Estimating Costs of Implementing Stroke Systems of Care and Data-Driven Improvements in the Paul Coverdell National Acute Stroke Program.
We evaluated the costs of implementing coordinated systems of stroke care by state health departments from 2012 through 2015 to help policy makers and planners gain a sense of the potential return on investments in establishing a stroke care quality improvement (QI) program. State health departments funded by the Paul Coverdell National Acute Stroke Program (PCNASP) implemented activities to support the start and proficient use of hospital stroke registries statewide and coordinate data-driven QI efforts. These efforts were aimed at improving the treatment and transition of stroke patients from prehospital emergency medical services (EMS) to in-hospital care and postacute care facilities. Health departments provided technical assistance and data to support hospitals, EMS agencies, and posthospital care agencies to carry out small, rapid, incremental QI efforts to produce more effective and efficient stroke care practices. Six of the 11 PCNASP-funded state health departments in the United States volunteered to collect and report programmatic costs associated with implementing the components of stroke systems of care. Six health departments reported costs paid directly by Centers for Disease Control and Prevention-provided funds, 5 also reported their own in-kind contributions, and 4 compiled data from a sample of their partners' estimated costs of resources, such as staff time, involved in program implementation. Costs were analyzed separately for PCNASP-funded expenditures and in-kind contributions by the health department by resource category and program activity. In-kind contributions by partners were also analyzed separately. PCNASP-funded expenditures ranged from $790,123 to $1,298,160 across the 6 health departments for the 3-year funding period. In-kind contributions ranged from $5,805 to $1,394,097. Partner contributions (n = 22) ranged from $3,912 to $362,868. Our evaluation reports costs for multiple state health departments and their partners for implementing components of stroke systems of care in the United States. Although there are limitations, our findings represent key estimates that can guide future program planning and efforts to achieve sustainability.


The influence of dietary diversity on anthropometric status among young children ages 12 and 24 months in Wuhan, China.
The relative research on investigating the association between dietary diversity scores and anthropometric status among young children is few and inconsistent. Since understanding this association is quite essential to give more detailed advice about diet to ensure young children's healthy growth, we sought to determine the association between dietary diversity levels and anthropometric status among young children under 24 months. The study included 1408 mother-child pairs from the Tongji Maternal and Child Health Cohort, whose children range in age from 12 to 24 months. Multivariable logistic regressions were used to examine the effect of dietary diversity on children's anthropometric failure and obesity. All obese children aged 12 and 24 months had low-medium diverse diets in their first year of life. Risks of anthropometric failure for 12-month young children consumed low-medium diverse diets in their first year and 24-month young children consumed low-medium diverse diets in their second year are, respectively, 1.27 (odds ratio [OR], 95% confidence interval [CI] = [1.06-1.53]) and 1.19 (OR, 95% CI = [1.02-1.40]) times of those who consumed high diverse diets in corresponding year. The risk of anthropometric failure for 24-month-old children who consumed low-medium diverse diets during their first year of life is 4.70 (OR, 95% CI = [1.62-19.91]) times that of young children who consumed highly diverse diets during their first year of life. Introducing more diverse diets to young children under 24 months of age may be an effective strategy to prevent anthropometric failure and obesity in young children in later life.


Sources of edaphic cyanobacterial diversity in the Dry Valleys of Eastern Antarctica.
Cyanobacteria are major components of Antarctic Dry Valley ecosystems. Their occurrence in lakes and ponds is well documented, however, less is known about their distribution in edaphic environments. There has been considerable debate about the contribution of aquatic organic matter derived largely from cyanobacteria to terrestrial ecosystems. In this study, automated rRNA intergenic spacer analysis (ARISA) and 16S rRNA gene clone libraries were used to investigate cyanobacterial diversity in a range of soil environments within the Miers and Beacon Valleys. These data were used to elucidate the input of aquatic cyanobacteria to soil communities. Thirty-eight samples were collected from a variety of soil environments including dry and moist soils, hypoliths and lake and hydroterrestrial microbial mats. The results from the ARISA and 16S rRNA clone library analysis demonstrated that diverse cyanobacterial communities exist within the mineral soils of the Miers Valley. The soil samples from Beacon Valley were depauparate in cyanobacterial signals. Within Miers Valley, significant portions (29%-58%) of ARISA fragment lengths found in aquatic cyanobacterial mats were also present in soil and hypolith samples, indicating that lacustrine and hydroterrestrial cyanobacteria play a significant role in structuring soil communities. The influence of abiotic variables on the community structure of soil samples was assessed using BEST analysis. The results of BEST analysis of samples from within Miers Valley showed that total percentage of carbon content was the most important variable in explaining differences in cyanobacterial community structure. The BEST analyses indicated that four elements contributed significantly to species compositional differences between valleys. We suggest that the complete absence of lakes or ponds from Beacon Valley is a contributing factor to the low cyanobacterial component of these soils.


Osseointegration of cemented and noncemented implants in artificial hip replacement: long-term findings in man.
Implant fixation is of utmost importance for pain-free function of endoprostheses. Primary fixation is achieved during implantation, whereas secondary fixation is a result of repair and bone remodelling during the healing process comparable to fracture healing. The chronologic course of the healing process follows three overlapping phases: (i) an initial phase with destruction and necroses of bone, (ii) a phase of repair with integration of the implant into the bone, and (iii) a phase of stabilization of the permanent implant bed with adaptation to load transfer and possible reactions to irritations of the interface like sepsis, mechanical instability, corrosion and degradation of implant materials, and wear products from articulating and anchoring surfaces.


Liver and heart: a new link?
Alanine aminotransferase (ALT) is a marker of non-alcoholic fatty liver disease (NAFLD) and predicts incident type 2 diabetes mellitus (DM2). Recently, ALT was shown to be also associated with endothelial dysfunction and carotid atherosclerosis. We studied the predictive value of ALT for all-cause mortality, incident cardiovascular disease (CVD) and coronary heart disease (CHD) events in a population-based cohort of Caucasian men and women aged 50-75 years, at baseline. The 10-year risk of all-cause mortality, fatal and non-fatal CVD and CHD events in relation to ALT was assessed in 1439 subjects participating in the Hoorn Study, using Cox survival analysis. Subjects with prevalent CVD/CHD and missing data were excluded. As compared with the first tertile, the age- and sex-adjusted hazard ratios (95% confidence intervals) for all-cause mortality, CVD events and CHD events were 1.30 (0.92-1.83), 1.40 (1.09-1.81) and 2.04 (1.35-3.10), respectively, for subjects in the upper tertile of ALT. After adjustment for components of the metabolic syndrome and traditional risk factors, the association of ALT and CHD events remained significant for subjects in the third relative to those in the first tertile, with a hazard ratio of 1.88 (1.21-2.92) and 1.75 (1.12-2.73), respectively. In conclusion, the predictive value of ALT for coronary events, seems independent of traditional risk factors and the features of the metabolic syndrome in a population-based cohort. Further studies should confirm these findings and elucidate the pathophysiological mechanisms.


Evaluation of a multiprofessional learning organisation: use of a questionnaire to investigate the learning experiences of a group of undergraduate pharmacy students attached to primary care.
This paper reports on the evaluation of the educational benefits to third-year MPharm students attached to four Nottingham inner-city training practices as part of the first cohort of learners to come to a multiprofessional learning organisation (MPLO). The aim was to identify areas of benefit above and beyond those available at their core course in order to identify areas for further study. This study used a mixture of both quantitative and qualitative methods to generate ideas through grounded theory. It used a hermeneutic approach to define multiprofessional learning and professional roles. A questionnaire was developed and all students were invited to complete it at the end of their attachments. It was analysed using an SPSS computer package. The main benefits perceived by pharmacy students were concerning development of professional role, behaviour in the field (legitimate peripheral participation) and emergence of professional identity. From the findings the authors have described an MPLO as 'an educational enterprise between different professions which has an ethos of mutual co-operation and understanding of each other's roles, emphasises communication and idea sharing and exists within a environment of 'smooth systems functioning". • An MPLO can be defined as: 'an educational enterprise between different professions which has an ethos of mutual co-operation and understanding of each other's roles, emphasises communication and idea sharing, and exists within a environment of 'smooth systems functioning'. • Neophyte professionals want to practise interprofessional behaviour. • Professional identity is enhanced when group differences are emphasised and the move to homogenise professional groups through interprofessional working may not be successful. • Educators must help learners challenge professional stereotypes and enable them to develop flexibility to meet future challenges.


Melanoma in Situ Treated with Topical Imiquimod for Management of Persistently Positive Margins: A Review of Treatment Methods.
Imiquimod is a topical cream approved by the US Food and Drug Administration for treatment of superficial basal cell carcinoma, actinic keratosis, and genital-perianal warts. Its successful use in patients with persistently positive margins of melanoma in situ (MIS) after surgical excision has been previously reported. A 75-year-old female presented with a primary melanoma that was removed through an elliptical excision with 1 cm margins. Pathology revealed 3 involved margins with residual MIS without an invasive component. After a second operation removed an additional 1 cm margin, pathology revealed 2 positive margins with residual MIS. Rather than undergoing a third excision, the patient decided to pursue a nonsurgical approach with topical imiquimod, and at the 4-month follow-up examination, the incision was completely healed with no clinical evidence of tumor recurrence. A nonsurgical approach with 5% topical imiquimod cream applied along the incision was utilized. In specific patient populations, the use of imiquimod is a reasonable alternative approach for the management of persistently positive MIS margins. Long-term follow-up is necessary to assess for evidence of recurrence and the ultimate success of this nonsurgical approach.


High-redshift star formation in the Atacama large millimetre/submillimetre array era.
The Atacama Large Millimetre/submillimetre Array (ALMA) is currently in the process of transforming our view of star-forming galaxies in the distant ( z ≳ 1 ) universe. Before ALMA, most of what we knew about dust-obscured star formation in distant galaxies was limited to the brightest submillimetre sources-the so-called submillimetre galaxies (SMGs)-and even the information on those sources was sparse, with resolved (i.e. sub-galactic) observations of the obscured star formation and gas reservoirs typically restricted to the most extreme and/or strongly lensed sources. Starting with the beginning of early science operations in 2011, the last 9 years of ALMA observations have ushered in a new era for studies of high-redshift star formation. With its long baselines, ALMA has allowed observations of distant dust-obscured star formation with angular resolutions comparable to-or even far surpassing-the best current optical telescopes. With its bandwidth and frequency coverage, it has provided an unprecedented look at the associated molecular and atomic gas in these distant galaxies through targeted follow-up and serendipitous detections/blind line scans. Finally, with its leap in sensitivity compared to previous (sub-)millimetre arrays, it has enabled the detection of these powerful dust/gas tracers much further down the luminosity function through both statistical studies of colour/mass-selected galaxy populations and dedicated deep fields. We review the main advances ALMA has helped bring about in our understanding of the dust and gas properties of high-redshift ( z ≳ 1 ) star-forming galaxies during these first 9 years of its science operations, and we highlight the interesting questions that may be answered by ALMA in the years to come.


Pathogenicity in mice of strains of herpes simplex virus which are resistant to acyclovir in vitro and in vivo.
Mice infected with three different isolates of herpes simplex virus (HSV) and treated with acyclovir (acycloguanosine; ACV) showed low levels of virus replication during the acute phase of infection. However, virus isolated from such treated mice did not show increased resistance to ACV. In contrast, resistant virus was readily isolated in vitro by passaging HSV in the presence of the drug. The degree of resistance was determined, in part, by the nature of the cells used to test the virus. The majority of ACV-resistant strains induced low or undetectable levels of HSV-specified thymidine kinase (TK), the enzyme responsible for phosphorylating ACV in infected cells. The TK-resistant strains were attenuated when injected into mice as indicated by reductions in virus replication, inflammation, and establishment of latent infections in sensory ganglia. The reduced virulence of the TK- strains was most marked after intracerebral inoculation, where the lethal dose was increased more than 100-fold compared with the parental isolates. However, one mutant is described which induced high levels of TK but was highly resistant to ACV and retained virulence for mice.


Electrical transport and field-effect transistors using inkjet-printed SWCNT films having different functional side groups.
The electrical properties of random networks of single-wall carbon nanotubes (SWNTs) obtained by inkjet printing are studied. Water-based stable inks of functionalized SWNTs (carboxylic acid, amide, poly(ethylene glycol), and polyaminobenzene sulfonic acid) were prepared and applied to inkjet deposit microscopic patterns of nanotube films on lithographically defined silicon chips with a back-side gate arrangement. Source-drain transfer characteristics and gate-effect measurements confirm the important role of the chemical functional groups in the electrical behavior of carbon nanotube networks. Considerable nonlinear transport in conjunction with a high channel current on/off ratio of approximately 70 was observed with poly(ethylene glycol)-functionalized nanotubes. The positive temperature coefficient of channel resistance shows the nonmetallic behavior of the inkjet-printed films. Other inkjet-printed field-effect transistors using carboxyl-functionalized nanotubes as source, drain, and gate electrodes, poly(ethylene glycol)-functionalized nanotubes as the channel, and poly(ethylene glycol) as the gate dielectric were also tested and characterized.


Comparison of the antimicrobial efficacy of irrigation using the EndoVac to endodontic needle delivery.
The purpose of this investigation was to compare the antimicrobial efficacy of root canal irrigation with the EndoVac (Discus Dental, Culver City, CA) to endodontic needle irrigation in the apical 5 mm of root canals infected with Enterococcus faecalis. Bilaterally matched, extracted human teeth were sterilized and inoculated with E. faecalis. Specimens in the EndoVac group were irrigated using the EndoVac system, whereas those in the needle group were irrigated with a 30-G side-vented needle. After chemomechanical preparation, the apical 5 mm of the roots were removed, frozen in liquid nitrogen, and pulverized to expose E. faecalis in dentinal tubules or other morphologic irregularities. The number of colony forming units (cfus) of E. faecalis per mg dentin was determined. The EndoVac Group had a mean of 31.6 cfu/mg, whereas the needle group had a mean of 157 cfu/mg. This represents a bacterial reduction of 99.7% in group A and 98.8% in group B when compared with positive controls. Although there were fewer cfu/mg when using the EndoVac, there was not a statistically significant difference between the EndoVac and needle groups.


Coronary artery calcium: absolute quantification in nonenhanced and contrast-enhanced multi-detector row CT studies.
(a) To determine the accuracy of multi-detector row computed tomography (CT) in the measurement of the calcium concentration in a cardiac CT calibration phantom and (b) to assess the correlation of a traditional 3-mm section width CT coronary screening protocol and a 1.25-mm section width CT angiography imaging protocol in the quantification of the absolute mass of coronary calcium in patients who underwent both coronary screening and CT angiography with a multi-detector row CT scanner. A heart phantom containing calcified cylinders was scanned to determine calibration factors and absolute calcium mass. In 50 patients, the variability (value 1 - value 2/mean value 1 - value 2), limit of agreement (+/-2SD value 1 - value 2), and systematic error (mean value 1 - value 2) of the total amount of coronary calcium calculated at traditional 3-mm section width CT and at 1.25-mm section width CT angiography were determined. The correlation coefficient between the 3-mm section width, nonenhanced protocol and the 1.25-mm section width CT angiography protocol was very high (r = 0.977) and the mean variability was low (19.7%) for the absolute mass. There was a systematic error of -6.7 mg and a limit of agreement between 45.0 mg and -58.5 mg. Use of the mass quantification algorithm in combination with a calibration phantom allows accurate quantification of coronary calcium. Measurements of calcium mass obtained at 1.25-mm section width CT angiography have the best agreement with those obtained at the traditional 3-mm section width imaging protocol.


Variational Information Bottleneck for Unsupervised Clustering: Deep Gaussian Mixture Embedding.
In this paper, we develop an unsupervised generative clustering framework that combines the variational information bottleneck and the Gaussian mixture model. Specifically, in our approach, we use the variational information bottleneck method and model the latent space as a mixture of Gaussians. We derive a bound on the cost function of our model that generalizes the Evidence Lower Bound (ELBO) and provide a variational inference type algorithm that allows computing it. In the algorithm, the coders' mappings are parametrized using neural networks, and the bound is approximated by Markov sampling and optimized with stochastic gradient descent. Numerical results on real datasets are provided to support the efficiency of our method.


Support from advisors on child rearing for alleviating maternal anxiety and depressive symptoms among Japanese women.
Accumulating evidence suggests that social support is an important factor with regard to maternal psychological distress. The associations between the contextual factors in terms of social support and the risk of maternal psychological distress have not been adequately studied in Japan. The objective of this study was to examine the association of the presence of advisors on child rearing with maternal anxiety and depressive symptoms among Japanese women at 2 time points after childbirth. A self-administered questionnaire that included items regarding the conditions of child rearing and a scale to estimate psychological distress was delivered to 2657 mothers when their infants were 3-4 months and 9-10 months old in 2004-2005. Multivariate logistic regression analysis was conducted for the statistical analyses. From the multivariate odds ratio, an environment with a few close advisors on child rearing was associated with the risks of maternal anxiety and depressive symptoms at 3-4 months and 9-10 months. The presence of few professional advisors on child rearing was also related to the risk of maternal depressive symptoms at the 2 time periods. The companionship of other child-rearing individuals was related to depressive symptoms at 9-10 months. An environment without advisors on child rearing was associated with maternal psychological distress. A similarity between the observations at the 2 time points was that the presence of personal and professional advisors was related to maternal anxiety and/or depressive symptoms. It was noted that the need for other child-rearing companions increases as the child grows older.


5-Lipoxygenase and cyclooxygenase inhibitory dammarane triterpenoid 1 from Borassus flabellifer seed coat inhibits tumor necrosis factor-α secretion in LPSInduced THP-1 human monocytes and induces apoptosis in MIA PaCa-2 pancreatic cancer cells.
Phospholipase A2 (PLA2), Cyclooxygenase (COX) and 5-Lipoxygenase (5-LOX) are arachidonic acid metabolizing enzymes and their inhibitors have been developed as therapeutic molecules for cancer and inflammation related disorders. In the present study, PLA2, COX 1&2 and 5-LOX inhibitory studies of Borassus flabellifer seed coat extract were carried out and substantial 5-LOX inhibitory activity was found. Dammarane triterpenoid 1 (Dammara-20,23-diene-3,25-diol) was isolated according to 5-LOX activity guided isolation, and screened for COX (1 & 2) inhibitory activities. Dammarane triterpenoid 1 inhibited carrageenan-induced rat paw edema and TNF-α secretion levels in lipopolysaccharide (LPS)-induced THP-1 human monocytes. Anticancer activity studies demonstrated the antiproliferative effect of dammarane triterpenoid 1 on various cancer cell lines including MIA PaCa-2 pancreatic, DU145 prostate, HL-60 leukemia and Caco-2 colon cancers. Dammarane triterpenoid 1 showed good antiproliferative activity on MIA PaCa-2 pancreatic cancer cell line with IC50 of 12.36±0.33 µM, among other tested cell lines. Apoptosis inducing activity of dammarane triterpenoid 1 was confirmed based on increased sub-G0 phase cell population in cell cycle analysis, loss of mitochondrian membrane potential, elevated levels of cytochrome c, nuclear morphological changes and DNA fragmentation in MIA PaCa-2 pancreatic cancer cells. Therefore, dammarane triterpenoid skeleton may raise the hope of developing novel anti-inflammatory and anticancer drugs in the future.


Development and validation of the Penn State Worry Questionnaire.
The present report describes the development of the Penn State Worry Questionnaire to measure the trait of worry. The 16-item instrument emerged from factor analysis of a large number of items and was found to possess high internal consistency and good test-retest reliability. The questionnaire correlates predictably with several psychological measures reasonably related to worry, and does not correlate with other measures more remote to the construct. Responses to the questionnaire are not influenced by social desirability. The measure was found to significantly discriminate college samples (a) who met all, some, or none of the DSM-III-R diagnostic criteria for generalized anxiety disorder and (b) who met criteria for GAD vs posttraumatic stress disorder. Among 34 GAD-diagnosed clinical subjects, the worry questionnaire was found not to correlate with other measures of anxiety or depression, indicating that it is tapping an independent construct with severely anxious individuals, and coping desensitization plus cognitive therapy was found to produce significantly greater reductions in the measure than did a nondirective therapy condition.


Utility of reverse transcriptase - Multiplex ligation-dependant probe amplification (RT-MLPA) in the molecular classification of Diffuse Large B cell lymphoma (DLBCL) by cell-of-origin (COO).
Classifying diffuse large B cell lymphomas, not otherwise specified (DLBCL, NOS), is based on their cell-of-origin (COO) which is included in the WHO classification (2016), is essential to characterize them better in context of prognostication. While gene expression profiling (GEP) considered the gold standard and more recently, the Nanostring-based approach, classify these tumors accurately, many laboratories with limited resources and instrumentation need an alternate approach that is reliable, inexpensive, and with a reasonable turnaround. The Reverse Transcriptase Multiplex Ligation Dependant Probe Amplification (RT-MLPA) to subtype DLBCL, NOS cases, as designed by CALYM group appears to provide a good alternative but needs to be validated in other centres. Therefore, this study evaluated DLBCL, NOS and compared the results of RT-MLPA to that obtained by immunohistochemistry using the Hans algorithm. Sixty-five DLBCL, NOS cases were included and the RT-MLPA was set up and standardized using probes that were designed by the CALYM study group. Briefly, RNA was extracted converted to cDNA and the 21-gene expression classifier that also included probes to detect MYD88 mutations and EBER mRNA was performed by MLPA. The results were analyzed by the open home grown software designed by the same group and compared to the results obtained by IHC. Forty-four of the sixty-five cases provided concordant results (k = 0.35) and if the MYD88 results were to be used as a classifier the concordance would have improved from 67.7% to 82%. The 21 discordant cases were divided into five categories to provide a possible explanation for the discordance. Further 26% and 31% of the samples tested were positive for MYD88 mutations and EBER mRNA, respectively. The test had a turnaround of three days. The test provided moderate (67.7%) concordance when compared with IHC and perhaps would have provided higher concordance if compared with GEP. The test also has the advantage of providing information on the MYD88 and EBV infection status. It was found to be reliable, easy to perform and standardize, requiring only routine instruments available in most molecular laboratories. The RT-MLPA assay therefore provides an alternative for laboratories that would require subtyping of DLBCL, NOS cases in the absence of an access to GEP or other instrument intensive methods.


Transcriptional and post-transcriptional control of odorant receptor choice in ants.
Insects and mammals have independently evolved odorant receptor genes that are arranged in large genomic tandem arrays. In mammals, each olfactory sensory neuron chooses to express a single receptor in a stochastic process that includes substantial chromatin rearrangements. Here, we show that ants, which have the largest odorant receptor repertoires among insects, employ a different mechanism to regulate gene expression from tandem arrays. Using single-nucleus RNA sequencing, we found that ant olfactory sensory neurons choose different transcription start sites along an array but then produce mRNA from many downstream genes. This can result in transcripts from dozens of receptors being present in a single nucleus. Such rampant receptor co-expression at first seems difficult to reconcile with the narrow tuning of the ant olfactory system. However, RNA fluorescence in situ hybridization showed that only mRNA from the most upstream transcribed odorant receptor seems to reach the cytoplasm where it can be translated into protein, whereas mRNA from downstream receptors gets sequestered in the nucleus. This implies that, despite the extensive co-expression of odorant receptor genes, each olfactory sensory neuron ultimately only produces one or very few functional receptors. Evolution has thus found different molecular solutions in insects and mammals to the convergent challenge of selecting small subsets of receptors from large odorant receptor repertoires.


Postoperative pain therapy: a survey of patients' expectations and their experiences.
For 2 months elective surgical patients (n = 259) were asked preoperatively about their expectations of pain and pain relief. At both 24 and 72 h after their surgery they were asked about their pain and pain control. The analgesics they received were monitored for the first 72 h. The survey revealed that patients do not have the necessary knowledge about pain relief to contribute effectively in their own pain management. Analgesics administered intermittently were generally effective when given, however, the dosing interval was too long for the agents used resulting in frequent reports of poor pain relief. We conclude that patients need better education on postoperative pain control therapy. Medical staff could prescribe, and nursing staff administer, analgesics more effectively.


An integrated analysis of ergonomics and time consumption in Swedish 'craft-type' car disassembly.
Car disassembly is at the edge of extensive rationalization due to increased legislative demands for recycling. This study focused on (1) assessing current mechanical exposures (physical work loads) for comparison with future rationalised systems, with particular emphasis on time aspects, (2) analysing disassembly work in terms of time consumption and exposures in constituent tasks as defined by a loss analysis technique, and (3) predicting the consequences of car disassembly rationalisation for mechanical exposures. The study showed that disassembly implied pronounced circulatory loads, and that more walking and higher lumbar peak loads were found than in studies of assembly work. Value-adding tasks comprised 30% of the total working time, and implied higher postural exposures for the head, arm, trunk and wrist, as well as less opportunities to recover, as compared to non-value-adding tasks. Organisational-type rationalization can be expected to increase the time spent in value-adding work, thus increasing local exposures for the average worker, while a concurrent increase in mechanization level might reduce circulatory exposures, the amount of walking, and peak lumbar loads.


Revelations from the Clinic: Protective Behaviors and Perceptions among People at High Risk for Severe Illness from COVID-19.
The CDC has warned of increased risk for severe COVID-19 illness among those with certain preexisting conditions. Protective behaviors such as social distancing and mask-wearing have been shown effective at curbing infection rates. These practices are subject to individual perceptions of risk and responsibility. This study aimed to characterize the risk perceptions and protective behaviors of residents in a rural central Michigan region. Specifically, we examined whether individual risk status predicted protective behaviors and concern about the pandemic. Participants were identified via medical records at participating clinics. The high-risk group was those with conditions that put them at increased risk of severe illness from COVID-19, and was compared to healthy controls. Data were collected via phone survey. Participants were asked about their protective behaviors and level of concern about the ongoing pandemic. A total of 150 patients participated in the survey; 73 were high-risk acknowledgers, 29 were high-risk deniers, and 48 were healthy controls. There was no significant difference between the groups on level of concern regarding the pandemic or protective behaviors (P > .05). Compared to other comorbidities, obese people were significantly more likely to deny their risk (P < .05). In this study, high risk, whether acknowledged or denied, did not appear to significantly impact behaviors or concern. The high percentage of those at high risk who did not acknowledge this suggests many factors including a potential lack of patient education regarding their comorbidities, specifically, how their illness increases their risk of severe illness from COVID-19.


Thermodynamics of Protein Folding Studied by Umbrella Sampling along a Reaction Coordinate of Native Contacts.
Spontaneous transitions between the native and non-native protein conformations are normally rare events that hardly take place in typical unbiased molecular dynamics simulations. It was recently demonstrated that such transitions can be well described by a reaction coordinate, Q, that represents the collective fraction of the native contacts between the protein atoms. Here we attempt to use this reaction coordinate to enhance the conformational sampling. We perform umbrella sampling simulations with biasing potentials on Q for two model proteins, Trp-Cage and BBA, using the CHARMM force field. Hamiltonian replica exchange is implemented in these simulations to further facilitate the sampling. The simulations appear to have reached satisfactory convergence, resulting in unbiased free energies as a function of Q. In addition to the native structure, multiple folded conformations are identified in the reconstructed equilibrium ensemble. Some conformations without any native contacts nonetheless have rather compact geometries and are stabilized by hydrogen bonds not present in the native structure. Whereas the enhanced sampling along Q reasonably reproduces the equilibrium conformational space, we also find that the folding of an α-helix in Trp-Cage is a slow degree of freedom orthogonal to Q and therefore cannot be accelerated by biasing the reaction coordinate. Overall, we conclude that whereas Q is an excellent parameter to analyze the simulations, it is not necessarily a perfect reaction coordinate for enhanced sampling, and better incorporation of other slow degrees of freedom may further improve this reaction coordinate.


Nocardioides albertanoniae sp. nov., isolated from Roman catacombs.
A Gram-reaction-positive, aerobic, non-spore-forming, rod- or coccoid-shaped, strain, CD40127(T), was isolated from a green biofilm covering the wall of the Domitilla Catacombs in Rome, Italy. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CD40127(T) belongs to the genus Nocardioides, closely related to Nocardioides luteus DSM 43366(T) and Nocardioides albus DSM 43109(T) with 98.86 % and 98.01 % similarity values, respectively. Strain CD40127(T) exhibited 16S rRNA gene sequence similarity values below 96.29 % with the rest of the species of the genus Nocardioides. The G+C content of the genomic DNA was 69.7 mol%. The predominant fatty acid was iso-C16 : 0 and the major menaquinone was MK-8(H4) in accordance with the phenotypes of other species of the genus Nocardioides. A polyphasic approach using physiological tests, fatty acid profiles, DNA base ratios and DNA-DNA hybridization showed that isolate CD40127(T) represents a novel species within the genus Nocardioides, for which the name Nocardioides albertanoniae is proposed. The type strain is CD40127(T) ( = DSM 25218(T) = CECT 8014(T)).


Gene-rich chromosomal regions are preferentially localized in the lamin B deficient nuclear blebs of atypical progeria cells.
More than 20 mutations in the gene encoding A-type lamins (LMNA) cause progeria, a rare premature aging disorder. The major pathognomonic hallmarks of progeria cells are seen as nuclear deformations or blebs that are related to the redistribution of A- and B-type lamins within the nuclear lamina. However, the functional significance of these progeria-associated blebs remains unknown. We have carried out an analysis of the structural and functional consequences of progeria-associated nuclear blebs in dermal fibroblasts from a progeria patient carrying a rare point mutation p.S143F (C428T) in lamin A/C. These blebs form microdomains that are devoid of major structural components of the nuclear envelope (NE)/lamina including B-type lamins and nuclear pore complexes (NPCs) and are enriched in A-type lamins. Using laser capture microdissection and comparative genomic hybridization (CGH) analyses, we show that, while these domains are devoid of centromeric heterochromatin and gene-poor regions of chromosomes, they are enriched in gene-rich chromosomal regions. The active form of RNA polymerase II is also greatly enriched in blebs as well as nascent RNA but the nuclear co-activator SKIP is significantly reduced in blebs compared to other transcription factors. Our results suggest that the p.S143F progeria mutation has a severe impact not only on the structure of the lamina but also on the organization of interphase chromatin domains and transcription. These structural defects are likely to contribute to gene expression changes reported in progeria and other types of laminopathies.


The relative contribution of abuse severity and PTSD severity on the psychiatric and social morbidity of battered women in shelters.
Intimate partner violence (IPV) is a severe health problem associated with significant distress and impairment in women. The most common psychiatric difficulty in battered women is posttraumatic stress disorder (PTSD); however, no research to date has investigated the relative impact of the severity of IPV and IPV-related PTSD symptoms on battered women's psychosocial functioning. In a sample of 177 sheltered battered women, PTSD severity was associated with considerable psychiatric morbidity, social maladjustment, and personal and social resource loss. Moreover, PTSD severity mediated the relationship between IPV severity and psychiatric severity and loss of personal and social resources. Results highlight the need for the assessment and treatment of IPV-related PTSD in battered women's shelters.


Depressed interleukin-12 (IL-12), but not IL-18, production in response to a 30- or 32-kilodalton mycobacterial antigen in patients with active pulmonary tuberculosis.
The secreted 30-kDa antigen (Ag) of Mycobacterium tuberculosis directly stimulates Th1-type protective cytokine responses in healthy tuberculin reactors but not in patients with active tuberculosis (TB). To examine the cytokine profiles attributable to Th1 suppression associated with active TB, interleukin-12 (IL-12), IL-18, and IL-10 production in response to a 30- or 32-kDa Ag in 16 patients with active pulmonary TB and 24 healthy controls was investigated by enzyme-linked immunosorbent assay. In TB patients, production of IL-12 p40, as well as gamma interferon (IFN-gamma), by 30- or 32-kDa Ag-stimulated peripheral blood mononuclear cells (PBMC) was significantly decreased compared with that in healthy tuberculin reactors. There were no significant differences in IL-18 production between patients and controls early during stimulation (16 h). However, PBMC from patients showed significantly enhanced IL-18 proteins after 96 h of stimulation. Similarly, higher IL-10 production was observed in the TB patients than in healthy tuberculin reactors. After 2 months of anti-TB therapy, the mean IFN-gamma and IL-12 p40 production and the mean blastogenic responses were significantly increased in PBMC in the 10 TB patients who were followed up. Our findings provide evidence that depressed IL-12 in response to the 30- or 32-kDa Ag is involved in the immunopathogenesis of human active pulmonary TB.


Effect of procedure duration on total hip arthroplasty and total knee arthroplasty survivorship in the United States Medicare population.
The effect of procedure duration on joint arthroplasty survivorship in the USA is unknown. We examined the association between procedure duration with primary total hip arthroplasty and total knee arthroplasty survivorship at 8 years in the Medicare population using 1997 to 2004 Medicare claims data. Procedure duration was determined using anesthesia time as a proxy. Kaplan-Meier analysis and Cox regression were used to determine implant survivorship at 8 years and hazard ratios associated with procedure duration. Total knee arthroplasty implant survival was significantly associated with procedure duration (P = .001), in contrast to total hip arthroplasty (P = .127). Total knee arthroplasty procedures shorter than 90 minutes, between 150 and 180 minutes, and more than 240 minutes had significantly higher revision rates than those lasting 120 to 150 minutes. Total hip arthroplasty procedures lasting more than 240 minutes also had a significantly higher revision risk than those lasting 120 to 150 minutes. Our findings support the general belief that longer procedures are associated with the greater probability of complications.


Workforce innovation: Embracing emerging technologies.
In a rapidly evolving digital world, it is crucial that general practice embraces the potential of artificial intelligence (AI) and virtual reality (VR) in a real and proactive manner. Using examples of AI and VR, the article outlines some of the benefits and challenges we face in integrating these digital tools into daily clinical practice and our training programs. It is clear that AI and VR digital innovations will continue to grow in significance, with more and more options being offered to clinicians. As we increase our understanding of the benefits of these technologies, adapting our traditional curricula and daily clinical practice will require an openness to change. This is somewhat easier with VR, as it is a low-risk intervention that is providing an additional clinical intervention modality. AI is generating more challenges that will require a balanced, ongoing discussion involving clinicians and AI practitioners.


Spray-combustion synthesis: efficient solution route to high-performance oxide transistors.
Metal-oxide (MO) semiconductors have emerged as enabling materials for next generation thin-film electronics owing to their high carrier mobilities, even in the amorphous state, large-area uniformity, low cost, and optical transparency, which are applicable to flat-panel displays, flexible circuitry, and photovoltaic cells. Impressive progress in solution-processed MO electronics has been achieved using methodologies such as sol gel, deep-UV irradiation, preformed nanostructures, and combustion synthesis. Nevertheless, because of incomplete lattice condensation and film densification, high-quality solution-processed MO films having technologically relevant thicknesses achievable in a single step have yet to be shown. Here, we report a low-temperature, thickness-controlled coating process to create high-performance, solution-processed MO electronics: spray-combustion synthesis (SCS). We also report for the first time, to our knowledge, indium-gallium-zinc-oxide (IGZO) transistors having densification, nanoporosity, electron mobility, trap densities, bias stability, and film transport approaching those of sputtered films and compatible with conventional fabrication (FAB) operations.


THC improves behavioural schizophrenia-like deficits that CBD fails to overcome: a comprehensive multilevel approach using the Poly I:C maternal immune activation.
Prenatal infections and cannabis use during adolescence are well-recognized risk factors for schizophrenia. As inflammation and oxidative stress (OS) contribute to this disorder, anti-inflammatory drugs have been proposed as potential therapies. This study aimed to evaluate the association between delta-9-tetrahydrocannabinol (THC) and schizophrenia-like abnormalities in a maternal immune activation (MIA) model. Additionally, we assessed the preventive effect of cannabidiol (CBD), a non-psychotropic/anti-inflammatory cannabinoid. THC and/or CBD were administered to Saline- and MIA-offspring during periadolescence. At adulthood, THC-exposed MIA-offspring showed significant improvements in sensorimotor gating deficits. Structural and metabolic brain changes were evaluated by magnetic resonance imaging, revealing cortical shrinkage in Saline- and enlargement in MIA-offspring after THC-exposure. Additionally, MIA-offspring displayed enlarged ventricles and decreased hippocampus, which were partially reverted by both cannabinoids. CBD prevented THC-induced reduction in the corpus callosum, despite affecting white matter structure. Post-mortem studies revealed detrimental effects of THC, including increased inflammation and oxidative stress. CBD partially reverted these pro-inflammatory alterations and modulated THC's effects on the endocannabinoid system. In conclusion, contrary to expectations, THC exhibited greater behavioural and morphometric benefits, despite promoting a pro-inflammatory state that CBD partially reverted. Further research is needed to elucidate the underlying mechanisms involved in the observed benefits of THC.


Rational design of HIV vaccines and microbicides: report of the EUROPRISE network annual conference 2010.
Novel, exciting intervention strategies to prevent infection with HIV have been tested in the past year, and the field is rapidly evolving. EUROPRISE is a network of excellence sponsored by the European Commission and concerned with a wide range of activities including integrated developmental research on HIV vaccines and microbicides from discovery to early clinical trials. A central and timely theme of the network is the development of the unique concept of co-usage of vaccines and microbicides. This review, prepared by the PhD students of the network captures much of the research ongoing between the partners. The network is in its 5th year and involves over 50 institutions from 13 European countries together with 3 industrial partners; GSK, Novartis and Sanofi-Pasteur. EUROPRISE is involved in 31 separate world-wide trials of Vaccines and Microbicides including 6 in African countries (Tanzania, Mozambique, South Africa, Kenya, Malawi, Rwanda), and is directly supporting clinical trials including MABGEL, a gp140-hsp70 conjugate trial and HIVIS, vaccine trials in Europe and Africa.


The effect of icing with the pro-stim edema management system on cutaneous cooling.
The simultaneous administration of ice, compression, and electrical stimulation is a technique sometimes used to control the magnitude and duration of edema. The Pro-Stim Edema Management System (TKO, Inc, Alameda, CA) was developed to make this simultaneous treatment both simplistic and more effective. The system is designed to be more effective because the stimulating electrodes are incorporated into the fabric of the ice pack thus providing little insulation to cold. The purpose of our study was to test the effectiveness of icing with Pro-Stim on cutaneous cooling by comparing it to ice bag application with conventional stimulator electrodes. Twelve subjects received the ice portion of the two experimental conditions for 30 minutes. Cutaneous temperatures were monitored at two sites: one under the electrode and one away from the electrode (centered between the stimulating electrodes). Temperatures were recorded via surface probes interfaced to digital thermometers each minute for 5 minutes before and after icing and during the 30 minutes of ice application. Temperature data were analyzed with three-way factorial analysis of variance with repeated measures. The administration of ice decreased the temperature for all conditions. However, the temperature under the electrode with Pro-Stim was significantly lower during the treatment period than the temperature under the electrode with the conventional system. Thus, Pro-Stim provides more cooling of the entire treatment area. Further research should include an investigation of the effect of the Pro-Stim Edema Management System on cooling while using electrical stimulation.


Local delivery of chondroitinase ABC with or without stromal cell-derived factor 1α promotes functional repair in the injured rat spinal cord.
Traumatic spinal cord injury (SCI) is a devastating event for which functional recovery remains elusive. Due to the complex nature of SCI pathology, a combination treatment strategy will likely be required for success. We hypothesized that tissue and functional repair would be achieved in a rat model of impact-compression SCI by combining degradation of the glial scar, using chondroitinase ABC (ChABC), with recruitment of endogenous neural precursor cells (NPCs), using stromal cell-derived factor 1α (SDF). To test this hypothesis, we designed a crosslinked methylcellulose hydrogel (XMC) for minimally invasive, localized, and sustained intrathecal drug delivery. ChABC was released from XMC using protein-peptide affinity interactions while SDF was delivered by electrostatic affinity interactions from polymeric nanoparticles embedded in XMC. Rats with SCI were treated acutely with a combination of SDF and ChABC, SDF alone, ChABC alone, or vehicle alone, and compared to injury only. Treatment with ChABC, both alone and in combination with SDF, resulted in faster and more sustained behavioural improvement over time than other groups. The significantly reduced chondroitin sulfate proteoglycan levels and greater distribution of NPCs throughout the spinal cord tissue with ChABC delivery, both alone and in combination with SDF, may explain the improved locomotor function. Treatment with SDF alone had no apparent effect on NPC number or distribution nor synergistic effect with ChABC delivery. Thus, in this model of SCI, tissue and functional repair is attributed to ChABC.


Astrocyte-specific genes are generally demethylated in neural precursor cells prior to astrocytic differentiation.
Epigenetic changes are thought to lead to alterations in the property of cells, such as differentiation potential. Neural precursor cells (NPCs) differentiate only into neurons in the midgestational brain, yet they become able to generate astrocytes in the late stage of development. This differentiation-potential switch could be explained by epigenetic changes, since the promoters of astrocyte-specific marker genes, glial fibrillary acidic protein (Gfap) and S100beta, have been shown to become demethylated in late-stage NPCs prior to the onset of astrocyte differentiation; however, whether demethylation occurs generally in other astrocyctic genes remains unknown. Here we analyzed DNA methylation changes in mouse NPCs between the mid-(E11.5) and late (E14.5) stage of development by a genome-wide DNA methylation profiling method using microarrays and found that many astrocytic genes are demethylated in late-stage NPCs, enabling the cell to become competent to express these genes. Although these genes are already demethylated in late-stage NPCs, they are not expressed until cells differentiate into astrocytes. Thus, late-stage NPCs have epigenetic potential which can be realized in their expression after astrocyte differentiation.


Corneal Sensitivity and Presence of Pathogenic Organisms Among Participants Who Have Undergone Trichiasis Surgery Differ by Surgical Outcome.
To explore the potential association between reduced corneal sensation and/or conjunctival bacterial colonization and postoperative trichiasis and eyelid contour abnormalities after corrective eyelid surgery among participants with a history of trachomatous trichiasis. As an ancillary study to the Partnership for Rapid Elimination of Trachoma (PRET) Surgery Trial in southern Tanzania, we collected data on 580 PRET participants who had undergone trichiasis surgery 1 year earlier and 200 age-group-matched individuals without trichiasis. Assessments included eyelid status evaluation (presence and severity of postoperative trichiasis and/or eyelid contour abnormality), corneal sensitivity by Cochet-Bonnet aesthesiometer, a questionnaire on symptoms of ocular irritation, and conjunctival microbiology. We divided PRET participants based on their eyelid status and compared results across PRET groups and versus normals. PRET participants had reduced corneal sensitivity compared with age-matched normals (mean sensitivity ranged from 2.8 to 3.8 cm in PRET participants vs. 5.9 cm in normals), and increasing severity of postoperative trichiasis was associated in a stepwise fashion with reduced corneal sensitivity (mean = 3.5 cm for mild and 2.6 cm for severe postoperative trichiasis). Conjunctival colonization with pathogenic bacteria was also associated with more severe postoperative trichiasis (Cochran-Armitage trend test P = 0.001) and with reduced corneal sensitivity (trend test P < 0.0001). Symptoms of ocular irritation were not associated with previous trichiasis surgery, postoperative trichiasis, or eyelid contour abnormality. These findings indicate that reduced corneal sensitivity accompanies trachomatous trichiasis and suggest that reduced corneal sensitivity may play an important role in the harboring of pathogenic bacteria on the ocular surface.


[Lithium in the therapy of hematologic diseases in childhood].
The literature as well as the author's data of this topic are reviewed. Lithium stimulates myelopoesis in vitro, especially via CSF-production. This effect is associated with a modulation of cyclic nucleotides. Lithium stimulates leukemic cell lines too. However, according to epidemiological data lithium does not play an etiological role in leukemia. Furthermore, lithium does not stimulate several tumor cell lines in culture. The effect of cytostatic drugs as well as remission rates are not lessened by lithium. In spite of increased production the functions of the granulocytes are not impaired. Because of the wide range of serum level variation serum level determinations are mandatory. To treat hematological disorders a serum level between 0.7 and 1.2 mmol/l should be achieved. Flame emission photometry and atomic absorption photometry are equivalent methods for determination of the serum level. CNS, thyroid gland, kidney, electrolyte balance, gastrointestinal tract have to be monitored for side effects. Lithium therapy has not be given in pregnancy and to breast feeding mothers. In neutropenia with increased susceptibility to infections lithium therapy including serum level monitoring can be given. Lithium reduces leukopenia and infections following cytotoxic chemotherapy for solid tumors. Current pediatric studies are investigating whether patients with chemotherapy induced neutropenia benefit from this effect in terms of increased and prolonged remission rates.


Preoperative diagnostic value of coronary CT angiography in acute Stanford type A aortic dissection involving the coronary arteries.
To assess the diagnostic value of coronary computed tomography angiography (CCTA) in acute type A aortic dissection (ATAAD) with coronary artery involvement and to evaluate whether CCTA could provide potentially useful information for selecting the surgical method. Patients with ATAAD treated from January 2019 to December 2020 were reviewed retrospectively. Involvement of the coronary arteries based on CCTA findings were grouped into three major types and five subtypes. Interobserver and intraobserver diagnostic agreement for five subtypes were determined. The patients were divided into the coronary artery bypass grafting (CABG) and non-CABG groups, and the proportions of the five subtypes between the two groups were compared. A total of 95 patients were enrolled in this study. Interobserver and intraobserver diagnostic agreement were both substantial in the left and right coronary arteries. Overall, the proportions of the five subtypes of coronary artery involvement were significantly different between the two groups (p<0.001). The proportion of Type A was elevated in the non-CABG group compared with the CABG group (22.6% versus 71.9%); by contrast, the proportions of Type B1 (35.5% versus 14.1%), Type B2 (19.4% versus 10.9%), Type C1 (6.5% versus 0%), and Type C2 (16.1% versus 3.1%) were elevated in the CABG group. CCTA is reliable in evaluating coronary artery involvement by ATAAD. The present retrospective study indicated that CABG may be considered if the intimal flap disrupts the coronary orifice and causes luminal stenosis >50%, particularly Type B, or if an intimal tear occurs in the coronary orifice (Type C), which deserve further validation through prospective studies.


Corticotropin-Releasing Factor Receptor-1 Antagonism Reduces Oxidative Damage in an Alzheimer's Disease Transgenic Mouse Model.
Reports from Alzheimer's disease (AD) biomarker work have shown a strong link between oxidative stress and AD neuropathology. The nonenzymatic antioxidant, glutathione (GSH), plays a crucial role in defense against reactive oxygen species and maintenance of GSH redox homeostasis. In particular, our previous studies on GSH redox imbalance have implicated oxidative stress induced by excessive reactive oxygen species as a major mediator of AD-like events, with the presence of S- glutathionylated proteins (Pr-SSG) appearing prior to overt AD neuropathology. Furthermore, evidence suggests that oxidative stress may be associated with dysfunction of the hypothalamic-pituitary-adrenal axis, leading to activation of inflammatory pathways and increased production of corticotropin-releasing factor (CRF). Therefore, to investigate whether oxidative insults can be attenuated by reduction of central CRF signaling, we administered the type-1 CRF receptor (CRFR1) selective antagonist, R121919, to AD-transgenic mice beginning in the preclinical/prepathologic period (30-day-old) for 150 days, a time point where behavioral impairments and pathologic progression should be measureable. Our results indicate that R121919 treatment can significantly reduce Pr-SSG levels and increase glutathione peroxide activity, suggesting that interference of CRFR1 signaling may be useful as a preventative therapy for combating oxidative stress in AD.


Evidence for a conserved binding motif of the dinuclear metal site in mammalian and plant purple acid phosphatases: 1H NMR studies of the di-iron derivative of the Fe(III)Zn(II) enzyme from kidney bean.
The di-iron core of mammalian purple acid phosphatases has been reproduced in the plant enzyme from kidney bean (Mr 111000) upon insertion of an Fe(II) ion in place of the native zinc(II) in the dinuclear Fe(III)Zn(II) core. The shortening of the electronic relaxation time of the metal centre allows detection of hyperfine-shifted 1H NMR resonances, although severe broadening due to Curie relaxation prevents independent signal assignment. Nevertheless, comparison of the spectral features of the structurally characterized plant enzyme with those of the mammalian species, which were previously extensively assigned, is consistent with a close similarity of the metal-binding sites, also suggested by previous sequence-alignment studies. Some differences appear to be mainly localized at the M(II) site. Spectral comparison was also carried out on the Fe(III)Co(II) derivatives.


2,4-Di-bromo-1,3-dihy-droxy-9H-xanthen-9-one.
The title compound, C13H6Br2O4, derived from xanthone, a fundamental structural framework of active ingredients in many medicinal plants, and was synthesized by bromination of 1,3-di-hydroxyxanthen-9-one with N-bromo-succinimide. The mol-ecular conformation is essentially planar, the dihedral angle between the benzene rings being 1.1 (4)°. This conformation is favorable for the formation of an intra-molecular O-H⋯O hydrogen bond between a hy-droxy group and the xanthone carbonyl group. In the crystal, mol-ecules are associated into chains along the b-axis direction via C=O⋯H-O hydrogen bonds involving the other hy-droxy group.


PROPOSED MEASURES OF CONTROL MANAGEMENT OF THE GRAPE MOTH, LOBESIA BOTRANA DEN AND SCHIFF (LEPIDOPTERA: TORTRICIDAE), IN REFERENCE TO INFESTATION PERCENTAGES, YIELD LOSS AND ECONOMICS OF CONTROL IN EGYPT.
This study aims to evaluate the efficacy of five measures; including the release of two strains of Trichogramma, Bacillus thuringiensis (B.t.). Sweetened B.t. and the environmentally friend insecticide (Tracer®), to manage the grape moth, Lobesia botrana that infested the grape vines c.v. "Thompson seedless " in Egypt severely during the two successive years of 2011 and 2012. In concern to the release of the worldwide, Trichogramma evanescens Westwood., the mean total grape yield ranged from 8.00 to 14.00 ton/fed and from 6.90 to 11.9, in respect to the two seasons and the mean infestation percentages fluctuated between 50.00 and 16.14; 43.48 and 21.01 in sequence for the same years. The corresponding grape bunches loss percentages averaged from 21.43 to 6.91; 18.63 to 9.00,respectively for the same periods of this study. Whereas, it was noticed that in releasing the indigenous T. bourarchae was more effective than T. evanescens in reducing all the above mentioned grape yield particularly. Applying Bacillus thuringiensis (B.t.) and/or adding sugar as a stimulant to improve yields reduced the infestation and the crop loss percentage. However, Bacillus thuringiensis mixed with sugar which overweighed the use of Bacillus thuringiensis alone. Although Tracer® provided good harvest in both years, but unfortunately it affected the grape berries components rather than the other treatments. Control plots indicated 48 and 50% infestation, with very low yield compared with the other five trials to manage the assigned insect pest. For the first time worldwide economics and profits were computed taking into account the whole market sale, the total control costs and the gross income to decide the most profitable treatment for the table grape growers under the Egyptian conditions. It was found that the mean (L.E.) profits/fed were arranged in a descending order as follows: 470.95, 513.28, 504.78, 500.82, 397.25 and 0.00 for Bacillus thuringiensis + sugar, Trichogramma bourarchae, Trichogramma evanescens Westwood, Dipel-2x®, Tracer® and control in respect in 2011. The corresponding values in the year 2012 were 453.85, 445.58, 427.18, 377.00, 349.18 and 0.00 for Trichogramma bourarchae, Bacillus thuringiensis + sugar, Dipel-2x®, Trichogramma evanescens Westwood, Tracer® and control in respect. The obtained results were analysed and discussed in the text.


[Multineuronal activity of the paraventricular nucleus of the hypothalamus during activation and inhibition of the adrenocortical system].
Multiunit activity of paraventricular nucleus and fornix was studied during activation and inhibition of the pituitary--adrenocortical system in chronic experiments on rabbits. Immobilization causing blood corticosteroid levels to rise was followed by the excitation of the neurons in paraventricular nucleus and by inhibition in the fornix. Administration of cortisol (100 micrograms/kg before the immobilization) causing inhibition of pituitary--adrenocortical system was followed by the inhibition of neurons in paraventricular nucleus and fornix. The activation of the paraventricular nucleus seems to be responsible for the activation of the pituitary--adrenocortical system whereas its inhibition induced the inhibition of this system.


Addressing the spiritual needs of people infected with and affected by HIV and AIDS in Swaziland.
Researchers seem to be in agreement that spirituality is an important component of the holistic care approach commonly found in palliative care. Shiselweni Home-Based Care (SHBC) is a faith-based organization in Swaziland working among people with HIV and AIDS in the poorest and most affected areas of the country. They endeavor to restore and build up each client's dignity through the way in which they are approached, not only when giving physical assistance, but also when they address their spiritual needs. This article emphasizes the need for spiritual care as part of the caregiving program and then also illustrates the positive feelings of both the SHBC caregivers as well as their clients as they share some of the experiences encountered during spiritual care.


Increased mortality among women with Rose angina who have not presented with ischaemic heart disease.
Little is known about the clinical importance of disease that is not presented to healthcare services. To determine the 5-year mortality among those with angina symptoms, known or not known by their general practitioner (GP) to have ischaemic heart disease (IHD). A prospective cohort study. The study was conducted in the United Kingdom as part of the Royal College of General Practitioners' Oral Contraception Study. In 1994-1995 women (n = 11,797) still under GP observation were sent a questionnaire that inquired about their smoking habits, other lifestyle issues, general health, and selected symptoms (including chest pain, assessed using the Rose angina questionnaire). The main outcome measure was the chances (odds) of dying during the next 5 years, among those with and without exertional chest pain, Rose angina or Rose myocardial infarction (MI), stratified by documented history of IHD. Overall, the lifetime prevalence of any exertional chest pain was 10.1% (95% confidence interval [CI] = 9.5 to 10.8); grade I Rose angina was 6.1% (95% CI = 5.6 to 6.6); grade II Rose angina was 1.3% (95% CI = 1.1 to 1.6); and Rose MI was 4.4% (95% CI = 4.0 to 4.9). The prevalence of each condition tended to increase with age, social class, parity, body mass index, and documented history of IHD. The proportion of women documented as having IHD was 23% among those with any exertional chest pain, 21.7% for grade I Rose angina, 37.7% for grade II Rose angina, and 31.4% for Rose MI. Compared to women without Rose angina, significantly higher odds ratios for all-cause mortality were observed among women with grade I Rose angina and no documented history of IHD (adjusted odds ratio [AOR] = 1.71, 95% CI = 1.05 to 2.79); those with grade II Rose angina and documented IHD (AOR = 3.94, 95% CI = 1.58 to 9.83); and women with grade II Rose angina and no documented history of IHD (AOR = 3.35, 95% CI = 1.47 to 7.62). Women with angina symptoms that have not been documented by their GP appear to have an increased risk of future mortality. Research is needed to determine the best way of identifying and managing these individuals.


Physical limits on atomic resolution.
It is shown that the ultimate resolution is not limited by the bandwidth of the microscope but by the bandwidth (i.e., the scattering power) of the object. In the case of a crystal oriented along a zone axis, the scattering is enhanced by the channeling of the electrons. However, if the object is aperiodic along the beam direction, the bandwidth is much more reduced. A particular challenge are the amorphous objects. For amorphous materials, the natural bandwidth is that of the single atom and of the order of 1 angstrom(-1), which can be reached with the present generation of medium voltage microscopes without aberration correctors. A clear distinction is made between resolving a structure and refining, that is, between resolution and precision. In the case of an amorphous structure, the natural bandwidth also puts a limit on the number of atom coordinates that can be refined quantitatively. As a consequence, amorphous structures cannot be determined from one projection, but only by using atomic resolution tomography. Finally a theory of experiment design is presented that can be used to predict the optimal experimental setting or the best instrumental improvement. Using this approach it is suggested that the study of amorphous objects should be done at low accelerating voltage with correction of both spherical and chromatic aberration.


Elimination of phenols, ammonia and cyanide in wash water from biomass gasification, and nitrogen recycling using planted trickling filters.
Trickling filters were used to treat wash water from a wood gasifier. This wash water contained toxic substances such as ammonium, cyanide, phenols, and PAH. The goal was to develop a system that degraded toxic substances, and achieved full nitrification of ammonia. A 1 kW model wood gasifier plant delivered wash water for the experiments, which was standardised to a conductivity of 3 mS/cm by dilution. Toxicity was assessed by bacterial luminescence detection, germination test with cress (Lepidium sativum), and pot plants cultivated in a hydroponic setup irrigated continuously with the wastewater. Treatment experiments were done in both planted and unplanted trickling filters. Plant yield was similar to conventional hydroponic production systems. The trickling filters achieved complete detoxification of phenol, PAH and cyanide as well as full nitrification. The specific elimination rates were 100 g m(-3) Leca d(-1) for phenols and 90 g m(-3) Leca d(-1) for ammonium in planted systems. In unplanted trickling filters circulated for 63 h, phenol concentration decreased from 83.5 mg/L to 2.5 mg/L and cyanide concentration from 0.32 mg/L to 0.02 mg/L. PAH concentrations were reduced from 3,050 microg/L to 0.89 microg/L within 68 days. The assays demonstrated the feasibility of using the technique to construct a treatment system in a partially closed circulation for gasifier wash water. The principal advantage is to convert toxic effluents from biomass gasifiers into a non-toxic, nitrogen-rich fertiliser water, enabling subsequent use in plant production and thus income generation. However, the questions of long-term performance and possible accumulation of phenols and heavy metals in the produce still have to be studied.


"Self-Peel-Off" Transfer Produces Ultrathin Polyvinylidene-Fluoride-Based Flexible Nanodevices.
Here, a new strategy, self-peel-off transfer, for the preparation of ultrathin flexible nanodevices made from polyvinylidene-fluoride (PVDF) is reported. In this process, a functional pattern of nanoparticles is transferred via peeling from a temporary substrate to the final PVDF film. This peeling process takes advantage of the differences in the work of adhesion between the various layers (the PVDF layer, the nanoparticle-pattern layer and the substrate layer) and of the high stresses generated by the differential thermal expansion of the layers. The work of adhesion is mainly guided by the basic physical/chemical properties of these layers and is highly sensitive to variations in temperature and moisture in the environment. The peeling technique is tested on a variety of PVDF-based functional films using gold/palladium nanoparticles, carbon nanotubes, graphene oxide, and lithium iron phosphate. Several PVDF-based flexible nanodevices are prepared, including a single-sided wireless flexible humidity sensor in which PVDF is used as the substrate and a double-sided flexible capacitor in which PVDF is used as the ferroelectric layer and the carrier layer. Results show that the nanodevices perform with high repeatability and stability. Self-peel-off transfer is a viable preparation strategy for the design and fabrication of flexible, ultrathin, and light-weight nanodevices.


Development of the Internet addiction scale based on the Internet Gaming Disorder criteria suggested in DSM-5.
This study was conducted to develop and validate a standardized self-diagnostic Internet addiction (IA) scale based on the diagnosis criteria for Internet Gaming Disorder (IGD) in the Diagnostic and Statistical Manual of Mental Disorder, 5th edition (DSM-5). Items based on the IGD diagnosis criteria were developed using items of the previous Internet addiction scales. Data were collected from a community sample. The data were divided into two sets, and confirmatory factor analysis (CFA) was performed repeatedly. The model was modified after discussion with professionals based on the first CFA results, after which the second CFA was performed. The internal consistency reliability was generally good. The items that showed significantly low correlation values based on the item-total correlation of each factor were excluded. After the first CFA was performed, some factors and items were excluded. Seven factors and 26 items were prepared for the final model. The second CFA results showed good general factor loading, Squared Multiple Correlation (SMC) and model fit. The model fit of the final model was good, but some factors were very highly correlated. It is recommended that some of the factors be refined through further studies.


Effects of Double-Side Labyrinth Seals on Aerodynamic Performance in a Transonic Shrouded Turbine Stage.
Labyrinth seals on both rotor casing and blade tip as an effective method to control the leakage flowrate of the shroud and improve aerodynamic performances in a transonic turbine stage are investigated in this study. Compared to the case without the labyrinth seal structure, the cases with three different types of sealing teeth have been shown to reduce significantly the tip leakage flow by computational simulations. The double-side sealing teeth case reduces the leakage flowrate m leakage / m passage from 3.4% to 1.3% and increases the efficiency by 1.4%, which is the maximum efficiency improvement of all cases. The sealing structures increase the loss inside the shroud while reducing the momentum mixing between shroud leakage flow and mainstream. Therefore, the circumferential distribution of leakage velocity is changed, as well as the distribution of high-loss zones at turbine outlet. Furthermore, the leakage-vortex loss, which is associated with the blockage effect of sealing structure to the tip leakage flow, gains more improvement than the passage-vortex at the rotor outlet section in double-side seal case. In addition, it has also been found that with a larger gap at tip, the double-side seal has better effects of reducing the leakage flow and improving the aerodynamic performance in the transonic turbine stage.


A simple and reliable technique to combine oligonucleotide probe in situ hybridization with neuronal tract tracing in vertebrate embryos.
We describe a simple and reliable combination of in situ hybridization with neuronal tracing. The technique uses recent advances in the field of neuronal tract tracing including fast diffusing, low molecular weight dextran amines and fade resistant fluorescent dyes, and combines them with in situ hybridization using a sensitive oligonucleotide probe. Using this technique we have investigated the mRNA encoding the trkB receptor for brain-derived neurotrophic factor in identified facial and vestibular afferent and efferent neurons. We found very low levels of trkB mRNA in facial efferent neurons, whereas in the vestibular afferent neurons, clear labeling for the trkB mRNA could be seen. This technique can be applied to the developing embryo to study topology of a variety of cellular markers with reference to neuronal population or fibers identified by their origin or target.


CD8(+) T-cell autoreactivity to an HLA-B27-restricted self-epitope correlates with ankylosing spondylitis.
HLA-B27 is highly associated with ankylosing spondylitis (AS), but the mechanism is unknown. Among the HLA-B27 alleles, B*2709, which differs by one amino acid from the susceptible B*2705, is not associated with the disease. Here, we analyze the reactivity, in patients with AS and in healthy controls carrying the B*2709 or B*2705 alleles, to an EBV epitope derived from LMP2 (236-244) and to a sequence-related self-peptide from vasoactive intestinal peptide receptor 1 (VIP1R 400-408). We found that both B*2705(+) and B*2709(+) subjects possess LMP2 236-244-specific, HLA-B27-restricted T cells, whereas only the B*2705(+) individuals respond significantly to VIP1R 400-408. These results prompted us to compare, by IFN-gamma ELISPOT analysis, the T-cell response to VIP1R 400-408 in patients with AS versus B*2705 healthy controls. The data show that VIP1R 400-408-specific reactivity is a major feature of the patients with AS. These findings show, for the first time to our knowledge, a widespread reactivity in patients with AS against a self-epitope that exhibits some features of a putative "arthritogenic" peptide.


Relationship between Maternal and First Year of Life Dispensations of Antibiotics and Antiasthmatics.
Antibiotics are the most frequent prescription drugs used by pregnant women. Our objective was to investigate if the dispensation of antibiotics and antiasthmatics in children less than 1 year of age is associated with prenatal antibiotic exposure. A secondary aim was to explore the incidence of dispensed antibiotics in pregnancy and dispensed antibiotics and antiasthmatics in children. We conducted an observational study using the Peer Academic Detailing study database to select patients eligible for match in the Medical Birth Registry of Norway, a total of 7747 mother-and-child pairs. Details on antibiotic and antiasthmatic pharmacy dispensations were obtained from the Norwegian Prescription Database. One quarter (1948 of 7747) of the mothers in the study had been dispensed antibiotics during pregnancy. In their first year of life, 17% (1289) of the children had had an antibiotic dispensation, 23% (1747) an antiasthmatic dispensation, and 8% (619) of the children had had both. We found a significant association between dispensed antibiotics in pregnancy and dispensed antibiotics to the child during their first year of life; OR = 1.16 (95% CI: 1.002⁻1.351). The association was stronger when the mothers were dispensed antibiotics at all, independent of the pregnancy period; OR = 1.60 (95% CI: 1.32⁻1.94). We conclude that the probability for dispensation of antibiotics was increased in children when mothers were dispensed antibiotics, independent of pregnancy. Diagnostic challenges in the very young and parental doctor-seeking behavior may, at least in part, contribute to the association between dispensations in mothers and children below the age of one year.


Photovoltaic restoration of sight with high visual acuity.
Patients with retinal degeneration lose sight due to the gradual demise of photoreceptors. Electrical stimulation of surviving retinal neurons provides an alternative route for the delivery of visual information. We demonstrate that subretinal implants with 70-μm-wide photovoltaic pixels provide highly localized stimulation of retinal neurons in rats. The electrical receptive fields recorded in retinal ganglion cells were similar in size to the natural visual receptive fields. Similarly to normal vision, the retinal response to prosthetic stimulation exhibited flicker fusion at high frequencies, adaptation to static images and nonlinear spatial summation. In rats with retinal degeneration, these photovoltaic arrays elicited retinal responses with a spatial resolution of 64 ± 11 μm, corresponding to half of the normal visual acuity in healthy rats. The ease of implantation of these wireless and modular arrays, combined with their high resolution, opens the door to the functional restoration of sight in patients blinded by retinal degeneration.


The importance of distance to resources in the spatial modelling of bat foraging habitat.
Many bats are threatened by habitat loss, but opportunities to manage their habitats are now increasing. Success of management depends greatly on the capacity to determine where and how interventions should take place, so models predicting how animals use landscapes are important to plan them. Bats are quite distinctive in the way they use space for foraging because (i) most are colonial central-place foragers and (ii) exploit scattered and distant resources, although this increases flying costs. To evaluate how important distances to resources are in modelling foraging bat habitat suitability, we radio-tracked two cave-dwelling species of conservation concern (Rhinolophus mehelyi and Miniopterus schreibersii) in a Mediterranean landscape. Habitat and distance variables were evaluated using logistic regression modelling. Distance variables greatly increased the performance of models, and distance to roost and to drinking water could alone explain 86 and 73% of the use of space by M. schreibersii and R. mehelyi, respectively. Land-cover and soil productivity also provided a significant contribution to the final models. Habitat suitability maps generated by models with and without distance variables differed substantially, confirming the shortcomings of maps generated without distance variables. Indeed, areas shown as highly suitable in maps generated without distance variables proved poorly suitable when distance variables were also considered. We concluded that distances to resources are determinant in the way bats forage across the landscape, and that using distance variables substantially improves the accuracy of suitability maps generated with spatially explicit models. Consequently, modelling with these variables is important to guide habitat management in bats and similarly mobile animals, particularly if they are central-place foragers or depend on spatially scarce resources.


Superficial Venous-Associated Inflammation from Direct IV Administration of RRx-001 in Rats.
RRx-001 is a small molecule NLRP3 inflammasome inhibitor with anti-CD47 and antiangiogenic/vascular normalization properties in a Phase 3 clinical trial that has been designated as a drug-device combination by the FDA. In the Phase 1 first-in-man dose escalation clinical trial, where RRx-001 was given by direct intravenous (IV) infusion, the main adverse event was a sterile painful infusion phlebitis (IP). Less pain was experienced when RRx-001 was infused at a slower rate over multiple hours which was impractical on an outpatient basis. In Phase 2, for reasons of convenience and safety, RRx-001 was co-administered with an aliquot of autologous blood from an ex-vivo device called the eLOOP on the premise that RRx-001 binds to hemoglobin on red blood cells (RBCs), making it unavailable to directly interact with venous nociceptors. Phlebitis has the potential to progress to deep venous thrombosis or septic thrombophlebitis or post-thrombotic syndrome in hypercoagulable and immunosuppressed cancer patients. In this 13-week toxicology study of once weekly IV RRx-001 administration to Wistar Han rats followed by a recovery period of 28 days. The main observed toxicity was a significant inflammatory response in the vein wall, consistent with superficial venous thrombosis observed in man. Due to this development, direct IV infusion of RRx-001 is relatively contraindicated in favor of co-administration with autologous blood.


RAMICS: trainable, high-speed and biologically relevant alignment of high-throughput sequencing reads to coding DNA.
The challenge presented by high-throughput sequencing necessitates the development of novel tools for accurate alignment of reads to reference sequences. Current approaches focus on using heuristics to map reads quickly to large genomes, rather than generating highly accurate alignments in coding regions. Such approaches are, thus, unsuited for applications such as amplicon-based analysis and the realignment phase of exome sequencing and RNA-seq, where accurate and biologically relevant alignment of coding regions is critical. To facilitate such analyses, we have developed a novel tool, RAMICS, that is tailored to mapping large numbers of sequence reads to short lengths (<10 000 bp) of coding DNA. RAMICS utilizes profile hidden Markov models to discover the open reading frame of each sequence and aligns to the reference sequence in a biologically relevant manner, distinguishing between genuine codon-sized indels and frameshift mutations. This approach facilitates the generation of highly accurate alignments, accounting for the error biases of the sequencing machine used to generate reads, particularly at homopolymer regions. Performance improvements are gained through the use of graphics processing units, which increase the speed of mapping through parallelization. RAMICS substantially outperforms all other mapping approaches tested in terms of alignment quality while maintaining highly competitive speed performance.


A nanotechnology based new approach for chemotherapy of Cutaneous Leishmaniasis: TIO2@AG nanoparticles - Nigella sativa oil combinations.
Since toxicity and resistance are the major drawbacks of current antileishmanial drugs, studies have been recently focused on combination therapy in fight against leishmaniasis. Combination therapy generally provides opportunity to decrease toxicity of applied agents and enhance their antimicrobial performance. Moreover, this method can be effective in preventing drug resistance. Highly antileishmanial effects of silver doped titanium dioxide nanoparticles (TiAgNps) and Nigella sativa oil were demonstrated in previous studies. However, toxicity is still an important factor preventing use of these molecules in clinic. By considering high antileishmanial potential of each agent and basic principles of combination therapy, we propose that use of combinations including non-toxic concentrations of TiAgNps and N. sativa oil may compose more effective and safer formulations against Leishmania parasites. Therefore, the main goal of the present study was to investigate antileishmanial effects of non-toxic concentrations of TiAgNps and Nigella sativa oil combinations on promastigote and amastigote-macrophage culture systems and also to develop nanotechnology based new antileishmanial strategies against Cutaneous Leishmaniasis. Numerous parameters such as proliferation, metabolic activity, apoptosis, amastigote-promastigote conversion, infection index analysis and nitric oxide production were used to detect antileishmanial efficacies of combinations. Investigated all parameters demonstrated that TiAgNps-N. sativa oil combinations had significant antileishmanial effect on each life forms of parasites. Tested combinations were found to decrease proliferation rates of Leishmania tropica promastigotes in a range between 1,5-25 folds and metabolic activity values between 2 and 4 folds indicating that combination applications lead to virtually inhibition of promastigotes and elimination of parasites were directly related to apoptosis manner. TiAgNps-N. sativa combinations also demonstrated killing effects on L. tropica amastigotes by decreasing infection index values of macrophages 5-20 folds, inhibiting their metabolic activities up to 5 fold, preventing amastigote-promastigote conversion and producing high amounts of nitric oxide. All these results emphasize high potential of TiAgNps-N. sativa oil combinations as new, safer and effective antileishmanial formulations against Cutaneous Leishmaniasis.


Short-term outcomes of down-referral in provision of paediatric antiretroviral therapy at Red Cross War Memorial Children's Hospital, Cape Town, South Africa: A retrospective cohort study.
The large scale-up of paediatric HIV care necessitated down-referral of many children receiving antiretroviral therapy (ART) from Red Cross War Memorial Children's Hospital (RCWMCH), Cape Town, South Africa. Few published data exist on the outcomes of these children. To assess outcomes of children receiving ART in the first 12 months after down-referral to primary healthcare (PHC) clinics and identify determinants of successful down-referral. A retrospective cohort study of children <15 years of age who initiated ART at RCWMCH and were subsequently down-referred to one of two PHC clinics between January 2006 and December 2012 was completed. Baseline characteristics of patients and caregivers as well as CD4+ counts, viral loads (VLs) and weights were collected 6 and 12 months after down-referral. Outcomes included retention in care and viral suppression. Of 116 children down-referred to the two study PHC clinics, 81.9% arrived at the designated PHC clinic and a further 8.6% continued care at other clinics, the remaining 9.5% being lost to follow-up. Of those successfully down-referred, 11.4% took >8 weeks to present, possibly experiencing treatment interruption. At 12 months after down-referral, only 81.0% remained in care. No factors were associated with retention in care in multivariable analysis. For children who remained in care at the designated PHC clinics, the clinical and immunological gains achieved prior to down-referral were sustained through 12 months of follow-up, and 54.7% of this cohort had documented viral suppression at 12 months. However, if only children with VL results are considered, 75.9% (41/54) were virally suppressed 12 months after down-referral. Down-referral of children on ART is complex, with risk of loss to follow-up and treatment interruption.


Comparison of three techniques using the Parkland Formula to aid fluid resuscitation in adult burns.
We performed a randomised study to compare the accuracy and speed of three different techniques (pen and paper, electronic calculator and a novel graphic device: 'nomogram') for calculation of resuscitation fluid requirements for adults in the first 24 h of burn injury, based on the Parkland Formula. We also assessed acceptability of each technique using visual analogue scores and qualitative analysis of free text responses. 28 participants performed 252 calculations using a series of computer generated simulated patient data. For nomogram, electronic calculator, pen and paper: Magnitude of error [low (≥25%), medium (≥50%), high (≥75%)]: [6.0%, 1.2%, 0%], [17.9%, 14.3%, 8.3%], [25%, 16.7%, 9.5%]; p<0.002. Calculation time: [sec: mean (SD)]: 94(34), 73(31), 214(103); p<0.001. The mean (SD) of the difficulty scores for each method were 23(17), 17(14) and 70(21) out of 100. Of the 28 participants 15 preferred the calculator, 12 preferred the nomogram and 1 scored the calculator and nomogram equally (table 3). The nomogram was significantly more accurate at all levels, almost as fast as an electronic calculator, and deemed easy to use. It is low cost and robust, and provides a rapid means of detecting and preventing the large errors that we have shown can occur when an electronic device is used as the only method of calculation. We therefore suggest that the Parkland Formula nomogram is a suitable method for calculation of resuscitation fluid requirements in adult burns. Fluid requirement should, however, be reviewed frequently, and adjusted to ensure adequate organ perfusion.


Geographic Variability in Discharge Setting and Outpatient Postacute Physical Therapy After Total Knee Arthroplasty: A Retrospective Cohort Study.
Despite the frequency of total knee arthroplasty (TKA) in the Medicare population, little is known about the use of postacute physical therapy among those discharged to home. The objectives of this study were to explore factors associated with geographic variability in discharge disposition and outpatient physical therapy utilization for Medicare patients after TKA discharged to home/self-care. The design of the study was a retrospective cohort study. Medicare patients with TKA discharged alive from July 1, 2010, to June 30, 2011, with discharge disposition to home/self-care (HSC), home health agency (HHA), inpatient rehabilitation facility (IRF), or skilled nursing facility (SNF) were selected. Geography was measured with Census region. Outpatient physical therapy utilization was calculated from Medicare Part B claims. Odds ratios for discharge disposition and adjusted means for physical therapy utilization variables by Census region were calculated, accounting for county-clustered data and adjusting for demographics, clinical, and environmental characteristics. There was significant variation with discharge destination by Census region among 18,278 patients. With discharge disposition analysis, the patients from the West region who were discharged home were the referent group. The patients from the South and Northeast regions had higher odds for discharge to HHAs (adjusted odds ratio [95% CI = 1.80 [1.48-2.19] and 2.20 [1.70-2.84]), SNFs (1.34 [1.08-1.66] and 4.42 [3.38-5.79]), and IRFs (2.36 [1.80-3.09] and 8.83 [6.41-12.18]). For those discharged to HSC, 40.4% received outpatient physical therapy within 4 weeks. Significant differences were found with time to first physical therapy visit (Midwest <South <[West = Northeast]) and length of therapy episode, but not with the number of therapy visits by geographic region. Geographic region was associated with discharge setting, postacute physical therapy, and outpatient therapy utilization in Medicare beneficiaries after TKA. Differences in outcomes of outpatient therapy should be assessed to better describe the impact of geographic variation in care.


Mixotrophic protists display contrasted biogeographies in the global ocean.
Mixotrophy, or the ability to acquire carbon from both auto- and heterotrophy, is a widespread ecological trait in marine protists. Using a metabarcoding dataset of marine plankton from the global ocean, 318,054 mixotrophic metabarcodes represented by 89,951,866 sequences and belonging to 133 taxonomic lineages were identified and classified into four mixotrophic functional types: constitutive mixotrophs (CM), generalist non-constitutive mixotrophs (GNCM), endo-symbiotic specialist non-constitutive mixotrophs (eSNCM), and plastidic specialist non-constitutive mixotrophs (pSNCM). Mixotrophy appeared ubiquitous, and the distributions of the four mixotypes were analyzed to identify the abiotic factors shaping their biogeographies. Kleptoplastidic mixotrophs (GNCM and pSNCM) were detected in new zones compared to previous morphological studies. Constitutive and non-constitutive mixotrophs had similar ranges of distributions. Most lineages were evenly found in the samples, yet some of them displayed strongly contrasted distributions, both across and within mixotypes. Particularly divergent biogeographies were found within endo-symbiotic mixotrophs, depending on the ability to form colonies or the mode of symbiosis. We showed how metabarcoding can be used in a complementary way with previous morphological observations to study the biogeography of mixotrophic protists and to identify key drivers of their biogeography.


Isaacs syndrome: A review.
Isaacs syndrome is a peripheral nerve hyperexcitability (PNH) syndrome that presents as continuous motor activity. Clinical findings include cramps, fasciculations, and myokymia. Electrodiagnosis plays a key role in diagnosis by demonstrating after-discharges on nerve conduction studies, and fasciculation potentials, myokymic discharges, neuromyotonic discharges, and other types of abnormal spontaneous activity on needle examination. Etiopathogenesis involves the interaction of genetic, autoimmune, and paraneoplastic factors, which requires a broad-ranging evaluation for underlying causes. Initial treatment is symptomatic, but immune therapy is often needed and can be effective. The purpose of this review is to describe the syndrome and its pathogenesis, assist the reader in evaluating patients with suspected Isaacs syndrome and distinguishing it from other disorders of PNH, and suggest an approach to management, including both symptomatic and immunomodulating therapy.


Bcl6/p53 expression, macrophages/mast cells infiltration and microvascular density in invasive breast carcinoma.
To better understand the breast cancer progression and therapeutic resistance is crucial deepen the molecular mechanisms related to regulation of cells behavior in the tumor microenvironment. Inappropriate expression or activation of transcription factors in tumor breast microenvironment can lead to the malignant behavior of breast cancer cells. Bcl6 is a transcriptional factor that may play a role in the pathogenesis of breast cancer. Moreover, cells surrounding tumor cells, including macrophages and mast cells play an important role during tumor progression enhancing angiogenesis. We have demonstrated: 1) An increase of the BCL6 translocation and Bcl6 positive cells in G3 degree of disease; 2) A reduction of the expression of p53 in G3 breast cancer samples as compared to G1/G2 specimens; 3) Macrophages CD68+ and CD163+ in interstitial and periglandular position, increase in G3 specimens as compared to G1/G2 and control samples; 4) Tryptase-positive mast cells in periglandular position are more numerous in G3 tumor specimens as compared to G1/G2 and control samples. Overall, these data confirm the important role played by epigenetic events, including BCL6 translocation, p53 expression, and microenvironment components, including macrophage and mast cell infiltration and microvascular density involved in the regulation of breast cancer progression.


Analysis of the aphthovirus 2A/2B polyprotein 'cleavage' mechanism indicates not a proteolytic reaction, but a novel translational effect: a putative ribosomal 'skip'.
The 2A region of the aphthovirus foot-and-mouth disease virus (FMDV) polyprotein is only 18 aa long. A 'primary' intramolecular polyprotein processing event mediated by 2A occurs at its own C terminus. FMDV 2A activity was studied in artificial polyproteins in which sequences encoding reporter proteins flanked the 2A sequence such that a single, long, open reading frame was created. The self-processing properties of these artificial polyproteins were investigated and the co-translational 'cleavage' products quantified. The processing products from our artificial polyprotein systems showed a molar excess of 'cleavage' product N-terminal of 2A over the product C-terminal of 2A. A series of experiments was performed to characterize our in vitro translation systems. These experiments eliminated the translational or transcriptional properties of the in vitro systems as an explanation for this imbalance. In addition, the processing products derived from a control construct encoding the P1P2 region of the human rhinovirus polyprotein, known to be proteolytically processed, were quantified and found to be equimolar. Translation of a construct encoding green fluorescent protein (GFP), FMDV 2A and beta-glucuronidase, also in a single open reading frame, in the presence of puromycin, showed this antibiotic to be preferentially incorporated into the [GFP2A] translation product. We conclude that the discrete translation products from our artificial polyproteins are not produced by proteolysis. We propose that the FMDV 2A sequence, rather than representing a proteolytic element, modifies the activity of the ribosome to promote hydrolysis of the peptidyl(2A)-tRNA(Gly) ester linkage, thereby releasing the polypeptide from the translational complex, in a manner that allows the synthesis of a discrete downstream translation product to proceed. This process produces a ribosomal 'skip' from one codon to the next without the formation of a peptide bond.