[The effect of low-frequency impulse electrotherapy on the function of the neurohumoral systems regulating the arterial pressure in hypertensive patients].
The function of humoral regulatory systems was studied in hypertensive patients. Relevant dysfunctions appeared related to hemodynamic types. In the hyperkinetic hemodynamic type the greatest benefit for pressor and depressor regulation was achieved with square-wave impulse 10 Hz currents under the orbital method, in the hypokinetic--with sinusoidal modulated currents at 100 Hz modulation frequency. 30 Hz sinusoidal modulated currents under orbital method are able to bring about a marked decrease in both pressor and depressor hormones levels in hypokinetic pattern of hemodynamics producing short-term hypotensive effects. Humoral action of low-frequency impulse electrotherapy depends on the current characteristics, frequency and site of exposure.


Dementia caregiving in the Middle East and North Africa: A scoping review.
Care for persons with dementia in the Middle East and North Africa (MENA) is undertaken predominantly by family members, domestic workers, and private nurses within the home. Domestic caregivers possess different understandings and varying degrees of knowledge of dementia that are influenced by complex socio-cultural and religious factors. With much of the burden falling on the shoulders of "invisible" caregivers, the role and needs of these individuals require deeper scrutiny. The purpose of this scoping review was to examine the empirical studies published on caring for persons with dementia in Arab countries of the MENA region. Using a systematic review technique, searches were conducted on PubMed, Embase, Web of Science, Scopus, and Google Scholar using database-specific terms associated with caregiving, dementia, aging, and the MENA region. To ensure local and regional research was captured, hand searches of regional journals, reference lists of included articles, and Arabic databases Al-Manhal and e-Marefa were also searched. No date restrictions were imposed. Twenty studies met inclusion criteria and the following themes were identified: caregiving experiences and the burden of care; barriers to caregiving; and caregiver recommendations to improve care. Results demonstrate that studies about informal caregivers and dementia within Arab-Muslim populations are underrepresented in the research. This review highlights the paucity of literature on service users' experiences and underscores the need for future research specific to dementia care within the Arab-Islamic sociocultural context. These trajectories are especially pertinent given the unprecedented aging demographics of the MENA populations.


Changes in histone synthesis and modification at the beginning of mouse development correlate with the establishment of chromatin mediated repression of transcription.
The transition from a late 1-cell mouse embryo to a 4-cell embryo, the period when zygotic gene expression begins, is accompanied by an increasing ability to repress the activities of promoters and replication origins. Since this repression can be relieved by either butyrate or enhancers, it appears to be mediated through chromatin structure. Here we identify changes in the synthesis and modification of chromatin bound histones that are consistent with this hypothesis. Oocytes, which can repress promoter activity, synthesized a full complement of histones, and histone synthesis up to the early 2-cell stage originated from mRNA inherited from the oocyte. However, while histones H3 and H4 continued to be synthesized in early 1-cell embryos, synthesis of histones H2A, H2B and H1 (proteins required for chromatin condensation) was delayed until the late 1-cell stage, reaching their maximum rate in early 2-cell embryos. Moreover, histone H4 in both 1-cell and 2-cell embryos was predominantly diacetylated (a modification that facilitates transcription). Deacetylation towards the unacetylated and monoacetylated H4 population in fibroblasts began at the late 2-cell to 4-cell stage. Arresting development at the beginning of S-phase in 1-cell embryos prevented both the appearance of chromatin-mediated repression of transcription in paternal pronuclei and synthesis of new histones. These changes correlated with the establishment of chromatin-mediated repression during formation of a 2-cell embryo, and the increase in repression from the 2-cell to 4-cell stage as linker histone H1 accumulates and core histones are deacetylated.


High macromolecular synthesis with low metabolic cost in Antarctic sea urchin embryos.
Assessing the energy costs of development in extreme environments is important for understanding how organisms can exist at the margins of the biosphere. Macromolecular turnover rates of RNA and protein were measured at -1.5 degrees C during early development of an Antarctic sea urchin. Contrary to expectations of low synthesis with low metabolism at low temperatures, protein and RNA synthesis rates exhibited temperature compensation and were equivalent to rates in temperate sea urchin embryos. High protein metabolism with a low metabolic rate is energetically possible in this Antarctic sea urchin because the energy cost of protein turnover, 0.45 joules per milligram of protein, is 1/25th the values reported for other animals.


Enzymatic Upcycling of PET Waste to Calcium Terephthalate for Battery Anodes.
Biotechnological recycling offers a promising solution to address the environmental concerns associated with waste plastics, particularly polyethylene terephthalate (PET), widely utilized in packaging materials and textiles. To advance the development of a bio-based circular plastic economy, innovative upcycling strategies capable of generating higher-value products are needed. In this study, we enhanced the enzymatic depolymerization of waste PET by incorporating highly concentrated calcium ions (up to 1 m) to the hydrolytic reaction catalyzed by the best currently known enzyme LCCICCG . The presence of calcium ions not only improved the thermal stability and activity of the biocatalyst but also significantly reduced the consumption of base required to maintain optimal pH levels. Employing optimized conditions at 80 °C for 12 h, we successfully converted ≈84 % of the waste PET (200 g L-1 ) into solid hydrated calcium terephthalate (CaTP ⋅ 3H2 O) as the primary product instead of soluble terephthalate salt. CaTP ⋅ 3H2 O was easily purified and employed as a raw material for battery electrode production, exhibiting an initial reversible specific capacity of 164.2 mAh g-1 . Through techno-economic analysis, we conclusively demonstrated that the one-pot biocatalysis-based synthesis of CaTP is a superior PET upcycling strategy than the secondary synthesis method employing recycled terephthalic acid.


Curiosity-driven memory enhancement persists over time but does not benefit from post-learning sleep.
Sleep-dependent memory processing is dependent on several factors at learning, including emotion, encoding strength, and knowledge of future relevance. Recent work documents the role of curiosity on learning, showing that memory associated with high-curiosity encoding states is retained better and that this effect may be driven by activity within the dopaminergic circuit. Here, we examined whether this curiosity effect was enhanced by or dependent on sleep-related consolidation. Participants learned the answers to trivia questions that they had previously rated on a curiosity scale, and they were shown faces between each question and answer presentation. Memory for these answers and faces was tested either immediately or after a 12-hour delay containing sleep or wakefulness, and polysomnography data was collected for a subset of the sleep participants. Although the curiosity effect for both the answers and incidentally-learned faces was replicated in immediate tests and after the 12-hour delay, the effect was not impacted by the presence of sleep in either case, nor did the effect show a relationship with total sleep time or time in slow-wave sleep. This study suggests that curiosity may be a learning factor that is not subsequently affected by sleep-dependent memory consolidation, but more work ought to examine the role of sleep on curiosity-driven memory in other contexts.


High risk sexual behavior among adolescent senior secondary school students in Nigeria.
The consequences of high risk sexual practices (HRSP) are enormous among adolescent senior secondary school students. They therefore need to have sufficient knowledge of HRSP. The study gauged the level of knowledge and perceptions of high risk sexual behavior among senior secondary school students in Ilorin, Nigeria with a view to improving their understanding of the current trends in HRSP.This was a quantitative, cross-sectional, descriptive study of adolescent secondary school students in Ilorin East Local Government Area. Multi - stage sampling method involving 3 stages was used. A semi-structured interviewer administered questionnaire was used to obtain data. Informed consent of respondents was obtained. The data was analyzed using SPSS windows software package version 17. Majority, 305 (69.5%) of the students were between 16 - 20 years. The major source of information was from movies, 42.5%, and the internet, 24.7%. Twenty-three percent (23.1%) had poor knowledge of HRSP. Thirty-eight percent (38.1%) did not consider indiscriminate sexual intercourse as HRSP while 27.9% still believed that unprotected sexual practice is safe. Thirty-four percent (34.2%) did not know that sex with multiple partners is a HRSP while 34.4% did not know that oral -genital sex is unsafe. Over thirty-two (32.9%) perceived that engaging in sex made them mature among peers. Twenty-four (24.7%) did not perceive any danger in keeping multiple sexual partners while 15.3% would still engage in unprotected sex. The students had relatively poor knowledge and perceptions of HRSP. Quite a number did not consider indiscriminate sexual intercourse as HRSP. An appreciable number did not perceive any danger in keeping multiple sexual partners or beingengaged in unprotected sex. Counselling on the dangers of HRSP should be a component of the school health services so as to curb the complications of HRSP in our secondary schools.


Abundance of Oligoflexales bacteria is associated with algal symbiont density, independent of thermal stress in Aiptasia anemones.
Many multicellular organisms, such as humans, plants, and invertebrates, depend on symbioses with microbes for metabolic cooperation and exchange. Reef-building corals, an ecologically important order of invertebrates, are particularly vulnerable to environmental stress in part because of their nutritive symbiosis with dinoflagellate algae, and yet also benefit from these and other microbial associations. While coral microbiomes remain difficult to study because of their complexity, the anemone Aiptasia is emerging as a simplified model. Research has demonstrated co-occurrences between microbiome composition and the abundance and type of algal symbionts in cnidarians. However, whether these patterns are the result of general stress-induced shifts or depletions of algal-associated bacteria remains unclear. Our study aimed to distinguish the effect of changes in symbiont density and thermal stress on the microbiome of symbiotic Aiptasia strain CC7 by comparing them with aposymbiotic anemones, depleted of their native symbiont, Symbiodinium linucheae. Our analysis indicated that overall thermal stress had the greatest impact on disrupting the microbiome. We found that three bacterial classes made up most of the relative abundance (60%-85%) in all samples, but the rare microbiome fluctuated between symbiotic states and following thermal stress. We also observed that S. linucheae density correlated with abundance of Oligoflexales, suggesting these bacteria may be primary symbionts of the dinoflagellate algae. The findings of this study help expand knowledge on prospective multipartite symbioses in the cnidarian holobiont and how they respond to environmental disturbance.


[Multiple transplantation of abdominal organs].
The transplantation of multiple abdominal viscera including liver-duodenum-pancreas, liver-stomach-duodenum-pancreas, and liver-intestine is being performed with increasing frequency and success. These procedures and other variations are derived from a seldom used multivisceral operation in which all of the foregoing organs are transplanted in bloc. It is described here how the full multivisceral transplantation and its less extensive derivatives are based on the same principles of procurement, preservation, and postoperative management. With all of these multiple organ permutations and with intestinal transplantation alone, management is complicated by inclusion in the grafts of a large lymphoreticular component which is capable of causing graft versus host disease (GVHD). Because of a systematic error in therapeutic philosophy, past efforts have been directed at altering or damaging the lymphoreticular cells by pretreatment of the donor or of the organs with drugs, irradiation or other means. From recent observations, the alternative approach is suggested of keeping these lymphoid depots intact which then become the site of 2 way cell traffic after transplantation. Under powerful immunosuppression such as that provided with FK 506, the donor lymphoreticular cells can circulate in the recipient without causing clinical GVHD, and the lymphoreticular cells in the graft become those of the recipient (local chimerism) without causing rejection. Even with avoidance of rejection and GVHD, metabolic interrelations between the grafted organs, and also between the graft organs and retained recipient viscera can affect the fate of the individual transplanted organs or retained recipient organs. The best delineated of these metabolic influences are mediated by the endogenous splanchnic hepatotrophic factors of which insulin has been the most completely studied. An understanding of these various immunologic and non-immunologic factors combined with the more potent immunosuppression which is now available is sure to stimulate efforts at transplantation of abdominal organs and particularly of the hollow viscera which heretofore have resisted such clinical efforts.


Lobbying and advocacy for the public's health: what are the limits for nonprofit organizations?
Nonprofit organizations play an important role in advocating for the public's health in the United States. This article describes the rules under US law for lobbying by nonprofit organizations. The 2 most common kinds of non-profits working to improve the public's health are "public charities" and "social welfare organizations." Although social welfare organizations may engage in relatively unlimited lobbying, public charities may not engage in "substantial" lobbying. Lobbying is divided into 2 main categories. Direct lobbying refers to communications with law-makers that take a position on specific legislation, and grassroots lobbying includes attempts to persuade members of the general public to take action regarding legislation. Even public charities may engage in some direct lobbying and a smaller amount of grassroots lobbying. Much public health advocacy, however, is not lobbying, since there are several important exceptions to the lobbying rules. These exceptions include "non-partisan analysis, study, or research" and discussions of broad social problems. Lobbying with federal or earmarked foundation funds is generally prohibited.


Musculoskeletal chest wall pain.
The musculoskeletal structures of the thoracic wall and the neck are a relatively common source of chest pain. Pain arising from these structures is often mistaken for angina pectoris, pleurisy or other serious disorders. In this article the clinical features, pathogenesis and management of the various musculoskeletal chest wall disorders are discussed. The more common causes are costochondritis, traumatic muscle pain, trauma to the chest wall, "fibrositis" syndrome, referred pain, psychogenic regional pain syndrome, and arthritis involving articulations of the sternum, ribs and thoracic spine. Careful analysis of the history, physical findings and results of investigation is essential for precise diagnosis and effective treatment.


Using gaming simulation to evaluate bioterrorism and emergency readiness training.
The University of Minnesota: Simulations, Exercises and Effective Education: Preparedness and Emergency Response Learning Center uses simulations, which allow trainees to participate in realistic scenarios, to develop and evaluate competency. In a previous study, participants in Disaster in Franklin County: A Public Health Simulation demonstrated that prior bioterrorism and emergency readiness training (BT/ER) is significantly associated with better performance in a simulated emergency. We conducted a second analysis with a larger data set, remapping simulation questions to the Public Health Preparedness and Response Core Competency Model, Version 1.0. We performed an outcome evaluation of the impact of public health preparedness training. In particular, we compared individuals with significant BT/ER training to individuals without training on the basis of performance in a simulated emergency. We grouped participants as group 1 (≥45 hours of BT/ER training) and group 2 (<45 hours). Dependent variables included effectiveness of chosen responses within the gaming simulation, which was measured as the proportion of questions answered correctly for each participant. The relationship of effectiveness with significant BT/ER training was estimated using either multiple linear or logistic regression. For overall effectiveness, group 1 had 2% more correct decisions, on average, than group 2 (P < .001). Group 1 performed significantly better, on average, than group 2 for competency 1.1 (P = .001) and competency 2.3 (P < .001). However, group 1 was significantly worse on competency 1.2 than group 2. Results indicate that prior training is significantly associated with better performance in a simulated emergency using gaming technology. Effectiveness differed by competency, indicating that more training may be needed in certain competency areas. Next steps to enhancing the usefulness of simulations in training should go beyond questioning if the learner learned and included questions related to the organizational factors that contributed to simulation effectiveness, and attributes of the simulation that encouraged competency and capacity building.


Vitamin A Enhances Macrophages Activity Against B16-F10 Malignant Melanocytes: A New Player for Cancer Immunotherapy?
Background and objectives: The incidence of cutaneous melanoma has been increasing. Melanoma is an aggressive form of skin cancer irresponsive to radiation and chemotherapy, rendering this cancer a disease with poor prognosis: In order to surpass some of the limitations addressed to melanoma treatment, alternatives like vitamins have been investigated. In the present study, we address this relationship and investigate the possible role of vitamin A. Materials and Methods: We perform a co-culture assay using a macrophage cell model and RAW 264.7 from mouse, and also a murine melanoma cell line B16-F10. Macrophages were stimulated with both Escherichia coli lipopolysaccharides (LPS) as control, and also with LPS plus vitamin A. Results: Using B16-F10 and RAW 264.7 cell lines, we were able to demonstrate that low concentrations of vitamin A increase cytotoxic activity of macrophages, whereas higher concentrations have the opposite effect. Conclusion: These findings can constitute a new point of view related to immunostimulation by nutrients, which may be considered one major preventive strategy by enhancing the natural defense system of the body.


Explaining Andean megadiversity: the evolutionary and ecological causes of glassfrog elevational richness patterns.
The Tropical Andes are an important global biodiversity hotspot, harbouring extraordinarily high richness and endemism. Although elevational richness and speciation have been studied independently in some Andean groups, the evolutionary and ecological processes that explain elevational richness patterns in the Andes have not been analysed together. Herein, we elucidate the processes underlying Andean richness patterns using glassfrogs (Centrolenidae) as a model system. Glassfrogs show the widespread mid-elevation diversity peak for both local and regional richness. Remarkably, these patterns are explained by greater time (montane museum) rather than faster speciation at mid-elevations (montane species pump), despite the recency of the major Andean uplift. We also show for the first time that rates of climatic-niche evolution and elevational change are related, supporting the hypothesis that climatic-niche conservatism decelerates species' shifts in elevational distributions and underlies the mid-elevation richness peak. These results may be relevant to other Andean clades and montane systems globally.


Modified sucrose, starch, and ATP levels in two alloplasmic male-sterile lines of B. napus.
Alloplasmic lines of Brassica napus with rearranged Arabidopsis thaliana mitochondrial DNA are male sterile and vegetatively altered compared with B. napus cv. Hanna. The CMS lines contain pure nuclear and plastid genomes from B. napus. Cross-sections of leaves revealed elevated starch accumulation and a higher number of chloroplasts per cell area in CMS plants compared with B. napus. The increase in chloroplast density was found to be the result of the smaller mesophyll cells. Sucrose concentration in the leaves of the CMS lines was reduced both in green leaves as well as in leaves from 2 d-etiolated plants. Flower meristem, flower buds, and leaves from green and 2 d-etiolated plants were analysed for ATP and ADP contents. All CMS plant tissues, except for green leaves, possessed lower ATP levels than B. napus. The results indicate that the reduced availability of energy, i.e. ATP and sucrose in the CMS plants, limits plant growth. This is supported by the reduced levels of two D-type cyclin transcripts and the reduced capacity of the CMS plants to recover after etiolation.


Clinical value of specific immunoglobulin E detection by enzyme-linked immunosorbent assay in cases of acquired and congenital toxoplasmosis.
The clinical value of immunoenzymatic (enzyme-linked immunosorbent assay) detection of anti-Toxoplasma immunoglobulin E (IgE) was assessed by studying 2,036 sera from 792 subjects, comprising seronegative controls and subjects with acute, active, reactivated, or congenital toxoplasmosis. Included were nonimmunized adults; pregnant women with recently acquired infection (acute toxoplasmosis); immunocompetent subjects with recently acquired severe infection (active toxoplasmosis) expressed as fever, adenopathies, splenomegaly, pneumonia, meningitis, or disseminated infection; subjects-some of them immunocompromised-whose previously moderate IgG antibody levels rose, suggesting a reactivation of quiescent toxoplasmosis; and infants born to seroconverted mothers and evaluated for diagnosis of congenital infection and therapeutic management. Specific IgE antibodies were never detected in seronegative subjects. They were present in 85.7% of asymptomatic seroconverters and in 100% of seroconverters with overt toxoplasmosis, following two different kinetics: in the former, the specific IgE titer generally presented a brief peak 2 to 3 months postinfection and then fell rapidly, whereas specific IgE persisted at a very high titer for several months in the latter. IgE emerged concomitantly with the increase in IgG during toxoplasmic reactivation. For neonatal diagnosis of congenital toxoplasmosis, IgE was less informative than IgM and IgA (sensitivities, 59.5, 64.3, and 76.2%, respectively) and had a specificity of 91.9%. Nevertheless, simultaneous measurement of the three isotypes at birth improved the diagnostic yield to 81% relative to the combination of IgA and IgM. Emergence of specific IgE during postnatal treatment for congenital toxoplasmosis is a sign of poor adherence or inadequate dosing.


Calcium dobesilate lowers the blood pressure in mild to moderate midtrimester hypertension: a pilot study.
To test the effects of calcium dobesilate (Doxium) in pregnancies complicated with pregnancy-induced hypertension or mild/moderate pre-eclampsia a double-blind, placebo-controlled pilot study was carried out. Primigravida patients (gestational age </=34 weeks) daily took 2 g Doxium or placebo until delivery. Twelve patients received placebo for 53 days, and 11 patients took the drug for 57 days on average. At the start of the study 2 patients in the placebo group (PG) and 8 in the Doxium group (DG) had pre-eclampsia. The mean arterial pressure (mean +/- SD) significantly decreased from 118 +/- 7 to 99 +/- 9 mm Hg in the DG (p = 0.003), while in the PG it had slightly increased by the end of the study. Proteinuria was higher in the DG at the start but not at the end; however, significant changes of this parameter were detected in neither of the groups throughout the study. Fibronectin decreased significantly in both groups but it was more pronounced in the DG (23.8 vs. 9.4%). Changes of platelet count, plasma and blood viscosity, and erythrocyte deformability were favourable in the DG but in the PG these parameters had deteriorated although the alterations were not significant. No marked differences were found between the two groups regarding fetal well-being, courses of deliveries, and the neonatal period. Neither maternal nor fetal/neonatal side effects were noticed. It seems that Doxium favourably influences the blood pressure and consequently decreases the requirement for medication and hospitalisation in cases of mild to moderate midtrimester hypertension.


Breast cancer and quality of life: medical information extraction from health forums.
Internet health forums are a rich textual resource with content generated through free exchanges among patients and, in certain cases, health professionals. We tackle the problem of retrieving clinically relevant information from such forums, with relevant topics being defined from clinical auto-questionnaires. Texts in forums are largely unstructured and noisy, calling for adapted preprocessing and query methods. We minimize the number of false negatives in queries by using a synonym tool to achieve query expansion of initial topic keywords. To avoid false positives, we propose a new measure based on a statistical comparison of frequent co-occurrences in a large reference corpus (Web) to keep only relevant expansions. Our work is motivated by a study of breast cancer patients' health-related quality of life (QoL). We consider topics defined from a breast-cancer specific QoL-questionnaire. We quantify and structure occurrences in posts of a specialized French forum and outline important future developments.


Unusual repertoire of vocalizations in the BTBR T+tf/J mouse model of autism.
BTBR T+ tf/J (BTBR) is an inbred mouse strain that displays social abnormalities and repetitive behaviors analogous to the first and third diagnostic symptoms of autism. Here we investigate ultrasonic vocalizations in BTBR, to address the second diagnostic symptom of autism, communication deficits. As compared to the commonly used C57BL/6J (B6) strain, BTBR pups called more loudly and more frequently when separated from their mothers and siblings. Detailed analysis of ten categories of calls revealed an unusual pattern in BTBR as compared to B6. BTBR emitted high levels of harmonics, two-syllable, and composite calls, but minimal numbers of chevron-shaped syllables, upward, downward, and short calls. Because body weights were higher in BTBR than B6 pups, one possible explanation was that larger thoracic size was responsible for the louder calls and different distribution of syllable categories. To test this possibility, we recorded separation calls from FVB/NJ, a strain with body weights similar to BTBR, and 129X1/SvJ, a strain with body weights similar to B6. BTBR remained the outlier on number of calls, displaying low numbers of complex, upward, chevron, short, and frequency steps calls, along with high harmonics and composites. Further, developmental milestones and growth rates were accelerated in BTBR, indicating an unusual neurodevelopmental trajectory. Overall, our findings demonstrate strain-specific patterns of ultrasonic calls that may represent different lexicons, or innate variations in complex vocal repertoires, in genetically distinct strains of mice. Particularly intriguing is the unusual pattern of vocalizations and the more frequent, loud harmonics evident in the BTBR mouse model of autism that may resemble the atypical vocalizations seen in some autistic infants.


Integrated testing and algorithms for visual inspection of integrated circuits.
This paper deals with the integrated pre-cap testing of integrated circuits (IC's), defined as a simultaneous combination of electrical testing and of visual inspection using image analysis techniques. The emphasis is on image analysis models and algorithms for integrated testing of small and large defects. Two algorithms are presented for the analysis of visible and infrared imagery during electrical testing. Algorithm 1 matches bridges or subgraphs derived from the topological layout. Algorithm 2 computes a figure of merit for the IC from a fuzzy language description.


Diversification and reproductive isolation: cryptic species in the only New World high-duty cycle bat, Pteronotus parnellii.
Molecular techniques are increasingly employed to recognize the presence of cryptic species, even among commonly observed taxa. Previous studies have demonstrated that bats using high-duty cycle echolocation may be more likely to speciate quickly. Pteronotus parnellii is a widespread Neotropical bat and the only New World species to use high-duty cycle echolocation, a trait otherwise restricted to Old World taxa. Here we analyze morphological and acoustic variation and genetic divergence at the mitochondrial COI gene, the 7th intron region of the y-linked Dby gene and the nuclear recombination-activating gene 2, and provide extensive evidence that P. parnellii is actually a cryptic species complex. Central American populations form a single species while three additional species exist in northern South America: one in Venezuela, Trinidad and western Guyana and two occupying sympatric ranges in Guyana and Suriname. Reproductive isolation appears nearly complete (only one potential hybrid individual found). The complex likely arose within the last ~6 million years with all taxa diverging quickly within the last ~1-2 million years, following a pattern consistent with the geological history of Central and northern South America. Significant variation in cranial measures and forearm length exists between three of the four groups, although no individual morphological character can discriminate these in the field. Acoustic analysis reveals small differences (5-10 kHz) in echolocation calls between allopatric cryptic taxa that are unlikely to provide access to different prey resources but are consistent with divergence by drift in allopatric species or through selection for social recognition. This unique approach, considering morphological, acoustic and multi-locus genetic information inherited maternally, paternally and bi-parentally, provides strong support to conclusions about the cessation of gene flow and degree of reproductive isolation of these cryptic species.


Dynamic volume imaging of moving organs.
The Dynamic Spatial Reconstructor system has been developed to dynamically (up to 60/sec) image the entire 3-D volume (up to 240 adjacent 1-mm-thick transverse sections) encompassing moving organs of the body, particularly the heart and lungs, or the circulation in any organ. This capability permits accurate regional and global measurements to be made of the important relationships between structure and function within and among these organs, which in turn facilitates achievement of new insights into the basic physiological processes of these organs, and promises increased sensitivity and specificity in the diagnosis of pathology that affects normal organ function. This article explains the biomedical and technological rationale for development of the DSR, describes the design concepts and practical operation of the system, and presents preliminary results obtained with the system, including initial data from one of the first patient studies.


The culture of long-term care: impact on a continence care program.
Continence care in long-term care settings is a major caregiver and economic burden, with incontinence affecting an estimated 50% to 70% of all residents. Traditionally the continence care of residents is assigned to the nursing assistants and continence programs have been on paper only. These programs have had dismal success rates. Factoring in the culture of the long-term care setting can make the continence program more comprehensive and improve success rates.


Decreased p27(Kip1) expression and cyclin D1 overexpression, alone and in combination, influence recurrence and survival of patients with resectable extrahepatic bile duct carcinoma.
This study was undertaken to identify potential abnormalities of p27(Kip1) and cyclin D1 expression in extrahepatic bile duct carcinomas and to assess the prognostic significance of p27(Kip1) and cyclin D1 levels for patients with this disease. Decreased p27(Kip1) expression (<50% nuclei staining) and cyclin D1 overexpression (>5% nuclei staining) was observed immunohistochemically in 19 (56%) and 23 (68%) of the 34 tumors examined, respectively. Both decreased p27(Kip1) and cyclin D1 overexpression were associated with relapse (P =.0005 for p27(Kip1) and P =.0004 for cyclin D1). Kaplan-Meier curves showed that both decreased p27(Kip1) and cyclin D1 overexpression correlate significantly with shortened survival rates (for p27(Kip1), P =.0419 and P =.002 for overall and disease-free survival; for cyclin D1, P =.0392 and P =.0021 for overall and disease-free survival). Cox regression model analyses identified decreased p27(Kip1) and cyclin D1 overexpression as independent markers predicting death from relapse (P =.0371, risk ratio: 3.891 for p27(Kip1); P =.0429, risk ratio: 8.31 for cyclin D1). Decreased p27(Kip1) was associated with cyclin D1 overexpression (P =.0202), and coincident abnormalities of the 2 proteins occurred in 16 of the 34 (47%) tumors, indicating that extrahepatic bile duct carcinoma progression may require synchronous dysfunction of p27(Kip1) and cyclin D1 in about half of patients. Patients with tumors showing coincident abnormalities of p27(Kip1) and cyclin D1 showed even more frequent recurrence than patients with an alteration in only 1 of the 2 proteins. In conclusion, decreased p27(Kip1) expression and cyclin D1 overexpression, alone and in combination, predict poor prognosis in patients with resectable extrahepatic bile duct carcinoma.


Anorectal malformations--update 1998.
Anorectal malformation is a common congenital anomaly. Its correction still challenges the wisdom and expertise of the pediatric surgeon. From 1977 through 1997, approximately 400 cases of this anomaly were treated at this institution. Prior to 1985, cut-back anoplasty and translocation anoplasty were the treatments of choice for the low anomalies, and abdominoperineal pull-through anoplasty or sacroperineal anoplasty (and their modifications) preferred for the intermediate or high defects. Since 1985, posterior sagittal anorectoplasty (PSARP) has been adopted exclusively as the operative procedure for the correction of the entire spectrum of anorectal malformations. Two hundred patients have undergone this procedure either primarily (N = 166) or secondarily (N = 34). PSARP is a procedure which enables the surgeon to repair the pelvic anatomy under direct vision, maximally utilizing all the existing continence muscles and hence resulting in better fecal continence. With minimal, limited or maximal division of the continence muscles under one same skin incision, the entire spectrum of this defect can be repaired. The result of cosmesis is generally regarded as better, and the immediate postoperative complications are fewer. In spite of all efforts, 10 to 30% of patients still suffer from total fecal incontinence which is intractable to all kinds of medications and enemas. A bowel management program with large volume enemas, either through the anus or a Malone appendicostomy, retrogradely or antegradely, to wash out stool in the colon and rectum may be necessary to keep the patient clean and more socially acceptable. Biofeedback therapy offers another alternative to improve continence with the development of better computer systems and manometry equipment. This review provides a new concept of the fecal continence mechanism and an operative procedure for constructing a new anorectum based on this concept for the treatment of patients with anorectal malformations.


Concurrent outbreaks of Shigella sonnei and enterotoxigenic Escherichia coli infections associated with parsley: implications for surveillance and control of foodborne illness.
In recent years, the globalization of the food supply and the development of extensive food distribution networks have increased the risk of foodborne disease outbreaks involving multiple states or countries. In particular, outbreaks associated with fresh produce have emerged as an important public health concern. During July and August 1998, eight restaurant-associated outbreaks of shigellosis caused by a common strain of Shigella sonnei occurred in the United States and Canada. The outbreak strain was characterized by unique pulsed-field gel electrophoresis patterns. Epidemiologic investigation determined that the illness was associated with the ingestion of parsley at four restaurants; at the other four restaurants, the majority of the people who contracted the illness ate parsley. Isolates from patrons in two unrelated restaurant-associated enterotoxigenic Escherichia coli (ETEC) outbreaks in Minnesota shared a common serotype and pulsed-field gel electrophoresis (PFGE) pattern. Parsley was the implicated or suspected source of both ETEC outbreaks. In each of the outbreak-associated restaurants, parsley was chopped, held at room temperature, and used as an ingredient or garnish for multiple dishes. Infected food workers at several restaurants may also have contributed to the propagation of the outbreak. The sources of parsley served in outbreak-associated restaurants were traced, and a 1,600-acre farm in Baja California, Mexico, was identified as a likely source of the parsley implicated in six of the seven Shigella outbreaks and as a possible source of the parsley implicated in the two ETEC outbreaks. Global food supplies and large distribution networks demand strengthened laboratory and epidemiologic capacity to enable state and local public health agencies to conduct foodborne disease surveillance and to promote effective responses to multistate outbreaks.


Postgraduate Emergency Nurse Practitioner Fellowships: Opportunities for Specialty Education.
Specialty trained emergency nurse practitioners (ENPs) can meet the demands of an unpredictable emergency care environment within an overburdened health care system. Although existing literature supports fellowship training as a method for bridging academic knowledge with clinical experiences for the novice nurse practitioner, the currently available emergency care postgraduate fellowship programs are inconsistent in approach. Building upon descriptive data provided by the existing 9 postgraduate ENP fellowship programs, a comparison and gap analysis of program content was conducted to identify perceived standards for ENP specialty education and the congruence with published ENP competencies. Standards to curricula, didactics, clinical rotations, and measures of competency were identified in the currently established ENP fellowships. A national ENP fellowship curriculum has the potential to afford consistency among programs, support attainment of competency, and provide clarity to the role and general education of advanced practice registered nurses seeking employment in emergency care.


Radiation induced endothelial cell retraction in vitro: correlation with acute pulmonary edema.
We determined the effects of low dose radiation (<200 cGy) on the cell-cell integrity of confluent monolayers of pulmonary microvascular endothelial cells (PMEC). We observed dose- and time-dependent reversible radiation induced injuries to PMEC monolayers characterized by retraction (loss of cell-cell contact) mediated by cytoskeletal F-actin reorganization. Radiation induced reorganization of F-actin microfilament stress fibers was observed > or =30 minutes post irradiation and correlated positively with loss of cell-cell integrity. Cells of irradiated monolayers recovered to form contact inhibited monolayers > or =24 hours post irradiation; concomitantly, the depolymerized microfilaments organized to their pre-irradiated state as microfilament stress fibers arrayed parallel to the boundaries of adjacent contact-inhibited cells. Previous studies by other investigators have measured slight but significant increases in mouse lung wet weight >1 day post thoracic or whole body radiation (> or =500 cGy). Little or no data is available concerning time intervals <1 day post irradiation, possibly because of the presumption that edema is mediated, at least in part, by endothelial cell death or irreversible loss of barrier permeability functions which may only arise 1 day post irradiation. However, our in vitro data suggest that loss of endothelial barrier function may occur rapidly and at low dose levels (< or =200 cGy). Therefore, we determined radiation effects on lung wet weight and observed significant increases in wet weight (standardized per dry weight or per mouse weight) in < or =5 hours post thoracic exposure to 50 200 cGy x-radiation. We suggest that a single fraction of radiation even at low dose levels used in radiotherapy, may induce pulmonary edema by a reversible loss of endothelial cell-cell integrity and permeability barrier function.


On the evolution of genetic incompatibility systems. VI. A three-locus modifier model for the origin of gametophytic self-incompatibility.
Recent genetic analyses have demonstrated that self-incompatibility in flowering plants derives from the coordinated expression of a system of loci. To address the selective mechanisms through which a genetic system of this kind evolves, I present a three-locus model for the origin of gametophytic self-incompatibility. Conventional models assume that a single locus encodes all physiological effects associated with self-incompatibility and that the viability of offspring depends only on whether they were derived by selfing or outcrossing. My model explicitly represents the genetic determination of offspring viability by a locus subject to symmetrically overdominant selection. Initially, the level of expression of the proto-S locus is insufficient to induce self-incompatibility. Weak gametophytic self-incompatibility arises upon the introduction of a rare allele at an unlinked modifier locus which enhances the expression of the proto-S locus. While conventional models predict that the origin of self-incompatibility requires at least two- to threefold levels of inbreeding depression, I find that the comparatively low levels of inbreeding depression generated by a single overdominant locus can ensure the invasion of an enhancer of self-incompatibility under sufficiently high rates of receipt of self-pollen. Associations among components of the incompatibility system promote the origin of self-incompatibility. Enhancement of heterozygosity at the initially neutral proto-S locus improves offspring viability through associative overdominance. Further, the modifier that enhances the expression of self-incompatibility develops a direct association with heterozygosity at the overdominant viability locus. These results suggest that the evolutionary processes by which incompatibility systems originate may differ significantly from those associated with their breakdown. The genetic mechanism explored here may apply to the evolution of other systems that restrict reproduction, including maternal-fetal incompatibility in mammals.


Interleukin-1beta enhances GABAA receptor cell-surface expression by a phosphatidylinositol 3-kinase/Akt pathway: relevance to sepsis-associated encephalopathy.
Sepsis-associated encephalopathy (SAE) is a frequent but poorly understood neurological complication in sepsis that negatively influences survival. Here we present clinical and experimental evidence that this brain dysfunction may be related to altered neurotransmission produced by inflammatory mediators. Compared with septic patients, SAE patients had higher interleukin-1beta (IL-1beta) plasma levels; interestingly, these levels decreased once the encephalopathy was resolved. A putative IL-1beta effect on type A gamma-aminobutyric acid receptors (GABA(A)Rs), which mediate fast synaptic transmission in most cerebral inhibitory synapses in mammals, was investigated in cultured hippocampal neurons and in Xenopus oocytes expressing native or foreign rat brain GABA(A)Rs, respectively. Confocal images in both cell types revealed that IL-1beta increases recruitment of GABA(A)Rs to the cell surface. Moreover, brief applications of IL-1beta to voltage-clamped oocytes yielded a delayed potentiation of the GABA-elicited chloride currents (I(GABA)); this effect was suppressed by IL-1ra, the natural IL-1 receptor (IL-1RI) antagonist. Western blot analysis combined with I(GABA) recording and confocal images of GABA(A) Rs in oocytes showed that IL-1beta stimulates the IL-1RI-dependent phosphatidylinositol 3-kinase activation and the consequent facilitation of phospho-Akt-mediated insertion of GABA(A)Rs into the cell surface. The interruption of this signaling pathway by specific phosphatidylinositol 3-kinase or Akt inhibitors suppresses the cytokine-mediated effects on GABA(A)R, whereas activation of the conditionally active form of Akt1 (myr-Akt1.ER*) with 4-hydroxytamoxifen reproduces the effects. These findings point to a previously unrecognized signaling pathway that connects IL-1beta with increased "GABAergic tone." We propose that through this mechanism IL-1beta might alter synaptic strength at central GABAergic synapses and so contribute to the cognitive dysfunction observed in SAE.


Electrochemical treatment of effluents containing Cr(VI). Influence of pH and current on the kinetic.
Compounds of Cr(VI) are very toxic and their reduction to Cr(III) is necessary to allow their further precipitation or adsorption. Chemical methods for Cr(VI) reduction are usually used for this purpose. As an alternative, electrochemical methods using three-dimensional electrodes, such as reticulated vitreous carbon (RVC) and polyaniline-modified RVC, have been used successfully. Since the pH affects reaction of Cr(VI) reduction, in this work its effect on the reaction rate was studied using electrodes of RVC and RVC/PANI. While a maximum in reaction rate was found for a pH 1.5 using the RVC, the RVC/PANI showed no differences in reaction rates in the range of pH between 0 and 1. Practically, no reaction was observed for any pH greater than 3. The effect of different current densities using optimized pH was also evaluated and the RVC/PANI electrode showed the best reaction rates, current efficiencies and energy consumption as a result of the polyaniline electrocatalytic effect.


Osmotic loading of in situ chondrocytes in their native environment.
Changes in the osmotic environment cause changes in volume of isolated cells and cells in tissue explants, and the osmotic environment becomes hypotonic in cartilage diseases such as osteoarthritis (OA). However, it is not known how cells respond to a hypotonic osmotic challenge when situated in the fully intact articular cartilage. A confocal laser scanning microscope was used to image chondrocytes of intact rabbit patellae in an isotonic (300 mOsm) and hypotonic (172 mOsm) immersion medium. Cell volumes were calculated before and 5, 15, 60, 120 and 240 minutes after the change in saline concentration. Local tissue strains and swelling of the entire tissue were estimated from the relative movements of cells and displacements of single cells, respectively. Cell volumes increased rapidly (< or = 5 minutes, p<0.05) by approximately 22%, after which they remained constant for an hour (p>0.05). However, two and four hours post the hypotonic challenge, cell volumes were statistically greater (p<0.05) than those at all earlier time points, and swelling of the entire tissue continued throughout the four hour loading period. The results of our study suggest that osmotic loading induced volume changes of in situ chondrocytes in their native environment occur quickly and continue for hours. Understanding the behaviour of cells in their native environment provides novel insigth into the cell mechanics in ostearthritic joints and so may help understand the onset and progression of this disease.


Comparison of pretreatment characteristics and treatment outcomes for alcohol-, cocaine-, and multisubstance-dependent patients.
We investigated whether pretreatment characteristics and measures of outcome differed for alcohol-, cocaine-, and multisubstance-dependent patients receiving outpatient substance abuse treatment. One hundred and forty substance dependent individuals (32 alcohol, 76 cocaine, and 32 multisubstance) enrolled in a 12-week outpatient treatment program were compared across measures of addiction severity, personality, and treatment-readiness at admission. In-treatment, end-of-treatment and 9-month follow-up assessments of treatment outcome were then compared across the three groups. Outcome measures included reduction in problem severity, abstinence, retention, number of sessions attended, dropout, and counselor and patient ratings of treatment benefit. At admission, the multisubstance group had a higher proportion of positive urines, reported more severe drug, alcohol and psychiatric problems, and displayed higher impulsivity and anxiety scores than one or both of the other groups. However, multisubstance patients were more treatment ready in terms of adopting a total abstinence orientation than alcohol or cocaine patients. While a significant reduction in symptoms occurred for the total sample during treatment as well as at follow-up, comparisons of outcomes did not consistently favor any particular group. The three groups had equivalent improvements in eleven of fourteen during-treatment and five of seven follow-up measures. Despite pretreatment differences, in severity and treatment-readiness, outcomes were more similar than different for alcohol-, cocaine-, and multisubstance-dependent patients. Clinicians should be cautious about forecasting treatment-outcomes for addicted patients based on their primary substances of abuse.


A diffraction-limited scanning system providing broad spectral range for laser scanning microscopy.
Diversified research interests in scanning laser microscopy nowadays require broadband capability of the optical system. Although an all-mirror-based optical design with a suitable metallic coating is appropriate for broad-spectrum applications from ultraviolet to terahertz, most researchers prefer lens-based scanning systems despite the drawbacks of a limited spectral range, ghost reflection, and chromatic aberration. One of the main concerns is that the geometrical aberration induced by off-axis incidence on spherical mirrors significantly deteriorates image resolution. Here, we demonstrate a novel geometrical design of a spherical-mirror-based scanning system in which off-axis aberrations, both astigmatism and coma, are compensated to reach diffraction-limited performance. We have numerically simulated and experimentally verified that this scanning system meets the Marechal condition and provides high Strehl ratio within a 3 degrees x 3 degrees scanning area. Moreover, we demonstrate second-harmonic-generation imaging from starch with our new design. A greatly improved resolution compared to the conventional mirror-based system is confirmed. This scanning system will be ideal for high-resolution linear/nonlinear laser scanning microscopy, ophthalmoscopic applications, and precision fabrications.


Difference between lung and spleen susceptibility of beta-adrenergic receptors to desensitization by terbutaline.
There are many reports about a marked down-regulation of beta-adrenergic receptors by beta agonists in human leukocytes. To determine whether beta receptors in lung tissue are down regulated by the long-term administration of beta agonists, as are those in the spleen (which consists largely of lymphocytes), we injected terbutaline (0.1 mg/kg, t.i.d.) intramuscularly into rats for either 3 or 6 days. We observed a significant decrease in beta-receptor density in spleen tissue but not in lung parenchyma, associated with terbutaline injection. The affinity for an antagonist did not change significantly in any group in either tissue. We did not observe any change in alpha 1-adrenergic receptors in the lung after this treatment. In in vitro studies, we also observed reduced beta-receptor density in spleen cells but not in lung parenchyma after incubation of these tissues with terbutaline. However, there was agonist-specific alteration in lung beta receptors. It was found that the isoproterenol competition curve for 3H-dihydroalprenolol binding shifted to the right and steepened, suggesting reduced affinity of the receptors for isoproterenol. We used whole lung and did not examine bronchial smooth muscle per se, nor were functional studies performed. Our results show a difference between lung parenchyma and spleen tissue in the susceptibility of beta receptors to desensitization by an adrenergic agonist and suggest that there may be such a difference in sensitivity between beta receptors in human lung and leukocytes.


Lack of prognostic significance of p53 and K-ras mutations in primary resected non-small-cell lung cancer on E4592: a Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy.
To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non-small-cell lung cancer (NSCLC). Patients were randomized preoperatively to receive adjuvant postoperative radiotherapy (Arm A) or radiotherapy plus concurrent chemotherapy (Arm B). p53 protein expression was studied by immunohistochemistry (IHC) and p53 mutations in exons 5 to 8 were evaluated by single-strand conformational analysis. K-ras mutations in codons 12, 13, and 61 were determined using engineered restriction fragment length polymorphisms. Four hundred eighty-eight patients were entered onto E3590; 197 tumors were assessable for analysis. Neither presence nor absence of p53 mutations, p53 protein expression, or K-ras mutations correlated with survival or progression-free survival. There was a trend toward improved survival for patients with wildtype K-ras (median, 42 months) compared with survival of patients with mutant K-ras who were randomized to chemotherapy plus radiotherapy (median, 25 months; P = .09). Multivariate analysis revealed only age and tumor stage to be significant prognostic factors, although there was a trend bordering on statistical significance for K-ras (P = .066). Analysis of survival difference by p53 by single-stranded conformational polymorphism and IHC, interaction of p53 and K-ras, interaction of p53 and treatment arm, nodal station, extent of surgery, weight loss, and histology did not reach statistical significance. p53 mutations and protein overexpression are not significant prognostic or predictive factors in resected stage II or IIIA NSCLC. K-ras mutations may be a weak prognostic marker. p53 or K-ras should not be routinely used in the clinical management of these patients.


The art of equity: critical health humanities in practice.
The American Association of Medical Colleges has called for incorporation of the health humanities into medical education, and many medical schools now offer formal programs or content in this field. However, there is growing recognition among educators that we must expand beyond empathy and wellness and apply the health humanities to questions of social justice - that is, critical health humanities. In this paper we demonstrate how this burgeoning field offers us tools for integrating social justice into medical education, utilizing the frameworks of critical consciousness and structural competency. Critical health humanities can be applied at multiple levels of learners, and in a variety of contexts. We are two physician-writers who have developed several educational programs that demonstrate this. We taught a seminar that introduced first-year and second-year undergraduates to concepts such as social determinants of health, intergenerational trauma, intersectionality, resilience, and cross-cultural care through works of fiction, poetry, film, podcasts, stand-up comedy, and more. Through creative projects and empathic reflection, students engaged with the complexities of structural forces that create and maintain health disparities. Medical students in their clinical years can engage in critical health humanities learning experiences as well. We teach several multidisciplinary electives that address social (in)justice in medicine, as well as mentor fourth-year students engaged in independent electives that foster critical awareness around health equity and ethics. Beyond the classroom, we have actively engaged in critical health humanities practices through story slams, literary journal clubs, conference presentations, and Grand Rounds. Through these activities we have included learners at GME and CME levels. These examples also demonstrate how community engagement and multidisciplinary partnerships can contribute to the practice of critical health humanities. In this paper, we explore the growing field of critical health humanities and its potential for teaching health equity through narrative practices. We provide concrete examples of educational activities that incorporate critical consciousness and structural competency - frameworks we have found useful for conceptualizing critical health humanities as a pedagogical practice. We also discuss the strengths and challenges of this work and suggest future directions.


Neural Correlates of Vocal Pitch Compensation in Individuals Who Stutter.
Stuttering is a disorder that impacts the smooth flow of speech production and is associated with a deficit in sensorimotor integration. In a previous experiment, individuals who stutter were able to vocally compensate for pitch shifts in their auditory feedback, but they exhibited more variability in the timing of their corrective responses. In the current study, we focused on the neural correlates of the task using functional MRI. Participants produced a vowel sound in the scanner while hearing their own voice in real time through headphones. On some trials, the audio was shifted up or down in pitch, eliciting a corrective vocal response. Contrasting pitch-shifted vs. unshifted trials revealed bilateral superior temporal activation over all the participants. However, the groups differed in the activation of middle temporal gyrus and superior frontal gyrus [Brodmann area 10 (BA 10)], with individuals who stutter displaying deactivation while controls displayed activation. In addition to the standard univariate general linear modeling approach, we employed a data-driven technique (independent component analysis, or ICA) to separate task activity into functional networks. Among the networks most correlated with the experimental time course, there was a combined auditory-motor network in controls, but the two networks remained separable for individuals who stuttered. The decoupling of these networks may account for temporal variability in pitch compensation reported in our previous work, and supports the idea that neural network coherence is disturbed in the stuttering brain.


[Isolation and identification of an antibiotic from culture 8-86].
An antibiotic complex was isolated from culture 8-86 referred to Bacillus. The complex consisted of components 8-86A and 8-86B active against gram-negative organisms. By its physico-chemical properties such as IR and UV spectra, amino acid composition, specific rotation and fatty acid composition component 8-86B was shown to be close to polymyxin F.


Self-assembly of subnanometer-diameter single-wall MoS2 nanotubes.
We report on the synthesis, structure, and self-assembly of single-wall subnanometer-diameter molybdenum disulfide tubes. The nanotubes are up to hundreds of micrometers long and display diverse self-assembly properties on different length scales, ranging from twisted bundles to regularly shaped "furry" forms. The bundles, which contain interstitial iodine, can be readily disassembled into individual molybdenum disulfide nanotubes. The synthesis was performed using a novel type of catalyzed transport reaction including C(60) as a growth promoter.


Part I: characterization of solid dispersions of nimodipine prepared by hot-melt extrusion.
The purpose of this study was to prepare and characterize solid dispersions of nimodipine with hydroxypropyl methylcellulose (HPMC, Methocel E5), polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA, Plasdone S630), and ethyl acrylate, methyl methacrylate polymer (Eudragit EPO). The goal was to investigate whether the solid dispersion prepared by hot-melt extrusion can improve the dissolution rate of nimodipine. The dissolution results indicated that three polymers are suitable carriers to enhance the in vitro dissolution rate of nimodipine in pH 4.5 medium. The solubility research and solubility parameters calculation was corresponded with dissolution data. XRPD and DSC data showed that the crystallinity was not observed in hot-melt extrudates. NMD acted as a plasticizer for PVP/VA and EPO and was miscible with the polymers as well as 10% NMD-HPMC systems, because a single T(g) was observed in these extrudates. However, two T(g)s were observed in the 30 and 50% NMD-HPMC samples, indicating phase separation. The weakening and shift of the N-H stretching vibration of the secondary amine groups of nimodipine as determined by FT-IR proved hydrogen bonding between the drug and polymers in the solid dispersion.


Agreement Between Child Self-report and Caregiver-Proxy Report for Symptoms and Functioning of Children Undergoing Cancer Treatment.
Adult patients are considered the best reporters of their own health-related quality of life (HRQOL). Self-report in pediatrics has been challenged by a limited array of valid measures. Caregiver report is therefore often used as a proxy for child report. To examine the degree of alignment between child and caregiver proxy report for Patient-Reported Outcomes Measurement Information System (PROMIS) HRQOL domains among children with cancer and to identify factors associated with better child and caregiver-proxy congruence. In this multicenter cohort study, children with a first cancer diagnosis and their caregivers completed surveys at 2 time points: within 72 hours preceding treatment initiation (T1) and during follow-up (T2), when symptom burden was expected to be higher (eg, 7-17 days later for chemotherapy). Data were collected from October 26, 2016, to October 5, 2018, at 9 pediatric oncology hospitals. Five hundred eighty children (aged 7-18 years) and their caregivers were approached; 482 child-caregiver dyads completed surveys at T1 (response rate 83%), and 403 completed surveys at T2 (84% of T1 participants). Data were analyzed from July 1, 2019, to April 22, 2020. Participants received up-front cancer treatment, including chemotherapy and radiotherapy. Congruence between child self-report and caregiver-proxy report of PROMIS pediatric domains of mobility (physical functioning), pain interference, fatigue, depressive symptoms, anxiety, and psychological stress. Of the 482 dyads included in the analysis, 262 children (54%) were male (mean [SD] age, 12.9 [3.4] years), 80 (17%) were Black, and 71 (15%) were Hispanic. Intraclass correlations between child self-report and caregiver proxy report showed moderate agreement for mobility (0.57 [95% CI, 0.50-0.63]) and poor agreement for symptoms (range, 0.32 [95% CI, 0.24-0.41] for fatigue to 0.42 [95% CI, 0.34-0.50] for psychological stress). Children reported lower symptom burden and higher mobility than caregivers reported. In a multivariable model adjusted for child and parent sociodemographic factors and the caregiver's own self-reported HRQOL, caregivers reported the child's mobility score 6.00 points worse than the child's self-report at T2 (95% CI, -7.45 to -4.51), exceeding the PROMIS minimally important difference of 3 points. Caregivers overestimated the child's self-reported symptom levels, ranging from 5.79 (95% CI, 3.99-7.60) points for psychological stress to 13.69 (95% CI, 11.60-15.78) points for fatigue. The caregiver's own self-reported HRQOL was associated with the magnitude of difference between child and caregiver scores for all domains except mobility; for example, for fatigue, the magnitude of difference between child and caregiver-proxy scores increased by 0.21 (95% CI, 0.13-0.30) points for each 1-point increase in the caregiver's own fatigue score. This study found that caregivers consistently overestimated symptoms and underestimated mobility relative to the children themselves. These results suggest that elicitation of the child's own report should be pursued whenever possible.


Effects of nucleotide analogues on human immunodeficiency virus type 1 integrase.
We extended our previous study with 3'-azido-3'-deoxythymidine nucleotides [Proc. Natl. Acad. Sci. USA 91:5771-5775 (1994)] and examined the effects on human immunodeficiency virus type 1 (HIV-1) integrase of the nucleotides of three nucleoside analogues currently under evaluation in clinical trials: beta-D-2',3'-didehydro-3'-deoxythymidine, beta-D-2'-ara-fluoro-2', 3'-dideoxyadenosine, and beta-L-2',3'-dideoxy-3'-thiacytidine. Beta-D-2',3'-Didehydro-3'-deoxythymidine and beta-D-2'-ara-fluoro-2',3'-dideoxyadenosine nucleotides had IC50 values for strand transfer of 100 and 200 microM, respectively, whereas the corresponding 2',3'-dideoxynucleoside triphosphates, ddT triphosphate and ddA triphosphate, did not inhibit the integrase at 800 and 200 microM, respectively. Beta-L-2',3'-Dideoxy-3'-thiacytidine triphosphate had no effect up to 500 microM. The L-enantiomers of 5-fluoro-2',3'-dideoxycytidine monophosphate and triphosphate had IC50 values of approximately 40 microM, whereas their D-enantiomer isomers showed no inhibition at 200 microM. NAD, pyridoxal phosphate, and coumermycin A1, which exhibit no antiviral activity but are typically used to probe nucleotide binding sites, were also tested. NAD was inactive, and its etheno derivative exhibited activity at 1 mM. In contrast, pyridoxal phosphate (IC50 = 18 microM and coumermycin A1 (IC50 = 5 microM were potent inhibitors. None of the coumermycin monomeric derivatives were active integrase inhibitors. The physiological ribonucleotides ATP and GTP inhibited HIV-1 integrase at or near cellular concentrations, suggesting that they may regulate HIV-1 integrase activity in cells. In general, the active nucleotides tested inhibited binding of HIV-1 integrase to its substrate DNA an inhibited an integrase deletion mutant containing only amino acids 50-212, indicating that nucleotides bind to the enzyme catalytic core. Consisently, the choice of nucleophile in the 3'-processing reaction was blocked to the same extent regardless of the nucleotide used (water, glycerol, or the viral DNA hydroxyl) by the enzyme. These observations suggest new strategies for antiviral drug development that could be based on nucleotide analogues as inhibitors of HIV-1 integrase.


Identification of the uvrD gene product of Salmonella typhimurium LT2.
The product of the uvrD gene of Salmonella typhimurium LT2 and Escherichia coli K-12 is thought to play a role in both the correction of mismatched bases and the repair of DNA damage, since insertion mutations in the uvrD gene increase the spontaneous mutation frequency and make the cells more sensitive to killing by UV irradiation. To clone the uvrD gene of S. typhimurium, we first generated a uvrD-specific probe by using DNA from an S. typhimurium uvrD421::Tn5 mutant. This probe was used to screen a lambda library of S. typhimurium DNA. Bacteriophage carrying intact uvrD+ genes were subsequently identified, and the uvrD+ gene was subcloned onto a low-copy-number vector. By using a combination of Tn1000 insertion mutagenesis and the maxicell technique, the product of the uvrD gene was shown to be a 75,000-dalton protein, and the relative direction of transcription of this protein was determined. Introduction of a low-copy-number plasmid carrying the S. typhimurium uvrD+ gene into uvrD insertion mutants of either S. typhimurium or E. coli restored the spontaneous mutation frequency and degree of UV sensitivity to the levels in the corresponding uvrD+ strains.


Parasites and parasite management practices of organic and conventional dairy herds in Minnesota.
The objective of this study was to describe the prevalence and practices used to manage internal helminth parasites and external arthropod parasites on organic and conventional dairy herds in Minnesota. All organic (ORG) dairy herds in Minnesota (n=114) and a convenience sample of conventional herds were invited to participate in the study. Thirty-five ORG herds and 28 conventional herds were visited once in summer and fall of 2012. Conventional dairy herds were split into small conventional (SC,<200 cows) and medium-sized conventional herds (MC, ≥200 cows) so that SC herds were comparable in size to the ORG herds. Dairy managers were surveyed to assess their farm management practices and perceptions about parasites, hygiene scores were recorded for adult stock, and fecal samples were collected from a nominal 20 breeding-age heifers to characterize abundance of internal parasites. Nonparametric tests were used to compare fecal egg counts per gram (FEC) among farms grouped by management systems and practices. Organic farms had more designated pasture and were more likely to use rotational grazing compared with conventional farms, but the stocking densities of animals on pasture were similar among farm types. The overall FEC were very low, and only a few individual ORG heifers had FEC >500 eggs/gram. Samples from heifers on ORG farms had significantly more strongyle-type eggs than those on SC and MC farms (ORG: 6.6±2.1; SC: 0.5±0.3; MC: 0.8±0.7), but egg counts of other types of gastrointestinal parasites did not differ significantly among the 3 herd groups. Fly control measures were applied mainly to milking cows and preweaned calves and were used on 88.6% of ORG herds, 60.0% of SC herds, and 91.7% of MC herds. Approximately half of the producers reported having seen skin conditions suggestive of lice or tail mange in their cattle during the previous winter (ORG: 48.6%, SC: 57.1%, MC: 53.9%). Although most conventional producers reported treating these skin conditions, most organic producers stated they had not treated them. In conclusion, gastrointestinal parasite egg counts were low overall at the time of the survey, and most surveyed producers did not perceive gastrointestinal parasites to be a problem for their animals' health. Independent of the herd type, fly control was mostly targeted at the lactating herd and preweaned calves.


Opioid peptides inhibit excitatory but not inhibitory synaptic transmission in the rat dorsal motor nucleus of the vagus.
Opioid peptides produce gastrointestinal inhibition and increase feeding when applied to the brainstem. The present studies were designed to determine the actions of opioid peptides on synaptic transmission within the dorsal motor nucleus of the vagus (DMV) and the localization of mu-opioid receptors. Whole-cell recordings were made from identified gastrointestinal-projecting DMV neurons in thin brainstem slices of the rat. Electrical stimulation of the nucleus of the tractus solitarius evoked EPSCs and IPSCs. In all neurons tested, methionine (Met)-enkephalin (0.003-30 microm) inhibited the peak amplitude of the EPSCs. The effect was prevented by naloxone (1 microm) as well as by naloxonazine (0.2 microm). An increase in the ratio of the evoked paired pulses indicated that the inhibition was attributable to actions at presynaptic receptors. This presynaptic inhibitory action was mimicked by [d-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (0.1 microm) and the analgesic dipeptide kyotorphin (10 microm) but not by cyclic[d-Pen(2), d-Pen(5)]-enkephalin (1 microm) and trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide methanesulfonate (1 microm). In contrast, the amplitude of evoked IPSCs was not altered either by Met-enkephalin or by any of the opioid receptor-selective agonists. Immunohistochemical studies revealed that nerve terminals apposing DMV neurons showed immunoreactivity to mu-opioid receptors colocalized with glutamate immunoreactivity but not glutamic acid decarboxylase immunoreactivity. These results suggest that within the DMV, mu-opioid receptors are present on the nerve terminals of excitatory but not inhibitory inputs to GI motoneurons. Such specificity may imply that the central inhibitory action of opioid peptides on gastrointestinal function targets selected pathways.


On contribution of known atomic partial charges of protein backbone in electrostatic potential density maps.
Partial charges of atoms in a molecule and electrostatic potential (ESP) density for that molecule are known to bear a strong correlation. In order to generate a set of point-field force field parameters for molecular dynamics, Kollman and coworkers have extracted atomic partial charges for each of all 20 amino acids using restrained partial charge-fitting procedures from theoretical ESP density obtained from condensed-state quantum mechanics. The magnitude of atomic partial charges for neutral peptide backbone they have obtained is similar to that of partial atomic charges for ionized carboxylate side chain atoms. In this study, the effect of these known atomic partial charges on ESP is examined using computer simulations and compared with the experimental ESP density recently obtained for proteins using electron microscopy. It is found that the observed ESP density maps are most consistent with the simulations that include atomic partial charges of protein backbone. Therefore, atomic partial charges are integral part of atomic properties in protein molecules and should be included in model refinement.


Variant Creutzfeldt-Jakob disease with extremely low lymphoreticular deposition of prion protein.
Human transmission of bovine spongiform encephalopathy causes the fatal neurodegenerative condition variant Creutzfeldt-Jakob disease (vCJD) and, based on recent human prevalence studies, significant subclinical prion infection of the UK population. To date, all clinical cases have been fatal, totaling 228 mostly young adults residing in the United Kingdom. Here we describe the investigation and case history of a patient recently diagnosed as having vCJD in the United Kingdom. Although his presentation, imaging findings, cerebrospinal fluid investigation results, and clinical progression were typical of other cases, tonsillar biopsy and subsequent examination of multiple tissues at autopsy showed minimal deposition of disease-associated prion protein in peripheral lymphoreticular tissue. The result of a blood test for vCJD, the Direct Detection Assay for vCJD, was negative. These findings suggest that some patients with vCJD have very low peripheral prion colonization and therefore may not have detectable prion deposition in diagnostic tonsillar biopsy or markers of prion infection in blood. These results have implications for accurate interpretation of diagnostic tests and prevalence studies based on lymphoreticular tissue or blood.


A KLF4-DYRK2-mediated pathway regulating self-renewal in CML stem cells.
Leukemia stem cells are a rare population with a primitive progenitor phenotype that can initiate, sustain, and recapitulate leukemia through a poorly understood mechanism of self-renewal. Here, we report that Krüppel-like factor 4 (KLF4) promotes disease progression in a murine model of chronic myeloid leukemia (CML)-like myeloproliferative neoplasia by repressing an inhibitory mechanism of preservation in leukemia stem/progenitor cells with leukemia-initiating capacity. Deletion of the Klf4 gene severely abrogated the maintenance of BCR-ABL1(p210)-induced CML by impairing survival and self-renewal in BCR-ABL1+ CD150+ lineage-negative Sca-1+ c-Kit+ leukemic cells. Mechanistically, KLF4 repressed the Dyrk2 gene in leukemic stem/progenitor cells; thus, loss of KLF4 resulted in elevated levels of dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 2 (DYRK2), which were associated with inhibition of survival and self-renewal via depletion of c-Myc protein and p53 activation. In addition to transcriptional regulation, stabilization of DYRK2 protein by inhibiting ubiquitin E3 ligase SIAH2 with vitamin K3 promoted apoptosis and abrogated self-renewal in murine and human CML stem/progenitor cells. Altogether, our results suggest that DYRK2 is a molecular checkpoint controlling p53- and c-Myc-mediated regulation of survival and self-renewal in CML cells with leukemic-initiating capacity that can be targeted with small molecules.


Hermite-cosine-Gaussian beams propagating in uniaxial crystals orthogonal to the optical axis.
The propagation of polarized Hermite-cosine-Gaussian (HCosG) beams in uniaxial crystals orthogonal to the optical axis is investigated. Analytical formulas for a HCosG beam propagating in uniaxial crystals orthogonal to the optical axis are derived, and the propagation properties of the beam are illustrated numerically. The results show that the HCosG beam can keep its initial beam profile almost invariant for a short propagation distance. However, the initial symmetry and the linear polarization of an incident HCosG beam cannot be preserved during propagation in uniaxial crystals. In addition, the distributions of optical fields are closely related to the decentered parameter.


Increased long noncoding RNA LINP1 expression and its prognostic significance in human breast cancer.
Mounting evidence suggests that the long noncoding RNAs (lncRNAs) function in multiple cancers. Dysregulation of lncRNA in non-homologous end joining (NHEJ) pathway 1 (LINP1) has been reported in breast cancer. However, its clinical significance in breast cancer remains unclear. The aim of this study was to investigate the prognostic relevance of LINP1 in breast cancer. Expression of LINP1 in tumor and their matched non-tumor tissues was determined by quantitative Real Time-PCR (qRT-PCR) in breast cancer patients. The relevance of LINP1 expression to the clinicopathological factors was assessed. Kaplan-Meier analysis was performed to evaluate the overall survival and disease-free survival of breast cancer patients with the expression level of LINP1. Cox proportional hazard regression analysis was performed at both univariate and multivariate levels. The results showed that LINP1 appeared to have higher expression in breast cancer tissues than in adjacent non-tumor tissues (p < 0.01). Increased expression of LINP1 was correlated with advanced TNM stage (p = 0.002), more lymph node metastasis (p = 0.000), and poorer pathological differentiation (p = 0.004). Furthermore, clinical assay indicated that patients with high LINP1 expression had a shorter overall survival and disease-free survival compared with the low LINP1 expression group. Finally, Cox regression analysis showed that LINP1 expression was an independent prognosis-predicting factor for breast cancer patients. LncRNA-LINP1 may be involved in the progression of the breast cancer and be a novel indicator of poor prognosis in patients with breast cancer.


A Drosophila melanogaster model shows that fast growing Metarhizium species are the deadliest despite eliciting a strong immune response.
We used Drosophila melanogaster to investigate how differences between Metarhizium species in growth rate and mechanisms of pathogenesis influence the outcome of infection. We found that the most rapid germinators and growers in vitro and on fly cuticle were the fastest killers, suggesting that pre-penetration competence is key to Metarhizium success. Virulent strains also induced the largest immune response, which did not depend on profuse growth within hosts as virulent toxin-producing strains only proliferated post-mortem while slow-killing strains that were specialized to other insects grew profusely pre-mortem. Metarhizium strains have apparently evolved resistance to widely distributed defenses such as the defensin Toll product drosomycin, but they were inhibited by Bomanins only found in Drosophila spp. Disrupting a gene (Dif), that mediates Toll immunity has little impact on the lethality of most Metarhizium strains (an exception being the early diverged M. frigidum and another insect pathogen Beauveria bassiana). However, disrupting the sensor of fungal proteases (Persephone) allowed rapid proliferation of strains within hosts (with the exception of M. album), and flies succumbed rapidly. Persephone also mediates gender differences in immune responses that determine whether male or female flies die sooner. We conclude that some strain differences in growth within hosts depend on immune-mediated interactions but intrinsic differences in pathogenic mechanisms are more important. Thus, Drosophila varies greatly in tolerance to different Metarhizium strains, in part because some of them produce toxins. Our results further develop D. melanogaster as a tractable model system for understanding insect-Metarhizium interactions.


Sorting out the spinning of autism: heavy metals and the question of incidence.
The reasons for the rise in autism prevalence are a subject of heated professional debate. Featuring a critical appraisal of some research used to question whether rising levels of autism are related to environmental exposure to toxins (Soden et al. 2007, Barbaresi et al. 2009, Thompson et al. 2007) we aim to evaluate the actual state of scientific knowledge. In addition, we surveyed the empirical research on the topic of autism and heavy metal toxins. In our opinion empirical investigations are finding support for a link with heavy metal toxins. The various causes that have led to the increase in autism diagnosis are likely multi-faceted, and understanding the causes is one of the most important health topics today. We argue that scientific research does not support rejecting the link between the neurodevelopmental disorder of autism and toxic exposures.


Hypolipidemia in a mutant strain of "acatalasemic" mice.
Mutant "acatalasemicm" mice have an unstable catalase in hepatic and renal peroxisomnes that is readily degraded, apparently into peroxidase subunits. The hypothesis that an in situ cataloperoxidase would affect serum lipids was tested in these mutants and serum triglycerides and cholesterol were found to be significantly lower than in the wild strain. This finding is in accordance with reports that a hypolipidemic response to the injection of peroxidase subunits of hepatic catalase occurs in humans and rabbits.


Investigation of nitrogen converters in membrane bioreactor.
In this study, the activity and diversity of nitrogen converters, ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB), ammonia-oxidizing archaea (AOA) and Anammox bacteria in a pilot-scale membrane bioreactor (MBR) were investigated and monitored using amoA and 16S rDNA-based molecular tools. The pilot-scale MBR (100 m(3)/day) was located inside the full-scale Pasakoy Advanced Wastewater Treatment Plant (WWTP), and operated for approximately 5 months without sludge purge. During 148 days of operation, volatile suspended solids (VSS) concentration increased from 2,454 mg/L to 10,855 mg/L and the average organic carbon and ammonia nitrogen removal rates were 92% and 99%, respectively. Real-time PCR results indicated that the fraction of AOB increased from 2.94% to 4.05% when VSS concentration reached to 3,750 mg/L throughout 148 days of operation. At higher VSS concentrations, the fraction of AOB declined gradually to 1.15% while the fraction of Nitrospira population was varied between 8.23 and 13.01%. However, significant change or any positive and negative correlations between VSS concentration and Nitrospira population were not observed in this period. The phylogenetic analysis revealed that MBR harbored diverse AOB community which was related to the Nitrosomonas and Nitrosospira lineage. Candidatus Nitrospira defluvii was the only detected NOB in this study.


Vitrification of calf oocytes: effects of maturation stage and prematuration treatment on the nuclear and cytoskeletal components of oocytes and their subsequent development.
This study was designed to establish the effects of the meiotic stage of bovine oocytes and of a prematuration treatment with roscovitine (ROS) on their resistance to cryopreservation. Oocytes from prepubertal calves at the stages of germinal vesicle breakdown (GVBD) or at metaphase II (MII) were vitrified by the open pulled straw (OPS) method. In another experiment, oocytes were kept under meiotic arrest with 50 microM ROS for 24 hr and vitrified at the GVBD stage. After warming, some oocyte samples were fixed, stained using specific fluorescent probes and examined under a confocal microscope. The remaining oocytes were fertilized, and cleavage and blastocyst rates recorded. Significantly lower cleavage rates were obtained for the vitrified GVBD and MII oocytes (9.9% and 12.6%, respectively) compared to control oocytes (73.9%). Significantly worse results in terms of cleavage rates were obtained when GVBD calf oocytes were exposed to cryoprotectants (CPAs: ethylene glycol plus dimethyl sulfoxide, DMSO) (13.1%) or vitrified (1.6%) after a prematuration treatment with ROS, when compared to untreated control oocytes (68.7%) or ROS-control oocytes (56.6%). None of the vitrification procedures yielded blastocysts, irrespective of the initial meiotic stage or previous prematuration treatment. Compared to the control oocytes, significantly fewer oocytes exhibited normal spindle configuration after being exposed to CPAs or after vitrification of either GVBD or MII calf oocytes. These results indicate that the vitrification protocol has a deleterious effect on the meiotic spindle organization of calf oocytes cryopreserved at both the GVBD and MII stage, which impairs the capacity for further development of the embryos derived from these vitrified oocytes. Prematuration treatment with ROS has no beneficial effect on the outcome of vitrification by the OPS method.


Chemical composition and anxiolytic evaluation of Achillea Wilhelmsii C. Koch essential oil in rat.
Herbal based remedies are used worldwide to treat psychiatric disorders. The aim of this study was to analyse the essential oil composition of Achillea Wilhemsii C. Koch (Asteraceae) and to evaluate its anxiolytic effects in the elevated plus maze (EPM) model of anxiety in rat. Gas chromatography/mass spectrometry (GC/MS) analysis of the essential oil showed that the main compounds of the oil were p-ocimen (23%), 1, 8-cineole (20.8%) and carvone (19.13%). The EPM results showed that 1 mg/kg (i.p.) of the oil significantly (P<0.05) increased the percentage of the time spent and the number of entries in the open arms of the maze while it did not change the total number of entries in the maze arms. These effects were not reversed with 2 mg/kg flumazenil and 5 mg/kg naloxone. We concluded that a minimum dose of 1 mg/kg of the oil has anxiolytic effects which are not probably mediated through GABA and opioid receptors.


Hip spica versus Rush pins for management of femoral diaphyseal fractures in children.
Femoral fractures are common in children between 2 and 12 years of age and 75% of the lesions affect the femoral shaft. Traction followed by a plaster cast is universally accepted as conservative treatment. We compared primary hip spica with closed reduction and fixation with retrogradely passed crossed Rush pins for diaphyseal femur fracture in children. The hypothesis was that Rush pin might provide better treatment with good clinical results in comparison with primary hip spica. Fifty children with femoral fractures were evaluated; 25 of them underwent conservative treatment using immediate hip spica (group A) and 25 were treated with crossed retrograde Rush pins (group B). The patients ages ranged from 3 to 13 years (mean of 9 years). Mean duration of fracture union was 15 weeks in group A and 12 weeks in group B. Mean duration of weight bearing 14 weeks in group and 7 weeks in group B. Mean hospital stay was 4 days in group A and 8 days in group B. Mean followup period in group A was 16 months and group B was 17 months. Complications such as angulation, shortening, infection were compared. Closed reduction and internal fixation with crossed Rush pins was superior in terms of early weight bearing and restoration of normal anatomy.


Disparities in Dental Use and Untreated Caries Prevalence by Income.
Untreated dental caries (UC), although preventable, is the most prevalent disease in the United States. UC diminishes quality of life and lowers productivity for millions of Americans and is notably higher among lower-income compared to higher-income persons. This study examines changes in disparities by income in past-year dental use (DU) and UC in 4 life stages (2-5, 6-19, 20-64, and ≥65 y) between 1999-2004 and 2011-2016. We also examined changes in dental safety net policies during this time. We obtained data on dependent variables, UC and DU, from cross-sectional, nationally representative surveys for 1999-2004 and 2011-2016. We used multivariable regression models with 3 main-effect explanatory variables: income (<200% or ≥200% federal poverty level), life stage, and survey period (1999-2004 or 2011-2016) and sociodemographic variables. We included 2-way interaction terms among main-effect variables to test whether disparities had changed over time in each life stage and a 3-way term to test changes in disparities differed across life stages. Model-adjusted disparities in DU decreased for both preschool-age and school-age children, and disparities in UC decreased for school-age children. Changes in DU and UC disparities were not detectable for working-age adults and increased for retirement-age adults. Changes in DU and UC among preschool and school-age children were not significantly different from one another and were significantly different from changes among retirement-age adults. Compared to working-age adults, changes in disparities for DU and UC were significantly different for school-age children, and changes in DU were significantly different for preschool-age children. Between surveys, the dental safety net was expanded for youth but remained largely unchanged for adults. Expanding the dental safety net for youth could have contributed to increased access to dental care among children relative to adults and contributed to the decrease in disparities in DU and UC among youth. Between 1999-2004 and 2011-2016, the dental safety net was expanded for youth but remained largely unchanged for adults. Using national survey data to compare changes in disparities in past-year dental use and untreated dental caries by income between adults and youth sheds light on the potential impact of expanding the dental safety net.


Bioelectrochromic hydrogel for fast antibiotic-susceptibility testing.
Materials science offers new perspectives in the clinical analysis of antimicrobial sensitivity. However, a biomaterial with the capacity to respond to living bacteria has not been developed to date. We present an electrochromic iron(III)-complexed alginate hydrogel sensitive to bacterial metabolism, here applied to fast antibiotic-susceptibility determination. Bacteria under evaluation are entrapped -and pre-concentrated- in the hydrogel matrix by oxidation of iron (II) ions to iron (III) and in situ formation of the alginate hydrogel in less than 2min and in soft experimental conditions (i.e. room temperature, pH 7, aqueous solution). After incubation with the antibiotic (10min), ferricyanide is added to the biomaterial. Bacteria resistant to the antibiotic dose remain alive and reduce ferricyanide to ferrocyanide, which reacts with the iron (III) ions in the hydrogel to produce Prussian Blue molecules. For a bacterial concentration above 107 colony forming units per mL colour development is detectable with the bare eye in less than 20min. The simplicity, sensitivity, low-cost and short response time of the biomaterial and the assay envisages a high impact of these approaches on sensitive sectors such as public health system, food and beverage industries or environmental monitoring.


FUS-CREB3L2/L1-positive sarcomas show a specific gene expression profile with upregulation of CD24 and FOXL1.
Low-grade fibromyxoid sarcoma (LGFMS) is typically characterized by the specific translocation t(7;16)(q33;p11) and the corresponding fusion gene FUS-CREB3L2. The present study aimed to extract LGFMS-specific, and putatively FUS-CREB3L2-dependent, gene expression patterns to learn more about the pathogenesis of this tumor. We carried out single nucleotide polymorphism (SNP) and global gene expression array analyses, and/or immunohistochemical (IHC) analyses on 24 LGFMS tumor biopsies. Tumor types that are important differential diagnoses to LGFMS were included as comparison in the gene and protein expression analyses. In addition, cells that stably expressed FUS-CREB3L2 were analyzed with gene expression array and the influence of FUS-CREB3L2 on gene expression was investigated in vitro. The SNP array analysis detected recurrent microdeletions in association with the t(7;16) chromosomal breakpoints and gain of 7q in cases with ring chromosomes. Gene expression analysis clearly distinguished LGFMS from morphologically similar tumors and MUC4 was identified as a potential diagnostic marker for LGFMS by gene expression and IHC analysis. FOXL1 was identified as the top upregulated gene in LGFMS and CD24 was upregulated in both LGFMS tumors and FUS-CREB3L2 expressing cells. FUS-CREB3L2 was capable of activating transcription from CD24 regulatory sequences in luciferase assays, suggesting an important role for the upregulation of this gene in LGFMS. The gene expression profile of LGFMS is distinct from that of soft tissue tumors with similar morphology. The data could be used to identify a potential diagnostic marker for LGFMS and to identify possible FUS-CREB3L2 regulated genes.


New taxa of the family Syringophilidae (Acari: Prostigmata) from African barbets and woodpeckers (Piciformes: Lybiidae, Picidae).
New taxa of quill mites (Acari: Syringophilidae) are described from African barbets and woodpeckers in the Ethiopian region. A new monotypic genus Picineoaulonastus gen. nov. is established for a new species Picineoaulonastus pogoniulus sp. nov., parasitising 2 lybiid species, Pogoniulus bilineatus (Sundevall) (type host) in Kenya and Tanzania and P. pusillus (Dumont) (Piciformes: Lybiidae) in Ethiopia. Additionally, 2 more new syringophilid species are described: Neosyringophilopsis lybidus sp. nov. from P. bilineatus in Kenya, and Syringophiloidus picidus sp. nov. from Dendropicos fuscescens (Vieillot) (Piciformes: Picidae) in Kenya, Uganda, and Tanzania.


Disease-modifying effect of atipamezole in a model of post-traumatic epilepsy.
Treatment of TBI remains a major unmet medical need, with 2.5 million new cases of traumatic brain injury (TBI) each year in Europe and 1.5 million in the USA. This single-center proof-of-concept preclinical study tested the hypothesis that pharmacologic neurostimulation with proconvulsants, either atipamezole, a selective α2-adrenoceptor antagonist, or the cannabinoid receptor 1 antagonist SR141716A, as monotherapy would improve functional recovery after TBI. A total of 404 adult Sprague-Dawley male rats were randomized into two groups: sham-injured or lateral fluid-percussion-induced TBI. The rats were treated with atipamezole (started at 30min or 7 d after TBI) or SR141716A (2min or 30min post-TBI) for up to 9 wk. Total follow-up time was 14 wk after treatment initiation. Outcome measures included motor (composite neuroscore, beam-walking) and cognitive performance (Morris water-maze), seizure susceptibility, spontaneous seizures, and cortical and hippocampal pathology. All injured rats exhibited similar impairment in the neuroscore and beam-walking tests at 2 d post-TBI. Atipamezole treatment initiated at either 30min or 7 d post-TBI and continued for 9 wk via subcutaneous osmotic minipumps improved performance in both the neuroscore and beam-walking tests, but not in the Morris water-maze spatial learning and memory test. Atipamezole treatment initiated at 7 d post-TBI also reduced seizure susceptibility in the pentylenetetrazol test 14 wk after treatment initiation, although it did not prevent the development of epilepsy. SR141716A administered as a single dose at 2min post-TBI or initiated at 30min post-TBI and continued for 9 wk had no recovery-enhancing or antiepileptogenic effects. Mechanistic studies to assess the α2-adrenoceptor subtype specificity of the disease-modifying effects of atipametzole revealed that genetic ablation of α2A-noradrenergic receptor function in Adra2A mice carrying an N79P point mutation had antiepileptogenic effects after TBI. On the other hand, blockade of α2C-adrenoceptors using the receptor subtype-specific antagonist ORM-12741 had no favorable effects on the post-TBI outcome. Finally, to assess whether regulation of the post-injury inflammatory response by atipametzole in glial cells contributed to a favorable outcome, we investigated the effect of atipamezole on spontaneous and/or lipopolysaccharide-stimulated astroglial or microglial cytokine release in vitro. We observed no effect. Our data demonstrate that a 9-wk administration of α2A-noradrenergic antagonist, atipamezole, is recovery-enhancing after TBI.