning in postmenopausal years for fractures of the forearm followed by spine and hip. A similar pattern was observed for the pelvis, humerus, femur and patella. Distal forearm, humerus, other forearm and ankle fractures showed incidence peaks during childhood and adolescence. For males, age-related changes mimicked the female pattern for fractures of the spine, hip, ribs, pelvis and humerus. Incidence at these sites was generally lower for males, particularly among the elderly. A similar childhood-adolescent peak was seen for the distal forearm and humerus. For ankle fractures, there was an increase during childhood and adolescence but this extended into early adult life; in contrast to females, there were no further age-related increases. An adolescent-young adult peak incidence was observed for fractures of the face, clavicle, carpal bones, hand, fingers, foot and toe, without further age-related increases. Examining patterns of fracture provides the evidence base for monitoring temporal changes in fracture burden, and for identifying high-incidence groups to which fracture prevention strategies could be directed.


Physical properties of Escherichia coli P pili measured by optical tweezers.
The mechanical behavior of individual P pili of uropathogenic Escherichia coli has been investigated using optical tweezers. P pili, whose main part constitutes the PapA rod, composed of approximately 10(3) PapA subunits in a helical arrangement, are distributed over the bacterial surface and mediate adhesion to host cells. They are particularly important in the pathogenesis of E. coli colonizing the upper urinary tract and kidneys. A biological model system has been established for in situ measurements of the forces that occur during mechanical stretching of pili. A mathematical model of the force-versus-elongation behavior of an individual pilus has been developed. Three elongation regions of pili were identified. In region I, P pili stretch elastically, up to a relative elongation of 16 +/- 3%. The product of elasticity modulus and area of a P pilus, EA, was assessed to 154 +/- 20 pN (n=6). In region II, the quaternary structure of the PapA rod unfolds under a constant force of 27 +/- 2 pN (n approximately 100) by a sequential breaking of the interactions between adjacent layers of PapA subunits. This unfolding can elongate the pilus up to 7 +/- 2 times. In region III, pili elongate in a nonlinear manner as a result of stretching until the bond ruptures.


A requirement for the Vgamma1+ subset of peripheral gammadelta T cells in the control of the systemic growth of Toxoplasma gondii and infection-induced pathology.
gammadelta T cells are a diverse population of T cells that are widely distributed and are a common feature of pathogen-induced immune responses. It is not clear, however, whether different populations of gammadelta T cells have specific functions, and what factors determine the functional properties of individual populations. A murine model of peroral Toxoplasma gondii infection was used to determine the contribution Vgamma1+ intestinal intraepithelial lymphocytes (IELs) vs systemic Vgamma1+ T cells make to the acute and chronic stages of the host immune response, and whether the macrophage cytocidal activity of Vgamma1+ T cells described in bacterial infections is seen in other, unrelated infectious disease models. In response to oral infection with virulent type 1 or avirulent type II strains of T. gondii, TCR-delta-/- mice rapidly developed severe ileitis. In contrast, in mice deficient in Vgamma1+ T cells and IELs and wild-type mice, inflammation was delayed in onset and less severe. The protective effect of (Vgamma1-) IELs to Toxoplasma infection was unrelated to their cytolytic and cytokine (Th1)-producing capabilities. Systemic Vgamma1+ T cells were shown to play an essential role in limiting parasite growth and inflammation in peripheral tissues and, in particular, in the CNS, that was associated with their ability to efficiently kill parasite-elicited and infected macrophages. These findings suggest that macrophage cytocidal activity of Vgamma1+ T cells may be a universal feature of pathogen-induced immune responses and that microenvironmental factors influence the involvement and function of gammadelta T cells in the host response to infection.


Evolution of French Bordetella pertussis and Bordetella parapertussis isolates: increase of Bordetellae not expressing pertactin.
Bordetella pertussis and Bordetella parapertussis are closely related bacterial agents of whooping cough. Whole-cell pertussis (wP) vaccine was introduced in France in 1959. Acellular pertussis (aP) vaccine was introduced in 1998 as an adolescent booster and was rapidly generalized to the whole population, changing herd immunity by specifically targeting the virulence of the bacteria. We performed a temporal analysis of all French B. pertussis and B. parapertussis isolates collected since 2000 under aP vaccine pressure, using pulsed-field gel electrophoresis (PFGE), genotyping and detection of expression of virulence factors. Particular isolates were selected according to their different phenotype and PFGE type and their characteristics were analysed using the murine model of respiratory infection and in vitro cell cytotoxic assay. Since the introduction of the aP vaccines there has been a steady increase in the number of B. pertussis and B. parapertussis isolates collected that are lacking expression of pertactin. These isolates seem to be as virulent as those expressing all virulence factors according to animal and cellular models of infection. Whereas wP vaccine-induced immunity led to a monomorphic population of B. pertussis, aP vaccine-induced immunity enabled the number of circulating B. pertussis and B. parapertussis isolates not expressing virulence factors to increase, sustaining our previous hypothesis.


Possible immunological disorders in autism: concomitant autoimmunity and immune tolerance.
Autism is a pervasive developmental disorder that affect children early in their life. Immunological disorders is one of several contributing factors that have been suggested to cause autism. Thirty autistic children aged 3-6 years and thirty non-autistic psychologically-free siblings were studied. Circulating IgA and IgG autoantibodies to casein and gluten dietary proteins were detected by enzyme-immunoassays (EIA). Circulating IgG antibodies to measles, mumps and rubella vaccine (M.M.R) and cytomeglovirus were investigated by EIA. Results revealed high seropositivity for autoantibodies to casein and gluten: 83.3% and 50% respectively in autistic children as compared to 10% and 6.7% positivity in the control group. Surprisingly, circulating anti-measles, anti-mumps and anti-rubella IgG were positive in only 50%, 73.3% and 53.3% respectively as compared to 100% positivity in the control group. Anti-CMV IgG was positive in 43.3% of the autistic children as compared to 7% in the control group. It is concluded that, autoimmune response to dietary proteins and deficient immune response to measles, mumps and rubella vaccine antigens might be associated with autism, as a leading cause or a resulting event. Further research is needed to confirm these findings.


MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines.
In patients presenting with a clinically isolated syndrome, MRI can support and substitute clinical information in the diagnosis of multiple sclerosis by showing disease dissemination in space and time and by helping to exclude disorders that can mimic multiple sclerosis. MRI criteria were first included in the diagnostic work-up for multiple sclerosis in 2001, and since then several modifications to the criteria have been proposed in an attempt to simplify lesion-count models for showing disease dissemination in space, change the timing of MRI scanning to show dissemination in time, and increase the value of spinal cord imaging. Since the last update of these criteria, new data on the use of MRI to establish dissemination in space and time have become available, and MRI technology has improved. State-of-the-art MRI findings in these patients were discussed in a MAGNIMS workshop, the goal of which was to provide an evidence-based and expert-opinion consensus on proposed modifications to MRI criteria for the diagnosis of multiple sclerosis.


Generalized cable theory for neurons in complex and heterogeneous media.
Cable theory has been developed over the last decade, usually assuming that the extracellular space around membranes is a perfect resistor. However, extracellular media may display more complex electrical properties due to various phenomena, such as polarization, ionic diffusion, or capacitive effects, but their impact on cable properties is not known. In this paper, we generalize cable theory for membranes embedded in arbitrarily complex extracellular media. We outline the generalized cable equations, then consider specific cases. The simplest case is a resistive medium, in which case the equations recover the traditional cable equations. We show that for more complex media, for example, in the presence of ionic diffusion, the impact on cable properties such as voltage attenuation can be significant. We illustrate this numerically, always by comparing the generalized cable to the traditional cable. We conclude that the nature of intracellular and extracellular media may have a strong influence on cable filtering as well as on the passive integrative properties of neurons.


Melatonin suppresses proinflammatory mediators in lipopolysaccharide-stimulated CRL1999 cells via targeting MAPK, NF-κB, c/EBPβ, and p300 signaling.
Melatonin is an indoleamine secreted by the pineal gland as well as a plant-derived product that exerts potential anti-inflammatory properties, but the mechanisms of action remain unclear. Here, we investigated the roles of melatonin in regulation of proinflammatory mediators and identified the underlying mechanisms in human vascular smooth muscle (VSM) cell line CRL1999 stimulated by lipopolysaccharide (LPS). We found that treatment with melatonin significantly inhibited the production and expression of TNF-α and interleukin (IL)-1β, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase, prostaglandin E(2) (PGE2), and nitric oxide (NO) in a dose-dependent manner. Moreover, we also found that the suppression of proinflammatory mediators by melatonin was mediated through inhibition of MAPK, NF-κB, c/EBPβ, and p300 signaling in LPS-stimulated CRL1999 cells. Treatment with melatonin markedly inhibited phosphorylation of ERK1/2, JNK, p38 MAPK, IκB-α, and c/EBPβ, blocked binding of NF-κB and c/EBPβ to promoters, and suppressed p300 histone acetyltransferase (HAT) activity and p300 HAT-mediated NF-κB acetylation. Transfection with an ERK-, IκB-, or c/EBPβ-specific siRNA or pretreatment with an ERK-, p38 MAPK-, or p300-selective inhibitor considerably abrogated the melatonin-mediated inhibition of proinflammatory mediators. Conversely, exogenous overexpression of a constitutively active p300, but not its HAT mutant, effectively reversed the melatonin-mediated inhibitions. Collectively, these results indicate that melatonin suppresses proinflammatory mediators by simultaneously targeting the multiple signaling such as ERK/p38 MAPK, c/EBPβ, NF-κB, and p300, in LPS-stimulated VSM cell line CRL1999, and suggest that melatonin is a potential candidate compound for the treatment of proinflammatory disorders.


Filtering genetic variants and placing informative priors based on putative biological function.
High-density genetic marker data, especially sequence data, imply an immense multiple testing burden. This can be ameliorated by filtering genetic variants, exploiting or accounting for correlations between variants, jointly testing variants, and by incorporating informative priors. Priors can be based on biological knowledge or predicted variant function, or even be used to integrate gene expression or other omics data. Based on Genetic Analysis Workshop (GAW) 19 data, this article discusses diversity and usefulness of functional variant scores provided, for example, by PolyPhen2, SIFT, or RegulomeDB annotations. Incorporating functional scores into variant filters or weights and adjusting the significance level for correlations between variants yielded significant associations with blood pressure traits in a large family study of Mexican Americans (GAW19 data set). Marker rs218966 in gene PHF14 and rs9836027 in MAP4 significantly associated with hypertension; additionally, rare variants in SNUPN significantly associated with systolic blood pressure. Variant weights strongly influenced the power of kernel methods and burden tests. Apart from variant weights in test statistics, prior weights may also be used when combining test statistics or to informatively weight p values while controlling false discovery rate (FDR). Indeed, power improved when gene expression data for FDR-controlled informative weighting of association test p values of genes was used. Finally, approaches exploiting variant correlations included identity-by-descent mapping and the optimal strategy for joint testing rare and common variants, which was observed to depend on linkage disequilibrium structure.


Fibrosis induced by resident macrophages has divergent roles in pancreas inflammatory injury and PDAC.
Tissue-resident macrophages (TRMs) are long-lived cells that maintain locally and can be phenotypically distinct from monocyte-derived macrophages. Whether TRMs and monocyte-derived macrophages have district roles under differing pathologies is not understood. Here, we showed that a substantial portion of the macrophages that accumulated during pancreatitis and pancreatic cancer in mice had expanded from TRMs. Pancreas TRMs had an extracellular matrix remodeling phenotype that was important for maintaining tissue homeostasis during inflammation. Loss of TRMs led to exacerbation of severe pancreatitis and death, due to impaired acinar cell survival and recovery. During pancreatitis, TRMs elicited protective effects by triggering the accumulation and activation of fibroblasts, which was necessary for initiating fibrosis as a wound healing response. The same TRM-driven fibrosis, however, drove pancreas cancer pathogenesis and progression. Together, these findings indicate that TRMs play divergent roles in the pathogenesis of pancreatitis and cancer through regulation of stromagenesis.


The anomalous halogen bonding interactions between chlorine and bromine with water in clathrate hydrates.
Clathrate hydrate phases of Cl2 and Br2 guest molecules have been known for about 200 years. The crystal structure of these phases was recently re-determined with high accuracy by single crystal X-ray diffraction. In these structures, the water oxygen-halogen atom distances are determined to be shorter than the sum of the van der Waals radii, which indicates the action of some type of non-covalent interaction between the dihalogens and water molecules. Given that in the hydrate phases both lone pairs of each water oxygen atom are engaged in hydrogen bonding with other water molecules of the lattice, the nature of the oxygen-halogen interactions may not be the standard halogen bonds characterized recently in the solid state materials and enzyme-substrate compounds. The nature of the halogen-water interactions for the Cl2 and Br2 molecules in two isolated clathrate hydrate cages has recently been studied with ab initio calculations and Natural Bond Order analysis (Ochoa-Resendiz et al. J. Chem. Phys. 2016, 145, 161104). Here we present the results of ab initio calculations and natural localized molecular orbital analysis for Cl2 and Br2 guests in all cage types observed in the cubic structure I and tetragonal structure I clathrate hydrates to characterize the orbital interactions between the dihalogen guests and water. Calculations with isolated cages and cages with one shell of coordinating molecules are considered. The computational analysis is used to understand the nature of the halogen bonding in these materials and to interpret the guest positions in the hydrate cages obtained from the X-ray crystal structures.


HIV-infected sex workers with beneficial HLA-variants are potential hubs for selection of HIV-1 recombinants that may affect disease progression.
Cytotoxic T lymphocyte (CTL) responses against the HIV Gag protein are associated with lowering viremia; however, immune control is undermined by viral escape mutations. The rapid viral mutation rate is a key factor, but recombination may also contribute. We hypothesized that CTL responses drive the outgrowth of unique intra-patient HIV-recombinants (URFs) and examined gag sequences from a Kenyan sex worker cohort. We determined whether patients with HLA variants associated with effective CTL responses (beneficial HLA variants) were more likely to carry URFs and, if so, examined whether they progressed more rapidly than patients with beneficial HLA-variants who did not carry URFs. Women with beneficial HLA-variants (12/52) were more likely to carry URFs than those without beneficial HLA variants (3/61) (p < 0.0055; odds ratio = 5.7). Beneficial HLA variants were primarily found in slow/standard progressors in the URF group, whereas they predominated in long-term non-progressors/survivors in the remaining cohort (p = 0.0377). The URFs may sometimes spread and become circulating recombinant forms (CRFs) of HIV and local CRF fragments were over-represented in the URF sequences (p < 0.0001). Collectively, our results suggest that CTL-responses associated with beneficial HLA variants likely drive the outgrowth of URFs that might reduce the positive effect of these CTL responses on disease progression.


A porcine model of intimal-medial hyperplasia in polytetrafluoroethylene arteriovenous grafts.
Vascular access polytetrafluoroethylene (PTFE) graft failure is a major cause of morbidity in the hemodialysis population. The most common cause of graft failure is thrombosis secondary to stenosis at the venous outflow tract. Venous outflow stenosis is characterized by intimal-medial hyperplasia. We have developed a porcine arteriovenous (AV) graft model that may be used to investigate this proliferative response and aid in the development of new therapies to prevent intimal-medial hyperplasia and improve graft patency. Left carotid to right external jugular vein PTFE (6 mm) grafts were implanted in the necks of swine. Immediately following anatomosis, flow rates were recorded. In one group of animals (n = 4) the venous outflow tract was harvested after 7 days and morphometric analysis of intimal and medial area was performed. In a second group (n = 8) the graft patency was monitored until 28 days. All porcine PTFE fistula grafts were patent at 7 days and 100% patency was maintained until 14 days. After 28 days, 75% of the grafts failed due to thrombosis. The venous outflow tract developed a significant proliferative response. After 7 days the intimal and medial areas were 469 +/- 9 microm2 and 875 +/- 26 microm2 respectively. At 28 days the intimal and medial areas were 913 +/- 55 microm2 and 1437 +/- 182 microm2 respectively. Luminal flow rate of the venous outflow tract was reduced significantly (344 +/- 11 ml/min at Day 0 to 129 +/- 14 ml/min at Day 7, p < 0.05). This porcine model rapidly, reliably and robustly reproduces the flow reducing stenosis and intimal-medial hyperplasia at the venous outflow tract of PTFE arteriovenous fistula. It represents a promising tool for investigating the mechanisms of intimal-medial hyperplasia, evaluating therapeutic interventions and new graft materials.


Pulsed high-intensity focused ultrasound enhances the relative permeability of the blood-tumor barrier in a glioma-bearing rat model.
The use of pulsed high-intensity focused ultrasound (HIFU) with an ultrasound contrast agent (UCA) has been shown to disrupt the blood-brain barrier (BBB) noninvasively and reversibly in the targeted regions. This study evaluated the relative permeability of the blood-tumor barrier (BTB) after sonication by pulsed HIFU. Entry into the brain of chemotherapeutic agents is impeded by the BBB even though the permeability of this barrier may be partially reduced in the presence of a brain tumor. F98 glioma-bearing rats were injected intravenously with Evans blue (EB) with or without BTB disruption induced by pulsed HIFU. Sonication was applied at an ultrasound frequency of 1 MHz with a 5% duty cycle, and a repetition frequency of 1 Hz. The accumulation of EB in brain tumor and the tumor-to-contralateral brain ratio of EB were highest after pulsed HIFU exposure. Sonication followed by EB injection showed a tumor-to-contralateral brain ratio in the target tumors which was about 2 times that of the control tumors. This research demonstrates that pulsed HIFU enhances the relative permeability of the BTB in glioma- bearing rats. The results of this pilot study support the idea that further evaluation of other treatment strategies, such as HIFU exposure in addition to combined chemotherapy or repeated pulsed HIFU exposure to increase delivery of drugs into brain tumors, might be useful.


Beneficial effect of eicosapentaenoic and docosahexaenoic acids in the management of systemic lupus erythematosus and its relationship to the cytokine network.
Systemic lupus erythematosus (SLE) is a chronic inflammatory condition characterised by arthritis, cutaneous rash, vasculitis, and involvement of central nervous system, renal and cardiopulmonary manifestations. Abnormalities in the cytokine network is believed to be involved in the pathobiology of this condition. The n-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can suppress T-cell proliferation and the production of interleukin-1, interleukin-2, and tumor necrosis factor by these cells both in vitro and in vivo. Oral supplementation of EPA and DHA induced prolonged remission of SLE in 10 consecutive patients without any side-effects. These results suggest that n-3 fatty acids, EPA and DHA, are useful in the management of SLE and possibly, other similar collagen vascular diseases.


Lymphocyte DNA damage in rats exposed to pyrethroids: effect of supplementation with Vitamins E and C.
Pesticides have been considered potential chemical mutagens. In fact, some studies show that various agrochemical ingredients possess mutagenic properties inducing mutations, chromosomal alterations or DNA damage. Experimental evidence shows a marked correlation between mutagenicity and carcinogenicity and indicates that short-term mutagenicity tests are useful for predicting carcinogenicity. The present study on rat exposed to two pyrethroids, cypermethrin and permethrin, showed different lymphocyte DNA damage depending on the type of pyrethroid, the dose, and the period of treatment. Data obtained from comet assay showed that oral treatment with 150 mg/kg body weight/day of permethrin (corresponding to 1/10 of LD50) for 60 days, induced a significant increase in all comet parameters. No lymphocyte DNA damage was measured after treatment with 25 mg/kg body weight/day of cypermethrin (corresponding to 1/10 of LD50) for the same period. A higher dose of permethrin (300 mg/kg body weight/day), for a shorter period (22 days), did not induce lymphocyte DNA damage, while supplementation with 200 mg/kg of Vitamins E and C protected erythrocytes against plasma membrane lipids peroxidation. Moreover, treatment with Vitamins E and C maintained the activity of glutathione peroxidase, which was reduced in the presence of permethrin, and reduced the osmotic fragility, which had increased following permethrin treatment.


miR-126 Suppresses Invasion and Migration of Malignant Glioma by Targeting Mature T Cell Proliferation 1 (MTCP1).
BACKGROUND The aim of this study was to assess the utility of miR-126 in promoting malignant glioma progression and determine if miR-126 might be a target for malignant glioma treatment. MATERIAL AND METHODS The expression of miR-126 in malignant glioma tissues and cells was detected by reverse transcription polymerase chain reaction (RT-PCR). Western blot analysis was used to detect changes in protein levels. Transwell assay was applied to assess the migration and invasion in vitro. Luciferase reporter assay was used to confirm the binding of miR-126 and mature T cell proliferation 1 (MTCP1). A nude mouse tumor model was used to assess the molecular mechanism in vivo. RESULTS The expression level of miR-126 in patients with stage III~IV malignant glioma was significant lower than that in patients with stage I~II. In different malignant glioma cell lines, the expression was significantly reduced in U87MG. Compared with the control mimics group, the expression of MTCP1 was significantly decreased. The results of Transwell assay showed that the invasiveness and migration in the miR-126 mimics group was significantly lower than in the control mimics groups. miR-126 mimics did not affect luciferase activity in the Mut-miR-126/MTCP1 group, while miR-126 mimics reduced luciferase activity by 54% in the Wt-miR-126/MTCP1 group. The results of invasion showed that the invasion ability in the miR-126 inhibitor group was significantly increased compared with that in the normal control (NC) group, while the invasion and migration abilities in the MTCP1 siRNA group were significantly increased. After 6 weeks, the tumor volume in the miR-126 inhibitor group was significantly increased, while that in the MTCP1 siRNA group was significantly decreased. CONCLUSIONS miR-126 inhibits the migration of malignant glioma cells by inhibiting MTCP1.


Sexual transmission of hepatitis C and early intervention.
The major risk factors for the transmission of hepatitis C virus (HCV) have been sharing needles for intravenous drug use (IDU) and receiving blood and blood products; however, recent findings suggest that HCV is being increasingly sexually transmitted, particularly among HIV-positive men who engage in high-risk, unprotected sexual behaviors with other men. Sixteen HIV-positive patients were diagnosed with sexually acquired HCV infection at a leading London HIV outpatient treatment center during 2002. All 16 patients were homosexual males with no history of IDU who had been involved in high-risk, unprotected sexual behaviors, which included active and passive anal intercourse, fisting, rimming, and oral sex. Six patients (37.5%) in the cohort spontaneously cleared HCV infection and consequently tested negative for HCV RNA. The remaining 10 patients were all started on HCV treatment, which consisted of pegylated interferon alpha-2b in combination with ribavirin. Three patients (43%) have achieved a significant reduction in HCV RNA after 12 to 24 weeks of HCV treatment. The earlier HCV seroconversion is detected and treated, the better the chance of achieving viral eradication.


Novel metrics reveal new structure and unappreciated heterogeneity in C. elegans development.
High throughput experimental approaches are increasingly allowing for the quantitative description of cellular and organismal phenotypes. Distilling these large volumes of complex data into meaningful measures that can drive biological insight remains a central challenge. In the quantitative study of development, for instance, one can resolve phenotypic measures for single cells onto their lineage history, enabling joint consideration of heritable signals and cell fate decisions. Most attempts to analyze this type of data, however, discard much of the information content contained within lineage trees. In this work we introduce a generalized metric, which we term the branch distance, that allows us to compare any two embryos based on phenotypic measurements in individual cells. This approach aligns those phenotypic measurements to the underlying lineage tree, providing a flexible and intuitive framework for quantitative comparisons between, for instance, Wild-Type (WT) and mutant developmental programs. We apply this novel metric to data on cell-cycle timing from over 1300 WT and RNAi-treated Caenorhabditis elegans embryos. Our new metric revealed surprising heterogeneity within this data set, including subtle batch effects in WT embryos and dramatic variability in RNAi-induced developmental phenotypes, all of which had been missed in previous analyses. Further investigation of these results suggests a novel, quantitative link between pathways that govern cell fate decisions and pathways that pattern cell cycle timing in the early embryo. Our work demonstrates that the branch distance we propose, and similar metrics like it, have the potential to revolutionize our quantitative understanding of organismal phenotype.


Skin regenerative potentials of curcumin.
Curcumin, an active constituent of the spice turmeric, is well known for its chemopreventive properties and is found to be beneficial in treating various disorders including skin diseases. Curcumin protects skin by quenching free radicals and reducing inflammation through the inhibition of nuclear factor-kappa B. Curcumin also affects other signaling pathways including transforming growth factor-β and mitogen-activated protein kinase pathway. Curcumin also modulates the phase II detoxification enzymes which are crucial in detoxification reactions and for protection against oxidative stress. In the present review, the biological mechanisms of the chemopreventive potential of curcumin in various skin diseases like psoriasis, vitiligo, and melanoma is discussed. The application of curcumin in skin regeneration and wound healing is also elucidated. We also explored the recent innovations and advances involved in the development of transdermal delivery systems to enhance the bioavailability of curcumin, particularly in the skin. Recent clinical trials pertaining to the use of curcumin in skin diseases establishes its benefits and also the need for additional clinical trials in other diseases are discussed.


Intensive Care Clinicians' Perspectives on Ethical Challenges Raised by Rapid Genomic Testing in Critically Ill Infants.
Rapid genomic testing (rGT) enables genomic information to be available in a matter of hours, allowing it to be used in time-critical settings, such as intensive care units. Although rGT has been shown to improve diagnostic rates in a cost-effective manner, it raises ethical questions around a range of different areas, including obtaining consent and clinical decision-making. While some research has examined the perspectives of parents and genetics health professionals, the attitudes of intensive care clinicians remain under-explored. To address this gap, we administered an online survey to English-speaking neonatal/paediatric intensivists in Europe, Australasia and North America. We posed two ethical scenarios: one relating to obtaining consent from the parents and the second assessing decision-making regarding the provision of life-sustaining treatments. Descriptive statistics were used to analyse the data. We received 40 responses from 12 countries. About 50-75% of intensivists felt that explicit parental consent was necessary for rGT. About 68-95% felt that a diagnosis from rGT should affect the provision of life-sustaining care. Results were mediated by intensivists' level of experience. Our findings show divergent attitudes toward ethical issues generated by rGT among intensivists and suggest the need for guidance regarding ethical decision-making for rGT.


The shapes and sizes of closed, pressurized random walks.
Two-dimensional cell-like membranes acted on by osmotic pressure differentials are represented by closed, unrestricted random walks. The treatment omits excluded-volume effects, and the pressure that is imposed thus favors an oriented area, so that the shriveled configuration of a vesicle with excess external pressure is inaccessible in this model. Nevertheless, the approach has the decided advantage of yielding analytic expressions in a complete statistical analysis. Results are presented for the average square of the radius of gyration, the asphericity, and the probability distribution of the principal components of the radius of gyration tensor. The analysis is done in both the constant-pressure and constant-area ensembles.


Socioeconomic status during youth and risk of car crash during adulthood. Findings from the DRIVE cohort study.
Young drivers of low socioeconomic status (SES) have a disproportionally high risk of crashing compared with their more affluent counterparts. Little is known if this risk persists into adulthood and if it differs between men and women. We used data from a 2003/2004 Australian survey of young drivers (n=20 806), which included measures of drivers' demographics and established crash risk factors. These data were linked to police-reported crash, hospital and death data up to 2016. We used negative binomial regression models to estimate the association between participants' SES, with car crash. After adjusting for confounding, drivers of lowest SES had 1.30 (95% CI 1.20 to 1.42), 1.90 (95% CI 1.25 to 2.88), 3.09 (95% CI 2.41 to 3.95) and 2.28 (95% CI 1.85 to 2.82) times higher rate of crash, crash-related hospitalisation, crash in country areas and crash on streets with a speed limit of 80 km/hour or above compared with drivers of highest SES, respectively. For single-vehicle crashes, women in the lowest SES groups had 2.88 (95% CI 1.83 to 4.54) times higher rate of crash compared with those in the highest SES group, but no differences were observed for men from different SES groups. Young drivers who lived in areas of low SES at the time of the survey had a sustained increased risk of crash over the following 13 years compared with drivers from the most affluent areas. Our findings suggest that in addition to traditional measures, road transport injury prevention needs to consider the wider social determinants of health.


RAB6 and microtubules restrict protein secretion to focal adhesions.
To ensure their homeostasis and sustain differentiated functions, cells continuously transport diverse cargos to various cell compartments and in particular to the cell surface. Secreted proteins are transported along intracellular routes from the endoplasmic reticulum through the Golgi complex before reaching the plasma membrane along microtubule tracks. Using a synchronized secretion assay, we report here that exocytosis does not occur randomly at the cell surface but on localized hotspots juxtaposed to focal adhesions. Although microtubules are involved, the RAB6-dependent machinery plays an essential role. We observed that, irrespective of the transported cargos, most post-Golgi carriers are positive for RAB6 and that its inactivation leads to a broad reduction of protein secretion. RAB6 may thus be a general regulator of post-Golgi secretion.


Encapsulation of babchi essential oil into microsponges: Physicochemical properties, cytotoxic evaluation and anti-microbial activity.
Babchi essential oil (BEO) is a valuable essential oil reported to possess a variety of biological activities such as antitumor, anti inflammatory, immunomodulatory, antioxidant, antifungal and antibacterial properties. Due to its anti-microbial properties, this oil possesses an immense potential for the treatment of dermatological disorders. Further, it has minimal tendency to develop resistance, a common issue with most of the antibiotics. However, its highly viscous nature and poor stability in the presence of light, air and high temperature, limits its practical applications. To surmount these issues, this research aims to encapsulate BEO in ethyl cellulose (EC) microsponges for enhanced stability, antibacterial effect and decreased dermal toxicity. The quasi emulsion solvent evaporation technique was used for fabrication of the BEO microsponges employing EC as polymer, polyvinyl alcohol (PVA) as stabilizer and dichloro methane (DCM) as solvent. The effect of formulation variables such as the amount of EC and PVA were also investigated. The prepared microformulations were evaluated for production yield, encapsulation efficiency, particle size and in vitro release. In vitro cytotoxicity was also checked to assess dermal safety of BEO microsponges. Results revealed that all the dispersions were in micro size range (20.44 ± 3.13 μm to 41.75 ± 3.65 μm), with good encapsulation efficiency (87.70 ± 1.20% of F2) and controlled release profile (cumulative drug release 73.34 ± 1.76%). Field emission scanning electron microscopy results showed that the microsponges possessed a spherical uniform shape with a spongy structure. Results of cytotoxicity study indicated that the prepared microsponges were safer on dermal cells in comparison to pure BEO. The optimized formulation was also evaluated for in vitro antimicrobial assay against dermal bacteria like Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, which confirmed their enhanced antibacterial activity. Furthermore, the results of photostability and stability analysis indicated improved stability of BEO loaded microsponges. Hence, encapsulation of BEO in microsponges resulted in efficacious carrier system in terms of stability as well as safety of this essential oil alongwith handling benefits.


User-Centered Design of a Tablet Waiting Room Tool for Complex Patients to Prioritize Discussion Topics for Primary Care Visits.
Complex patients with multiple chronic conditions often face significant challenges communicating and coordinating with their primary care physicians. These challenges are exacerbated by the limited time allotted to primary care visits. Our aim was to employ a user-centered design process to create a tablet tool for use by patients for visit discussion prioritization. We employed user-centered design methods to create a tablet-based waiting room tool that enables complex patients to identify and set discussion topic priorities for their primary care visit. In an iterative design process, we completed one-on-one interviews with 40 patients and their 17 primary care providers, followed by three design sessions with a 12-patient group. We audiorecorded and transcribed all discussions and categorized major themes. In addition, we met with 15 key health communication, education, and technology leaders within our health system to further review the design and plan for broader implementation of the tool. In this paper, we present the significant changes made to the tablet tool at each phase of this design work. Patient feedback emphasized the need to make the tablet tool accessible for patients who lacked technical proficiency and to reduce the quantity and complexity of text presentation. Both patients and their providers identified specific content choices based on their personal experiences (eg, the ability to raise private or sensitive concerns) and recommended targeting new patients. Stakeholder groups provided essential input on the need to augment text with video and to create different versions of the videos to match sex and race/ethnicity of the actors with patients. User-centered design in collaboration with patients, providers, and key health stakeholders led to marked evolution in the initial content, layout, and target audience for a tablet waiting room tool intended to assist complex patients with setting visit discussion priorities.


Mechanical modulation method for ultrasensitive phase measurements in photonics biosensing.
A novel polarimetry methodology for phase-sensitive measurements in single reflection geometry is proposed for applications in optical transduction-based biological sensing. The methodology uses altering step-like chopper-based mechanical phase modulation for orthogonal s- and p- polarizations of light reflected from the sensing interface and the extraction of phase information at different harmonics of the modulation. We show that even under a relatively simple experimental arrangement, the methodology provides the resolution of phase measurements as low as 0.007 deg. We also examine the proposed approach using Total Internal Reflection (TIR) and Surface Plasmon Resonance (SPR) geometries. For TIR geometry, the response appears to be strongly dependent on the prism material with the best values for high refractive index Si. The detection limit for Si-based TIR is estimated as 10(-5) in terms Refractive Index Units (RIU) change. SPR geometry offers much stronger phase response due to a much sharper phase characteristics. With the detection limit of 3.2*10(-7) RIU, the proposed methodology provides one of best sensitivities for phase-sensitive SPR devices. Advantages of the proposed method include high sensitivity, simplicity of experimental setup and noise immunity as a result of a high stability modulation.


High-speed detection of DNA translocation in nanopipettes.
We present a high-speed electrical detection scheme based on a custom-designed CMOS amplifier which allows the analysis of DNA translocation in glass nanopipettes on a microsecond timescale. Translocation of different DNA lengths in KCl electrolyte provides a scaling factor of the DNA translocation time equal to p = 1.22, which is different from values observed previously with nanopipettes in LiCl electrolyte or with nanopores. Based on a theoretical model involving electrophoresis, hydrodynamics and surface friction, we show that the experimentally observed range of p-values may be the result of, or at least be affected by DNA adsorption and friction between the DNA and the substrate surface.


Road vehicle transportation of children with physical and behavioral disabilities: A literature review.
Background: A literature review in 2001 found that children with disabilities were frequently transported in unsafe conditions and further research was required to investigate the gap between regulations, standards and actual transportation practices.Objectives: To synthesize available evidence on the transportation of children with disabilities in road vehicles.Methods: Four databases were systematically searched: CINAHL; Medline; National Transport Library Catalogue (Sweden); and Transport Research International Documentation.Results: Nineteen studies ranging in methodological quality from poor to excellent were included in the review. The findings are presented under the following six major themes: child safety restraints, wheelchairs, vehicles, travel habits, parental and professional knowledge. The results are mapped onto two groups of children, those with behavioral problems and those with physical disabilities.Conclusion: The literature reflected little change across the six major themes since the previous review. Children with disabilities continue to be inappropriately restrained in vehicles, constituting an ongoing road safety problem. There is a strong need to increase parent knowledge, upskill health professionals and provide families with financial assistance to enable them to ensure the safe transportation of children with disabilities to minimize the risk of injury and fatalities on the road, and enhance their participation in the community.


Model-based image analysis of a tethered Brownian fibre for shear stress sensing.
The measurement of fluid dynamic shear stress acting on a biologically relevant surface is a challenging problem, particularly in the complex environment of, for example, the vasculature. While an experimental method for the direct detection of wall shear stress via the imaging of a synthetic biology nanorod has recently been developed, the data interpretation so far has been limited to phenomenological random walk modelling, small-angle approximation, and image analysis techniques which do not take into account the production of an image from a three-dimensional subject. In this report, we develop a mathematical and statistical framework to estimate shear stress from rapid imaging sequences based firstly on stochastic modelling of the dynamics of a tethered Brownian fibre in shear flow, and secondly on a novel model-based image analysis, which reconstructs fibre positions by solving the inverse problem of image formation. This framework is tested on experimental data, providing the first mechanistically rational analysis of the novel assay. What follows further develops the established theory for an untethered particle in a semi-dilute suspension, which is of relevance to, for example, the study of Brownian nanowires without flow, and presents new ideas in the field of multi-disciplinary image analysis.


Kinetics of HIV-1 Latency Reversal Quantified on the Single-Cell Level Using a Novel Flow-Based Technique.
HIV-1 establishes a pool of latently infected cells early following infection. New therapeutic approaches aiming at diminishing this persisting reservoir by reactivation of latently infected cells are currently being developed and tested. However, the reactivation kinetics of viral mRNA and viral protein production, and their respective consequences for phenotypical changes in infected cells that might enable immune recognition, remain poorly understood. We adapted a novel approach to assess the dynamics of HIV-1 mRNA and protein expression in latently and newly infected cells on the single-cell level by flow cytometry. This technique allowed the simultaneous detection of gagpol mRNA, intracellular p24 Gag protein, and cell surface markers. Following stimulation of latently HIV-1-infected J89 cells with human tumor necrosis factor alpha (hTNF-α)/romidepsin (RMD) or HIV-1 infection of primary CD4(+) T cells, four cell populations were detected according to their expression levels of viral mRNA and protein. gagpol mRNA in J89 cells was quantifiable for the first time 3 h after stimulation with hTNF-α and 12 h after stimulation with RMD, while p24 Gag protein was detected for the first time after 18 h poststimulation. HIV-1-infected primary CD4(+) T cells downregulated CD4, BST-2, and HLA class I expression at early stages of infection, proceeding Gag protein detection. In conclusion, here we describe a novel approach allowing quantification of the kinetics of HIV-1 mRNA and protein synthesis on the single-cell level and phenotypic characterization of HIV-1-infected cells at different stages of the viral life cycle. Early after infection, HIV-1 establishes a pool of latently infected cells, which hide from the immune system. Latency reversal and immune-mediated elimination of these latently infected cells are some of the goals of current HIV-1 cure approaches; however, little is known about the HIV-1 reactivation kinetics following stimulation with latency-reversing agents. Here we describe a novel approach allowing for the first time quantification of the kinetics of HIV-1 mRNA and protein synthesis after latency reactivation or de novo infection on the single-cell level using flow cytometry. This new technique furthermore enabled the phenotypic characterization of latently infected and de novo-infected cells dependent on the presence of viral RNA or protein.