Analyses of the interactions between retinoid-binding proteins and embryonal carcinoma cells.
[3H]Retinoic acid (RA) and [3H]retinol bind in an unsaturable manner to isolated nuclei from Nulli-SCC1 and PCC4.aza1R embryonal carcinoma (EC) cells. When nuclei are challenged with the same labeled retinoids on their respective binding proteins (CRABP and CRBP), much less binding is observed and the binding is saturable. RA-CRABP does not compete with [3H]retinol-CRBP for binding to specific Nulli-SCC1 nuclear sites, whereas retinol-CRBP (but not apo-CRBP) actually potentiates the binding of [3H]RA-CRABP to these nuclei. The binding of [3H]RA-CRABP and [3H]retinol-CRBP is not dramatically affected by prior removal of the outer nuclear membrane with Triton X-100. However, treatment with the detergent after the binding reaction is complete removes about half of the bound [3H]RA-CRABP and almost all of the bound [3H]retinol-CRBP. We measured specific retinoid-binding activities in nucleoplasmic extracts of Nulli-SCC1 and PCC4.aza1R cells. The only readily detectable specific binding activity in nucleoplasmic extracts from untreated cells was for [3H]retinol in PCC4.aza1R preparations. Nucleoplasmic extracts from Nulli-SCC1 and PCC4.aza1R cells pretreated with RA had considerable levels of specific [3H]RA-binding activity with little or no increase in [3H]retinol binding. By contrast, similar extracts from Nulli-SCC1 cells treated with retinol bound large amounts of both [3H]retinol and [3H]RA. Under the same conditions, PCC4.aza1R extracts also contained [3H]RA-binding activity with no increase in [3H]retinol binding above the high endogenous levels. Although these results might reflect translocation of binding proteins from cytoplasm to nucleus, other interpretations must be considered since we often observed an increase, rather than the expected reduction, in cytoplasmic retinoid-binding protein levels.


Scalable modulator for frequency shift keying in free space optical communications.
Frequency shift keyed (FSK) modulation formats are well-suited to deep space links and other high loss links. FSK's advantage comes from its use of bandwidth expansion. I.e., FSK counteracts power losses in the link by using an optical bandwidth that is greater than the data rate, just as pulse position modulation (PPM) does. Unlike PPM, increasing FSK's bandwidth expansion does not require increased bandwidth in electronic components. We present an FSK modulator whose component count rises logarithmically with the bandwidth expansion. We tested it with four-fold bandwidth expansion at 5 and 20 Gbit/s. When paired with a pre-amplified receiver, the required received power was about 4 and 5 dB from the theoretical best for such receivers. We also tested the FSK transmitter with a photon counting receiver.


Data dimensionality reduction with application to simplifying RBF network structure and improving classification performance.
For high dimensional data, if no preprocessing is carried out before inputting patterns to classifiers, the computation required may be too heavy. For example, the number of hidden units of a radial basis function (RBF) neural network can be too large. This is not suitable for some practical applications due to speed and memory constraints. In many cases, some attributes are not relevant to concepts in the data at all. In this paper, we propose a novel separability-correlation measure (SCM) to rank the importance of attributes. According to the attribute ranking results, different attribute subsets are used as inputs to a classifier, such as an RBF neural network. Those attributes that increase the validation error are deemed irrelevant and are deleted. The complexity of the classifier can thus be reduced and its classification performance improved. Computer simulations show that our method for attribute importance ranking leads to smaller attribute subsets with higher accuracies compared with the existing SUD and Relief-F methods. We also propose a modified method for efficient construction of an RBF classifier. In this method we allow for large overlaps between clusters corresponding to the same class label. Our approach significantly reduces the structural complexity of the RBF network and improves the classification performance.


From west to east; experience with adapting a curriculum in evidence-based medicine.
Clinical epidemiology (CE) and evidence-based medicine (EBM) have become an important part of medical school curricula. This report describes the implementation and some preliminary outcomes of an integrated CE and EBM module in the Faculty of Medicine Universitas Indonesia (UI), Jakarta and in the University of Malaya (UM) in Kuala Lumpur. A CE and EBM module, originally developed at the University Medical Center Utrecht (UMCU), was adapted for implementation in Jakarta and Kuala Lumpur. Before the start of the module, UI and UM staff followed a training of teachers (TOT). Student competencies were assessed through pre and post multiple-choice knowledge tests, an oral and written structured evidence summary (evidence-based case report, EBCR) as well as a written exam. All students also filled in a module evaluation questionnaire. The TOT was well received by staff in Jakarta and Kuala Lumpur and after adaptation the CE and EBM modules were integrated in both medical schools. The pre-test results of UI and UM were significantly lower than those of UMCU students (p < 0.001). The post test results of UMCU students were comparable (p = 0.48) with UI, but significantly different (p < 0.001) from UM. Common problems for the modules in both UI and UM were limited access to literature and variability of the tutors' skills. Adoption and integration of an existing Western CE-EBM teaching module into Asian medical curricula is feasible while learning outcomes obtained are quite similar.


Intergenerational mobility in the post-1965 immigration era: estimates by an immigrant generation cohort method.
The new second generation of the post-1965 immigration era is observed as children with their parents in 1980 and again as adults 25 years later. Intergenerational mobility is assessed for both men and women in four major racial/ethnic groups, both in regard to children's status attainment relative to parents and with regard to the rising societal standards proxied by native-born non-Hispanic whites. A profile of intergenerational mobility is prepared using multiple indicators of status attainment: high school and college completion, upper white-collar occupation, poverty, and homeownership. The immigrant generation cohort method we introduce accounts for four distinct temporal dimensions of immigrant progress, clarifying inconsistencies in the literature and highlighting differences in mobility between racial/ethnic groups and with respect to different outcome measures. The immigrant generation cohort method consistently finds greater intergenerational mobility than suggested by alternative approaches. Our analysis also shows that the intergenerational progress of women is greater than that of men and provides a more complete record of immigrant mobility overall. Findings for individual racial/ethnic groups accord with some expectations in the literature and contradict others.


DSM-5 and ICD-11 as competing models of PTSD in preadolescent children exposed to a natural disaster: assessing validity and co-occurring symptomatology.
Background: Major revisions have been made to the DSM and ICD models of post-traumatic stress disorder (PTSD). However, it is not known whether these models fit children's post-trauma responses, even though children are a vulnerable population following disasters. Objective: Using data from Hurricane Ike, we examined how well trauma-exposed children's symptoms fit the DSM-IV, DSM-5 and ICD-11 models, and whether the models varied by gender. We also evaluated whether elevated symptoms of depression and anxiety characterized children meeting PTSD criteria based on DSM-5 and ICD-11. Method: Eight-months post-disaster, children (N = 327, 7-11 years) affected by Hurricane Ike completed measures of PTSD, anxiety and depression. Algorithms approximated a PTSD diagnosis based on DSM-5 and ICD-11 models. Results: Using confirmatory factor analysis, ICD-11 had the best-fitting model, followed by DSM-IV and DSM-5. The ICD-11 model also demonstrated strong measurement invariance across gender. Analyses revealed poor overlap between DSM-5 and ICD-11, although children meeting either set of criteria reported severe PTSD symptoms. Further, children who met PTSD criteria for DSM-5, but not for ICD-11, reported significantly higher levels of depression and general anxiety than children not meeting DSM-5 criteria. Conclusions: Findings support the parsimonious ICD-11 model of PTSD for trauma-exposed children, although adequate fit also was obtained for DSM-5. Use of only one model of PTSD, be it DSM-5 or ICD-11, will likely miss children with significant post-traumatic stress. DSM-5 may identify children with high levels of comorbid symptomatology, which may require additional clinical intervention.


A randomized trial of radical radiotherapy for the management of pT1G3 NXM0 transitional cell carcinoma of the bladder.
We conducted a multicenter randomized trial in the United Kingdom to determine the efficacy of radical radiotherapy in reducing the incidence of progression of pT1G3 transitional cell carcinoma of the bladder to muscle invasive disease and subsequent disease fatality. Patients with a new diagnosis of pT1G3 NXM0 transitional cell carcinoma with unifocal disease and no carcinoma in situ (group 1), or with multifocal disease and/or carcinoma in situ (group 2) were eligible for the trial. Patients in group 1 were randomized between observation and radiotherapy to the bladder, and in group 2 between intravesical therapy and radiotherapy. From September 1991 to February 2003 a total of 210 patients from 37 centers in the United Kingdom were entered into the study. There were 77 patients in group 1 and 133 patients in group 2, and 6 patients were excluded from analysis because they were found to have pT2 disease by the reference pathologist. No evidence of an advantage with radiotherapy was found in terms of progression-free interval (hazard ratio 1.07; 95% CI 0.65, 1.74; p = 0.785), progression-free survival (hazard ratio 1.35; 95% CI 0.92, 1.98; p = 0.133) or overall survival (hazard ratio 1.32; 95% CI 0.86, 2.04; p = 0.193). To our knowledge this is the largest randomized trial performed in patients with pT1G3 disease for which 210 patients were recruited during 11 years. There is no evidence that radiotherapy is better than more conservative treatment. The prognosis of this group of patients appears to be poor irrespective of treatment and new treatment strategies need to be investigated.


A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures.
Improving accuracy and efficiency of computational methods that predict pseudoknotted RNA secondary structures is an ongoing challenge. Existing methods based on free energy minimization tend to be very slow and are limited in the types of pseudoknots that they can predict. Incorporating known structural information can improve prediction accuracy; however, there are not many methods for prediction of pseudoknotted structures that can incorporate structural information as input. There is even less understanding of the relative robustness of these methods with respect to partial information. We present a new method, Iterative HFold, for pseudoknotted RNA secondary structure prediction. Iterative HFold takes as input a pseudoknot-free structure, and produces a possibly pseudoknotted structure whose energy is at least as low as that of any (density-2) pseudoknotted structure containing the input structure. Iterative HFold leverages strengths of earlier methods, namely the fast running time of HFold, a method that is based on the hierarchical folding hypothesis, and the energy parameters of HotKnots V2.0.Our experimental evaluation on a large data set shows that Iterative HFold is robust with respect to partial information, with average accuracy on pseudoknotted structures steadily increasing from roughly 54% to 79% as the user provides up to 40% of the input structure.Iterative HFold is much faster than HotKnots V2.0, while having comparable accuracy. Iterative HFold also has significantly better accuracy than IPknot on our HK-PK and IP-pk168 data sets. Iterative HFold is a robust method for prediction of pseudoknotted RNA secondary structures, whose accuracy with more than 5% information about true pseudoknot-free structures is better than that of IPknot, and with about 35% information about true pseudoknot-free structures compares well with that of HotKnots V2.0 while being significantly faster. Iterative HFold and all data used in this work are freely available at http://www.cs.ubc.ca/~hjabbari/software.php.


[Check list for the use of thrombolytics and other drugs in acute myocardial infarction].
Data on all patients with acute myocardial infarction who were treated in Nordland County Hospital in a six-month period in 1996 were analyzed retrospectively (137 patients). After the introduction of checklists for the treatment of such patients, we did a prospective six-month registration in 1997 (111 patients) in order to find out whether treatment and delay times had improved. The proportion of patients who received thrombolytic treatment did not change (28% in 1996 as compared to 25% in 1997). The in-hospital delay time before treatment did not differ before and after the introduction of a check-list (approximately 40 minutes in both periods). There was an increase in the use of intravenous beta blockers and aspirin. The percentage of patients with acute myocardial infarction receiving thrombolytics in our hospital does not differ substantially from that of other hospitals in Norway.


Does brain swelling increase estimated specific gravity?
At the acute phase of traumatic brain injury (TBI), brain swelling contributes substantially to the development of secondary neurological lesions. Elucidating the pathophysiology of brain swelling is crucial to improve TBI management. In a previous study, specific gravity (SG) of the noncontused hemisphere, as estimated by computed tomography (CT), was higher in patients with high Marshall CT scores and severe brain swelling. The aim of this study was to investigate the relationship between estimated specific gravity (eSG) and clinical variable suggestive of brain swelling. Retrospective study of data from a prospectively established database. Neurology ICU in a teaching hospital in Paris, France. We studied 20 patients with severe traumatic brain injury (TBI), 20 patients with high-grade subarachnoid hemorrhage (SAH) presenting similar brain-swelling criteria, 20 patients with low-grade SAH, and 20 healthy controls. None. Estimated brain specific gravity was acquired from CT images obtained at ICU admission. eSG was estimated in the overall intracerebral content and in a region-of-interest composed of white matter and the diencephalon. eSG in the region of interest was significantly higher in the TBI patients than in the high-grade SAH patients (1.0350 +/- 0.0041 vs. 1.0310 +/- 0.0019 g/ml, P < 0.05). eSG was similar in the high-grade SAH, low-grade SAH, and control groups. Our findings do not support a causal link between brain swelling and eSG elevation. The eSG increase in severe TBI patients is not due to brain swelling.


Agreement between self and partner reports of paternal drinking and smoking. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.
We examined agreement between self and proxy reports of paternal drinking and smoking behaviour using data collected as part of the prospective, population-based Avon (England) Longitudinal Study of Pregnancy and Childhood. Information on the smoking and drinking habits of pregnant women's male partners was obtained through self-administered questionnaires completed by pregnant participants and by their partners. For dichotomous indicators (e.g. smoker versus non-smoker), we evaluated self/proxy agreement by calculating Kappa coefficients and per cent agreement. For ordinal measures of smoking and drinking amounts, we calculated per cent perfect agreement, per cent agreement within one category, and Spearman correlation coefficients. Data from 8414 respondent pairs were included in the analyses. Men's and women's reports of paternal smoking and drinking status were in nearly complete agreement (95% and 98%, respectively). For analyses of smoking and drinking amounts, agreement within one category remained high (90% and 98% for smoking and drinking, respectively), but perfect agreement on amount was somewhat lower (81% and 71%, respectively). Per cent perfect agreement on smoking amount was especially low (50%) when non-smokers were excluded. When couples' reports were not in perfect agreement, women tended to report lower amounts of smoking and drinking for their partners compared to the men's self reports. Our results suggest that women's proxy reports of their partners' drinking and smoking status can be used with considerable confidence in reproductive epidemiological studies when the enrollment of both women and men as participants is infeasible for financial or logistical reasons. Caution is warranted, however, when proxy reports are used for more detailed information on smoking and drinking amounts.


A survey of blindness and poor vision in leprosy patients.
To determine the prevalence, cause and distributions of blindness and poor vision in patients with leprosy. An epidemiological survey of blindness and poor vision among 1045 cases of leprosy was carried out in Taixing City of Jiangsu Province, China. The prevalence of bilateral blindness was 7.67%, unilateral blindness 4.4%, bilateral poor vision of various degrees 9.28% and unilateral poor vision 5.84%. The prevalence of eye complications varied significantly among different groups of patients; females had a higher prevalence than males, multibacillary patients higher than paucibacillary patients, and in-patients higher than out-patients. Corneal disease was the most common cause of blindness in study groups, followed by iritic disease and cataract; while the main cause of poor vision was cataract, then corneal and iritic diseases. Treatable blindness accounted for 62.7% of the cases and treatable poor vision for 88.6% of the patients studied. 56.62% of cases with eye complications expressed their willingness to be treated. Although prevention and treatment of low vision and blindness in leprosy patients is very hard, it is necessary for doctors and medical workers to make clear of the factors to cause low vision and blindness, especially those in leprosy patients so that some measures for prevention and treatment of the disease could be taken accordingly.


Hyperleptinemia contributes to antipsychotic drug-associated obesity and metabolic disorders.
Despite their high degree of effectiveness in the management of psychiatric conditions, exposure to antipsychotic drugs, including olanzapine and risperidone, is frequently associated with substantial weight gain and the development of diabetes. Even before weight gain, a rapid rise in circulating leptin concentrations can be observed in most patients taking antipsychotic drugs. To date, the contribution of this hyperleptinemia to weight gain and metabolic deterioration has not been defined. Here, with an established mouse model that recapitulates antipsychotic drug-induced obesity and insulin resistance, we not only confirm that hyperleptinemia occurs before weight gain but also demonstrate that hyperleptinemia contributes directly to the development of obesity and associated metabolic disorders. By suppressing the rise in leptin through the use of a monoclonal leptin-neutralizing antibody, we effectively prevented weight gain, restored glucose tolerance, and preserved adipose tissue and liver function in antipsychotic drug-treated mice. Mechanistically, suppressing excess leptin resolved local tissue and systemic inflammation typically associated with antipsychotic drug treatment. We conclude that hyperleptinemia is a key contributor to antipsychotic drug-associated weight gain and metabolic deterioration. Leptin suppression may be an effective approach to reducing the undesirable side effects of antipsychotic drugs.


Underutilizers of mammography screening today: characteristics of women planning, undecided about, and not planning a mammogram.
Using concepts from the Precaution Adoption Process Model, we identified behavioral factors, sociodemographic and psychosocial variables, and beliefs about breast cancer that discriminated among women at different stages with regard to their intention to obtain mammography screening. An independent survey company conducted telephone interviews with 2,507 women aged 50 to 80 who were identified as underutilizers of mammography screening. Each underutilizer was assigned to one of three stages with regard to intention to get a mammogram: (a) definitely planning, (b) thinking about, and (c) not planning. Estimated actual risk of breast cancer, perceived risk to breast cancer, worry about breast cancer, and fear of learning from a mammogram that one has breast cancer were variables found to be significantly associated with intention to obtain a mammogram for several subgroups of underutilizing women. There are significant behavioral and psychosocial variables, beliefs and feelings about breast cancer, and demographic characteristics that distinguish underutilizing women at various stages with regard to intention to obtain mammography screening. Our findings provide new information that could help the health care professional motivate women who are not planning to utilize this preventive health measure to become regular utilizers.


Addiction research centres and the nurturing of creativity: Centre for Social Research on Alcohol and Drugs (SoRAD), Stockholm University, Sweden.
The Centre for Social Research on Alcohol and Drugs (SoRAD) was established as a national research centre and department within the Faculty of Social Science at Stockholm University in 1997, following a Government Report and with the aim to strengthen social alcohol and drug research. Initially, core funding came from the Swedish Council for Working Life and Social Research and from the Ministry of Health and Social Affairs for several long-term projects. Today, SoRAD, with 25 senior and junior researchers, has core funding from the university but most of its funding comes from external national and international grants. Research is organized under three themes: consumption, problems and norms, alcohol and drug policy and societal reactions, treatment and recovery processes. SoRADs scientific approach, multi-disciplinarity, a mix of qualitative and quantitative methods and international comparisons was established by the centre's first leader, Robin Room. Regular internal seminars are held and young researchers are encouraged to attend scientific meetings and take part in collaborative projects. SoRAD researchers produce government-funded monthly statistics on alcohol consumption and purchase, and take part in various national government committees, but SoRADs research has no clear political or bureaucratic constraints. One of the future challenges for SoRAD will be the proposed system for university grants allocation, where applied social science will have difficulties competing with basic biomedical research if decisions are based on publication and citation measures.


Clinical and therapeutic implications of Sprouty2 feedback dysregulation in BRAF V600E-mutation-positive papillary thyroid cancer.
The BRAF V600E (BRAF+) mutation activates the mitogen-activated protein kinase (MAPK/ERK) pathway and may confer an aggressive phenotype in papillary thyroid cancer (PTC). Clinically, the behavior of BRAF+ PTC, however, varies from an indolent to an aggressive course. SPRY2 is a negative feedback regulator of the MAPK/ERK pathway. We hypothesize that the level of SPRY2 expression contributes to MAPK/ERK pathway output and accounts for BRAF+ and clinical heterogeneity. A tissue microarray with BRAF-positive PTCs (BRAF+ PTCs) was constructed and analyzed for SPRY2 expression and MAPK/ERK output. Data were studied in the context of clinicopathologic factors to develop a risk stratification system predictive of tumor biology. SPRY2 function was studied by silencing SPRY2 in BRAF+ PTC cells. These cells were treated with MAPK/ERK pathway inhibitors and assessed for growth effects. BRAF+ PTCs with an intact MAPK/ERK feedback pathway do not exhibit lymph node metastases. BRAF+ PTCs with dysregulated feedback pathways have nodal metastasis. When SPRY2 is silenced, the BRAF+ PTC cells are significantly more sensitive to MAPK/ERK inhibition. PTC behavior likely is dependent on both the driver of the MAPK/ERK pathway and its regulatory feedback. When the feedback pathway is intact, the tumor phenotype seems to be less aggressive. This observation has direct and important clinical implications and may alter our treatment strategies.


The role of dasatinib in the management of chronic myeloid leukemia.
Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) for chronic, blastic, or accelerated phase chronic myeloid leukemia (CML) patients who are resistant or intolerant to previous treatment. It potently inhibits BCR/ABL and SRC-family kinases (SRC, LCK, HCK, YES, FYN, FGR, BLK, LYN, FRK), as well as c-KIT, PDGFR-a and -b, and ephrin receptor kinase. Various clinical trials have provided evidence that it has more durable complete hematologic and cytogenetic responses, as well as more potency in imatinib-resistant or -intolerant CML, and it has also shown its advantages in newly diagnosed CML compared to imatinib. In this review, we mainly focus on the structure, mechanisms, pharmacokinetics, and pharmacogenetics of dasatinib. We also summarize clinical trials with dasatinib on CML and provide our recommendations for dasatinib in the treatment of CML.


The impacts of email reminder/recall on adolescent influenza vaccination.
We sought to: (1) explore the feasibility of using email for seasonal influenza vaccination reminders to parents of adolescents and (2) assess influenza vaccination rates among adolescents whose parents were randomized to either receive or not receive email reminders. Email addresses were obtained for parents of patients 10-18years from 4 practices in Michigan. Addresses were randomized to either receive email reminders, or not. Reminder messages were sent during October 2012-March 2013 (Season 1) and October 2013-March 2014 (Season 2). Vaccination status was determined 60days following the last email reminder for each season using the statewide Michigan Care Improvement Registry (MCIR); per protocol bivariate and multivariate logistic regression analyses were conducted to evaluate reminder notification. After email cleaning, testing, and matching with MCIR, approximately half of email addresses (2348 of 5312 in Season 1; 3457 of 6549 in Season 2) were randomized. Bivariate analyses found that influenza vaccination within 60days after notification date was similar among those notified (34%) versus not notified (29%) in both Season 1 (p=0.06) and Season 2 (39% vs. 37%, p=0.20). However, multivariate models adjusted for season, site, and receipt of notification in two seasons found a higher likelihood of influenza vaccination among children that received notification (aOR=1.28, 95% CI=1.09, 1.51); in addition, differences in influenza vaccination were also observed between practice sites (range: p=0.15 to p<0.001). We found that practice-based email influenza vaccine reminders to parents of adolescents are feasible, but not without complications. Our study demonstrates that email reminders from practices can yield increases in influenza vaccination rates among adolescents. Practices should consider email as an option for influenza reminders and establish business practices for collecting and maintaining patient email addresses. This study is registered at www.ClinicalTrials.gov id #NCT01732315.


Attitudes and perceptions of naloxone dispensing among a sample of Massachusetts community pharmacy technicians.
There is limited research on the attitudes of pharmacy technicians toward pharmacy naloxone provision, despite their widespread role in the pharmacy. We examined attitudes and perceptions of pharmacy technicians in the provision of naloxone in a sample of Massachusetts pharmacies. Thirty-nine community retail pharmacies from 1 U.S. chain were purposely sampled in 13 municipalities across Massachusetts. Pharmacies were divided into high-risk municipalities (HRMs) versus low-risk municipalities (LRMs) based on the state average opioid-related death rate from 2011 to 2015. A pharmacy technician working in each pharmacy was administered an in-person survey. Survey topics included technician beliefs about current naloxone provision practices; patient groups at greater risk of overdose; whether individuals filling prescriptions would benefit from naloxone; and whether individuals purchasing syringes would benefit from naloxone. Closed-ended responses were analyzed by Mann-Whitney U, Fisher exact, and chi-square tests. Open-ended responses were summarized for themes and then contrasted by municipality risk status. Technician participation was 100% (n = 39). Technicians in both groups believed they could identify patient groups at risk of overdose in their practice, but HRM technicians recognized the need for naloxone for more of their at-risk patients (81% in HRM vs. 33% in LRM believed > 25% of patients need naloxone, P < 0.01). A willingness to provide naloxone was high (> 89%) in both groups. Open-ended responses revealed commonalities between groups, including the belief that patients need lower-cost naloxone, and a lack of patient and technician awareness that naloxone could prevent overdose in individuals at risk through use of prescription opioids not just through use of illicit drugs. Pharmacy technicians would benefit from overdose prevention training and are well positioned to recognize overdose risk and offer preventive interventions, such as naloxone. Among technicians, there is a high willingness to be involved in implementing broader naloxone access in pharmacies.


Experimental demography and the vital rates of generalist and specialist insect herbivores on native and novel host plants.
1. Colonization success of species when confronted with novel environments is of interest in ecological, evolutionary and conservation contexts. Such events may represent the first step for ecological diversification. They also play an important role in adaptive divergence and speciation. 2. A species that is able to do well across a range of environments has a higher plasticity than one whose success is restricted to a single or few environments. The breadth of environments in which a species can succeed is ultimately determined by the full pattern of its vital rates in each environment. 3. Examples of organisms colonizing novel environments are insect herbivores expanding their diets to novel host plants. One expectation for insect herbivores is that species with specialized diets may display less plasticity when faced with novel hosts than generalist species. 4. We examine this hypothesis for two generalist and two specialist neotropical beetles (genus Cephaloleia: Chrysomelidae) currently expanding their diets from native to novel plants of the order Zingiberales. Using an experimental approach, we estimated changes in vital rates, life-history traits and lifetime fitness for each beetle species when feeding on native or novel host plants. 5. We did not find evidence supporting more plasticity for generalists than for specialists. Instead, we found similar patterns of survival and fecundity for all herbivores. Larvae survived worse on novel hosts; adults survived at least as well or better, but reproduced less on the novel host than on natives. 6. Some of the novel host plants represent challenging environments where population growth was negative. However, in four novel plant-herbivore interactions, instantaneous population growth rates were positive. 7. Positive instantaneous population growth rates during initial colonization of novel host plants suggest that both generalist and specialist Cephaloleia beetles may be pre-adapted to feed on some novel hosts. This plasticity in host use is a key factor for successful colonization of novel hosts. Future success or failure in the colonization of these novel hosts will depend on the demographic rates described in this research, natural selection and the evolutionary responses of life-history traits in novel environments.


Prevalence of SARS-CoV-2 antibodies among university athletic club members: A cross-sectional survey.
School-based coronavirus disease 2019 (COVID-19) testing is an important part of a comprehensive prevention strategy in public health. To assess the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in a university athletic club community with repeated occurrences of SARS-CoV-2 infections, we conducted a cross-sectional survey for asymptomatic antibody prevalence using a SARS-CoV-2 rapid antibody test kit. On January 26, 2021 we administered questionnaires to determine their history of contact with infected individuals and took blood samples from 129 undergraduates. The prevalence of SARS-CoV-2 antibodies among the subjects was 3.9%. Only 6.2% of the participants reported close contact with infected individuals. In this study, we clarified the prevalence of asymptomatic SARS-CoV-2 antibodies in university athletic clubs where SARS-CoV-2 infections had repeatedly occurred, which will be helpful in discussing how to identify and prevent the transmission of infections within university athletic club communities.


The insulin-like effects of low molecular weight thiols: role of trace metal contamination of commercial thiols.
During the investigation of insulin-like effects of low molecular weight thiols in rat adipocytes it was found that thiol autoxidation to H2O2 occurred even in the absence of albumin and cells. Since chromatography of the thiols on a chelating ion exchange resin prevented H2O2 formation, it is likely that trace metal contaminations of the thiol preparations catalyzed thiol autoxidation in oxygenated solutions. Incubation of rat adipocytes with 1 mM dithioerythritol and low concentrations of dialyzed albumin stimulated 2-deoxyglucose transport, glucose metabolism to CO2 and lipids, and formate resin or in most instances incubation with EDTA or catalase prevented these effects. The antilipolytic effect of dithioerythritol was also abolished by catalase. The insulin-like effects of thiols therefore appear to be solely mediated by H2O2 generated during thiol autoxidation catalyzed by trace metal contaminants either of albumin or of the commercial thiol preparation itself.


Perfectionism in Eating Disorders: Are Long-Term Outcomes Influenced by Extent and Changeability in Initial Perfectionism?
Perfectionism has been found to predict outcomes in the treatment of eating disorders (ED). In the present study, we took advantage of longitudinal data to: a) investigate whether there are different patterns of perfectionism during the first six months after admission in a clinical sample of patients with ED, and b) describe how these patterns are related to long-term outcome. A sample of patients (N=294) from the Coordinated Evaluation and Research at Specialized Units for Eating Disorders database was divided into clusters according to perfectionism patterns measured with the EDI-2 perfectionism scale at baseline, and six months in treatment. Cluster analysis was performed on the extent and perseverance/changeability of self-oriented and socially described perfectionism. Outcome was measured with the EDI-2 and the SCL-63. Frequencies of eating disorder diagnoses were investigated. Five clusters were identified. Low perfectionism was associated with lower levels of ED and psychiatric symptomatology at baseline. There were no significant differences between clusters on outcome variables at 36-month follow-up. Results indicated better psychiatric and psychological health three years after the initial measure. Patterns of relations between the extent and possible changes of perfectionism, measured with the EDI-P at baseline and after six months, did not appear to be associated with long-term outcomes on psychiatric health ratings.


Unveiling a New Aspect of Simple Arylboronic Esters: Long-Lived Room-Temperature Phosphorescence from Heavy-Atom-Free Molecules.
Arylboronic esters can be used as versatile reagents in organic synthesis, as represented by Suzuki-Miyaura cross-coupling. Here we report a serendipitous finding that simple arylboronic esters are phosphorescent in the solid state at room temperature with a lifetime on the order of several seconds. The phosphorescence properties of arylboronic esters are remarkable in light of the general notion that phosphorescent organic molecules require heavy atoms and/or carbonyl groups for the efficient generation of a triplet excited state. Theoretical calculations on phenylboronic acid pinacol ester indicated that this molecule undergoes an out-of-plane distortion at the (pinacol)B-Cipso moiety in the T1 excited state, which is responsible for its phosphorescence. A compound survey with 19 arylboron compounds suggested that the phosphorescence properties might be determined by solid-state molecular packing rather than by the patterns and numbers of boron substituents on the aryl units. The present finding may update the general notion of phosphorescent organic molecules.


Pediatricians' focus of sight at pain assessment during a neonatal heel puncture.
To evaluate the focus of pediatricians' gaze during the heel prick of neonates. Prospective study in which pediatricians wearing eye tracker glasses evaluated neonatal pain before/after a heel prtick. Pediatricians scored the pain they perceived in the neonate in a verbal analogue numerical scale (0=no pain; 10=maximum pain). The outcomes measured were number and time of visual fixations in upper face, lower face, and hands, in two 10-second periods, before (pre) and after the puncture (post). These outcomes were compared between the periods, and according to pediatricians' pain perception: absent/mild (score: 0-5) and moderate/intense (score: 6-10). 24 pediatricians (31 years old, 92% female) evaluated 24 neonates. The median score attributed to neonatal pain during the heel prick was 7.0 (Interquartile range: 5-8). Compared to pre-, in the post-periods, more pediatricians fixed their gaze on the lower face (63 vs. 92%; p=0.036) and the number of visual fixations was greater on the lower face (2.0 vs. 5.0; p=0.018). There was no difference in the number and time of visual fixations according to the intensity of pain. At bedside, pediatricians change their focus of attention on the neonatal face after a painful procedure, focusing mainly on the lower part of the face.


Thin-film stack based integrated GRIN coupler with aberration-free focusing and super-high NA for efficient fiber-to-nanophotonic-chip coupling.
Nanophotonic chip coupling using an optical thin-film stack forming a micro graded-refractive-index (GRIN) lens with a super-high numerical aperture (NA) that is highly compact (tens of micron long) and can be directly integrated is presented. We explore the lens' integration on the surface of Silicon-On-Insulator (SOI) platform with an asymmetric GRIN profile. We show that to achieve high efficiency for optical coupling between an optical fiber and a nanophotonic waveguide with a sub-wavelength (lambda/n) beam size, conventional asymmetric parabolic GRIN profile is no longer adequate due to the super-high NA needed (>3.1), which results in severe spatial beam aberration at the focal plane. We present an efficient algorithm to computationally generate the ideal GRIN profile that is completely aberration free even at super-high NA, which improves the coupling efficiency from ~66% (parabolic case) to ~95%. A design example involving an optical thin-film stack using an improved dual-material approach is given. The performance of the thin-film stack is analyzed. This thin-film stack based GRIN lens is shown to be high in coupling efficiency, wavelength insensitive and compatible with standard thin-film process.


Novel multiresistance cfr plasmids in linezolid-resistant methicillin-resistant Staphylococcus epidermidis and vancomycin-resistant Enterococcus faecium (VRE) from a hospital outbreak: co-location of cfr and optrA in VRE.
Linezolid is often the drug of last resort to treat infections caused by Gram-positive cocci. Linezolid resistance can be mutational (23S rRNA or L-protein) or, less commonly, acquired [predominantly cfr, conferring resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins and streptogramin A compounds (PhLOPSA) or optrA, encoding oxazolidinone and phenicol resistance]. To investigate the clonality and genetic basis of linezolid resistance in 13 linezolid-resistant (LZDR) methicillin-resistant Staphylococcus epidermidis (MRSE) isolates recovered during a 2013/14 outbreak in an ICU in an Irish hospital and an LZDR vancomycin-resistant Enterococcus faecium (VRE) isolate from an LZDR-MRSE-positive patient. All isolates underwent PhLOPSA susceptibility testing, 23S rRNA sequencing, DNA microarray profiling and WGS. All isolates exhibited the PhLOPSA phenotype. The VRE harboured cfr and optrA on a novel 73 kb plasmid (pEF12-0805) also encoding erm(A), erm(B), lnu(B), lnu(E), aphA3 and aadE. One MRSE (M13/0451, from the same patient as the VRE) harboured cfr on a novel 8.5 kb plasmid (pSEM13-0451). The remaining 12 MRSE lacked cfr but exhibited linezolid resistance-associated mutations and were closely related to (1-52 SNPs) but distinct from M13/0451 (202-223 SNPs). Using WGS, novel and distinct cfr and cfr/optrA plasmids were identified in an MRSE and VRE isolate, respectively, as well as a cfr-negative LZDR-MRSE ICU outbreak and a distinct cfr-positive LZDR-MRSE from the same ICU. To our knowledge, this is the first report of cfr and optrA on a single VRE plasmid. Ongoing surveillance of linezolid resistance is essential to maintain its therapeutic efficacy.


The relationship between patient factors and the refusal of analgesics in adult Emergency Department patients with extremity injuries, a case-control study.
Background and aims Previous studies have described the phenomenon of oligo-analgesia in Emergency Department patients with traumatic injuries, despite the high prevalence of pain among these patients. Besides aspects related to health care staff, patient related factors might also play a role in suboptimal pain treatment, however evidence is scarce. Therefore, the objective of the current study was to evaluate patient related factors in adult patients refusing offered analgesics during an Emergency Department presentation with extremity injuries. Methods This was a case control study in the Emergency Department of a level 1 Trauma Centre. Cases were defined as adult patients with an extremity injury who declined analgesia, when offered. They were matched to controls from the same population, who accepted analgesics, in a 1:2 ratio using gender as matching variable. Primary outcome was difference in NRS pain score. Secondary outcomes were the relationship between categorical severity of pain scores and refusal of analgesics, exploration of independent predictors of analgesia refusal utilizing multivariate logistic regression and the evaluation of eight beliefs among patients who refuse analgesics. Results Between August 1st and 31st 2016, a total of 253 patients were eligible for inclusion of whom 55 declined analgesic treatment. They were included as cases and matched to 110 controls. Difference in median NRS pain score was significant between the groups: 5.0 (IQR 3.0-8.0) vs. 8.0 (IQR 6.0-9.0), respectively (p < 0.01). Nearly 20% of patients with severe pain declined analgesics, compared to 41% with moderate and 69% with mild pain (p < 0.01). The NRS pain score was the only independent predictor of refusal of analgesic treatment with a mean Odds Ratio of 0.67 (95%-CI 0.54-0.83). Most common patients' beliefs were that pain medication should be used in extreme pain only, fear of decreasing the doctor's ability to judge the injury and fear of addiction to analgesics. Conclusions Pain severity is the single independent predictor of refusal of analgesia, however the following patient beliefs are important as well: pain medication should be used in extreme pain only; fear of decreasing the doctor's ability to judge the injury and the fear of becoming addicted to pain medication. Implications In case patients refuse offered analgesics, the health care provider should actively address patient beliefs that might exist and lead to suboptimal pain treatment.


Examining the diagnostic value of the mnemonic discrimination task for classification of cognitive status and amyloid-beta burden.
Alzheimer's disease (AD) is the most common type of dementia, characterized by early memory impairments and gradual worsening of daily functions. AD-related pathology, such as amyloid-beta (Aβ) plaques, begins to accumulate many years before the onset of clinical symptoms. Predicting risk for AD via related pathology is critical as the preclinical stage could serve as a therapeutic time window, allowing for early management of the disease and reducing health and economic costs. Current methods for detecting AD pathology, however, are often expensive and invasive, limiting wide and easy access to a clinical setting. A non-invasive, cost-efficient platform, such as computerized cognitive tests, could be potentially useful to identify at-risk individuals as early as possible. In this study, we examined the diagnostic value of an episodic memory task, the mnemonic discrimination task (MDT), for predicting risk of cognitive impairment or Aβ burden. We constructed a random forest classification algorithm, utilizing MDT performance metrics and various neuropsychological test scores as input features, and assessed model performance using area under the curve (AUC). Models based on MDT performance metrics achieved classification results with an AUC of 0.83 for cognitive status and an AUC of 0.64 for Aβ status. Our findings suggest that mnemonic discrimination function may be a useful predictor of progression to prodromal AD or increased risk of Aβ load, which could be a cost-efficient, noninvasive cognitive testing solution for potentially wide-scale assessment of AD pathological and cognitive risk.


The effect of vitamin D supplements on the severity of restless legs syndrome.
Clinical observation hinted improved symptoms of restless legs syndrome (RLS) after vitamin D supplements. Hence, the aim of this study is to evaluate the effect of vitamin D supplementation on the severity of RLS symptoms. Twelve adult subjects diagnosed with primary RLS and vitamin D deficiency were recruited. Patients with secondary RLS were excluded from this study. The complete cell count; serum levels of ferritin, iron, glycated hemoglobin, and vitamin D3 (25 (OH) vitamin D); and renal and bone profiles of the patients were assayed. Patients with vitamin D deficiency (<50 nmol/l) were treated with vitamin D3 supplements (high oral dose or intramuscular injection). The severity scores of RLS were reassessed after the vitamin D3 level was corrected to >50 nmol/l and compared with those before the administration of the supplements. The median pretreatment vitamin D level was 21.7 nmol/l (13.45-57.4), which improved to 61.8 nmol/l (42.58-95.9) (P = 0.002) with the treatment. The median RLS severity score improved significantly from 26 (15-35) at baseline to 10 (0-27) after correction of the vitamin D levels (P = 0.002). This study indicates that vitamin D supplementation improves the severity of RLS symptoms and advocates that vitamin D deficiency is conceivably associated with RLS.


Effect of intracoronary shunt on right ventricular function during off-pump grafting of dominant right coronary artery with poor collateral.
Although numerous studies have validated the efficacy of intracoronary shunt on reducing left ventricular dysfunction during off-pump coronary artery bypass surgery (OPCAB), there is lack of evidence supporting its role on right ventricular (RV) function during right coronary artery (RCA) revascularization. Therefore, we studied the effect of intracoronary shunt during grafting of dominant RCA without visible collateral supply on global RV function using thermodilution method. Forty patients scheduled for multivessel OPCAB with right dominant coronary circulation without collateral supply confirmed by angiography were randomized to RCA revascularization either with a shunt (n=20) or soft snare occlusion (n=20). RV ejection fraction (RVEF) was recorded at baseline, during RCA grafting, and 15 min after reperfusion. Corresponding RV stroke work index (RVSWI) was calculated. RVEF and RVSWI decreased significantly during RCA grafting and returned to baseline values after reperfusion in both groups without any significant differences between the groups. Intracoronary shunt did not exert any beneficial effect on global RV function during RCA grafting, even in the absence of visible collateral supply. Regarding the possibility of graft failure by intracoronary shunt-induced endothelial damage, routine use of intracoronary shunt during RCA grafting is not recommended in patients with preserved biventricular function.


The role of nutrition in the prevention of cognitive decline.
Dementia is a growing concern and underscores the urgent need for effective preventive measures targeting modifiable risk factors. Nutrition is a key player in the onset and progression of inflammation and cognitive decline. This review provides a comprehensive overview of the effects of different dietary patterns, vitamins and nutrients for preventing cognitive decline, mainly among healthy individuals and those with mild cognitive impairment. The Mediterranean diet, omega-3 long-chain polyunsaturated fatty acids and B vitamins are the most investigated, with evidence supporting protection against cognitive decline among older adults varying across studies. More recent interventions examined in this review, such as MIND Diet, are promising with positive results, but further research is needed to conclusively establish their efficacy. It is also crucial to consider complete lifestyle as physical activity for preventing cognitive decline. Definitive conclusions are difficult to draw. Future studies should adopt a comprehensive approach and focus on multinutrient strategies and whole diets.


Cdc42 coordinates proliferation, polarity, migration, and differentiation of small intestinal epithelial cells in mice.
Cdc42 is a Rho GTPase that regulates diverse cellular functions, including proliferation, differentiation, migration, and polarity. In the intestinal epithelium, a balance among these events maintains homeostasis. We used genetic techniques to investigate the role of Cdc42 in intestinal homeostasis and its mechanisms. We disrupted Cdc42 specifically in intestinal epithelial cells by creating Cdc42flox/flox-villin-Cre+ and Cdc42flox/flox-Rosa26-CreER+ mice. We collected intestinal and other tissues, and analyzed their cellular, molecular, morphologic, and physiologic features, compared with the respective heterozygous mice. In all mutant mice studied, the intestinal epithelium had gross hyperplasia, crypt enlargement, microvilli inclusion, and abnormal epithelial permeability. Cdc42 deficiency resulted in defective Paneth cell differentiation and localization without affecting the differentiation of other cell lineages. In mutant intestinal crypts, proliferating stem and progenitor cells increased, compared with control mice, resulting in increased crypt depth. Cdc42 deficiency increased migration of stem and progenitor cells along the villi, caused a mild defect in the apical junction orientation, and impaired intestinal epithelium polarity, which can contribute to the observed defective intestinal permeability. The intestinal epithelium of the Cdc42flox/flox-villin-Cre+ and Cdc42flox/flox-Rosa26-CreER+ mice appeared similar to that of patients with microvillus inclusion disease. In the digestive track, loss of Cdc42 also resulted in crypt hyperplasia in the colon, but not the stomach. Cdc42 regulates proliferation, polarity, migration, and differentiation of intestinal epithelial cells in mice and maintains intestine epithelial barrier and homeostasis. Defects in Cdc42 signaling could be associated with microvillus inclusion disease.


[The effect of point amino acid substitutions on T4 phage lysozyme stability. II. Transition of a protein molecule to the "molten globule" state with replacements Asp10---His, Asn101---Asp, Arg148---Ser].
The amino acid replacements (Asp10-->His, Asn101-->Asp, Arg148-->Ser) in the T4 phage lysozyme were obtained by site directed mutagenesis and the plasmid for mutant protein expression was constructed. At acid pH (pH 2.7) the mutant is in the conformational state with properties of the molten globule (Ptitsyn, 1992): 1) the mutant protein molecule is essentially compact, 2) its circular dichroism (CD) spectrum in the near ultra violet (UV) region is drastically reduced in intensity as compared with the wild type protein spectrum, 3) the CD spectrum in the far UV region indicates the presence of a pronounced secondary structure in the mutant, 4) unlike the wild type protein, the mutant protein can bind the hydrophobic fluorescent probe ANS.


Kinetics of lactose and rhamnose oxidation over supported metal catalysts.
Several mono- and bimetallic Pd, Pt, Rh and Ru supported on alumina and active carbon catalysts were characterized by CO chemisorption, nitrogen adsorption, XPS and XRD and acidity titrations were performed for active carbon supported catalysts. These catalysts were tested in oxidation of two sugars, namely lactose and rhamnose, at 60 °C and at 70 °C under slightly alkaline conditions (pH 8) with molecular oxygen. The results revealed that there is an optimum metal particle size in a range of 3-10 nm giving the highest initial TOFs for both oxidations. Furthermore, the catalytic activities and conversions were related to other catalyst properties, such as the type and amount of promoters and the presence of different phases. In situ catalyst potential measurements revealed that there is an inverse correlation between the increase of catalyst potential as a function of sugar conversion and the catalyst activity after prolonged reaction times. This method is a valuable tool for in situ characterization of catalysts correlating well with their activities.


Could erectile dysfunction be a side effect of CGRP inhibition? A case report.
Recently, antimigraine drugs targeting the calcitonin gene-related peptide pathway have been approved for clinical use as preventive migraine medication. We present a case of a 54-year-old male migraine patient, who reported erectile dysfunction as a possible side effect of treatment with galcanezumab, a monoclonal antibody targeting calcitonin gene-related peptide. His potency recovered after treatment discontinuation. As calcitonin gene-related peptide is involved in mammalian penile erection, erectile dysfunction is a conceivable side effect associated with calcitonin gene-related peptide inhibition. Postmarketing surveillance will elucidate the actual incidence of erectile dysfunction in patients using these new antimigraine drugs, and determine whether a causal relationship between calcitonin gene-related peptide inhibition and erectile dysfunction exists. This would be relevant not only because of the direct sexual consequences of erectile dysfunction, but also considering the potential cardiovascular consequences of calcitonin gene-related peptide (receptor) blockade and the association of both migraine and erectile dysfunction with cardiovascular disease. Erectile dysfunction might be an overlooked, but reversible side effect in male migraine patients using monoclonal antibodies that inhibit the calcitonin gene-related peptide pathway, including galcanezumab. This paper may raise clinical awareness and suggest that this potential side effect needs to be studied further.


William Henry Bragg in Adelaide: beginning research at a colonial locality.
This essay presents an account of W. H. Bragg's earliest research program in Australia during the years 1904-1907: a study of the behavior of alpha particles from radioactive decay. It is suggested that problems associated with distance and isolation played a pivotal role in Bragg's thinking and acting during this period and that his use of two "advocates," Ernest Rutherford and Frederick Soddy, was essential to the success of the program. It is further argued that this account supports a substantial amendment of the center-periphery model of colonial science to embrace a much closer attention to place and locality; that is, it supports a polycentric model (in which the center might still be prominent).


Carbon-nanotube-embedded hydrogel sheets for engineering cardiac constructs and bioactuators.
We engineered functional cardiac patches by seeding neonatal rat cardiomyocytes onto carbon nanotube (CNT)-incorporated photo-cross-linkable gelatin methacrylate (GelMA) hydrogels. The resulting cardiac constructs showed excellent mechanical integrity and advanced electrophysiological functions. Specifically, myocardial tissues cultured on 50 μm thick CNT-GelMA showed 3 times higher spontaneous synchronous beating rates and 85% lower excitation threshold, compared to those cultured on pristine GelMA hydrogels. Our results indicate that the electrically conductive and nanofibrous networks formed by CNTs within a porous gelatin framework are the key characteristics of CNT-GelMA leading to improved cardiac cell adhesion, organization, and cell-cell coupling. Centimeter-scale patches were released from glass substrates to form 3D biohybrid actuators, which showed controllable linear cyclic contraction/extension, pumping, and swimming actuations. In addition, we demonstrate for the first time that cardiac tissues cultured on CNT-GelMA resist damage by a model cardiac inhibitor as well as a cytotoxic compound. Therefore, incorporation of CNTs into gelatin, and potentially other biomaterials, could be useful in creating multifunctional cardiac scaffolds for both therapeutic purposes and in vitro studies. These hybrid materials could also be used for neuron and other muscle cells to create tissue constructs with improved organization, electroactivity, and mechanical integrity.


Maximum strength-power-performance relationships in collegiate throwers.
Presently the degree to which peak force influences power production or explosive performance such as strength training movements or throwing (shot-put and weight-throw) is unclear. This study describes the relationships between a measure of maximum strength, isometric peak force (IPF), dynamic peak force (PF), peak power (PP), the 1-repetition movement power snatch (SN), and throwing ability over an 8-week training period. Five male and 6 female (n = 11) well-trained collegiate throwers participated. PF was measured using an AMTI force plate; PP was measured using an infrared-ultrasonic tracking device (V-Scope, Lipman Electronics). Clean pulls from the midthigh position were assessed isometrically and dynamically at a constant load, 30% and 60% of IPF. Specific explosive strength was evaluated using an SN and using the shot-put (SP) and weight-throw (WGT) measured under meet conditions. Variables (PF, PP, SN) were assessed 3 times at 0 weeks, 4 weeks, and 8 weeks. Each measurement period preceded a field meet by 3 days. Peak force, peak rate of force development, and PP increased over the 8 weeks. Correlation coefficients (r) indicate that IPF is strongly related to dynamic PF and PP 30%, 60% of the IPF. Furthermore, strong correlations were found for the SN and the distance for the SP and WGT, and these relationships tended to increase over time. Results suggest that maximum strength (i.e., IPF) is strongly associated with dynamic PF. In addition, maximum strength is strongly associated with PP even at relatively light loads such as those associated with sport-specific dynamic explosiveness (i.e., SN, SP, WGT).


T-even bacteriophage-tolerant mutants of Escherichia coli B. I. Isolation and preliminary characterization.
A general procedure is described for isolation of T-even phage-tolerant mutants of Escherichia coli. Two such mutants of E. coli B have been examined in some detail. These mutants adsorb T-even phages but are unable to release viable progeny. Under certain conditions, viability of the cells is completely unaffected by phage infection in one mutant, and there is but a slight decrease in colony-forming ability in the other. Phage deoxyribonucleic acid (DNA) is injected into these cells, as shown by the formation of phage-specific enzymes, but it is not degraded to acid-soluble material. Some phage DNA replication occurs in both strains. The mutants are both more resistant to ultraviolet light than is the parent strain.


Soybean flour induces a greater increase of the antioxidant defenses in rats fed with a normocaloric diet compared with a hypercaloric diet.
Soybeans, due to their antioxidant properties, present beneficial health effects. The objective was to evaluate if replacing casein with soy flour, modifies antioxidant defenses in rat liver, compared to animals that continued being fed with casein based diets (normocaloric and hypercaloric). Four groups of rats were used: CC (control casein), CS (control soy), HC (hypercaloric casein) and HS (hypercaloric soy). Malondialdehyde, in serum and liver, did not present differences. In liver, when comparing CS vs. CC: increased superoxide dismutase 1 (P < 0.001), catalase (P < 0.01) and glutathione reductase (P < 0.05) activities, the total glutathione (P < 0.001) and reduced glutathione (P < 0.05) content and decreased oxidized glutathione content (P < 0.05). In HS vs. HC: increased carbonyl groups (P < 0.01) and superoxide dismutase 1 activity (P < 0.05), and decreased glutathione peroxidase activity (P < 0.01), total glutathione (P < 0.05) and oxidized glutathione content (P < 0.001). In HS vs. CS: decreased glutathione reductase activity (P < 0.01), total glutathione (P < 0.001) and reduced glutathione (P < 0.01) content, and increased oxidized glutathione content (P < 0.05). Replacing casein by soybean flour improves antioxidant defenses, mainly in normocaloric diets.


Coronary cyclic flow variations "precondition" ischemic myocardium.
Repeated brief episodes of myocardial ischemia performed by mechanical clamping of a coronary artery "precondition" the heart and reduce infarct size after a subsequent sustained ischemia. It is not known, however, whether spontaneous episodes of transient ischemia caused by formation of platelet thrombi, which may occur in unstable angina, have a similar cardioprotective effect. Therefore, our objective was to determine whether brief spontaneous thrombotic episodes of ischemia/reperfusion could limit infarct size and preserve contractile function following 60 minutes (protocol 1) or 90 minutes (protocol 2) of sustained ischemia and 4-4.5 hours of reperfusion in the canine model. Before the sustained coronary occlusion, dogs underwent a 30-minute "treatment" period consisting of: no intervention (control group), four repeated episodes of 3-minute mechanical occlusion plus 5-minute reperfusion (preconditioned group), or coronary artery stenosis and endothelial injury, resulting in a mean of four spontaneous episodes of cyclic flow variations (CFV group) caused by formation and dislodgment of platelet thrombi. In protocol 1 (60-minute sustained ischemia plus 4.5-hour reperfusion), infarct size was significantly smaller in both the preconditioned and CFV groups compared with controls (3.5 +/- 1.4%,* 3.4 +/- 2.1%,* and 9.9 +/- 2.7% of the myocardium at risk, respectively; *p less than 0.05 versus control). In contrast, neither preconditioning nor CFV preserved contractile function: Segment shortening during sustained occlusion was equally depressed at -15% to -20% of baseline values among the three groups and equally stunned at +12% to +18% of baseline during the 4.5 hours of reflow. In protocol 2 (90-minute sustained ischemia plus 4-hour reperfusion), only CFV continued to exert a cardioprotective effect: Infarct size averaged 15.0 +/- 4.1%, 7.4 +/- 2.5%,* and 16.5 +/- 4.4% of the region at risk in the preconditioned, CFV, and control groups, respectively (*p less than 0.05 versus control). Contractile function, however, was similar among all three groups both during 90 minutes of sustained occlusion and throughout 4 hours of reperfusion. We therefore conclude that repeated coronary thrombus formation preconditions the ischemic myocardium: In fact, in contrast to mechanical preconditioning, cardioprotection provided by CFV persisted following 90 minutes of sustained coronary occlusion. However, preconditioning by thrombotic or mechanical occlusion neither preserved myocardial contractile function during sustained coronary occlusion nor prevented stunning after reperfusion. These data raise the possibility that clinical episodes of unstable angina prior to acute myocardial infarction may precondition the ischemic myocardium.


Development of a hierarchical double application of crisp cluster validity indices: a proof-of-concept study for automated FTIR spectral histology.
Fourier-transform infrared (FTIR) spectral imaging is currently used as a non-destructive and label-free method for analyzing biological specimens. However, to highlight the different tissue regions, unsupervised clustering methods are commonly used leading to a subjective choice of the number of clusters. Here, we develop a hierarchical double application of 9 selected crisp cluster validity indices (CCVIs) using K-Means clustering. This approach when tested first on an artificial dataset showed that the indices Pakhira-Bandyopadhyay-Maulik (PBM) and Sym-Index (SI) perfectly estimated the expected 9 sub-clusters. Then, the concept was applied to a real dataset consisting of FTIR spectral images of normal human colon tissue samples originating from 5 patients. PBM and SI were revealed to be the most efficient indices that correctly identified the different colon histological components including crypts, lamina propria, muscularis mucosae, submucosa, and lymphoid aggregates. In conclusion, these results strongly suggest that the hierarchical double CCVI application is a promising method for automated and informative spectral histology.


A 42-year-old man considering whether to drink alcohol for his health.
Alcohol consumption is widespread and, in excess, a leading cause of morbidity and mortality worldwide. At the same time, a consistent body of observational evidence has found that individuals who consume alcohol within recommended limits have a lower risk of coronary heart disease than do abstainers. These observations have led many to consider small amounts of alcohol as a cardioprotective strategy. Mr Q, a 42-year-old man who has consistently sought ways to preserve his health, is at a crossroads in his discussions with his physicians about the health effects of his regular, limited alcohol intake. The discussion reviews the epidemiology of drinking in the United States, the established effects of moderate alcohol intake on key pathophysiological biomarkers and pathways, the strengths and limitations of observational evidence linking alcohol intake to lower risk of coronary heart disease, other chronic diseases linked to moderate alcohol intake, and a framework in which Mr Q can discuss the potential risks and benefits of alcohol consumption with his physicians.


[Development and performance test of the environment scale of unintentional injury in the home for children aged 0-6 years old in urban area of China].
Objective: To develop the environment scale of unintentional injury in the home for children aged 0-6 years living in urban area of China, and test its validity and reliability. Methods: The content of the environment scale was established through the literature review, expert consultation and pilot study. A total of 1 104 children aged 0-6 years in urban area of Changsha were enrolled in this study by using a multi-stage stratified cluster random sampling method. The questionnaire was used to collect the basic information of children, the incidence of unintentional injury and the status of home environment. The reliability of the scale was tested by using Cronbach's α coefficient and split-half reliability coefficient. The content validity and construct validity were tested by using Pearson correlation analysis and factor analysis. All children were divided into two groups according to the incidence of unintentional injury in the home and the discrimination validity of the scale was tested by using t-test. Results: The scale had 54 items in 6 dimensions. The number of eligible questionnaires was 1 074, including 554 (51.6%) from boys and 519 (48.3%) from children under 3 years old. The incidence rate of unintentional injury and in-home injury was 18.34% (197 children) and 10.71% (115 children). The internal consistency reliability (Cronbach's α) coefficient for the scale was 0.87 and the split-efficacy reliability coefficient was 0.82, both meeting the standard of reliability above 0.70. The Pearson correlation coefficient between each dimension and the whole scale ranged from 0.53 to 0.84 (all P values <0.001). The common factor cumulative variance contribution rate of the scale was 58.34%. There were 54 items with factor loadings greater than 0.30. The root mean square error of approximation, comparative fit index and goodness-of-fit index were 0.07, 0.61 and 0.71, respectively. The score of scale in children with injury was significantly higher than that in children without injury (P=0.022). Conclusion: The validity and reliability of the environment scale for unintentional injury in the home for children aged 0-6 years old in the urban area of China are good.


Physical and biological properties of cationic triesters of phosphatidylcholine.
The properties of a new class of phospholipids, alkyl phosphocholine triesters, are described. These compounds were prepared from phosphatidylcholines through substitution of the phosphate oxygen by reaction with alkyl trifluoromethylsulfonates. Their unusual behavior is ascribed to their net positive charge and absence of intermolecular hydrogen bonding. The O-ethyl, unsaturated derivatives hydrated to generate large, unilamellar liposomes. The phase transition temperature of the saturated derivatives is very similar to that of the precursor phosphatidylcholine and quite insensitive to ionic strength. The dissociation of single molecules from bilayers is unusually facile, as revealed by the surface activity of aqueous liposome dispersions. Vesicles of cationic phospholipids fused with vesicles of anionic lipids. Liquid crystalline cationic phospholipids such as 1, 2-dioleoyl-sn-glycero-3-ethylphosphocholine triflate formed normal lipid bilayers in aqueous phases that interacted with short, linear DNA and supercoiled plasmid DNA to form a sandwich-structured complex in which bilayers were separated by strands of DNA. DNA in a 1:1 (mol) complex with cationic lipid was shielded from the aqueous phase, but was released by neutralizing the cationic charge with anionic lipid. DNA-lipid complexes transfected DNA into cells very effectively. Transfection efficiency depended upon the form of the lipid dispersion used to generate DNA-lipid complexes; in the case of the O-ethyl derivative described here, large vesicle preparations in the liquid crystalline phase were most effective.


Relationship among leaf (Puccinia recondita Roberge ex Desmaz f. sp. tritici) and yellow (Puccinia striiformis Westendorp. f. sp. tritici) rust resistance and some agro-morphologic traits in wheat hybrids at seedling stage.
This research was carried out to determine if dominant morphological traits can be use instead of the rust resistance tests as marker characters for some agro-morphologic traits both leaf (Puccinia recondita Roberge ex Desmaz. f. sp. tritici.) and yellow rust (Puccinia striiformis Westendorp f. sp. tritici) disease. For this, 13 wheat parent (4 are T. durum Desf. and 9 are T. aestivum L.) were used and three main agro-morphologic traits (Namely, Leaf Colour (LC) (Dark and light green, Dg and Lg, relatively); Auricle Colour (AC) (White and Red, Wh and Re, relatively) and Leaf Waxiness (LW) (Waxy and Non waxy, Wx and Nw, relatively) were investigated at the seedling stage. They were found as dominant and concluded that investigated traits could be used as a morphological marker character for the leaf and yellow rust disease resistance tests under greenhouse conditions without doing complex and risky rust tests. And determined that, these traits may be use effectively without doing the complex rust tests in the limited populations or for the pre-selections. Doing with this, it will be bring a great accuracy, successful, correction and speed to the rust disease studies and provides important and valuable information for the plant breeders and pathologists. In addition, knowing of the resistance type (genetic mechanism etc.) in wheat facilitates it will be make to find out the suit and most appropriate breeding and selection methodology/methodologies.


Mesenchymal stem cells and cancer-associated fibroblasts as a therapeutic strategy for breast cancer.
Breast cancer is the most common type of cancer and the leading cause of death among women. Recent evidence suggests that mesenchymal stromal/stem cells and cancer-associated fibroblasts (CAFs) have an essential role in cancer progression, invasion and therapy resistance. Therefore, they are considered as highly promising future therapeutic targets against breast cancer. The intrinsic tumour tropism and immunomodulatory capacities of mesenchymal stromal/stem cells are of special relevance for developing mesenchymal stromal/stem cells-based anti-tumour therapies that suppress primary tumour growth and metastasis. In addition, the utilization of therapies that target the stromal components of the tumour microenvironment in combination with standard drugs is an innovative tool that could improve patients' response to therapies and their survival. In this review, we discuss the currently available information regarding the possible use of mesenchymal stromal/stem cells-derived anti-tumour therapies, as well as the utilization of therapies that target CAFs in breast cancer microenvironment. Finally, these data can serve as a guide map for future research in this field, ultimately aiding the effective transition of these results into the clinic.


In complete SCI patients, long-term functional electrical stimulation of permanent denervated muscles increases epidermis thickness.
Our studies have shown that atrophic Quadriceps muscles from spinal cord injury patients suffering with permanent denervation-induced atrophy and degeneration of muscle fibers, were almost completely rescued to normal size after two years of home-based functional electrical stimulation (h-bFES). Because we used surface electrodes to stimulate the muscle, we wanted to know how the skin was affected by the treatments. Here, we report preliminary data from histological morphometry of Hematoxylin-Eosin-stained paraffin-embedded skin sections harvested from the legs of three SCI patients before and after two years of h-bFES. Despite the heterogeneity of gender and time from SCI, comparing pre vs post h-bFES in these three SCI patients, the data show that: (1) In one subject skin biopsies from both the right and left leg experienced a statistically significant increase in thickness of the epidermis after two years of H-bFES; (2) In the other two subjects, one leg showed a significant increase in epidermis thickness, while in the other leg there was either small positive or negative non-significant changes in epidermis thickness; and (3) more importantly, comparison of grouped data from the three subjects shows that there was a significant 28% increase in the thickness of the epidermis in response to two years of h-bFES rehabilitation. In conclusion, the three educational cases show a long-term positive modulation of epidermis thickness after two years of h-bFES, thus extending to skin the positive results previously demonstrated in skeletal muscle, specifically, a substantial recovery of muscle mass and contractile function after long-term h-bFES.


Psychosocial Factors Mediating the Effect of the CHoBI7 Mobile Health Program on Handwashing With Soap and Household Stored Water Quality: A Randomized Controlled Trial.
Household members of diarrhea patients are at higher risk of developing diarrheal diseases (>100 times for cholera) than the general population during the 7 days after the diarrhea patient is admitted at a health facility. There is growing evidence demonstrating that theory-driven water, sanitation, and hygiene (WASH) interventions are likely to yield greater behavior change than those based on health education alone. The Cholera Hospital-Based Intervention for 7-Days (CHoBI7) mobile health (mHealth) program is a theory-driven WASH intervention initially delivered to a diarrhea patient by a health promoter during a health facility visit and reinforced through weekly voice and text messages. In the recent randomized controlled trial (RCT) of the CHoBI7-mHealth program in Bangladesh, this intervention significantly reduced diarrheal disease and stunting, and increased handwashing with soap and stored drinking water quality over the 12-month program period. The aim of this study was to assess the underlying mechanism of change of this intervention. Handwashing with soap was measured by 5-hour structured observation. Stored drinking water quality was assessed by the presence of Escherichia coli during unannounced spot checks. Psychosocial factors were measured among 1,468 participants in the CHoBI7-mHealth RCT. Perceived susceptibility, response efficacy, self-efficacy, dirt reactivity, and diarrhea knowledge were mediators of the CHoBI7-mHealth program's effect on stored drinking water quality at the 1-week follow-up. Self-efficacy, response efficacy, and diarrhea knowledge were mediators of the intervention's effect on handwashing with soap habit maintenance and stored drinking water quality at the 12-month follow-up. This study demonstrates how theory-driven approaches for intervention design can facilitate WASH behavior change.


Hb Regina or alpha 2 beta 2 96(FG3)Leu----Val: a high oxygen affinity variant discovered by cation-exchange HPLC.
Results are reported of studies of the hemoglobin from one member of a Canadian family with a mild erythrocytosis. This variant, which accounted for about 40% of the hemoglobin, could be separated from Hb A and Hb A2 by cation-exchange chromatography. Micro methodology allowed the characterization of a Leu----Val replacement at position beta 96(FG3). Hb Regina has an increased oxygen affinity, which adequately explains the hematological observations.


Purification and physiological characterization of neurotoxins from venoms of the scorpions centruroides sculpturatus and leiurus quinquestriatus.
Several different toxins having specific effects on the kinetics of sodium channels have been isolated from the venoms of two scorpions. A combination of two steps of ion-exchange chromatography has been used to purify these toxins, whose sizes and purities have been assayed by gel filtration, urea/sodium dodecyl sulfate/polyacrylamide gel electrophoresis, and isoelectric focusing. The actions of the toxins and their relative potencies have been determined by studying the modifications they produce in action potential shape, using the sucrose-gap method, and in ionic current kinetics, measured under voltage-clamp, both assays performed on myelinated axons of frogs and toads. The venom of Leiurus quinquestriatus scorpions yielded two active neurotoxins; the major neurotoxin has a mass of approximately 7000 daltons. This major toxin affected the sodium channel inactivation process exclusively, slowing the rates of inactivation as well as preventing complete inactivation from occurring in some of the channels. Such slowed and incomplete sodium inactivation resulted in action potentials that were prolonged, from their usual duration of 5-8 msec to hundreds of milliseconds or even seconds. Five toxins were isolated from the venom of Centruroides sculpturatus Ewing scorpions, all of which also had masses of approximately 7000-7500 daltons. Four of these toxins acted primarily on the activation process of sodium channels, producing a novel increase in sodium permeability upon repolarization of the nerve membrane following a depolarizing pulse, as previously described for the crude venom [Cahalan, M. D. J. Physiol. (Lond.) 244:511-534 (1975)]. These toxins also caused repetitive firing of action potentials in single axons in response to one stimulating pulse, as well as spontaneous impulse firing. A fifth neurotoxin from C. sculpturatus venom had effects similar to those of the L. quinquestriatus toxins, slowing and preventing complete sodium inactivation. The effect of this toxin was slowly removed during external perfusion by Ringer's solution.


Associations of parenting dimensions and styles with externalizing problems of children and adolescents: An updated meta-analysis.
The present meta-analysis integrates research from 1,435 studies on associations of parenting dimensions and styles with externalizing symptoms in children and adolescents. Parental warmth, behavioral control, autonomy granting, and an authoritative parenting style showed very small to small negative concurrent and longitudinal associations with externalizing problems. In contrast, harsh control, psychological control, authoritarian, permissive, and neglectful parenting were associated with higher levels of externalizing problems. The strongest associations were observed for harsh control and psychological control. Parental warmth, behavioral control, harsh control, psychological control, autonomy granting, authoritative, and permissive parenting predicted change in externalizing problems over time, with associations of externalizing problems with warmth, behavioral control, harsh control, psychological control, and authoritative parenting being bidirectional. Moderating effects of sampling, child's age, form of externalizing problems, rater of parenting and externalizing problems, quality of measures, and publication status were identified. Implications for future research and practice are discussed. (PsycINFO Database Record


Local therapy to distant metastatic sites in stage IV rhabdomyosarcoma.
To determine the impact of surgery and/or radiation therapy on distant metastatic sites (DMS) in children with stage IV rhabdomyosarcoma (RMS). A retrospective chart review was conducted on all patients with stage IV RMS at Texas Children's Hospital from 1992 to 2012. Data analyzed included age, gender, primary site, histologic subtype, number and sites of metastases, treatment including local therapy to DMS, and Oberlin score. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 20% and 25%. The 5-year PFS in patients receiving local therapy to all DMS (n = 16) and to less than all DMS (n = 19) was 31.3% versus 0% (P = 0.002), whereas the 5-year OS was 37.3% versus 0% (P < 0.001), respectively. The 5-year PFS in patients with isolated lung metastasis versus other types of metastasis was 29% versus 7% (P = n.s.), whereas the 5-year OS was 43% versus 10% (P = 0.01). The 5-year pulmonary local control was improved by the use of whole lung irradiation (WLI; 56% vs. 10%, P = 0.03). Local treatment to all metastatic sites was associated with improved PFS and OS at 5 years. The use of WLI improved pulmonary control in patients with lung metastasis. We recommend an aggressive approach including local therapy to DMS in children with stage IV RMS.


A population-based seroepidemiologic study of human granulocytic ehrlichiosis and Lyme borreliosis on the west coast of Sweden.
Ehrlichioses are emerging infections in the United States. Human granulocytic ehrlichiosis (HGE) and Lyme borreliosis (LB) are acquired after Ixodes ricinus-complex tick bites. An ongoing seroepidemiologic study of the 185 of the 356 permanent residents of the Koster Islands in Sweden was expanded to include ehrlichioses. Ehrlichial antibodies were measured by IFA using Ehrlichia equi and Ehrlichia chaffeensis. Borrelia burgdorferi IgG ELISA-seropositive subjects were confirmed by Western blot. E. equi and E. chaffeensis antibodies (titer > or = 80) were found in 21 (11.4%) and 2 (1.1%) of 185 samples, respectively. Antibodies to B. burgdorferi were found in 25 (13.5%) of 185. Six persons were seropositive for both HGE and LB. Among data from questionnaires, clinical symptoms, antibiotic treatments, or tick bites were not more frequent in E. equi- or B. burgdorferi-seropositive than -seronegative persons. The seroprevalence of HGE was similar to that of Lyme borreliosis. Prospective studies of European HGE are needed.


The Effect of pT-TMS on Beta Rhythm in Children with Autism Disorder. A MEG Study.
We investigated the beta rhythm in 10 children with autism disorders (six boys and four girls) aged 5-12 (mean± SD: 8.3± 2.1) before and after the application of pico Tesla transcranial magnetic stimulation (pT-TMS) using magnetoencephalography (MEG). The MEG was car-ried out in a magnetically shielded room with a whole-head 122-channel gradiometer. After applying pT-TMS, we observed a beta rhythm increase towards the frequency range of 18-26 Hz in seven out of 10 patients (70%). We created a score that rated the level of improvement for each patient: 1=some change; 2=minor change; and 3=major change. All patients had an improvement in their clinical symptoms after the application of pT-TMS. There was a correlation between the clinical score and the increase of channels in the frequency range 18-26 Hz after pT-TMS. We concluded that the application of pT-TMS affected the beta rhythm in children with autism disorder. Therefore, more studies need to be further conducted.


A newly described activity of guinea pig IgG1 antibodies: transfer of cutaneous basophil reactions.
Hapten-specific delayed time course skin reactions containing predominant accumulations of basophils and eosinophils were elicited in newborn guinea pigs after i.v. transfer of small amounts of oxazolone immune serum. The immune serum was fractionated by column chromatography procedures, and the fractions were examined for their ability in transferring this form of cutaneous basophil hypersensitivity (CBH). Only the 7S IgG-containing peak from Sephadex G-200 columns, and only the IgG1-containing fractions from DEAE columns, transferred CBH. An affinity column of bound oxazolone removed the activity from immune serum, and it could be recovered from the column by eluting with soluble oxazolone. About 35 microgram of purified IgG1 anti-oxazolone antibody could systemically transfer CBH reactivity. An immunoadsorbant column of anti-IgG1 removed this activity, but a column of anti-IgG2 did not. None of the procedures were able to separate activity in transferring CBH from passive cutaneous anaphylactic (PCA) activity classically associated with guinea pig IgG1 antibody. IgG1 from 8-day immune and 31-day hyperimmune donors were both effective. The average association constant of 8-day antibody was 8 X 10(-4) M-1. Transfer of cutaneous basophil reactions can be mediated by low affinity serum 7S IgG1 antibody.


Exocytosis of Progeny Infectious Varicella-Zoster Virus Particles via a Mannose-6-Phosphate Receptor Pathway without Xenophagy following Secondary Envelopment.
The literature on the egress of different herpesviruses after secondary envelopment is contradictory. In this report, we investigated varicella-zoster virus (VZV) egress in a cell line from a child with Pompe disease, a glycogen storage disease caused by a defect in the enzyme required for glycogen digestion. In Pompe cells, both the late autophagy pathway and the mannose-6-phosphate receptor (M6PR) pathway are interrupted. We have postulated that intact autophagic flux is required for higher recoveries of VZV infectivity. To test that hypothesis, we infected Pompe cells and then assessed the VZV infectious cycle. We discovered that the infectious cycle in Pompe cells was remarkably different from that of either fibroblasts or melanoma cells. No large late endosomes filled with VZV particles were observed in Pompe cells; only individual viral particles in small vacuoles were seen. The distribution of the M6PR pathway (trans-Golgi network to late endosomes) was constrained in infected Pompe cells. When cells were analyzed with two different anti-M6PR antibodies, extensive colocalization of the major VZV glycoprotein gE (known to contain M6P residues) and the M6P receptor (M6PR) was documented in the viral highways at the surfaces of non-Pompe cells after maximum-intensity projection of confocal z-stacks, but neither gE nor the M6PR was seen in abundance at the surfaces of infected Pompe cells. Taken together, our results suggested that (i) Pompe cells lack a VZV trafficking pathway within M6PR-positive large endosomes and (ii) most infectious VZV particles in conventional cell substrates are transported via large M6PR-positive vacuoles without degradative xenophagy to the plasma membrane.IMPORTANCE The long-term goal of this research has been to determine why VZV, when grown in cultured cells, invariably is more cell associated and has a lower titer than other alphaherpesviruses, such as herpes simplex virus 1 (HSV1) or pseudorabies virus (PRV). Data from both HSV1 and PRV laboratories have identified a Rab6 secretory pathway for the transport of single enveloped viral particles from the trans-Golgi network within small vacuoles to the plasma membrane. In contrast, after secondary envelopment in fibroblasts or melanoma cells, multiple infectious VZV particles accumulated within large M6PR-positive late endosomes that were not degraded en route to the plasma membrane. We propose that this M6PR pathway is most utilized in VZV infection and least utilized in HSV1 infection, with PRV's usage being closer to HSV1's usage. Supportive data from other VZV, PRV, and HSV1 laboratories about evidence for two egress pathways are included.


Micropapillary bladder cancer: a review of Léon Bérard Cancer Center experience.
Micropapillary bladder cancer is a rare and aggressive variant of urothelial carcinoma. A retrospective review of our experience in management of patients with muscle-invasive or metastatic micropapillary bladder cancer was performed to better define the behavior of this disease. We reviewed the records of the 11 patients with micropapillary bladder cancer who were evaluated and treated at Léon Bérard Cancer Center between 1994 and 2007, accounting for 1,2% of all urothelial tumors treated in this institution. Mean patients age was 60 years. The majority of patients (72%) were diagnosed after 2004. After a median follow-up of 31.7 months, median overall survival was 19 months. Two patients presented with stage II, one with stage III and eight with stage IV disease All 5 patients who had node positive metastases and treated with radical surgery and adjuvant chemotherapy relapsed and had a disease free survival of 9.6 months. Micropapillary bladder cancer is probably an underreported variant of urothelial carcinoma associated with poor prognosis. Adjuvant chemotherapy might have a questionable efficacy and the optimal treatment strategy is yet to be defined.


Health information exchange in the wild: the association between organizational capability and perceived utility of clinical event notifications in ambulatory and community care.
Event notifications are real-time, electronic, automatic alerts to providers of their patients' health care encounters at other facilities. Our objective was to examine the effects of organizational capability and related social/organizational issues upon users' perceptions of the impact of event notifications on quality, efficiency, and satisfaction. We surveyed representatives (n = 49) of 10 organizations subscribing to the Bronx Regional Health Information Organization's event notification services about organizational capabilities, notification information quality, perceived usage, perceived impact, and organizational and respondent characteristics. The response rate was 89%. Average item scores were used to create an individual domain summary score. The association between the impact of event notifications and organizational characteristics was modeled using random-intercept logistic regression models. Respondents estimated that organizations followed up on the majority (83%) of event notifications. Supportive organizational policies were associated with the perception that event notifications improved quality of care (odds ratio [OR] = 2.12; 95% CI, = 1.05, 4.45), efficiency (OR = 2.06; 95% CI = 1.00, 4.21), and patient satisfaction (OR = 2.56; 95% CI = 1.13, 5.81). Higher quality of event notification information was also associated with a perceived positive impact on quality of care (OR = 2.84; 95% CI = 1.31, 6.12), efficiency (OR = 3.04; 95% CI = 1.38, 6.69), and patient satisfaction (OR = 2.96; 95% CI = 1.25, 7.03). Health care organizations with appropriate processes, workflows, and staff may be better positioned to use event notifications. Additionally, information quality remains critical in users' assessments and perceptions.


Real-world clinical characteristics of post-essential thrombocythemia and post-polycythemia vera myelofibrosis.
There are few prospective studies on patients with post-essential thrombocythemia myelofibrosis (PET-MF) and post-polycythemia vera myelofibrosis (PPV-MF). Therefore, we conducted a nationwide longitudinal prospective survey to clarify the clinical characteristics of these diseases. A total of 197 PET-MF and 117 PPV-MF patients diagnosed between 2012 and 2021 were analyzed. The median age at diagnosis was 70.0 years for both diseases. The time from diagnosis of ET or PV to that of MF was 9.6 and 10.4 years, respectively, with no significant difference. Patients with PPV-MF had higher hemoglobin levels and white blood cell counts than those with PET-MF, whereas those with PET-MF had higher platelet counts than those with PPV-MF. Although splenomegaly was more frequent in patients with PPV-MF at diagnosis, there was no difference in the frequency of constitutional symptoms. Ruxolitinib was the most common treatment administered to 74.6% and 83.8% of patients with PET-MF and PPV-MF, respectively. Patients with PET-MF and PPV-MF had similar prognoses, with 3-year overall survival (OS) of 0.742 in PET-MF and 0.768 in PPV-MF patients. In both diseases, leukemic transformation was the leading cause of death, followed by infection. The 3-year OS for patients with PET/PPV-MF and primary MF diagnosed during the same period was 0.754 and 0.626, respectively, with no significant difference. This survey provides real-world clinical features and prognostic data on secondary myelofibrosis in the ruxolitinib era.


Does doctor-patient communication affect patient satisfaction with hospital care? Results of an analysis with a novel instrumental variable.
To determine the relationship between physicians' communication behaviors and patients' overall satisfaction with hospital care using a novel instrumental variable to address possible confounding of this association by patient attributes. Administrative records and postdischarge survey data were obtained from patients discharged from the General Medicine service at an urban tertiary-care academic hospital between July 1, 1997 and June 30, 2000. Administrative data included comorbidities, demographic data, and payer status. In the discharge survey, patients rated their attending physician on four communication behaviors, other aspects of their hospital stay, and their overall hospital care. The primary outcome was patients' ratings of their overall satisfaction with hospital care, and the primary independent variable was patients' ratings of their physicians' communication behaviors. To remove possible confounding of the association between patient ratings of physician communication and overall satisfaction by other patient-specific attributes, we created an instrumental variable (IV) in a two-stage linear regression. The IV was the mean of the communication ratings given to each physician by the other patients cared for by that physician. PRINCIPLE FINDINGS/CONCLUSIONS: Three thousand one hundred and twenty-three patients were included in the analysis. In the ordinary least squares regression, there was a significant positive relationship between overall satisfaction and overall ratings of attendings' communication behaviors, with an increase in overall satisfaction of 0.58 points on a 5-point scale for each 1-point increase in overall attendings' communication behaviors, p<.001. This relationship was maintained but attenuated in the IV regression, with a coefficient of 0.40, p=.046. Although we find that the relationship between patient communication ratings and overall patient satisfaction may be confounded by patient-level factors, we nevertheless continue to find evidence of a statistically significant and sizable relationship between physicians' communication behaviors and overall patient satisfaction after controlling for such factors.