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Racial-ethnic backgrounds of rehabilitation counseling clientele have become increasingly diverse. Additionally, the current emphasis on globalization and international rehabilitation in diverse communities requires educators to examine teaching methods and strategies to best train rehabilitation counselors working within these complex diverse populations. Rehabilitation counseling training programs have begun to embrace multicultural practices as they are implemented in accreditation standards; however, implementation of multicultural practices in educational programs is still unclear. The purpose of this article is to define multicultural education and its role in rehabilitation counselor education. A multifaceted approach to multicultural education in rehabilitation counseling education is presented. Implications for rehabilitation counselor education programs is discussed. [ABSTRACT FROM AUTHOR]

Coexisting disabilities involve persons with physical, cognitive, and psychiatric disabilities together with alcohol and other drug (AOD) abuse concerns. Prevalence rates of coexisting disabilities are high and access to treatment is limited. This study examined the attitudes of AOD abuse counselors as well as their perceptions of competency in working with people with coexisting disabilities. A significant negative relationship was found between counselor competence and their knowledge of the impact of coexisting disabilities (r = -.519). A significant relationship was also found between counselor attitude toward the problems associated with coexisting disabilities in treatment and both their accurate responses (r = .784) and their inaccurate responses on the impact of coexisting disabilities (r = .726). [ABSTRACT FROM AUTHOR]

Mental health counselors, school counselors, and rehabilitation counselors, much like other professional counselors, encounter clients whose lives are somehow affected by substance use and addictions. Although counselors regularly encounter substance-dependent clients, spouses, children, and/or employers affected by substance abuse, training in substance abuse and related issues is often not included in counselor training programs. This paper offers caution and considerations to be addressed when developing the objectives and techniques of a pedagogy that uses films, biographies, memoirs, and other forms of contemporary mass media as an adjunct in addiction training in counselor education. [ABSTRACT FROM AUTHOR]

Unlike many regions of the United States that live with seasonal disasters such as hurricanes, snow storms, or flooding from torrential rains, the greatest threat of natural disaster in California still comes from earthquakes (TransPacific Renal Network, 1998). This was proven on October 17, 1989 when the Loma Prieta earthquake rolled through northern California. Measured as 7.1 on the Richter scale, the quake's epicenter was located about 10 miles northeast of Santa Crux along a segment of the San Andreas Fault near the town of Loma Prieta in the Santa Crux Mountains. The impact, however, was felt throughout most of the northern portion of the state. [ABSTRACT FROM AUTHOR]

When initially introduced into a susceptible population, a disease may die out or result in a major outbreak. We present a Continuous-Time Markov Chain model for enzootic WNV transmission between two avian host species and a single vector, and use multitype branching process theory to determine the probability of disease extinction based upon the type of infected individual initially introducing the disease into the population - an exposed vector, infectious vector, or infectious host of either species. We explore how the likelihood of disease extinction depends on the ability of each host species to transmit WNV, vector biting rates on host species, and the relative abundance of host species, as well as vector abundance. Theoretical predictions are compared to the outcome of stochastic simulations. We find the community composition of hosts and vectors, as well as the means of disease introduction, can greatly affect the probability of disease extinction.

Throughout the vector-borne disease modeling literature, there exist two general frameworks for incorporating vector management strategies (e.g. area-wide adulticide spraying and larval source reduction campaigns) into vector population models, namely, the "implicit" and "explicit" control frameworks. The more simplistic "implicit" framework facilitates derivation of mathematically rigorous results on disease suppression and optimal control, but the biological connection of these results to real-world "explicit" control actions that could guide specific management actions is vague at best. Here, we formally define a biological and mathematical relationship between implicit and explicit control, and we provide mathematical expressions relating the strength of implicit control to management-relevant properties of explicit control for four common intervention strategies. These expressions allow the optimal control and basic reproduction number analyses typically utilized in implicit control modeling to be interpreted directly in terms of real-world actions and real-world monetary costs. Our methods reveal that only certain sub-classes of explicit control protocols are able to be represented as implicit controls, and that implicit control is a meaningful approximation of explicit control only when resonance-like synergistic effects between multiple explicit controls have negligible effects on population reduction. When non-negligible synergy exists, implicit control results, despite their mathematical tidiness, fail to provide accurate predictions regarding vector control and disease spread. Collectively, these elements build an effective bridge between analytically interesting and mathematically tractable implicit control and the challenging, action-oriented explicit control., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Management strategies for control of vector-borne diseases, for example Zika or dengue, include using larvicide and/or adulticide, either through large-scale application by truck or plane or through door-to-door efforts that require obtaining permission to access private property and spray yards. The efficacy of the latter strategy is highly dependent on the compliance of local residents. Here we develop a model for vector-borne disease transmission between mosquitoes and humans in a neighborhood setting, considering a network of houses connected via nearest-neighbor mosquito movement. We incorporate large-scale application of adulticide via aerial spraying through a uniform increase in vector death rates in all sites, and door-to-door application of larval source reduction and adulticide through a decrease in vector emergence rates and an increase in vector death rates in compliant sites only, where control efficacies are directly connected to real-world experimentally measurable control parameters, application frequencies, and control costs. To develop mechanistic insight into the influence of vector motion and compliance clustering on disease controllability, we determine the basic reproduction number R0 for the system, provide analytic results for the extreme cases of no mosquito movement, infinite hopping rates, and utilize degenerate perturbation theory for the case of slow but non-zero hopping rates. We then determine the application frequencies required for each strategy (alone and combined) in order to reduce R0 to unity, along with the associated costs. Cost-optimal strategies are found to depend strongly on mosquito hopping rates, levels of door-to-door compliance, and spatial clustering of compliant houses, and can include aerial spray alone, door-to-door treatment alone, or a combination of both. The optimization scheme developed here provides a flexible tool for disease management planners which translates modeling results into actionable control advice adaptable to system-specific details., Competing Interests: The authors have declared that no competing interests exist.

Hurricanes have profound impacts on zoonotic pathogen ecosystems that exhibit spatial and temporal waves in both distance from and time since the event. Wind, rain, and storm surge directly affect mosquito vectors and animal hosts of these pathogens. In this analysis, we apply a West Nile virus transmission model parameterized for the Northern coast of the Gulf of Mexico to explore the effect of event timing of hurricane landfall, time since the event, and damage extent on human West Nile virus neuro-invasive disease (WNV-NID) risk. Early-season hurricanes, which make landfall prior to the peak of baseline WNV transmission activity, increase the average total WNV-infectious mosquitoes for the year by 7.8% and human WNV-NID incidence by 94.3% across all areas with hurricane damage. The indirect effects on human exposure to mosquito bites in the immediate aftermath and long-term recovery from the event have strong impacts on the risk of infection. The resultant interactive direct and indirect storm effects on the pathogen system are spatially and temporally heterogenous among the generalized time and space categories modeled., (Copyright © 2020 by The American Mosquito Control Association, Inc.)

Background: Fungi are constantly exposed to nitrogen limiting environments, and thus the efficient regulation of nitrogen metabolism is essential for their survival, growth, development and pathogenicity. To understand how the rice blast pathogen Magnaporthe oryzae copes with limited nitrogen availability, a global proteome analysis under nitrogen supplemented and nitrogen starved conditions was completed., Methods: M. oryzae strain 70-15 was cultivated in liquid minimal media and transferred to media with nitrate or without a nitrogen source. Proteins were isolated and subjected to unfractionated gel-free based liquid chromatography-tandem mass spectrometry (LC-MS/MS). The subcellular localization and function of the identified proteins were predicted using bioinformatics tools., Results: A total of 5498  M. oryzae proteins were identified. Comparative analysis of protein expression showed 363 proteins and 266 proteins significantly induced or uniquely expressed under nitrogen starved or nitrogen supplemented conditions, respectively. A functional analysis of differentially expressed proteins revealed that during nitrogen starvation nitrogen catabolite repression, melanin biosynthesis, protein degradation and protein translation pathways underwent extensive alterations. In addition, nitrogen starvation induced accumulation of various extracellular proteins including small extracellular proteins consistent with observations of a link between nitrogen starvation and the development of pathogenicity in M. oryzae ., Conclusion: The results from this study provide a comprehensive understanding of fungal responses to nitrogen availability.

Background: Physician burnout is a problem that often is attributed to the use of the electronic health record (EHR)., Objective: To estimate the prevalence of burnout and work-life balance satisfaction in primary care residents and teaching physicians, and to examine the relationship between these outcomes, EHR use, and other practice and individual factors., Methods: Residents and faculty in 19 primary care programs were anonymously surveyed about burnout, work-life balance satisfaction, and EHR use. Additional items included practice size, specialty, EHR characteristics, and demographics. A logistic regression model identified independent factors associated with burnout and work-life balance satisfaction., Results: In total, 585 of 866 surveys (68%) were completed, and 216 (37%) respondents indicated 1 or more symptoms of burnout, with 162 (75%) attributing burnout to the EHR. A total of 310 of 585 (53%) reported dissatisfaction with work-life balance, and 497 (85%) indicated that use of the EHR affected their work-life balance. Respondents who spent more than 6 hours weekly after hours in EHR work were 2.9 times (95% confidence interval [CI] 1.9-4.4) more likely to report burnout and 3.9 times (95% CI 1.9-8.2) more likely to attribute burnout to the EHR. They were 0.33 times (95% CI 0.22-0.49) as likely to report work-life balance satisfaction, and 3.7 times (95% CI 2.1-6.7) more likely to attribute their work-life balance satisfaction to the EHR., Conclusions: More after-hours time spent on the EHR was associated with burnout and less work-life satisfaction in primary care residents and faculty., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Though seasonal West Nile virus (WNV) outbreaks have been widely observed to be associated with the end of the avian nesting season, specific ecological mechanisms accounting for this synchronicity remain poorly understood. In this paper we develop and evaluate a novel mathematical model of enzootic WNV transmission to gain insight into the mechanisms responsible for structuring WNV dynamics. We incorporate avian (host) stage-structure (nestling, fledgling, and adult) and within-species heterogeneity in the form of stage-specific mosquito (vector) biting rates. We determine the extent to which temporal fluctuations in host stage and vector abundance throughout the season, along with the differential exposure of these stages to mosquito bites, affect the timing and magnitude of WNV outbreaks in the vector population. We find heterogeneity in avian stage exposure, particularly an increase in juvenile exposure, to result in earlier, more intense transmission. The effects of differential exposure are dependent upon vector abundance, both at carrying capacity as well as during initial stages of nestling production., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Waterborne diseases such as cholera continue to pose serious public health problems in the world today. Transmission parameters can vary greatly with socioeconomic class (SEC) and the availability of clean water. We formulate a multi-patch waterborne disease model such that each patch represents a particular SEC with its own water source, allowing individuals to move between SECs. For a 2-SEC model, we investigate the conditions under which each SEC is responsible for driving a cholera outbreak. We determine the effect of SECs on disease transmission dynamics by comparing the basic reproduction number of the 2-SEC model to that of a homogeneous model that does not take SECs into account. We conclude by extending several results of the 2-SEC model to an n-SEC model., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Clostridium perfringens enterotoxin (CPE) action starts when the toxin binds to claudin receptors. Claudins contain two extracellular loop domains, with the second loop (ECL-2) being slightly smaller than the first. CPE has been shown to bind to ECL-2 in receptor claudins. We recently demonstrated that Caco-2 cells (a naturally CPE-sensitive enterocyte-like cell line) can be protected from CPE-induced cytotoxicity by preincubating the enterotoxin with soluble full-length recombinant claudin-4 (rclaudin-4), which is a CPE receptor, but not with recombinant nonreceptor claudins, such as rclaudin-1. The current study evaluated whether a synthetic peptide corresponding to the claudin-4 ECL-2 sequence can similarly inhibit CPE action in vitro and in vivo. Significant protection of Caco-2 cells was also observed using either rclaudin-4 or the claudin-4 ECL-2 peptide in both a preincubation assay and a coincubation assay. This inhibitory effect was specific, since rclaudin-1 and a synthetic peptide based on the claudin-1 ECL-2 offered no protection to Caco-2 cells. However, the claudin-4 ECL-2 peptide was unable to neutralize cytotoxicity if CPE had already bound to Caco-2 cells. When the study was repeated in vivo using a rabbit small intestinal loop assay, preincubation or coincubation of CPE with the claudin-4 ECL-2 peptide significantly and specifically inhibited the development of CPE-induced luminal fluid accumulation and histologic lesions in rabbit small intestinal loops. No similar in vivo protection from CPE was afforded by the claudin-1 ECL-2 peptide. These results suggest that claudin-4 ECL-2 peptides should be further investigated for their potential therapeutic application against CPE-associated disease., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Cholera and many waterborne diseases exhibit multiple characteristic timescales or pathways of infection, which can be modeled as direct and indirect transmission. A major public health issue for waterborne diseases involves understanding the modes of transmission in order to improve control and prevention strategies. An important epidemiological question is: given data for an outbreak, can we determine the role and relative importance of direct vs. environmental/waterborne routes of transmission? We examine whether parameters for a differential equation model of waterborne disease transmission dynamics can be identified, both in the ideal setting of noise-free data (structural identifiability) and in the more realistic setting in the presence of noise (practical identifiability). We used a differential algebra approach together with several numerical approaches, with a particular emphasis on identifiability of the transmission rates. To examine these issues in a practical public health context, we apply the model to a recent cholera outbreak in Angola (2006). Our results show that the model parameters-including both water and person-to-person transmission routes-are globally structurally identifiable, although they become unidentifiable when the environmental transmission timescale is fast. Even for water dynamics within the identifiable range, when noisy data are considered, only a combination of the water transmission parameters can practically be estimated. This makes the waterborne transmission parameters difficult to estimate, leading to inaccurate estimates of important epidemiological parameters such as the basic reproduction number (R0). However, measurements of pathogen persistence time in environmental water sources or measurements of pathogen concentration in the water can improve model identifiability and allow for more accurate estimation of waterborne transmission pathway parameters as well as R0. Parameter estimates for the Angola outbreak suggest that both transmission pathways are needed to explain the observed cholera dynamics. These results highlight the importance of incorporating environmental data when examining waterborne disease., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Many factors influencing disease transmission vary throughout and across populations. For diseases spread through multiple transmission pathways, sources of variation may affect each transmission pathway differently. In this paper we consider a disease that can be spread via direct and indirect transmission, such as the waterborne disease cholera. Specifically, we consider a system of multiple patches with direct transmission occurring entirely within patch and indirect transmission via a single shared water source. We investigate the effect of heterogeneity in dual transmission pathways on the spread of the disease. We first present a 2-patch model for which we examine the effect of variation in each pathway separately and propose a measure of heterogeneity that incorporates both transmission mechanisms and is predictive of R(0). We also explore how heterogeneity affects the final outbreak size and the efficacy of intervention measures. We conclude by extending several results to a more general n-patch setting.

Purpose: Muscle twitch threshold has been used to determine optimal stimulus intensity for somatosensory evoked potentials but neuromuscular blockade precludes the use of muscle twitch during surgery. Accordingly, nerve action potential (NAP) amplitude was investigated as a surrogate to muscle twitch., Methods: The ulnar and tibial nerves were stimulated at the wrist and ankle, respectively, in 27 patients undergoing spine and brain surgery. After neuromuscular blockade was gone, the stimulus intensity for just maximal NAP amplitude recorded from Erb's point and the popliteal fossa was compared with the stimulus intensity for hypothenar and plantar foot muscle twitch threshold (times two), respectively (Wilcoxon matched pairs test)., Results: There was no significant difference between stimulus intensity for just maximal Erb's point and popliteal fossa NAP amplitude when compared with stimulus intensity for hypothenar and plantar foot twitch threshold (times two), respectively. Eight patients required more than twitch intensity (times two) to obtain maximum NAP., Conclusions: The NAP amplitude may be used to determine optimal somatosensory evoked potential stimulus intensity when muscle twitch is not visible. This method should improve the success of intraoperative somatosensory evoked potential monitoring and decrease erroneous interpretation.

In many stage-structured species, different life stages often occupy separate spatial niches in a heterogeneous environment. Life stages of the giant flour beetle Tribolium brevicornis (Leconte), in particular adults and pupae, occupy different locations in a homogeneous habitat. This unique spatial pattern does not occur in the well-studied stored grain pests T. castaneum (Herbst) and T. confusum (Duval). We propose density dependent dispersal as a causal mechanism for this spatial pattern. We model and explore the spatial dynamics of T. brevicornis with a set of four density dependent integrodifference and difference equations. The spatial model exhibits multiple attractors: a spatially uniform attractor and a patchy attractor with pupae and adults spatially separated. The model attractors are consistent with experimental observations.

Clostridium perfringens enterotoxin (CPE) is responsible for causing the gastrointestinal symptoms of C. perfringens type A food poisoning, the second most commonly identified bacterial food-borne illness in the United States. CPE is produced by sporulating C. perfringens cells in the small intestinal lumen, where it then causes epithelial cell damage and villous blunting that leads to diarrhea and cramping. Those effects are typically self-limiting; however, severe outbreaks of this food poisoning, particularly two occurring in psychiatric institutions, have involved deaths. Since animal models are currently limited for the study of the CPE action, a mouse ligated intestinal loop model was developed. With this model, significant lethality was observed after 2 h in loops receiving an inoculum of 100 or 200 μg of CPE but not using a 50-μg toxin inoculum. A correlation was noted between the overall intestinal histological damage and lethality in mice. Serum analysis revealed a dose-dependent increase in serum CPE and potassium levels. CPE binding to the liver and kidney was detected, along with elevated levels of potassium in the serum. These data suggest that CPE can be absorbed from the intestine into the circulation, followed by the binding of the toxin to internal organs to induce potassium leakage, which can cause death. Finally, CPE pore complexes similar to those formed in tissue culture cells were detected in the intestine and liver, suggesting that (i) CPE actions are similar in vivo and in vitro and (ii) CPE-induced potassium release into blood may result from CPE pore formation in internal organs such as the liver.

Background: Adolescent males are more likely to sustain intentional and unintentional injuries, be involved in a physical confrontation, and be successful in suicide attempts. Body image dissatisfaction (BID) has been linked as a possible contributing factor to these negative health behaviors and risks; however, research is limited with males. The interaction of intrapersonal, interpersonal, and social variables in a holistic model has yet to be explored for males. Variables precipitating adolescent males to develop an unhealthy body image and act on negative health behaviors, such as body image drug use, were the impetus for this study., Methods: A randomized cross-sectional sample of 330 adolescent males answered questions concerning body image using the Adolescent Body Image Satisfaction Scale (ABISS). Pearson product moment correlations and stepwise regression analyses identified the strongest predictive variables of BID., Results: The strongest contributing variables accounting for 56.7% of model variance were desire for the body of another person (r = .571, p < .001), teasing (r = .490, p < .001), satisfaction with their body when they were younger (r = .450, p < .001), and difficulty coping with criticism (r = .443, p < .001). No statistically significant differences were found for racial/ethnic background (p < .822, n.s.)., Conclusions: Educators and school districts should consider the confluence of psychosocial variables affecting body image and adolescent male health risk behaviors based on a statistically sound predictive model as provided by the ABISS. Targeted programming to enhance body image and address teasing/bullying behaviors is strongly recommended., (© 2011, American School Health Association.)

Clostridium perfringens epsilon toxin (ETX) rapidly kills MDCK II cells at 37°C, but not 4°C. The current study shows that, in MDCK II cells, ETX binds and forms an oligomeric complex equally well at 37°C and 4°C but only forms a pore at 37°C. However, the complex formed in MDCK cells treated with ETX at 4°C has the potential to form an active pore, since shifting those cells to 37°C results in rapid cytotoxicity. Those results suggested that the block in pore formation at 4°C involves temperature-related trapping of ETX in a prepore intermediate on the MDCK II cell plasma membrane surface. Evidence supporting this hypothesis was obtained when the ETX complex in MDCK II cells was shown to be more susceptible to pronase degradation when formed at 4°C vs. 37°C; this result is consistent with ETX complex formed at 4°C remaining present in an exposed prepore on the membrane surface, while the ETX prepore complex formed at 37°C is unaccessible to pronase because it has inserted into the plasma membrane to form an active pore. In addition, the ETX complex rapidly dissociated from MDCK II cells at 4°C, but not 37°C; this result is consistent with the ETX complex being resistant to dissociation at 37°C because it has inserted into membranes, while the ETX prepore readily dissociates from cells at 4°C because it remains on the membrane surface. These results support the identification of a prepore stage in ETX action and suggest a revised model for ETX cytotoxicity, i) ETX binds to an unidentified receptor, ii) ETX oligomerizes into a prepore on the membrane surface, and iii) the prepore inserts into membranes, in a temperature-sensitive manner, to form an active pore.

Clostridium perfringens enterotoxin (CPE), a single polypeptide of approximately 35 kDa in size, is -associated with type A food poisoning and such non-foodborne gastrointestinal diseases as antibiotic-associated diarrhea and sporadic diarrhea. CPE action begins with binding of the toxin to a claudin -receptor, forming a ∼90 kDa small complex that then rapidly oligomerizes into a hexamer of ∼450 kDa termed CH-1 (CPE hexamer-1). CH-1 is essentially a pore through which calcium gains entry to the cytoplasm, altering cell permeability and resulting in cell death by oncosis or apoptosis. Additionally, tight junctions are disrupted, allowing CPE access to the basolateral membrane so it can produce additional CH-1 -complexes and also the CH-2 complex (∼600 kDa) that contains occludin. We have recently demonstrated the presence of claudins-3 and -4 in both the CH-1 and CH-2 CPE complexes formed after CPE treatment naturally sensitive Caco-2 cells. Interestingly, claudin-1, which binds CPE poorly (if at all), was also present in these complexes.

The 24-member claudin protein family plays a key role in maintaining the normal structure and function of epithelial tight junctions. Previous studies with fibroblast transfectants and naturally sensitive Caco-2 cells have also implicated certain claudins (e.g., Claudin-4) as receptors for Clostridium perfringens enterotoxin (CPE). The present study first provided evidence that the second extracellular loop (ECL-2) of claudins is specifically important for mediating the host cell binding and cytotoxicity of native CPE. Rat fibroblast transfectants expressing a Claudin-4 chimera, where the natural ECL-2 was replaced by ECL-2 from Claudin-2, exhibited no CPE-induced cytotoxicity. Conversely, CPE bound to, and killed, CPE-treated transfectants expressing a Claudin-2 chimera with a substituted ECL-2 from Claudin-4. Site-directed mutagenesis was then used to alter an ECL-2 residue that invariably aligns as N in claudins known to bind native CPE but as D or S in claudins that cannot bind CPE. Transfectants expressing a Claudin-4(N149D) mutant lost the ability to bind or respond to CPE, while transfectants expressing a Claudin-1 mutant with the corresponding ECL-2 residue changed from D to N acquired CPE binding and sensitivity. Identifying carriage of this N residue in ECL-2 as being important for native CPE binding helps to explain why only certain claudins can serve as CPE receptors. Finally, preincubating CPE with soluble recombinant Claudin-4, or Claudin-4 fragments containing ECL-2 specifically blocked the cytotoxicity on Caco-2 cells. This result opens the possibility of using receptor claudins as therapeutic decoys to ameliorate CPE-mediated intestinal disease.

Clostridium perfringens enterotoxin (CPE) causes the symptoms of a very common food poisoning. To assess whether CPE-induced cytotoxicity is necessary for enterotoxicity, a rabbit ileal loop model was used to compare the in vivo effects of native CPE or recombinant CPE (rCPE), both of which are cytotoxic, with those of the noncytotoxic rCPE variants rCPE D48A and rCPE(168-319). Both CPE and rCPE elicited significant fluid accumulation in rabbit ileal loops, along with severe mucosal damage that starts at villus tips and then progressively affects the entire villus, including necrosis of epithelium and lamina propria, villus blunting and fusion, and transmural edema and hemorrhage. Similar treatment of ileal loops with either of the noncytotoxic rCPE variants produced no visible histologic damage or fluid transport changes. Immunohistochemistry revealed strong CPE or rCPE(168-319) binding to villus tips, which correlated with the abundant presence of claudin-4, a known CPE receptor, in this villus region. These results support (i) cytotoxicity being necessary for CPE-induced enterotoxicity, (ii) the CPE sensitivity of villus tips being at least partially attributable to the abundant presence of receptors in this villus region, and (iii) claudin-4 being an important intestinal receptor for CPE. Finally, rCPE(168-319) was able to partially inhibit CPE-induced histologic damage, suggesting that noncytotoxic rCPE variants might be useful for protecting against some intestinal effects of CPE.

Clostridium perfringens enterotoxin (CPE) binds to host cell receptors, forming a small complex precursor for two large complexes reportedly having molecular masses of approximately 155 or approximately 200 kDa. Formation of the approximately 155 kDa complex causes a Ca(2+) influx that leads to apoptosis or oncosis. CPE complex composition is currently poorly understood, although occludin was identified in the approximately 200 kDa complex. The current study used heteromer gel shift analysis to show both CPE large complexes contain six CPE molecules. Ferguson plots and size exclusion chromatography re-sized the approximately 155 and approximately 200 kDa complexes as approximately 425-500 kDa and approximately 550-660 kDa respectively. Co-immunoprecipitation and electroelution studies demonstrated both CPE-binding and non-CPE-binding claudins are associated with all three CPE complexes in Caco-2 cells and with small complex and approximately 425-500 kDa complex of claudin 4 transfectants. Fibroblast transfectants expressing claudin 4 or C-terminal truncated claudin 4 were CPE-sensitive and formed the approximately 425 kDa complex, indicating claudin-induced cell signalling is not required for CPE action and that expression of a single receptor claudin suffices for approximately 425-500 kDa CPE complex formation. These results identify CPE as a unique toxin that combines with tight junction proteins to form high-molecular-mass hexameric pores and alter membrane permeability.

Cell-proliferation in Drosophila Kc167 cells was inhibited by 50% when cell cultures contained 1.7 x 10(-7) M azadirachtin for 48 h (a tertranortriterpenoid from the neem tree Azadirachta indica). Drosophila Kc167 cells exhibited direct nuclear damage within 6-h exposure to azadirachtin (5 x 10(-7) M and above) or within 24 h when lower concentrations were used (1 x 10(-9) M). Fractionation of an extract of Drosophila Kc167 cells combined with ligand overlay technique resulted in the identification of a putative azadirachtin binding complex. Identification of the members of this complex by Peptide Mass Fingerprinting (PMF) and N-terminal sequencing identified heat shock protein 60 (hsp60) as one of its components., (c 2007 Wiley-Liss, Inc.)

Background: Warfarin therapy substantially reduces stroke in atrial fibrillation (AF), yet medical literature reports it is only prescribed in 15-60% of eligible patients. No current national benchmarks for warfarin use in AF patients exist, and it is unclear whether the reported poor compliance represents current rates within primary care practices. The primary study objective was to measure the rate of warfarin use in eligible, high-risk AF patients in a large southeastern group family practice. Secondary objectives were to report the demographics, stroke-risk profiles, contraindications, and reasons for discontinuation of warfarin therapy, Methods: A retrospective chart review was performed on all active patients with documented AF in a large southeastern group family practice/residency between July 1, 2000 and June 30, 2002. Data was abstracted on warfarin use, contraindications, stroke risk, and reasons for discontinuation., Results: Four hundred ninety-one (491) patients were identified from the electronic billing system as potential study subjects. Two hundred eighty-three (283) patients met study criteria, with 210 patients considered to be at high-risk of stroke without contraindications to warfarin therapy. Ninety-four percent (198/210) of these patients were prescribed warfarin during the study period, and 87% (172/198) continued warfarin throughout the study period., Conclusion: Family physicians in this practice prescribe warfarin in AF more frequently than published rates demonstrating that high rates of physician adherence to standards are achievable in primary care. Most patients in this setting were considered high-risk for stroke.

The relation between tactile sensory impairments and functional activity of the hand was studied in a group of 10 subjects with cerebrovascular accidents (CVAs) that involved the left hemisphere. Pressure sensitivity and static and moving two-point discrimination thresholds were measured on the thumbs and index fingers of both hands of these subjects and on a group of 14 control subjects. Functional use of the hand was assessed using object and material recognition tests and the Jebsen test of hand function. Prehensile capacity was evaluated with a pinch-force test that examined the influence of load force and surface texture on the forces used to grasp an object. For this group of subjects with left-hemisphere CVAs, elevated sensory thresholds were associated with slower performance on the recognition tests, but not with the Jebsen test. The ability to control the forces used to grasp an object was also found to be deficient in these subjects, although the forces were still adapted to the loads being supported and the surface properties of the object being held.

A 67.1 kg alligator (Alligator mississippiensis), tested in air, heated twice as fast as it cooled. The cooling thermal time constant was 425 min while alive. Warming and cooling thermal time constants were 421 min after death. The thermal time constant was not appropriate in describing warming in air of mature alligators. Surface and subdermal heat flow measurements of the 67.1 kg animal indicate greater blood flow in the skin during warming compared to cooling. Two mature alligators, 49.9 and 103 kg, were heated and cooled in water. Warming time constants were 67 and 110 min respectively. Cooling time constants were 180 and 246 min. Data from this study were combined with previously published thermal time constants for alligators providing regression equations for alligators ranging from 37 g to 103 kg. Regression equations for alligators tested in water are: tau w = 8.81 M050 tau c = 12.6 M0.62. Time constants (tau) are in minutes (w = warming, c = cooling) with all measurements in stirred water; mass, M, is in kg. Thermal conductance and metabolism data are combined to provide an estimate of the amount the body temperature of theoretical alligators ranging from 50 g to 1000 kg would be elevated by metabolism. A body temperature of 34.2 degrees C is predicted for a 1000 kg theoretical alligator in 30 degrees C water.