Providing comprehensive contraceptive services in primary care at a rural Federally Qualified Health Center in the USA: adapting to patient need in a culturally conservative, rural environment.
In the USA, approximately 45% of pregnancies are unintended. Accessing quality contraceptives can be a barrier for some individuals, especially low-income, uninsured, minority or younger women. These problems are exacerbated in rural areas{1}. Integrating contraceptive services into primary care is an approach to ensure that sexually active women receive access to contraceptives. This study documented how one rural Federally Qualified Health Center (FQHC) adapted to their culturally conservative environment by offering contraceptive counseling, comprehensive education on birth control, and access to contraceptive services directly through primary care. Twenty-one semi structured interviews were conducted and analyzed in Atlas.ti®. All women patients who had received contraceptive services through primary care in the previous 6 months were invited to participate in a semi-structured interview. A sample of current and past board members were invited to participate in semi-structured interviews. A sample of five primary care providers and nurses who interact with women receiving contraceptive services was invited to participate in a semi-structured, in-person interview. In addition, the executive director, the clinic manager, and the current and past medical directors were interviewed. A hybrid of inductive and deductive coding methods was used for theme generation. Interviews helped to highlight some of the barriers to accessing contraceptives currently experienced by women in this rural area, and showcased how this FQHC is adapting their approach and their services to be able to meet patient needs. The following themes emerged: lack of knowledge about services offered, lack of knowledge about birth control, misinformation and misconceptions, education on birth control, and care model. The cultural context of Southwest Virginia, including the cultural conservatism and stigma associated with talking about sex, has a big impact on people's willingness to access contraceptive services. Stigma limits educational opportunities being offered in schools, therefore limiting people's knowledge about services and birth control methods. This FQHC has adapted to their surrounding culture by ensuring that every woman seeking primary care at the FQHC is screened for contraceptive need, offered contraceptive counseling and comprehensive contraceptive methods. This FQHC's integration of contraceptive services is a model that can be replicated by other FQHCs, by local health departments, and by private physicians.


Contrasting genetic structure between Magnaporthe grisea populations associated with the golf course turfgrasses Lolium perenne (perennial ryegrass) and Pennisetum clandestinum (kikuyugrass).
Gray leaf spot (GLS) disease of perennial ryegrass (Lolium perenne) and kikuyugrass (Pennisetum clandestinum) in golf courses in California was first noted in 2001 and 2003, respectively, and within 5 years had become well established. The causal agent of the disease is the fungus Magnaporthe grisea, which is known to consist primarily of clonal lineages that are highly host specific. Therefore, our objective was to investigate host specificity and population dynamics among isolates associated primarily from perennial ryegrass and kikuyugrass since the disease emerged at similar times in California. We also obtained isolates from additional hosts (tall fescue, St. Augustinegrass, weeping lovegrass, and rice) and from the eastern United States for comparative purposes. A total of 38 polymorphic amplified fragment length polymorphism makers were scored from 450 isolates which clustered by host with high bootstrap support (71 to 100%). Genetic structure between kikuyugrass and perennial ryegrass isolates differed significantly. Isolates from kikuyugrass were genotypically diverse (n = 34), possessed both mating types, and some tests for random mating could not be rejected, whereas isolates from perennial ryegrass were less genotypically diverse (n = 10) and only consisted of a single mating type. Low genotypic diversity was also found among the other host specific isolates which also only consisted of a single mating type. This is the first study to document evidence for the potential of sexual reproduction to occur in M. grisea isolates not associated with rice (Oryza sativa). Moreover, given the significant host specificity and contrasting genetic structures between turfgrass-associated isolates, the recent emergence of GLS on various grass hosts in California suggests that potential cultural practices or environmental changes have become conducive for the disease and that the primary inoculum may have already been present in the state, despite the fact that two genotypes associated with perennial ryegrass and St. Augustinegrass in California were the same as isolates collected from the eastern United States.


Dissipative Kerr solitons, breathers, and chimera states in coherently driven passive cavities with parabolic potential.
We analyze the stability and dynamics of dissipative Kerr solitons (DKSs) in the presence of a parabolic potential. This potential stabilizes oscillatory and chaotic regimes, favoring the generation of static DKSs. Furthermore, the potential induces the emergence of new dissipative structures, such as asymmetric breathers and chimera-like states. Based on a mode decomposition of these states, we unveil the underlying modal interactions.


Financing reform and structural change in the health services industry.
This paper reviews the major trends in financing reform, emphasizing their impact on those characteristics of the market for health services that economists have viewed as monopolistic, and discusses the implications of structural change for the allied health professions. Hopefully, by understanding the fundamental forces of change and responding to uncertainty with flexibility and imagination, the allied health professions can capitalize on the opportunities afforded by structural change. Overall, these trends should result in the long-term outlook for use of allied health services to increase at an average annual rate of 9% to 10%. Allied health professionals may also witness an increase in independent practice opportunities. Finally, redistribution of jobs will likely occur in favor of outpatient facilities, home health agencies, and nontraditional settings. This in turn will have an impact on allied health education, which will need to adapt to these types of reforms.


In vitro pancreatic ductal cell carcinogenesis.
Our experiments were designed to identify initial biochemical and biological changes that occur during pancreatic carcinogenesis. TAKA-1, an immortal hamster pancreatic ductal cell line, was treated in vitro for up to 11 weeks with the pancreatic carcinogen N-nitorosobis(2-oxopropyl)amine (BOP). These treated cells were designated TAKA-1 + BOP. The growth of TAKA-1 and TAKA-1 + BOP cell lines was investigated in soft agar and in hamsters intradermally. The resulting tumor from TAKA-1 + BOP was re-cultured in vitro and designated TAKA-1 + BOP-T. Mutation of c-K-ras and p53 oncogenes, chromosomal changes, expression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) receptor and several biochemical markers were examined in all cell lines. TAKA-1 + BOP but not TAKA-1 cells grew in soft agar and produced an invasive tumor in vivo. However, there were no differences in cell growth rate, DNA flow cytometry, or immunohistochemical findings between the non-transformed and transformed cells. TAKA-1, TAKA-1 + BOP and TAKA-1 + BOP-T cells all expressed mRNA of TGF-alpha and EGF receptor in a comparable pattern. DNA sequence analysis following polymerase chain reaction showed that neither TAKA-1 nor TAKA-1 + BOP cells has a mutation of c-K-ras or p53. Karyotype analysis demonstrated that TAKA-1 + BOP cells had more chromosomal abnormalities compared with TAKA-1 cells. Mutation of c-K-ras and p53 was not essential for carcinogenesis in hamster pancreatic ductal cells in vitro. In conclusion, immortality of the TAKA-1 cells caused expression of TGF-alpha to the same extent as in malignant cells. Chromosomal and ultrastructural patterns were the only differences detected between the non-transformed and BOP-transformed cells.


An Observational Study of the Implementation of the Tobacco-Free Film and Television Policy in India.
Positive portrayals of tobacco use in entertainment media can normalize and perpetuate use. In 2012, the Government of India implemented the Tobacco-Free Film and Television Rules, a first-of-its-kind comprehensive regulation to restrict tobacco depiction in films and television programs. Two complementary studies were undertaken to assess the implementation of the film rules on television and in movie theaters. In the first part, movie theater observations and exit surveys were conducted from Feb. 3 to March 24, 2015. In total, 308 movie theaters were selected for the observation of films. A total of 3080 exit surveys were conducted to assess moviegoers' reactions toward the film rule. The second part comprised the systematic observation of 424 prerecorded television programs that aired from Nov. 20 to Dec. 30, 2015. Compliance with the Tobacco-Free Film and Television Rules policy was lower on television than in movie theaters. While 66% of television programs with tobacco scenes implemented at least 1 of the 3 elements of the film rule, not a single program executed all required elements correctly. In movie theaters, 99% of films that contained tobacco scenes implemented at least one element of the film rule. However, all elements of the film rules were implemented correctly during 27% of the films observed. Exit surveys showed that among moviegoers who recalled viewing at least one element of the film rule, there was increased concern about tobacco's harms and intentions to quit. Implementation of the film rules was higher in movie theaters than on television, though there were gaps in implementation for both. Despite inconsistent application, audience reactions to the anti-tobacco messages were favorable, with increased concern about tobacco's harms and intention to quit. Overall, the film rules offer a strong tool for countering tobacco promotion, reaching hundreds of millions with anti-tobacco messaging.


Relationships between Microbial Indicators and Pathogens in Recreational Water Settings.
Fecal pollution of recreational waters can cause scenic blight and pose a threat to public health, resulting in beach advisories and closures. Fecal indicator bacteria (total and fecal coliforms, Escherichia coli, and enterococci), and alternative indicators of fecal pollution (Clostridium perfringens and bacteriophages) are routinely used in the assessment of sanitary quality of recreational waters. However, fecal indicator bacteria (FIB), and alternative indicators are found in the gastrointestinal tract of humans, and many other animals and therefore are considered general indicators of fecal pollution. As such, there is room for improvement in terms of their use for informing risk assessment and remediation strategies. Microbial source tracking (MST) genetic markers are closely associated with animal hosts and are used to identify fecal pollution sources. In this review, we examine 73 papers generated over 40 years that reported the relationship between at least one indicator and one pathogen group or species. Nearly half of the reports did not include statistical analysis, while the remainder were almost equally split between those that observed statistically significant relationships and those that did not. Statistical significance was reported less frequently in marine and brackish waters compared to freshwater, and the number of statistically significant relationships was considerably higher in freshwater (p < 0.0001). Overall, significant relationships were more commonly reported between FIB and pathogenic bacteria or protozoa, compared to pathogenic viruses (p: 0.0022⁻0.0005), and this was more pronounced in freshwater compared to marine. Statistically significant relationships were typically noted following wet weather events and at sites known to be impacted by recent fecal pollution. Among the studies that reported frequency of detection, FIB were detected most consistently, followed by alternative indicators. MST markers and the three pathogen groups were detected least frequently. This trend was mirrored by reported concentrations for each group of organisms (FIB > alternative indicators > MST markers > pathogens). Thus, while FIB, alternative indicators, and MST markers continue to be suitable indicators of fecal pollution, their relationship with waterborne pathogens, particularly viruses, is tenuous at best and influenced by many different factors such as frequency of detection, variable shedding rates, differential fate and transport characteristics, as well as a broad range of site-specific factors such as the potential for the presence of a complex mixture of multiple sources of fecal contamination and pathogens.


The effect of inducing ventricular fibrillation with 50-Hz pacing versus T wave stimulation on the ability to defibrillate.
When testing an ICD, there are at least two techniques for inducing ventricular fibrillation: (1) high frequency (approximately equal to 50 Hz) pacing; and (2) a single T wave stimulus. It is generally assumed that these two methods yield similar results. This study directly tested this assumption. In six dogs, one defibrillation electrode was placed in the right ventricular (RV) apex and the second was placed cutaneously on the left thorax. All defibrillation and T wave stimuli were biphasic between these two electrodes. Pacing was monophasic from the tip of the RV catheter to the cutaneous patch. The voltage which defibrillates 50% of the time (DF50) was measured using a 10-step Bayesian up-down method. Observations for two DF50 measurements were randomly interleaved. For one DF50 measurement, fibrillation was induced with 99 pacing stimuli at a 20-ms pacing interval (50-Hz pacing). For the second DF50 measurement, fibrillation was induced with a single defibrillation shock of approximately 1/2 J delivered at a time corresponding to the peak of the T wave in the lead II electrogram (T wave stimuli). The average DF50 when measured after fibrillation induced with 50-Hz pacing was 379 +/- 54.6 V, as compared to 382 +/- 50.3 V when fibrillation was induced with T wave stimuli. The difference of 3 V was not statistically significant. If these results are confirmed in humans, it is reasonable to assume that the efficacy of a defibrillation shock is the same whether T wave stimuli or 50-Hz pacing are used to induce fibrillation.


Trends in cancer mortality in Mexico, 1981-2007.
The objective of this study was to provide information on recent trends in cancer mortality in Mexico. We analyzed data provided by the World Health Organization, using joinpoint analysis to detect changes in trends between 1981 and 2007. For most cancers, mortality was upward but started to decline in the late 1980's/early 1990's for both sexes. Overall cancer mortality was 75.53/100 000 men, world standard, and 69.2/100 000 women in 2005-2007. Mortality from uterine cancer declined by approximately 2.5% per year in the 1990s, and by approximately 5% per year in the last decade, but its rates remained exceedingly high (9.7/100 000 in 2005-2007). Other major declines over recent years were those of stomach cancer (approximately 2.5% per year, with rates of 6.6/100 000 in men and 4.9/100 000 in women in 2005-2007) and lung cancer (2-2.5% per year, 11.0/100 000 in men and 4.5/100 000 in women in 2005-2007). Mortality leveled off only since the early 1990s for breast and prostate, and since the late 1990s for colorectal cancer. Death rates from cancer in Mexico remained low on a worldwide scale and showed favorable trends over more recent calendar years. Mortality from (cervix) uterine cancer still represents a major public health priority in this country.


[Male violence against heterosexual partners: facts and challenges. Review of Mexican literature].
Violence against women by partners (VAWP) has been systematically studied in Mexico in the past 15 years. The aim of this paper is to reflect on the contributions on this topic in Mexico. The discussion focuses on the magnitude of this phenomenon, stressing its theoretical, methodological, and technical implications; the relationship between violence and a variety of factors; and the outcomes of VAWP on women themselves. The manuscript features the main contributions from quantitative and qualitative studies.


Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: a meta-analysis.
Trials comparing efficacy of melphalan prednisone (MP) with MP plus thalidomide in transplant ineligible, elderly patients with multiple myeloma have provided conflicting evidence. Although there is agreement regarding improved response rates (RRs) and higher toxicity with the addition of thalidomide to MP, the impact on progression free survival (PFS) and overall survival (OS) is less clear. We performed a meta-analysis comparing efficacy of melphalan, prednisone and thalidomide (MPT) and MP by pooling results on RR, PFS and OS reported in all the identified randomized controlled trials (RCTs) under a random effects model. Overall, six prospective RCTs, with data extractable from five published trials (n=1571) [corrected] were identified. The pooled odds ratio of responding to therapy with MPT vs MP was 3.39 (P<0.001, 95% CI: 2.24-5.12). The pooled hazard ratios for PFS and OS were and 0.68 (P<0.001; 95% CI: 0.55-0.82) and 0.80 (P=0.07; 95% CI: 0.63-1.02), respectively, in favor of MPT. The odds ratios for high grade peripheral neuropathy and deep venous thrombosis were 6.6 and 2.4, respectively, in favour of MP. There was significant heterogeneity among the RCTs. Our meta-analysis demonstrates that in previously untreated, transplant ineligible, elderly myeloma patients, the addition of T to MP results in significantly improved RR and PFS with a trend towards improvement in OS compared with MP alone, but at a cost of significantly greater toxicity.


Inhibition of sporulation by DNA gyrase inhibitors.
The effects of oxolinic acid and novobiocin - which respectively inhibit the A and B subunits of DNA gyrase, and therefore inhibit DNA synthesis - have examined in sporulating cultures of Bacillus subtilis. Although both inhibitors prevent sporulation, this is not due to inhibition of DNA synthesis. Instead, they affect protein synthesis generally, though weakly, but have very marked effects on the formation of individual enzymes. These effects are reproducible, but the type of enzyme that will be affected is not predictable. The results point to an involvement of DNA gyrase in the transcription of some genes. This is suggested as the reason for the effect of the inhibitors on spore formation, which they block mainly at Stage O-I.


The Biological Roles of Exosomal Long Non-Coding RNAs in Cancers.
Although it has many treatment strategies, cancer is still one of the most common causes of morbidity and mortality in the world. Exosomes are small extracellular vesicles (EVs) that can be secreted by almost all cells. Exosomes can encapsulate various types of molecules, including lipids, proteins, DNA, messenger RNAs, and non-coding RNAs [microRNAs (miRNAs) and long non-coding RNAs (lncRNAs)]. Exosome release is a way of communication between cells. They act as powerful signaling molecules between cancer cells and the surrounding cells that make up the cancer microenvironment. lncRNAs are a class of non-coding P, with a length of more than 200 bp, which are differentially expressed in many cancers. lncRNAs have been widely regarded as a new medium for cancer behavior. The presence of lncRNAs in circulation can be acellular or encapsulated in exosomal bodies released by cancer cells. Exosomal lncRNAs are functional and can transmit different phenotypic patterns to neighboring cells. Here, we reviewed the molecular mechanism of exosomal lncRNAs in regulating cancer progression, angiogenesis, and chemotherapy resistance, as well as the prospective applications of exosomal lncRNAs in cancer diagnosis, treatment and prognosis. These findings potentially promote the current understanding of exosomal lncRNAs and provide a new research direction for exosomal lncRNAs in cancer prevention, diagnosis, and treatment.


Depressed T-cell interferon-gamma responses in pulmonary tuberculosis: analysis of underlying mechanisms and modulation with therapy.
Immunological and clinical profiles were evaluated in 2 groups: human immunodeficiency virus (HIV)-uninfected and HIV-infected patients, with newly diagnosed pulmonary tuberculosis (TB), and tuberculin-skin-test-reactive healthy control subjects. HIV-uninfected patients with TB were also followed up longitudinally during and after chemotherapy. At the time of diagnosis, purified protein derivative (PPD)-stimulated production of interferon (IFN)-gamma by peripheral blood mononuclear cells from TB patients was depressed, compared with that of healthy control subjects, whereas levels of transforming growth factor (TGF)-beta and interleukin (IL)-10 were increased. In longitudinal studies, PPD stimulated production of IL-10 and TGF-beta returned to baseline by 3 months, whereas IFN-gamma production remained depressed for at least 12 months. These data indicate that the immunosuppression of TB is not only immediate and apparently dependent (at least in part) on immunosuppressive cytokines early during the course of Mycobacterium TB infection but is also long lasting, presumably relating to a primary abnormality in T-cell function.


Novel Intact Polar and Core Lipid Compositions in the Pyrococcus Model Species, P. furiosus and P. yayanosii, Reveal the Largest Lipid Diversity Amongst Thermococcales.
Elucidating the lipidome of Archaea is essential to understand their tolerance to extreme environmental conditions. Previous characterizations of the lipid composition of Pyrococcus species, a model genus of hyperthermophilic archaea belonging to the Thermococcales order, led to conflicting results, which hindered the comprehension of their membrane structure and the putative adaptive role of their lipids. In an effort to clarify the lipid composition data of the Pyrococcus genus, we thoroughly investigated the distribution of both the core lipids (CL) and intact polar lipids (IPL) of the model Pyrococcus furiosus and, for the first time, of Pyrococcus yayanosii, the sole obligate piezophilic hyperthermophilic archaeon known to date. We showed a low diversity of IPL in the lipid extract of P. furiosus, which nonetheless allowed the first report of phosphatidyl inositol-based glycerol mono- and trialkyl glycerol tetraethers. With up to 13 different CL structures identified, the acid methanolysis of Pyrococcus furiosus revealed an unprecedented CL diversity and showed strong discrepancies with the IPL compositions reported here and in previous studies. By contrast, P. yayanosii displayed fewer CL structures but a much wider variety of polar heads. Our results showed severe inconsistencies between IPL and CL relative abundances. Such differences highlight the diversity and complexity of the Pyrococcus plasma membrane composition and demonstrate that a large part of its lipids remains uncharacterized. Reassessing the lipid composition of model archaea should lead to a better understanding of the structural diversity of their lipidome and of their physiological and adaptive functions.


A robust methodology to subclassify pseudokinases based on their nucleotide-binding properties.
Protein kinase-like domains that lack conserved residues known to catalyse phosphoryl transfer, termed pseudokinases, have emerged as important signalling domains across all kingdoms of life. Although predicted to function principally as catalysis-independent protein-interaction modules, several pseudokinase domains have been attributed unexpected catalytic functions, often amid controversy. We established a thermal-shift assay as a benchmark technique to define the nucleotide-binding properties of kinase-like domains. Unlike in vitro kinase assays, this assay is insensitive to the presence of minor quantities of contaminating kinases that may otherwise lead to incorrect attribution of catalytic functions to pseudokinases. We demonstrated the utility of this method by classifying 31 diverse pseudokinase domains into four groups: devoid of detectable nucleotide or cation binding; cation-independent nucleotide binding; cation binding; and nucleotide binding enhanced by cations. Whereas nine pseudokinases bound ATP in a divalent cation-dependent manner, over half of those examined did not detectably bind nucleotides, illustrating that pseudokinase domains predominantly function as non-catalytic protein-interaction modules within signalling networks and that only a small subset is potentially catalytically active. We propose that henceforth the thermal-shift assay be adopted as the standard technique for establishing the nucleotide-binding and catalytic potential of kinase-like domains.


Preparing protein microarrays by soft-landing of mass-selected ions.
Intact, multiply protonated proteins of particular mass and charge were selected from ionized protein mixtures and gently landed at different positions on a surface to form a microarray. An array of cytochrome c, lysozyme, insulin, and apomyoglobin was generated, and the deposited proteins showed electrospray ionization mass spectra that matched those of the authentic compounds. Deposited lysozyme and trypsin retained their biological activity. Multiply charged ions of protein kinase A catalytic subunit and hexokinase were also soft-landed into glycerol-based liquid surfaces. These soft-landed kinases phosphorylated LRRASLG oligopeptide and D-fructose, respectively.


Dietary and Behavioral Factors Associated with Diet Quality among Low-income Overweight and Obese African American Women.
The goal of this research was to assess the roles of demographic and home food environment characteristics on diet quality measured with the U.S. Department of Agriculture's Healthy Eating Index (HEI) in a population of low-income overweight and obese African American women. Cross-sectional analysis of baseline data. A community-based study of low-income overweight and obese African American women. Participants enrolled in the Healthy Homes/Healthy Families study including a home environment survey (e.g., food availability, food practices and social support) and 24-hour recall dietary data collected on one weekday and one weekend day (n = 198). In multivariate regression analyses, demographic characteristics were not significantly associated with diet quality; however, several home food environment characteristics were significantly associated with higher quality diets, including healthy shopping (e.g., regularly purchasing fresh fruits and vegetables), selecting healthy beverages (e.g., without added sugar), healthy food preparation, and serving behaviors. Eating while watching television was associated with lower quality diets. Nearly 33% (p < 0.001) of the variance in HEI total score was explained by the home food environment factors, far surpassing that explained by demographic characteristics (3.5%, p = 0.21). Interventions targeting the home food environment may improve overall diet quality in low-income overweight African American populations.


Non-peptidergic OP4 receptor agonist inhibits morphine antinociception but does not influence morphine dependence.
The non-peptidergic opioid receptor-like 1 (ORL1, OP4) receptor ligand, Ro 64-6198 [(1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4,5]decan-4-one], is a full agonist of the OP4 receptor. The aim of this study was to evaluate whether this compound influences morphine antinociception and dependence in mice. Ro 64-6198 inhibits the acute analgesic effect of morphine in the tail-immersion test, however, when given chronically during the acquisition of morphine dependence, development of this dependence is not prevented. The acute injection of Ro 64-6198 suppresses withdrawal escape jumps in morphine dependent mice, though this effect may be a result of the loss of locomotor activity induced by this compound and/or its myorelaxant action. The study provides evidence that stimulation of the OP4 receptor suppresses acute morphine antinociception, but is not sufficient to inhibit the development of morphine dependence in mice.


Cell cycle molecules and vertebrate neuron death: E2F at the hub.
Vertebrate neuron cell death is both a normal developmental process and the catastrophic outcome of nervous system trauma or degenerative disorders. Although the mechanisms of such death include an evolutionarily conserved core apoptotic pathway that is highly homologous to that first described by Horvitz and co-workers in Caenorhabditis elegans, it appears that many instances of neuron death additionally require the transcription-dependent induction of proapoptotic molecules. One such proapoptotic transcriptional pathway revealed by studies over the past decade revolves about the transcription factor E2F and those molecules that either regulate E2F activity or that are direct or indirect transcriptional targets of E2F. Many of the molecules associated with the E2F apoptotic pathway in postmitotic neurons also participate in the cell cycle in proliferating cells. Observations in human material and in animal and cell culture models show widespread correlation between changes in expression, activity and subcellular localization of E2F-related cell cycle molecules and developmental and catastrophic neuron death. A variety of experimental approaches support a causal role for such changes in the death process and are beginning to indicate how the neuronal E2F pathway activates the core apoptotic machinery. The discovery and elaboration of the neuronal apoptotic E2F pathway provides abundant targets as well as small molecule candidates for potential therapeutic intervention in nervous system trauma and degenerative disease.


[Cyclic processes in the dynamics of the population count of the taiga tick and their relation to weather and climatic conditions].
The paper continues the discussion of published materials on the dynamic of Ixodes persulcatus number in mountain forests of the central part of the Krasnoyarsk region during 1958-1990 (Korotkov e. a., 1992). An unstationarity and polycyclicity of examined processus is confirmed. It is shown, that long-term and middle-term quasi-periodical fluctuations of the tick number are determined by successive changing in forest biocenoses going under the influence of respective fluctuations of the climate. The synchronization of climatic and biocenotic processes is complicatedly organized in time and is not indicated phenomenologically. Certain quasi-periodical components in their indices of the tick number and climate are quite different by their amplitude, value of phase displacement, and longevity of terms. However, these structural differences are natural and determined by peculiarities of the response reaction of I. persulcatus to different intensivity of acting factor. This reaction under extreme environment conditions, both minimal and maximal ones, leads to the same result, the decreasing of the vital activity and the tick number.


Regional differences in the risk of insomnia symptoms among patients from general hospital outpatient clinics.
Region-specific differences in the prevalence of insomnia symptoms in outpatient clinics in China have received little systematic study. This study was conducted preliminarily to examine region-specific differences in the risk of insomnia symptoms in Chinese outpatients. In total, 4,399 adult outpatients (urban vs rural residents: 1,768 vs 2,631) who completed three questions focusing on insomnia symptoms were included. Their sociodemographic and clinical information were collected with standardized questionnaires. The prevalence of self-reported insomnia symptoms in urban residents (23.4%) was more frequent than the prevalence in rural residents (21.2%). The estimated prevalence of insomnia symptoms was significantly lower in rural than urban residents after adjusting for the potential confounders (P=0.015). Similarly, more urban (22.9%) than rural (13.4%) residents with insomnia symptoms had significantly higher treatment rates (χ 2=14.9, P<0.001). Multiple regression analyses showed that depressive symptoms, old age, and low education level were the most common risk factors for insomnia symptoms in both urban and rural residents. Our findings show that the prevalence of insomnia symptoms was relatively lower in rural than urban residents. Longitudinal studies are warranted to confirm the current findings.


Retinoic Acid Receptor β: A Potential Therapeutic Target in Retinoic Acid Treatment of Endometrial Cancer.
Several studies have reported that retinoic acid (RA) might be used to treat malignancies. The effects of RA are mediated by the RA receptor (RAR), and RARα/RARβ especially acts as a tumor suppressor. However, little is known about its role in human endometrial cancer. In this study, we examined the effects of all-trans RA (ATRA) on progression of human endometrial cancer cell line, RL95-2 and Hec1A. We then examined the expression of RARα and RARβ in 50 endometrial cancer tissues by using immunohistochemistry. We found inhibitory effects of ATRA on cell proliferation, apoptosis, and migration in RL95-2 cells, but not in Hec1A cells. RARα or RARβ knockdown individually could not cancel out the inhibition of cell proliferation by ATRA in RL95-2 cells, but simultaneous knockdown of RARα and RARβ could block its effect on proliferation. RARα and RARβ knockdown dose dependently reduced the inhibition of migration by ATRA, but the effect was more pronounced with RARβ knockdown than with RARα knockdown. We confirmed that RARβ gene was directly regulated by ATRA in microarray and real-time reverse transcription polymerase chain reaction. Furthermore, the RARβ agonist (BMS453) significantly suppressed proliferation of RL95-2 cells. In immunohistochemical analysis, RARα expression was positively correlated with tumor grade, and RARβ showed the opposite tendency in endometrial cancer. Retinoic acid might have multiple antitumor effects, and RARβ may be a potent therapeutic target in RA treatment for endometrial cancers.


Cerebral blood flow asymmetries in headache-free migraineurs.
Regional cerebral blood flow (rCBF) asymmetries were studied in controls and patients with common and classic/complicated migraine using 133Xe inhalation with 8 homologously situated external collimators over each cerebral hemisphere. Migraine patients as a group more frequently had posterior rCBF asymmetries than controls (p less than 0.03). Although there were no differences in the number of anterior rCBF asymmetries, migraine patients had 2 or more asymmetric probe pairs more often than controls (p less than 0.02). The posterior rCBF asymmetries, consistent with the site of activation of many migraine attacks, may be related to more labile control of the cerebral circulation.


Natural killer cells activated by interleukin 2 treatment in vivo respond to interleukin 2 primarily through the p75 receptor and maintain the p55 (TAC) negative phenotype.
Interleukin 2 (IL-2) induced activation of unstimulated resting natural killer (NK) cells or resting T-cells initially occurs following binding of IL-2 through the p75 receptor that is expressed primarily by these cells. However, this IL-2/p75 interaction induces TAC chain synthesis and formation of high affinity IL-2 receptor required for the proliferation of resting peripheral blood lymphocytes. In this study, we present data indicating that NK cells activated by in vivo IL-2 treatment, in contrast to resting NK cells, respond and proliferate to further IL-2 in vitro using primarily the p75 receptor with only a minor component of cells responding through the high affinity receptor. These in vivo activated NK cells minimally expressed the TAC chain and maintained this TAC negative phenotype while proliferating in response to IL-2. The primary involvement of the p75 receptor in the proliferative response of these cells to IL-2 was demonstrated by the need for concentrations of IL-2 higher than 44 pM to obtain a significant response and by the dramatic inhibition of this response by anti-p75 monoclonal antibody. Anti-TAC monoclonal antibody inhibited only the poor proliferation obtained at low doses of IL-2 suggesting a minor role for TAC and high affinity IL-2 receptors. This was in contrast to the partial inhibition of proliferation by anti-p75 or anti-TAC observed in unstimulated pretherapy peripheral blood lymphocytes suggesting that these cells respond to IL-2 through both high affinity receptors and intermediate affinity p75 receptors. The T-cells isolated from in vivo activated peripheral blood lymphocytes, despite expressing TAC, were not responsive to IL-2, suggesting that these cells express predominantly nonfunctional low affinity TAC receptors. NK cells activated by IL-2 in vivo represent a unique model system of IL-2 dependent cells that respond and proliferate to IL-2 essentially through the p75 IL-2 receptor.


Development and Validation of a Nomogram for Predicting Incidence of Early Allograft Dysfunction Following Liver Transplantation.
Early allograft dysfunction (EAD) is frequent complication post-liver transplantation and is closely related to recipient's mortality and morbidity. We sought to develop a nomogram for predicting incidence of EAD. Based on multivariate analysis of donor, recipient, and operation data of 199 liver transplants from deceased donors between 2013 and 2015, we identified 5 significant risk factors for EAD to build a nomogram. The model was subjected to prospective validation with a cohort of 42 patients who was recruited between January and June 2016. The predictive accuracy and discriminative ability were measured by area under the receiver operating characteristic curve (AUC). The agreement between nomogram prediction and actual observation was showed by the calibration curve. Incidence rate of EAD in the training set and validation cohort were 55.91% (104/199) and 54.76% (23/42), respectively. In the training set, according to the results of univariable and multivariable analysis, 5 independent risk factors including donor gender, donor serum gamma-glutamyl transpeptidase level, donor serum urea level, donor comorbidities (respiratory, cardiac, and renal dysfunction), and recipient Model for End-stage Liver Disease score were identified and assembled into the nomogram. The AUC of internal validation using bootstrap resampling and prospective validation using the external cohort of 42 patients was 0.74 and 0.60, respectively. The calibration curves for probability of EAD showed acceptable agreement between nomogram prediction and actual observation. According to the score table, the probability of EAD was under 30% when the total point tally was under 72. But when the total was up to 139, the risk of EAD increased to 60%. We've established and validated a nomogram that can provide individual prediction of EAD for liver transplant recipients. The practical prognostic model may help clinicians to qualify the liver graft accurately, making a more reasonable allocation of organs.


Soybean exports and deforestation from a world-systems perspective: a cross-national investigation of comparative disadvantage.
This article draws on world-system theorizing to explore the relationship between deforestation and the vertical flow of soybean exports from less-developed nations to more-developed nations as a specific form of ecologically unequal exchange. Despite overwhelming case-study research exploring soybean-deforestation dynamics in less-developed countries, the current literature lacks any cross-national investigation of this trend. Ordinary least squares regression is used to examine whether soybean exports are associated with deforestation and if the magnitude of this relationship varies by region. Overall, the findings confirm the proposed hypotheses and suggest that having a comparative advantage in soybean production is not a viable development strategy.


Norovirus strains belonging to the GII.4 genotype dominate as a cause of nosocomial outbreaks of viral gastroenteritis in Sweden 1997--2005. Arrival of new variants is associated with large nation-wide epidemics.
In recent years an increase of the incidence of nosocomial outbreaks caused by noroviruses has been observed throughout Sweden, with high peaks noted in the winter seasons 2002/2003 and 2004/2005, respectively. To phylogenetically characterize norovirus strains causing nosocomial outbreaks from 1997 to 2005 and estimate the impact of norovirus-like disease on the Swedish health care system during the peak season 2002/2003 when a new variant of norovirus occurred. Stool samples from 115 randomly selected nosocomial outbreaks occurring during 1997--2005 throughout Sweden were studied by RT-PCR and sequencing. In addition, to investigate the impact on the health-care system, a questionnaire was distributed to infection control units (n=90) serving all Swedish hospitals, nursing homes and other health-care institutions during the largest epidemic of nosocomial outbreaks. Sequencing of 279 nucleotides of the norovirus RNA polymerase gene in stools containing norovirus RNA showed that strains belonging to the GII.4 genotype dominated. Each of the two large epidemics was due to a new variant within this cluster. The questionnaire revealed that 30,000-35,000 episodes of nosocomial norovirus-like infections occurred in 80 of 82 major Swedish hospitals affected in 2002/2003. New norovirus variants within the cluster GGII.4 may have a major impact on the health-care system.


Short-term clinical results of bicruciate-retaining total knee arthroplasty using personalized alignment.
Bicruciate-retaining (BCR) prosthesis has been introduced to recreate normal knee movement by preserving both the anterior and posterior cruciate ligaments. However, the use of BCR total knee arthroplasty (TKA) is still debatable because of several disappointing reports. We have been performing BCR TKAs with personalized alignment (PA). This study aimed to reveal the limb alignment and soft tissue balance of FA-BCR TKAs and compare the clinical outcomes of FA-BCR TKAs with those of unicompartmental knee arthroplasty (UKA). Fifty BCR TKAs and 58 UKAs were included in this study. The joint component gaps of BCR TKA were evaluated intraoperatively and the postoperative hip-knee-ankle (HKA) angle, medial proximal tibial angle (MPTA), and lateral distal femoral angle (LDFA) were measured using full-length standing radiography. The short-term clinical outcomes of BCR TKAs were compared with those of UKA using the scoring system of 2011 Knee Society Scoring (KSS) and the knee injury and osteoarthritis outcome score (KOOS) at an average of 2 years postoperatively (1-4yeras). The coronal alignment values of PA-BCR TKA were as follows: HKA angle, 177.9° ± 2.3°; MPTA, 85.4° ± 1.9°; and LDFA, 87.5° ± 1.9°. The joint component gaps at flexion angles of 10°, 30°, 60°, and 90° were 11.1 ± 1.2, 10.9 ± 1.4, 10.7 ± 1.3, and 11.2 ± 1.4 mm for the medial compartment and 12.9 ± 1.5, 12.6 ± 1.8, 12.5 ± 1.8 and 12.5 ± 1.7 mm for the lateral compartment, respectively. The patient expectation score and maximum extension angle of PA-BCR TKA were significantly better than those of UKAs. The short-term clinical outcomes of PA-BCR TKA were comparable or a slightly superior to those of UKAs.


Measurement of longitudinal β-amyloid change with 18F-florbetapir PET and standardized uptake value ratios.
The accurate measurement of β-amyloid (Aβ) change using amyloid PET imaging is important for Alzheimer disease research and clinical trials but poses several unique challenges. In particular, reference region measurement instability may lead to spurious changes in cortical regions of interest. To optimize our ability to measure (18)F-florbetapir longitudinal change, we evaluated several candidate regions of interest and their influence on cortical florbetapir change over a 2-y period in participants from the Alzheimer Disease Neuroimaging Initiative (ADNI). We examined the agreement in cortical florbetapir change detected using 6 candidate reference regions (cerebellar gray matter, whole cerebellum, brain stem/pons, eroded subcortical white matter [WM], and 2 additional combinations of these regions) in 520 ADNI subjects. We used concurrent cerebrospinal fluid Aβ1-42 measurements to identify subgroups of ADNI subjects expected to remain stable over follow-up (stable Aβ group; n = 14) and subjects expected to increase (increasing Aβ group; n = 91). We then evaluated reference regions according to whether cortical change was minimal in the stable Aβ group and cortical retention increased in the increasing Aβ group. There was poor agreement across reference regions in the amount of cortical change observed across all 520 ADNI subjects. Within the stable Aβ group, however, cortical florbetapir change was 1%-2% across all reference regions, indicating high consistency. In the increasing Aβ group, cortical increases were significant with all reference regions. Reference regions containing WM (as opposed to cerebellum or pons) enabled detection of cortical change that was more physiologically plausible and more likely to increase over time. Reference region selection has an important influence on the detection of florbetapir change. Compared with cerebellum or pons alone, reference regions that included subcortical WM resulted in change measurements that are more accurate. In addition, because use of WM-containing reference regions involves dividing out cortical signal contained in the reference region (via partial-volume effects), use of these WM-containing regions may result in more conservative estimates of actual change. Future analyses using different tracers, tracer-kinetic models, pipelines, and comparisons with other biomarkers will further optimize our ability to accurately measure Aβ changes over time.


Antiretroviral therapy for prevention of HIV transmission: implications for Europe.
The aim of this review is to summarise the evidence on the population-level effect of antiretroviral therapy (ART) in preventing HIV infections, and to discuss potential implications in the European context of recommending starting ART when the CD4 count is above 350 cells/mm3. The ability of ART to reduce the risk of HIV transmission has been reported in observational studies and in a randomised controlled trial (HPTN 052), in which ART initiation reduced HIV transmission by 96% within serodiscordant couples. As yet, there is no direct evidence for such an effect among men having sex with men or people who inject drugs. HPTN 052 led international organisations to develop recommendations with a higher CD4 threshold for ART initiation. However, there remains a lack of strong evidence of clinical benefit for HIV-positive individuals starting ART with CD4 count above 350 cells/mm3. The main goal of ART provision should be to increase ART coverage for all those in need, based on the current guidelines, and the offer of ART to those who wish to reduce infectivity; increased HIV testing is therefore a key requirement. Other proven prevention means such as condom use and harm reduction for people who inject drugs remain critical.


Ins2 deficiency augments spontaneous HLA-A*0201-restricted T cell responses to insulin.
Type 1 diabetes results from the autoimmune destruction of insulin-producing beta cells by T cells specific for beta cell Ags, including insulin. In humans, the non-MHC locus conferring the strongest disease susceptibility is the insulin gene, and alleles yielding lower thymic insulin expression are predisposing. We sought to incorporate this characteristic into an HLA-transgenic model of the disease and to determine the influence of reduced thymic insulin expression on CD8+ T cell responses to preproinsulin. We examined NOD.Ins2(-/-) mice, which do not express insulin in the thymus and show accelerated disease, to determine whether they exhibit quantitative or qualitative differences in CD8+ T cell responses to preproinsulin. We also generated NOD.Ins2(-/-) mice expressing type 1 diabetes-associated HLA-A*0201 (designated NOD.beta2m(-/-).HHD.Ins2(-/-)) in an effort to obtain an improved humanized disease model. We found that CD8+ T cell reactivity to certain insulin peptides was more readily detected in NOD.Ins2(-/-) mice than in NOD mice. Furthermore, the proportion of insulin-reactive CD8+ T cells infiltrating the islets of NOD.Ins2(-/-) mice was increased. NOD.beta2m(-/-).HHD.Ins2(-/-) mice exhibited rapid onset of disease and had an increased proportion of HLA-A*0201-restricted insulin-reactive T cells, including those targeting the clinically relevant epitope Ins B10-18. Our results suggest that insulin alleles that predispose to type 1 diabetes in humans do so, at least in part, by facilitating CD8+ T cell responses to the protein. We propose the NOD.beta2m(-/-).HHD.Ins2(-/-) strain as an improved humanized disease model, in particular for studies seeking to develop therapeutic strategies targeting insulin-specific T cells.


Factors in the admission decision: skilled nursing facilities in New York State.
Little is known about the policies, practices, or procedures that affect the selection of applicants for nursing home admission. Results of a study of skilled nursing facilities (SNFs) in the state of New York revealed that fewer than 5% of the respondents viewed their goal as merely keeping patients comfortable; about half of the facilities reported their goal as preventing further decline. More than 70% of the respondents stated that skilled nursing beds were in short supply in the area served by their facility, while 91% of the respondents reported that their geographic area had a backlog of patients in acute care hospitals awaiting placement in SNFs. The authors discuss the study results in terms of the respondents' type of facility--public, proprietary, or voluntary. They also discuss admissions personnel, multidisciplinary teams, information collection, family involvement, and other factors that influence admission (eg, philosophy of care). The authors conclude that further research is needed to help coordinate the medical and social needs of patients and their families with the administrative needs of the facility.


Polarizable Molecular Dynamics and Experiments of 1,2-Dimethoxyethane Electrolytes with Lithium and Sodium Salts: Structure and Transport Properties.
The structure and transport properties of electrolyte solutions of 1,2-dimethoxyethane (DME) having salts of Li+ with bis(trifluoromethanesulfonyl)imide ([TFSI]-) or Na+ with [TFSI]- are investigated with polarizable molecular dynamics and experiments. Polarizable force fields for Li+ and Na+ with DME and [TFSI]- were developed based on quantum chemistry calculations, ab initio molecular dynamics simulations, and thermodynamic liquid-state properties. Simulation results for density, viscosity, self-diffusion coefficient, and conductivity of the electrolytes all agree well with the trends and magnitudes of available experimental data for a wide range of salt concentrations. As the concentration of salt increases, the electrolytes become more viscous and molecular species become less mobile. Ionic conductivity does not change monotonically with salt concentration and exhibits a maximum between 0.5 and 1.0 M for both Li[TFSI] and Na[TFSI] electrolytes. Comparatively, both cations are solvated by 5-6 DME or [TFSI]- oxygen atoms and exhibit similar diffusivities and conductivities. The solvation shell of Na+ is found to be more weakly bound and to have a lower binding residence time than that of Li+. The transport of Li+ therefore is more vehicular, through the motion of the solvation shell, while the transport of Na+ is based more on exchange, through the replacement of solvating species. The atomistic insight provided by this work can be used as the basis for future rational design of improved electrolyte solvents for lithium-oxygen, sodium-oxygen, and lithium-sulfur batteries.


Effective number of breeders from sibship reconstruction: empirical evaluations using hatchery steelhead.
Effective population size (Ne ) is among the most important metrics in evolutionary biology. In natural populations, it is often difficult to collect adequate demographic data to calculate Ne directly. Consequently, genetic methods to estimate Ne have been developed. Two Ne estimators based on sibship reconstruction using multilocus genotype data have been developed in recent years: sibship assignment and parentage analysis without parents. In this study, we evaluated the accuracy of sibship reconstruction using a large empirical dataset from five hatchery steelhead populations with known pedigrees and using 95 single nucleotide polymorphism (SNP) markers. We challenged the software COLONY with 2,599,961 known relationships and demonstrated that reconstruction of full-sib and unrelated pairs was greater than 95% and 99% accurate, respectively. However, reconstruction of half-sib pairs was poor (<5% accurate). Despite poor half-sib reconstruction, both estimators provided accurate estimates of the effective number of breeders (Nb ) when sample sizes were near or greater than the true Nb and when assuming a monogamous mating system. We further demonstrated that both methods provide roughly equivalent estimates of Nb . Our results indicate that sibship reconstruction and current SNP panels provide promise for estimating Nb in steelhead populations in the region.


[Pathology service of the public health system of Russia: conceptual directions of creation].
The principles of effective pathology service in the public health system are presented and discussed, by taking into account its state-social administration on the basis of an industrial management model. To set up official pathology committees as pathology service-controlling centers monitoring the situation in the pathology institutions (respective subdivisions of health care facilities and other organizations) developing and implementing proposals to improve the system is the most important condition for the qualitative performance of work and services in the specialty of anatomical pathology.


[Surgical treatment of ulcer disease in arterio-mesenterial compression of the duodenum].
Experience in surgical treatment of 124 patients with gastric and duodenal ulcers associated with chronic duodenal obstruction due to arterio-mesenterial compression of the duodenum is analyzed. This combination occurred in 12% of all patients with ulcers over 20-year period. Special methods of examination were used for diagnosis: probe duodenography with duodeno-manometry, hepato-bili-scintigraphy. Differential approach to choice of surgical method was developed, and two original methods of surgery are presented: selective proximal vagotomy and resection of the stomach in combination with duodeno-jejuno-anastomosis. Long-term results were studied in 75 patients, and in 93% of them they were assessed as excellent and good. Quality of life of patients after surgery depends on severity of chronic duodenal insufficiency.


Transfusion in palliative cancer patients: a review of the literature.
Transfusion is not an exceptional circumstance in palliative cancer patients (PCPs). This makes it necessary to confront not only medical aspects but also those of infrastructure and ethical issues. On some occasions, literature needs to be consulted to work out the best approach in a patient's particular case. Our aim was to review the literature contained in PubMed and EMBASE so as to find out about the information available on transfusion in PCPs. A search for literature was carried out in databases PubMed and EMBASE, using "transfusion," "cancer," "end-of-life care," "terminal care," and "palliative care" as key words. Publications were classified according to the main topic discussed (clinical, infrastructure, and ethics) and the information included in each article critically assessed. We found 334 articles but only 43 were considered valuable for the present study. Of these 43 articles, 21 deal with clinical topics while 12 deal with infrastructure and 10 with ethical issues. There is an absolute lack of randomized controlled trials or clinical guidelines. Trigger parameters for transfusion are not clearly established. Benefits of the procedure are shortly experienced and remain controversial. Home transfusions are encouraged, but this sole procedure has not been demonstrated to be cost effective. Different cultures, cases, and realities illustrate the diversity of the ethical management of transfusion in PCPs. Although transfusion is certainly a common practice in PCPs, there is a relative lack of literature on this topic. Publications are unconnected and hardly any prospective studies have been performed. A large part of the little literature available only concerns descriptive and very general aspects of the issue. As transfusional products and financial and human resources are finite, it would be desirable to establish clear research lines on the different aspects considered (clinical, infrastructure, and ethical) that can help clinicians, nurses, patients, and carers to make a decision.


The Versatile Functions of G. Lucidum Polysaccharides and G. Lucidum Triterpenes in Cancer Radiotherapy and Chemotherapy.
G. lucidum has a long history of thousands of years in China and is closely related with the lives of the Chinese people. It is reported to cure various diseases due to its high nutritional value and wide range of uses. The fascinating effects of G. lucidum have tethered a multitude of efforts to explore its effective ingredients and supplement functions. At present, many cancer research studies have reported the G. lucidum polysaccharides (GLPs) and G. lucidum triterpenes (GLTs) as the main active ingredients in G. lucidum, which have shown positive effects on radiotherapy and chemotherapy. GLPs or GLTs treatment synergizes with radiotherapy and chemotherapy through multiple pathways, including oxidative stress, apoptosis, immune microenvironment, etc. Therefore, this review aims to analyze and summarize these complex molecules from G. lucidum in order to create more treatment options for cancer patients in the future.


Effects of Stress on Itch.
Psychological stress and ensuing modulation of the immune and nervous systems can have a significant impact on itch. Stress can exacerbate itch and vice versa, resulting in a vicious cycle that can greatly impair a patient's quality of life. This review summarizes the association between stress and itch, elucidates the mechanism by which these two phenomena influence one another, and explores treatment modalities that aim to reduce stress-induced itch. A complete search of the PubMed and Google Scholar databases was completed and literature pertinent to this review was compiled. Both acute and chronic stress can significantly affect itch in healthy individuals and in those diagnosed with itchy skin diseases as well as systemic diseases, thus resulting in a vicious cycle in which stress exacerbates itch and vice versa. The mechanisms by which stress induces or aggravates itch include both central and peripheral activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. Activation of these systems, in turn, affects the mast cells, keratinocytes, and nerves that secrete neuropeptides, such as substance P, nerve growth factor, acetylcholine, histamine, and itchy cytokines. A dysfunctional parasympathetic response is thought to be involved in the chronic stress/itch response. Brain structures associated with emotion, such as the limbic system and periaqueductal gray, which work on the descending facilitation of itch, play a significant role in stress-induced itch. As specific brain structures are associated with stress, drug treatments targeting these areas (ie, γ-aminobutyric acid-ergic drugs, serotonin and norepinephrine reuptake inhibitors) may help to modulate itch. Stress can also be combatted using nonpharmacologic treatments such as cognitive-behavioral therapies and stress-relieving holistic approaches (eg, yoga, acupuncture).


Psychosis from subthalamic nucleus deep brain stimulator lesion effect.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in particular is highly effective in relieving symptoms of Parkinson's disease (PD). However, it can also have marked psychiatric side effects, including delirium, mania, and psychosis. The etiologies of those effects are not well-understood, and both surgeons and consulting psychiatrists are in need of treatment strategies. Two patients with young onset of PD and without significant prior psychiatric problems presented for bilateral STN DBS when medications became ineffective. Both had uneventful operative courses but developed florid psychosis 1-2 weeks later, before stimulator activation. Neither showed signs of delirium, but both required hospitalization, and one required treatment with a first-generation antipsychotic drug. Use of that drug did not worsen PD symptoms, contrary to usual expectations. These cases describe a previously unreported post-DBS syndrome in which local tissue reaction to lead implantation produces psychosis even without electrical stimulation of subcortical circuits. The lesion effect also appears to have anti-Parkinsonian effects that may allow the safe use of otherwise contraindicated medications. These cases have implications for management of PD DBS patients postoperatively, and may also be relevant as DBS is further used in other brain regions to treat behavioral disorders.


Compressed air noise reductions from using advanced air gun nozzles in research and development environments.
The aims of this study were to evaluate sound levels produced by compressed air guns in research and development (R&D) environments, replace conventional air gun models with advanced noise-reducing air nozzles, and measure changes in sound levels to assess the effectiveness of the advanced nozzles as engineering controls for noise. Ten different R&D manufacturing areas that used compressed air guns were identified and included in the study. A-weighted sound level and Z-weighted octave band measurements were taken simultaneously using a single instrument. In each area, three sets of measurements, each lasting for 20 sec, were taken 1 m away and perpendicular to the air stream of the conventional air gun while a worker simulated typical air gun work use. Two different advanced noise-reducing air nozzles were then installed. Sound level and octave band data were collected for each of these nozzles using the same methods as for the original air guns. Both of the advanced nozzles provided sound level reductions of about 7 dBA, on average. The highest noise reductions measured were 17.2 dBA for one model and 17.7 dBA for the other. In two areas, the advanced nozzles yielded no sound level reduction, or they produced small increases in sound level. The octave band data showed strong similarities in sound level among all air gun nozzles within the 10-1,000 Hz frequency range. However, the advanced air nozzles generally had lower noise contributions in the 1,000-20,000 Hz range. The observed decreases at these higher frequencies caused the overall sound level reductions that were measured. Installing new advanced noise-reducing air nozzles can provide large sound level reductions in comparison to existing conventional nozzles, which has direct benefit for hearing conservation efforts.


Ethnic Differences in Family Stress Processes Among African-Americans and Black Caribbeans.
Several theories of stress exposure, including the stress process and the family stress model for economically disadvantaged families, suggest that family processes work similarly across race/ethnic groups. Much of this research, however, treats African-Americans as a monolithic group and ignores potential differences in family stress processes within race that may emerge across ethnic groups. This study examines whether family stress processes differ intraracially in African-American and Black Caribbean families. Using data from the National Survey of American Life, a national representative data set of African-American and Black Caribbean families, we assess the extent to which parents' stress appraisals and psychological adjustment are related to their adolescent children's stress appraisals, psychological adjustment, and depressive symptoms. Our study illustrates that stress processes differ by ethnicity and operate through varying pathways in African-American and Black Caribbean families. The implications of intraracial variations in stress processes are discussed.


Surveying Nutrient Assessment with Photographs of Meals (SNAPMe): A Benchmark Dataset of Food Photos for Dietary Assessment.
Photo-based dietary assessment is becoming more feasible as artificial intelligence methods improve. However, advancement of these methods for dietary assessment in research settings has been hindered by the lack of an appropriate dataset against which to benchmark algorithm performance. We conducted the Surveying Nutrient Assessment with Photographs of Meals (SNAPMe) study (ClinicalTrials ID: NCT05008653) to pair meal photographs with traditional food records. Participants were recruited nationally, and 110 enrollment meetings were completed via web-based video conferencing. Participants uploaded and annotated their meal photos using a mobile phone app called Bitesnap and completed food records using the Automated Self-Administered 24-h Dietary Assessment Tool (ASA24®) version 2020. Participants included photos before and after eating non-packaged and multi-serving packaged meals, as well as photos of the front and ingredient labels for single-serving packaged foods. The SNAPMe Database (DB) contains 3311 unique food photos linked with 275 ASA24 food records from 95 participants who photographed all foods consumed and recorded food records in parallel for up to 3 study days each. The use of the SNAPMe DB to evaluate ingredient prediction demonstrated that the publicly available algorithms FB Inverse Cooking and Im2Recipe performed poorly, especially for single-ingredient foods and beverages. Correlations between nutrient estimates common to the Bitesnap and ASA24 dietary assessment tools indicated a range in predictive capacity across nutrients (cholesterol, adjusted R2 = 0.85, p < 0.0001; food folate, adjusted R2 = 0.21, p < 0.05). SNAPMe DB is a publicly available benchmark for photo-based dietary assessment in nutrition research. Its demonstrated utility suggested areas of needed improvement, especially the prediction of single-ingredient foods and beverages.


AARS2 as a novel biomarker for prognosis and its molecular characterization in pan-cancer.
The mitochondrial alanyl-tRNA synthetase 2 (AARS2) as one of aminoacyl-tRNA synthases (ARSs) performs amino acid transportation and involves protein synthesis. However, its role in cancer remains largely unexplored. In this study, more than 10,000 samples were enrolled to explore genomic alterations, biological function, prognosis, and clinical treatment based on AARS2 across pan-cancer. The molecular characterization of AARS2 was confirmed in hepatocellular carcinoma (HCC) using proteomics analysis, quantitative real-time PCR, western blotting, immunohistochemical staining, and cell experiments. For genomic landscape, the AARS2 was dramatically upregulated in multiple cancers, which might be mainly caused by copy number alteration rather than mutation and methylation. The abnormal expression of AARS2 was prominently associated with activity of cancer pathways and performed oncogenic roles in most cancers. Systematic experiments in vitro substantiated the elevated expression of AARS2, and the deficiency of it inhibited cell proliferation and cell migration in HCC. Meanwhile, our findings suggested that AARS2 could serve as a novel promising and stable biomarker for assessing prognosis and immunotherapy. Moreover, a variety of therapeutic drugs and targeted pathways were proposed for cancer treatment, which might enhance clinical efficacy. The AARS2 could serve as a new oncogenic gene that promotes cell proliferation and migration in HCC. The comprehensive investigations increased the understanding of AARS2 across human cancers and generated beginning insights of AARS2 in genomic landscape, molecular biological function, prognosis, and clinical treatment.


Kinetics of 3'-deoxy-3'-18F-fluorothymidine during treatment monitoring of recurrent high-grade glioma.
3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is used as a biomarker of cell proliferation. We investigated the kinetics of (18)F-FLT during treatment of malignant glioma with bevacizumab and irinotecan. Fifteen patients with recurrent high-grade brain tumors (2 grade III, 13 grade IV) were studied at baseline (study 1 [S1]), after 1 course of therapy (2 wk, study 2 [S2]), and at the end of therapy (6 wk, study 3 [S3]). (18)F-FLT (1.5 MBq/kg) was administered intravenously, and dynamic PET was performed for 1 h. Curves representing blood clearance and tumor uptake were derived from factor images and summed frames with thresholding techniques or with a fixed cube. The standard (18)F-FLT model was used to estimate the rate constants. (18)F-FLT uptake was measured at 2 time points (early standardized uptake value [SUV(early)] and late SUV [SUV(late)]). Parameters appeared similar for curves derived from factor images and summed frames; the steepest drop occurred between S1 and S2 for transport, influx, SUV(early), and SUV(late). Three groups were distinguished on the basis of clinical outcome: patients who died within 6 mo (group 1 [G1], n = 4), survived 6-12 mo (group 2 [G2], n = 6), and survived more than 1 y (group 3 [G3], n = 5). None of the rate constants was significantly different between the groups. Long-term survivors (G3) showed a significantly different SUV change (in percentage) between S1 and S3, whereas short-term survivors (G1 and G2) did not. Overall, the relative SUV change from S1 to S3 predicted a favorable clinical outcome, whereas the SUV change from S1 to S2 did not. Long-term survivors (G3) showed a significant drop in SUV from S1 to S2 and from S1 to S3. Significant correlations were found between SUV and both the rate constant and the influx rate. The correlation coefficient between SUV(late) and influx rate was 0.91, permitting response monitoring by the measurement of (18)F-FLT uptake changes.


Biological evaluation of biomaterials for cardiovascular applications: some current results.
The proper biologic evaluation of biomaterials for blood-contacting applications must include considerations of hemorheologic parameters, species-related differences, and damages to the reticuloendothelial system. Although there are no materials currently available that are completely blood compatible, several smooth-surfaced polymers are quite tolerable in the physiological environment. These include chemically grafted polyacrylamide hydrogels, glow-discharge polymers of silica-free hexamethldisiloxane, and ethyl cellulose perfluorobutyrate.


Higher energy collision dissociation (HCD) product ion-triggered electron transfer dissociation (ETD) mass spectrometry for the analysis of N-linked glycoproteins.
Large scale mass spectrometry analysis of N-linked glycopeptides is complicated by the inherent complexity of the glycan structures. Here, we evaluate a mass spectrometry approach for the targeted analysis of N-linked glycopeptides in complex mixtures that does not require prior knowledge of the glycan structures or pre-enrichment of the glycopeptides. Despite the complexity of N-glycans, the core of the glycan remains constant, comprising two N-acetylglucosamine and three mannose units. Collision-induced dissociation (CID) mass spectrometry of N-glycopeptides results in the formation of the N-acetylglucosamine (GlcNAc) oxonium ion and a [mannose+GlcNAc] fragment (in addition to other fragments resulting from cleavage within the glycan). In ion-trap CID, those ions are not detected due to the low m/z cutoff; however, they are detected following the beam-type CID known as higher energy collision dissociation (HCD) on the orbitrap mass spectrometer. The presence of these product ions following HCD can be used as triggers for subsequent electron transfer dissociation (ETD) mass spectrometry analysis of the precursor ion. The ETD mass spectrum provides peptide sequence information, which is unobtainable from HCD. A Lys-C digest of ribonuclease B and trypsin digest of immunoglobulin G were separated by ZIC-HILIC liquid chromatography and analyzed by HCD product ion-triggered ETD. The data were analyzed both manually and by search against protein databases by commonly used algorithms. The results show that the product ion-triggered approach shows promise for the field of glycoproteomics and highlight the requirement for more sophisticated data mining tools.


[Comparative analysis of osteotomy methods in open setting of congenital hip dislocation in children].
There is given an analysis of the treatment of 89 children (99 joints) with congenital femur dislocation, which were subjected to corrective osteotomy at the open setting by three different methods. There are shown the advantages of oblique osteotomy, proposed by the authors. There have been developed and substantiated the indications for application of oblique and transversal osteotomy of the femur.


Molecular Investigation of SARS-CoV-2 Proteins and Their Interactions with Antiviral Drugs.
A new Coronavirus strain, named SARS-CoV-2, suddenly emerged in early December 2019. SARS-CoV-2 resulted in being dramatically infectious, with thousands of people infected. In this scenario, and without effective vaccines available, the importance of an immediate tool to support patients and against viral diffusion becomes evident. In this study, we exploit the molecular docking approach to analyze the affinity between different viral proteins and several inhibitors, originally developed for other viral infections. Our data show that, in some cases, a relevant binding can be detected. These findings support the hypothesis to develop new antiviral agents against COVID-19, on the basis of already established therapies.


Sensory acceptability of biofortified foods and food products: a systematic review.
It is important to understand the sensory acceptability of biofortified food products among target population groups if biofortification is to be realized as a sustainable strategy for mitigation of micronutrient deficiencies, able to be scaled up and applied through programs. This systemic review aims to summarize and synthesize the sensory acceptability of conventionally bred iron-, zinc-, and provitamin A-biofortified food products. MEDLINE (PubMed), AGRICOLA, AgEcon, CABI Abstracts (Web of Science), and organizational websites (eg, those of HarvestPlus and CGIAR and their partners) were searched for relevant articles. No access to any market research that may have been internally conducted for the commercial biofortified food products was available. This review identified articles measuring the sensory acceptability of conventionally bred biofortified food products. Extraction of the hedonic ratings of food products was performed. An "Acceptability Index %" was defined based on hedonic scoring to determine an overall rating, and used to categorize biofortified food products as "acceptable" (≥70%) or "not acceptable" (<70%). Additionally, this review narratively synthesized studies using methods other than hedonic scoring for assessing sensory acceptability. Forty-nine studies assessed the acceptability of 10 biofortified crops among children and adults, in mostly rural, low-income settings across Africa, Latin America, and India; food products made from mineral and provitamin A-biofortified food products were generally acceptable. Compared with studies on provitamin-A biofortified food products, few studies (1 to 2 each) on mineral-enhanced crops such as rice, cowpeas, lentils, and wheat were found, limiting the generalizability of the findings. Similarly, few studies examined stored biofortified food products. Few commercial food products have so far been developed, although new varieties of crops are being continuously tested and released globally. Certain crop varieties were found to be acceptable while others were not, suggesting that particular varieties should be prioritized for scale-up. Determining sensory acceptability of biofortified food products is important for informing programmatic scale-up and implementation across diverse populations and settings.


Complementary and Alternative Medicine Use and Symptom Burden in Women Undergoing Chemotherapy for Breast Cancer in Malaysia.
Complementary and alternative medicine (CAM) is commonly used for cancer- and chemotherapy-related symptoms. Nurses are likely to encounter many CAM users in their practice. The aims of this study were to assess CAM use and examine the symptom burden of CAM and non-CAM users among patients with breast cancer who are undergoing chemotherapy. A CAM use questionnaire and the Side-Effect Burden Scale were administered to 546 patients. Complementary and alternative medicine use was categorized as mind-body practices (MBPs), natural products (NPs), or traditional medicine (TM). We identified 386 CAM users (70.7%) in this study. The CAM users reported a higher marginal mean total symptom burden score (40.39 ± 2.6) than non-CAM users (36.93 ± 3.21), although this difference was not statistically significant (P = .09). Triple-modality (MBP-NP-TM) CAM users had a significantly higher marginal mean total symptom burden score (47.44 ± 4.12) than single-modality (MBP) users (34.09 ± 4.43). The risk of having a high total symptom burden score was 12.9-fold higher among the MBP-NP-TM users than among the MBP users. Complementary and alternative medicine use is common among Malaysian patients who are undergoing chemotherapy for breast cancer. However, CAM and non-CAM users reported similar symptom burdens, although single-modality use of MBP is likely associated with a lower symptom burden. Nurses should keep abreast of current developments and trends in CAM use. Understanding CAM use and the related symptom burden will allow nurses to initiate open discussion and guide their patients in seeking additional information or referrals for a particular therapy.


[Hypoglycemic activity of hypolipidemic preparations].
The system of glucose metabolism regulation is millions of years older than the insilin system and locomotor function. For this reason, the hypoglycemic activity of the hormone is mediated through fatty acid (FA) metabolism. Insulin blocks the ability of mitochondria to oxidize ketone bodies, short-, medium- and long-chain FA and makes them oxidize glucose, i.e. a physiologically unoptimal substrate. The relationship between FA and glucose in the Rnadle cycle is apparent only on the autocrine level (in the cell); they determine alternation of nutritive function (trophology) and biological exo/endo-reactions (after and without feeding respectively). Most antidiabetic medicines exhibit hypoglycemic activity, like insulin; they reduce the level of lipid substrates of oxidation in cytosol and mitochondria have to oxidize glucose. In these conditions, insulin increases glucose uptake by the cells mediated through GLUT4 transporters. Sulfonylurea derivatives enhance secretion of insulin by beta-cell. Biguanides covalently and irreversibly bind ketone bodies thereby preventing their oxidation by mitochondria. Fibrates, glitazones, flavonides, flavones, lipoic thio-FA, endogenous eicosanoids, derivatives of Ω-3 and Ω-6 essential polyenic FA, and conjugated unsaturated FA are agonists of peroxisome proliferator-activated receptors. They stimulate α-, β-, and Ω-oxidation of all exogenous a physiological FA and excessive palmitic saturated FA in peroxisomes which leads to cytosol hypolipidemia. Hypoglycemic preparations with the activity of oxidation beta-blockers arrest FA uptake by mitochondria. Hypoglycemic Ω-3 essential polyenoic FA activate GLUT4 function. Type 2 diabetes in middle-aged patients is a symptom of atherosclerosis, i.e. deficit of essential polyenoic FA caused by disturbed phospholipid synthesis and GLUT4 function. Diabetes should be in the first place considered as pathological FA metabolism and only in the second place as glucose pathology. This inference needs to be taken into account in the treatment of diabetes and in strategic programs of its prophylaxis.


Effects of preoperative administration of ketoprofen on whole blood platelet aggregation, buccal mucosal bleeding time, and hematologic indices in dogs undergoing elective ovariohysterectomy.
To determine effects of preoperative administration of ketoprofen on whole blood platelet aggregation, buccal mucosal bleeding time, and hematologic indices in dogs after elective ovariohysterectomy. Randomized, masked clinical trial. 22 healthy dogs. 60 minutes before induction of anesthesia, 11 dogs were given 0.9% NaCl solution (control), and 11 dogs were given ketoprofen (2 mg/kg [0.9 mg/lb], IM). Thirty minutes before induction of anesthesia, glycopyrrolate (0.01mg/kg [0.005 mg/lb]), acepromazine (0.05 mg/kg [0.02 mg/lb]), and butorphanol (0.2 mg/kg 10.09 mg/lb]) were given IM to all dogs. Anesthesia was induced with thiopental (5 to 10 mg/kg [2.3 to 4.5 mg/lb], IV) and maintained with isoflurane (1 to 3%). Ovariohysterectomy was performed and butorphanol (0.1 mg/kg [0.05 mg/lb], IV) was given 15 minutes before completion of surgery. Blood samples for measurement of variables were collected at intervals before and after surgery. In dogs given ketoprofen, platelet aggregation was decreased 95 +/- 10% and 80 +/- 35% (mean +/- SD) immediately after surgery and 24 hours after surgery, respectively, compared with preoperative values. At both times, mean values in dogs given ketoprofen differed significantly from those in control dogs. Significant differences between groups were not observed for mucosal bleeding time or hematologic indices. Preoperative administration of ketoprofen inhibited platelet aggre gation but did not alter bleeding time. Ketoprofen can be given before surgery to healthy dogs undergoing elective ovariohysterectomy, provided that dogs are screened for potential bleeding problems before surgery and monitored closely after surgery.


The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients.
The X-linked hyper-IgM (XHIGM) syndrome is an uncommon primary immunodeficiency disease caused by mutations in the gene for CD40 ligand and characterized by normal or elevated serum IgM, reduced levels of IgG and IgA, and defective T-cell function. Because of its rarity, it has been difficult for any single investigator or institution to develop a comprehensive clinical picture of this disorder. Accordingly, a national registry was developed in the United States to provide demographic, genetic, immunologic, and clinical information on a relatively large number of patients with the XHIGM syndrome.A total of 79 patients from 60 unrelated families were registered between January 1997 and July 2002. The estimated minimal incidence was approximately 1/1,030,000 live births. All of the patients had significant IgG deficiency and most had IgA deficiency, but only one-half had elevated IgM levels. Most patients presented initially with a history of an increased susceptibility to infection including Pneumocystis carinii pneumonia. The average age of diagnosis was significantly earlier in patients born into a family with a previously affected individual. However, only one-third of the patients born into a family with a previously affected individual were diagnosed exclusively because of the presence of the positive family history before any clinical symptoms developed. Over half the patients developed symptoms of immunodeficiency and were diagnosed by 1 year of age, and over 90% by 4 years of age. The most prominent clinical infections were pneumonia (81% of patients), upper respiratory infections (49%) including sinusitis (43%) and recurrent otitis (43%), recurrent/protracted diarrhea (34%), central nervous system infections (14%), sepsis (13%), cellulitis (13%), hepatitis (9%), and osteomyelitis (1%). In addition to infections caused by encapsulated bacteria, opportunistic infections were relatively common and were caused by P. carinii, members of the herpes virus family (including cytomegalovirus), Cryptosporidium, Cryptococcus, Candida, Histoplasma, and Bartonella. Sclerosing cholangitis occurred in 5 patients and in 4 of these was associated with Cryptosporidium infection. Eight patients had died at the time of their entry into the Registry; 2 of pneumonia (1 P. carinii and 1 cytomegalovirus), 2 of encephalitis (1 ECHO virus and 1 cytomegalovirus), 2 of malignancy (both hepatocellular carcinoma), 1 of sclerosing cholangitis caused by Cryptosporidium, and 1 of hemolytic uremic syndrome.


The time course and extracellular Ca2+ involvement of growth hormone (GH) releasing factor-induced GH secretion in perifused dispersed rat pituitary cells.
The time course of GH secretion in response to hpGRF and its dependency on the extracellular Ca2+ concentration were studied in perifused dispersed anterior pituitary cells. The onset of GH secretion in response to 1 nM hpGRF was relatively rapid (within 5 s) but removal of hpGRF after 10-min application further increased the rate of secretion (off-response). The threshold and maximum concentrations of hpGRF in stimulatory secretion were 10(-12) and 10(-8) M respectively. Between these two concentrations, the responses showed dose dependency. A reduction in the extracellular Ca2+ concentration to 0.25 mM or to nominally zero reduced hpGRF-induced GH secretion to 64.4% or to 1.9%, respectively, of the control response in the presence of 2.5 mM Ca2+. Two mM Co2+, known as a strong calcium channel blocker, completely suppressed hpGRF-induced GH secretion. The removal of Ca2+ from the perifusion buffer immediately after the offset of 1 min-applied 1 nM hpGRF accelerated the falling phase of GH secretion, which is parallel to the decline in [Ca2+]o in the perifusion chamber. Under nominal Ca2+-free conditions, hpGRF produced no increase in GH secretion. However, 10 min after the offset of 1 min-applied hpGRF under Ca2+-free conditions, the introduction of normal buffer containing 2.5 mM Ca2+ substantially restored GH secretion, although after 20 min the introduction of normal buffer produced only a slight increase in GH secretion. In perifusion experiment of 10(6) cells, intracellular cyclic AMP (cAMP) content was raised from the basal value of 4 to 26 pmol by 2-min application of 1 nM hpGRF. After cessation of hpGRF application, cAMP content decreased to 8.7 pmol at 11 min and returned to the basal value by 20 min. The same tendency was observed in Ca2+-free buffer. In conclusion, the extracellular Ca2+ was essential for hpGRF-induced GH secretion. This indicates the importance of the influx of Ca2+ in response to hpGRF. The time course of hpGRF-induced rise and fall in cAMP content was roughly parallel to the GH secretion. The possible explanations of the off-response and the restoration of GH secretion by reintroducing normal buffer were discussed.


Discriminating and classifying odontocete echolocation clicks in the Hawaiian Islands using machine learning methods.
Passive acoustic monitoring (PAM) has proven a powerful tool for the study of marine mammals, allowing for documentation of biologically relevant factors such as movement patterns or animal behaviors while remaining largely non-invasive and cost effective. From 2008-2019, a set of PAM recordings covering the frequency band of most toothed whale (odontocete) echolocation clicks were collected at sites off the islands of Hawai'i, Kaua'i, and Pearl and Hermes Reef. However, due to the size of this dataset and the complexity of species-level acoustic classification, multi-year, multi-species analyses had not yet been completed. This study shows how a machine learning toolkit can effectively mitigate this problem by detecting and classifying echolocation clicks using a combination of unsupervised clustering methods and human-mediated analyses. Using these methods, it was possible to distill ten unique echolocation click 'types' attributable to regional odontocetes at the genus or species level. In one case, auxiliary sightings and recordings were used to attribute a new click type to the rough-toothed dolphin, Steno bredanensis. Types defined by clustering were then used as input classes in a neural-network based classifier, which was trained, tested, and evaluated on 5-minute binned data segments. Network precision was variable, with lower precision occurring most notably for false killer whales, Pseudorca crassidens, across all sites (35-76%). However, accuracy and recall were high (>96% and >75%, respectively) in all cases except for one type of short-finned pilot whale, Globicephala macrorhynchus, call class at Kaua'i and Pearl and Hermes Reef (recall >66%). These results emphasize the utility of machine learning in analysis of large PAM datasets. The classifier and timeseries developed here will facilitate further analyses of spatiotemporal patterns of included toothed whales. Broader application of these methods may improve the efficiency of global multi-species PAM data processing for echolocation clicks, which is needed as these datasets continue to grow.


Adenoviral mediated delivery of FAS ligand to arthritic joints causes extensive apoptosis in the synovial lining.
Rheumatoid arthritis (RA) is an autoimmune disease where the synovial lining layer of the joint becomes thickened, hypercellular, and highly aggressive. Invading synovial tissue erodes cartilage and subchondral bone and leads to loss of joint function. FasL, a cell-surface molecule on activated T-cells interacts with its receptor, Fas, to induce apoptosis in target cells. We addressed the feasibility of using adenoviral gene transfer of FasL therapeutically to mediate apoptosis in arthritic joints similar in size to the small joints of the hands and feet that are the primary sites of RA in humans. Adenoviral vectors were used to transfer FasL and LacZ cDNAs into human RA and rabbit synovial fibroblasts in culture where apoptosis was evaluated using MTT and TUNEL analyses. The ability of Ad.FasL to mediate synovial apoptosis in vivo was then addressed in an IL-1-induced arthritis model in the rabbit knee. In culture, delivery of FasL was found to efficiently induce apoptosis in both human RA and rabbit synovial fibroblasts. The ability of Ad.FasL to induce synovial apoptosis was then evaluated in rabbit knee joints. 24 h after intra-articular injection of 10(11) Ad.FasL particles, large regions of synovial tissue were observed histologically consisting primarily of fibrous matrix and cellular debris. TUNEL staining of corresponding sections was highly positive for fragmented DNA. Glycosaminoglycan (GAG) synthesis from cartilage shavings from treated joints suggests that Ad.FasL does not induce significant apoptosis in resident articular chondrocytes. Infection of human and rabbit synovial fibroblasts with Ad.FasL results in significant apoptotic cell death in vitro. Direct intra-articular injection of Ad.FasL in the arthritic rabbit knee results in extensive apoptosis in the synovium without affecting chondrocyte viability.


Spinal subdural hemorrhage in abusive head trauma: a retrospective study.
To compare the relative incidence, distribution, and radiologic characteristics of spinal subdural hemorrhage after abusive head trauma versus that after accidental trauma in children. This study received prior approval from the Human Subjects Protection Office. Informed consent was waived. This study was HIPAA compliant. Two hundred fifty-two children aged 0-2 years treated for abusive head trauma at our institute between 1997 and 2009 were identified through retrospective chart review. A second group of 70 children aged 0-2 years treated at our institute for well-documented accidental trauma between 2003 and 2010 were also identified through retrospective chart review. All clinical data and cross-sectional imaging results, including computed tomographic and magnetic resonance imaging of the brain, spine, chest, abdomen, and pelvis, were reviewed for both of these groups. A Fisher exact test was performed to assess the statistical significance of the proportion of the spinal canal subdural hemorrhage in abusive head trauma versus that in accidental trauma. In the abusive head trauma cohort, 67 (26.5%) of 252 children had evaluable spinal imaging results. Of these, 38 (56%) of 67 children had undergone thoracolumbar imaging, and 24 (63%) of 38 had thoracolumbar subdural hemorrhage. Spinal imaging was performed in this cohort 0.3-141 hours after injury (mean, 23 hours ± 27 [standard deviation]), with 65 (97%) of 67 cases having undergone imaging within 52 hours of injury. In the second cohort with accidental injury, only one (1%) of 70 children had spinal subdural hemorrhage at presentation; this patient had displaced occipital fracture. The comparison of incidences of spinal subdural hemorrhage in abusive head trauma versus those in accidental trauma was statistically significant (P < .001). Spinal canal subdural hemorrhage was present in more than 60% of children with abusive head trauma who underwent thoracolumbar imaging in this series but was rare in those with accidental trauma.


Do Attentional Lapses Account for the Worst Performance Rule?
The worst performance rule (WPR) describes the phenomenon that individuals' slowest responses in a task are often more predictive of their intelligence than their fastest or average responses. To explain this phenomenon, it was previously suggested that occasional lapses of attention during task completion might be associated with particularly slow reaction times. Because less intelligent individuals should experience lapses of attention more frequently, reaction time distribution should be more heavily skewed for them than for more intelligent people. Consequently, the correlation between intelligence and reaction times should increase from the lowest to the highest quantile of the response time distribution. This attentional lapses account has some intuitive appeal, but has not yet been tested empirically. Using a hierarchical modeling approach, we investigated whether the WPR pattern would disappear when including different behavioral, self-report, and neural measurements of attentional lapses as predictors. In a sample of N = 85, we found that attentional lapses accounted for the WPR, but effect sizes of single covariates were mostly small to very small. We replicated these results in a reanalysis of a much larger previously published data set. Our findings render empirical support to the attentional lapses account of the WPR.


Body size and activity times mediate mammalian responses to climate change.
Model predictions of extinction risks from anthropogenic climate change are dire, but still overly simplistic. To reliably predict at-risk species we need to know which species are currently responding, which are not, and what traits are mediating the responses. For mammals, we have yet to identify overarching physiological, behavioral, or biogeographic traits determining species' responses to climate change, but they must exist. To date, 73 mammal species in North America and eight additional species worldwide have been assessed for responses to climate change, including local extirpations, range contractions and shifts, decreased abundance, phenological shifts, morphological or genetic changes. Only 52% of those species have responded as expected, 7% responded opposite to expectations, and the remaining 41% have not responded. Which mammals are and are not responding to climate change is mediated predominantly by body size and activity times (phylogenetic multivariate logistic regressions, P < 0.0001). Large mammals respond more, for example, an elk is 27 times more likely to respond to climate change than a shrew. Obligate diurnal and nocturnal mammals are more than twice as likely to respond as mammals with flexible activity times (P < 0.0001). Among the other traits examined, species with higher latitudinal and elevational ranges were more likely to respond to climate change in some analyses, whereas hibernation, heterothermy, burrowing, nesting, and study location did not influence responses. These results indicate that some mammal species can behaviorally escape climate change whereas others cannot, analogous to paleontology's climate sheltering hypothesis. Including body size and activity flexibility traits into future extinction risk forecasts should substantially improve their predictive utility for conservation and management.


Inclusion membrane proteins of Protochlamydia amoebophila UWE25 reveal a conserved mechanism for host cell interaction among the Chlamydiae.
Chlamydiae are a group of obligate intracellular bacteria comprising several important human pathogens. Inside the eukaryotic cell, chlamydiae remain within a host-derived vesicular compartment, termed the inclusion. They modify the inclusion membrane through insertion of unique proteins, which are involved in interaction with and manipulation of the host cell. Among chlamydiae, inclusion membrane proteins have been exclusively found in members of the family Chlamydiaceae, which predominantly infect mammalian and avian hosts. Here, the presence of inclusion membrane proteins in Protochlamydia amoebophila UWE25, a chlamydial endosymbiont of free-living amoebae, is reported. A genome-wide screening for secondary structure motifs resulted in the identification of 23 putative inclusion membrane proteins for this organism. Immunofluorescence analysis demonstrated that five of these proteins were expressed, and four of them could be localized to a halo surrounding the intracellular bacteria. Colocalization studies showed an almost complete overlap of the signals obtained for the four putative inclusion membrane proteins, and immuno-transmission electron microscopy unambiguously demonstrated their location in the inclusion membrane. The presence of inclusion membrane proteins (designated IncA, IncQ, IncR, and IncS) in P. amoebophila shows that this strategy for host cell interaction is conserved among the chlamydiae and is used by chlamydial symbionts and pathogens alike.