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Administration of plerixafor with granulocyte-colony stimulating factor (G-CSF) mobilizes CD34+ cells much more effectively than G-CSF alone, but cost generally limits plerixafor use to patients at high risk of insufficient CD34+ cell collection based on low peripheral blood (PB) CD34+ counts following 4 days of G-CSF. We analyzed costs associated with administering plerixafor to patients with higher day 4 CD34+ cell counts to decrease apheresis days and explored the use of a fixed split dose of plerixafor instead of weight-based dosing. We analyzed 235 patients with plasma cell disorders or non-Hodgkin's lymphoma who underwent progenitor cell mobilization and autologous hematopoietic cell transplantation (AHCT) between March 2014 and December 2017. Two hundred ten (89%) received G-CSF plus Plerixafor and 25 (11%) received G-CSF alone. Overall, 180 patients (77%) collected in 1 day, 53 (22%) in 2 days and 2 (1%) in 3 days. Based on our data, we present a probabilistic algorithm to identify patients likely to require more than one day of collection using G-CSF alone. CD34+ cell yield, ANC and platelet recovery were not significantly different between fixed and standard dose plerixafor. Plerixafor enabled collection in 1 day and with estimated savings of $5000, compared to patients who did not receive plerixafor and required collection for three days. While collection and processing costs and patient populations vary among institutions, our results suggest re-evaluation of current algorithms., (© 2021 Wiley Periodicals LLC.)

Empathy has held a vital and enduring standing in the theory and practice of clinical social work. Defining and conceptualizing empathy is a continuing challenge in social work and across the human services. A multitude of definitions of empathy exist in the therapeutic literature, creating confusion relating to research findings and treatment processes. Recent trends emphasize an overarching and expansive way of conceiving empathic understanding in the therapeutic relationship and informing treatment practice. Multiple perspectives of empathy facilitate a broad and wide-ranging engagement of the practitioner and the client in the therapeutic process. With significant implications for clinical social workers, an integral model capitalizes on the engagement of empathy from multiple ways of knowing: subjective, objective, and interpersonal. Numerous clinical examples illustrate applications of the tripartite model in social work practice. The integral empathy model is amenable to research and training across therapeutic contexts in social work and related fields., (© 2020 National Association of Social Workers.)

Burkholderia pseudomallei ( B. pseudomallei ), the etiological agent of melioidosis, is a Gram-negative bacterium with additional concern as a biothreat pathogen. The mortality rate from B. pseudomallei varies depending on the type of infection and extent of available health care, but in the case of septicemia left untreated it can range from 50 - 90%. Current therapy for melioidosis is biphasic, consisting of parenteral acute-phase treatment for two weeks or longer, followed by oral eradication-phase treatment lasting several months. An effective oral therapeutic for outpatient treatment of acute-phase melioidosis is needed. GC-072 is a potent, 4-oxoquinolizine antibiotic with selective inhibitory activity against bacterial topoisomerases. GC-072 has demonstrated in vitro potency against susceptible and drug-resistant strains of B. pseudomallei and is also active against Burkholderia mallei , Bacillus anthracis , Yersinia pestis , and Francisella tularensis GC-072 is bactericidal both extra- and intracellularly, with rapid killing noted within a few hours and reduced development of resistance compared to ceftazidime. GC-072, delivered intragastrically to mimic oral administration, promoted dose-dependent survival in mice using lethal inhalational models of B. pseudomallei infection following exposure to a 24 or 339 LD 50 challenge with B. pseudomallei strain 1026b. Overall, GC-072 appears to be a strong candidate for first-line, oral treatment of melioidosis., (Copyright © 2019 Shearer et al.)

Objective: To define cognitive apprenticeship and describe how it can be applied to orthopedic education., Design: Traditional apprenticeships have been used through history as a teaching model for wide variety of skills. These apprenticeships are characterized by practical, on-the-job training in which the apprentice observes and assists a master in the completion of a task, and thereby learns the skills needed to complete that task on his or her own., Results: Cognitive apprenticeship is differentiated from the traditional apprenticeship model primarily by its educational goals. Cognitive apprenticeships are used to teach skills which require internal though processes which cannot be readily observed externally by the teacher or the student., Conclusion: Here, we review the history of the cognitive apprenticeship concept, its basic principles, its applications to a wide variety of educational circumstances, and its potential use a framework for developing orthopedic curricula., (Copyright © 2019 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Under the Continuous Medication Monitoring (CoMM) approach, community pharmacists prevent, identify, resolve, and document drug therapy problems during the dispensing process., Objective: To describe the patients receiving CoMM interventions and the pattern of delivery of CoMM interventions., Methods: Pharmacy dispensing and clinical records were reviewed for patients filling at least one prescription and receiving at least one continuous medication monitoring intervention at a community pharmacy from April 2014 through March 2015. The proportion of patients receiving an intervention type and the number of interventions per patient were computed., Results: Nearly 2500 patients received 16,986 continuous medication monitoring interventions over the year. The average age of the patients receiving the interventions was 59.1 years, and they filled an average of 8.0 unique medications. An average of 6.8 interventions was delivered to each patient. About half (49.7%) of interventions addressed drug therapy problems. The pharmacists delivered 3.0 patient counseling and education and 3.4 drug therapy problem interventions per patient on average., Conclusion: There are many opportunities to improve patients' medication use that can be identified and addressed under a Continuous Medication Monitoring model. Movement to this model of practice is desirable, but changes are needed to facilitate the shift., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Perfectionism is recognized as a significant risk factor for psychopathology. Emerging research links attachment to perfectionism in adult and college-age samples. The Frost Multidimensional Perfectionism Scale (FMPS) has been used in adults and adolescents with a variety of factor structures found. This study sought to establish the factor structure in a general adolescent sample prior to testing for associations between perfectionism, attachment, and psychopathology in the same sample., Design: A cross-sectional survey design was used. Confirmatory factor analysis, and correlational and regression analyses were employed., Methods: A total of 290 adolescents, aged 12-18 years, were recruited from a state secondary school. All completed the FMPS along with brief measures of attachment and psychopathology., Result: Exploratory and confirmatory factor analyses failed to replicate previously published models, and a new six-item, 1-factor model representing perfectionism was found instead. This new variable was then used to establish a role for perfectionism and attachment anxiety in predicting internalizing problems. Perfectionism also correlated with conduct problems and hyperactivity., Conclusion: This study established a novel factor structure for the FMPS, allowing proof of principle of the role of perfectionism in a relationship with attachment and psychopathology, which after replication, may inform new interventions for perfectionism. Caution is noted about the use of extant perfectionism measures that are not properly developmentally informed and which do not capture the dynamic nature of adolescence and adolescent perfectionism., Practitioner Points: Perfectionism is a feature of adolescent psychopathology, including internalizing and externalizing problems. Perfectionism is associated with attachment anxiety and together contributes to internalizing problems. Current conceptualizations of perfectionism may not capture the specific developmental and dynamic aspects of adolescence and should not be regarded as a stable personality trait., (© 2017 The British Psychological Society.)

Commercial fishers have used fish aggregating devices throughout the Mediterranean Sea for over 40 years. These devices attract numerous predatory and forage species in both coastal and offshore environments. This study examined the influence of fish aggregating devices on schooling and aggregating behaviour by small forage fish in quasi-natural mesocosms. Anti-predator behaviour was evaluated for juvenile Caranx crysos under a variety of treatment conditions. Results suggest that, in the absence of physical structure, C. crysos first respond to a predatory threat by forming a school. When a physical structure is present, however, C. crysos show an occasional tendency to aggregate near the structure. These results suggest that a threatened prey species can change their defensive strategy against predatory behaviour. Further examination is required to explain if fish aggregating devices can increase survival rates of post-larval and juvenile prey species in the southern Mediterranean Sea. Management agencies should consider the relationship between the use of fish aggregating devices by commercial fisheries and the potential influence such devices possess on population dynamics of aggregating fish species., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A combination of stomach contents, nitrogen stable-isotope and tissue C:N values are presented to demonstrate feeding activity of Atlantic bluefin tuna Thunnus thynnus on the Gulf of Mexico (GOMEX) spawning grounds. Diets include teleosts, cephalopods, crustaceans and a pelagic tunicate (Pyrosoma atlanticum). Results reveal the need to classify the GOMEX as a T. thynnus feeding ground., (© 2014 The Fisheries Society of the British Isles.)

Background: Anaplasma phagocytophilum is the etiological agent of granulocytic anaplasmosis in humans and animals. Wild animals and ticks play key roles in the enzootic cycles of the pathogen. Potential ecotypes of A. phagocytophilum have been characterized genetically, but their host range, zoonotic potential and transmission dynamics has only incompletely been resolved., Methods: The presence of A. phagocytophilum DNA was determined in more than 6000 ixodid ticks collected from the vegetation and wildlife, in 289 tissue samples from wild and domestic animals, and 69 keds collected from deer, originating from various geographic locations in The Netherlands and Belgium. From the qPCR-positive lysates, a fragment of the groEL-gene was amplified and sequenced. Additional groEL sequences from ticks and animals from Europe were obtained from GenBank, and sequences from human cases were obtained through literature searches. Statistical analyses were performed to identify A. phagocytophilum ecotypes, to assess their host range and their zoonotic potential. The population dynamics of A. phagocytophilum ecotypes was investigated using population genetic analyses., Results: DNA of A. phagocytophilum was present in all stages of questing and feeding Ixodes ricinus, feeding I. hexagonus, I. frontalis, I. trianguliceps, and deer keds, but was absent in questing I. arboricola and Dermacentor reticulatus. DNA of A. phagocytophilum was present in feeding ticks and tissues from many vertebrates, including roe deer, mouflon, red foxes, wild boar, sheep and hedgehogs but was rarely found in rodents and birds and was absent in badgers and lizards. Four geographically dispersed A. phagocytophilum ecotypes were identified, that had significantly different host ranges. All sequences from human cases belonged to only one of these ecotypes. Based on population genetic parameters, the potentially zoonotic ecotype showed significant expansion., Conclusion: Four ecotypes of A. phagocytophilum with differential enzootic cycles were identified. So far, all human cases clustered in only one of these ecotypes. The zoonotic ecotype has the broadest range of wildlife hosts. The expansion of the zoonotic A. phagocytophilum ecotype indicates a recent increase of the acarological risk of exposure of humans and animals.

Equine piroplasmosis (EP) has not been considered indigenous in The Netherlands. However, following the detection of an apparently indigenous subclinical Babesia caballi infection in a horse on Schouwen-Duiveland (an island in the Zeeland Province), a survey was undertaken between May and September 2010 to assess the prevalence of the causative agents of EP in the South-West of The Netherlands. Blood samples from 300 randomly selected horses were tested for specific antibodies against Theileria equi and B. caballi using an indirect fluorescence antibody test (IFAT), and for parasite DNA using a specific polymerase chain reaction combined with reverse line blotting (PCR-RLB). Twelve of the horses (4%) were seropositive for EP. Of these, nine (75%) were positive (titre⩾1:160) for B. caballi alone and three (25%) were also positive for T. equi. PCR-RLB detected T. equi DNA in five horses (1.6%), two of which were seronegative. Four (1.3%) of the positive horses (three positive for T. equi and one for both B. caballi and T. equi) were considered truly indigenous. During the study, two indigenous ponies from a farm situated outside the sampling area were diagnosed with acute clinical piroplasmosis characterized by severe anaemia and pyrexia. Blood smears showed T. equi - like inclusions in red blood cells, and T. equi infection was confirmed in both ponies by PCR-RLB. The initial subclinical B. caballi infection, the survey results and the two acute clinical EP cases confirmed the autochthonous transmission of B. caballi and T. equi infections in The Netherlands., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Equine inflammatory small bowel disease (ISBD) is an idiopathic pathologic condition seeming to increase in prevalence., Objective: To investigate the potential role of gluten in equine ISBD., Animals & Methods: Antibodies known to be important in the diagnosis of human coeliac disease (CD): IgA antibodies to human recombinant and guinea pig tissue-transglutaminase (TGA), native gliadin (AGA), deamidated-gliadin-peptides (DGPA), and primate and equine endomysium (EMA) were assessed in blood samples from three different groups of horses: ISBD affected (n = 12) on a gluten-rich diet and controls either on gluten-rich (n = 22) or gluten-poor (n = 25) diets. Significant differences (p < 0.05) between groups were assessed using the Wilcoxon test., Results: Both ISBD-affected horses and gluten-rich controls had significantly (p < 0.0004) higher hrTGA titers than gluten-poor controls. However, ISBD horses did not show significantly increased levels of any of the CD related antibodies when compared to gluten-rich controls. Nevertheless, markedly increased antibody levels (TGA, EMA and DGPA) were found in one of the ISBD horses. The introduction of a gluten-free ration in this 14-year-old warmblood stallion resulted after 6 months in the reduction of antibody levels and clinical recovery associated with improved duodenal histopathology., Conclusion: To the best of our knowledge, this is the first study assessing gluten-related antibodies in horses and results suggest a potential pathogenic role of gluten in at least some cases of equine ISBD. Clinical importance and impact for human medicine: Given serology and concurrent clinical findings, this study warrants further investigations into the immunologic basis of possible gluten-sensitive enteropathy in horses and analogy with human disease.

Equine proliferative enteropathy (EPE) is an emerging infectious enteric disease caused by the obligate intracellular gram-negative bacterium Lawsonia intracellularis. EPE was tentatively diagnosed in six weanling foals, aged between 5 and 7 months. Clinical signs included depression, anorexia, ventral oedema, and weight loss. Plasma biochemistry consistently revealed severe hypoproteinaemia. The ante-mortem diagnosis of EPE was based on clinical signs, hypoproteinaemia (6/6), the detection of moderate-to-high titres of L. intracellularis antibody (6/6), and severe thickening of the small intestinal wall on ultrasonography (2/2), or L. intracellularis detected in faeces by PCR (I/2). The first foal died despite treatment and at post-mortem examination the tentative diagnosis was EPE. Three foals from the same farm, which showed similar clinical symptoms were treated with azithromycin and rifampicin; two survived. Post-mortem examination of the foal that died confirmed the tentative clinical diagnosis of EPE on the basis of the lesions found and the detection of L. intracellularis--DNA in the ileum and jejunum. The fifth foal died despite intensive treatment and the post-mortem examination revealed lymphohistiocytic enteritis, typhlitis, and widespread thrombosis in several organs. The sixth foal recovered completely after treatment. This report confirms the presence of clinical L. intracellularis infection in weanling foals in the Netherlands and shows the difficulty in reaching a definitive ante-mortem diagnosis.

Rigorous measurement of intercellular binding energy can only be made using methods grounded in thermodynamic principles in systems at equilibrium. We have developed tissue surface tensiometry (TST) specifically to measure the surface free energy of interaction between cells. The biophysical concepts underlying TST have been previously described in detail. The method is based on the observation that mutually cohesive cells, if maintained in shaking culture, will spontaneously assemble into clusters. Over time, these clusters will round up to form spheres. This rounding-up behavior mimics the behavior characteristic of liquid systems. Intercellular binding energy is measured by compressing spherical aggregates between parallel plates in a custom-designed tissue surface tensiometer. The same mathematical equation used to measure the surface tension of a liquid droplet is used to measure surface tension of 3D tissue-like spherical aggregates. The cellular equivalent of liquid surface tension is intercellular binding energy, or more generally, tissue cohesivity. Previous studies from our laboratory have shown that tissue surface tension (1) predicts how two groups of embryonic cells will interact with one another, (2) can strongly influence the ability of tissues to interact with biomaterials, (3) can be altered not only through direct manipulation of cadherin-based intercellular cohesion, but also by manipulation of key ECM molecules such as FN and 4) correlates with invasive potential of lung cancer, fibrosarcoma, brain tumor and prostate tumor cell lines. In this article we will describe the apparatus, detail the steps required to generate spheroids, to load the spheroids into the tensiometer chamber, to initiate aggregate compression, and to analyze and validate the tissue surface tension measurements generated.

A quantitative real-time polymerase chain reaction (qPCR) assay using a TaqMan minor groove binder (MGB) probe was developed for the detection of Babesia caballi infection in equids from South Africa. Nine previously published sequences of the V4 hypervariable region of the B. caballi 18S rRNA gene were used to design primers and probes to target unique, conserved regions. The B. caballi TaqMan MGB qPCR assay was shown to be efficient and specific. The detection limit, defined as the concentration at which 95% of positive samples can be detected, was determined to be 0.000114% parasitized erythrocytes (PE). We further evaluated a previously reported Theileria equi-specific qPCR assay and showed that it was able to detect the 12 T. equi 18S rRNA sequence variants previously identified in South Africa. Both qPCR assays were tested on samples from two ponies experimentally infected with either T. equi or B. caballi. The qPCR assays were more sensitive than the indirect fluorescent antibody test (IFAT) and the reverse-line blot (RLB) during the early onset of the disease. The assays were subsequently tested on field samples collected from 41 horses, resident on three stud farms in the Northern Cape Province, South Africa. The IFAT detected circulating T. equi and B. caballi antibody in, respectively, 83% and 70% of the samples. The RLB detected T. equi parasite DNA in 73% of the samples, but none of the samples were positive for B. caballi, although 19 T. equi-positive samples also hybridized to the Babesia genus-specific probe. This could indicate a mixed T. equi and B. caballi infection in these samples, with either the B. caballi parasitaemia at a level below the detection limit of the B. caballi RLB probe, or the occurrence of a novel Babesia genotype or species. In contrast, the qPCR assays correlated fairly well with the IFAT. The B. caballi TaqMan MGB qPCR assay was able to detect B. caballi parasite DNA in 78% of the samples. The T. equi-specific qPCR assay could positively detect T. equi DNA in 80% of the samples. These results suggest that the qPCR assays are more sensitive than the RLB assay for the detection of T. equi and B. caballi infections in field samples.

Dysregulation of tissue development pathways can contribute to cancer initiation and progression. In murine embryonic prostate epithelia, the transcription factor SOX9 is required for proper prostate development. In this study, we examined a role for SOX9 in prostate cancer in mouse and human. In Pten and Nkx3.1 mutant mice, cells with increased levels of SOX9 appeared within prostate epithelia at early stages of neoplasia, and higher expression correlated with progression at all stages of disease. In transgenic mice, SOX9 overexpression in prostate epithelia increased cell proliferation without inducing hyperplasia. In transgenic mice that were also heterozygous for mutant Pten, SOX9 overexpression quickened the induction of high-grade prostate intraepithelial neoplasia. In contrast, Sox9 attenuation led to a decrease proliferating prostate epithelia cells in normal and homozygous Pten mutant mice with prostate neoplasia. Analysis of a cohort of 880 human prostate cancer samples showed that SOX9 expression was associated with increasing Gleason grades and higher Ki67 staining. Our findings identify SOX9 as part of a developmental pathway that is reactivated in prostate neoplasia where it promotes tumor cell proliferation.

The mammalian prostate arises from the urogenital sinus and few factors have been identified to be important in the early stages of prostate development. In this study we show that the transcription factor Sox9 is expressed in the epithelia of all mouse prostatic lobes from the initial stages of their development. We used a conditional approach with mice expressing Cre recombinase under the control of Nkx3.1 regulatory sequences to delete Sox9 from the developing prostate. Mice with a prostate specific deletion of Sox9 showed a lack of ventral prostate development and abnormal anterior prostate differentiation. Analysis of these mutant animals revealed an early loss of expression of genes specific to the prostate epithelia such as Nkx3.1 and Shh and a marked reduction in proliferation in the ventral prostate but not in other lobes. Fgf signalling, through the MAPK pathway, has been shown to be important in prostate development and a lobe specific phenotype was reported for a prostate specific Fgfr2 mutant mouse model. Here we show that the levels of Fgfr2 and Sprouty2, a downstream target of Fgf signalling, were severely reduced in the ventral prostate of Sox9 mutant animals but not in other lobes. Prostate organ culture studies with a Mek inhibitor, U0126, and a Fgf receptor inhibitor, SU5402, indicate that the timing of expression of Cre in the mutant animals could account for the lobe specific phenotype in the Sox9 and Fgfr2 mutants. These studies imply that Sox9 is required for the early differentiation of the prostate bud epithelia.

Imidocarb treatment of horses infected with Babesia caballi is supposed to eliminate the infection, but data on the efficacy of this treatment is scarce. The study presented here concerns four Paso Fino horses, which were imported into the island of Curacao on the basis of a piroplasmosis negative complement fixation test (CFT). Upon re-testing with an indirect fluorescent antibody test immediately after arrival in Curacao, two horses appeared to have antibodies to B. caballi and all horses had antibodies to Theileria equi. Subsequent testing with polymerase chain reaction combined with a reverse line blot yielded positive results for both agents in all four horses. Treatment with five consecutive doses of imidocarb dipropionate (4.7 mg/kg BW im q 72 h), temporarily resulted in negative results, but B. caballi and T. equi were detected again in the samples taken at 6 and 18 weeks after completion of the treatment. These results confirm that the CFT is not a suitable test for pre-import testing and that even high dose treatment with imidocarb may not be capable of eliminating B. caballi and T. equi infections from healthy carriers.

Environmental conditions during seed maturation influence germination, but the genetic basis of maternal environmental effects on germination is virtually unknown. Using single and multiple mutants of phytochromes, it is shown here that different phytochromes contributed to germination differently, depending on seed-maturation conditions. Arabidopsis thaliana wild-type seeds that were matured under cool temperatures were intensely dormant compared with seeds matured at warmer temperature, and this dormancy was broken only after warm seed-stratification followed by cold seed-stratification. The warm-cold stratification broke dormancy in fresh seeds but not in dry after-ripened seeds. Functional PHYB and PHYD were necessary to break cool-induced dormancy, which indicates a previously unknown and ecologically important function for PHYD. Disruption of PHYA in combination with PHYD (but not PHYB) restored germination to near wild-type levels, indicating that PHYA contributes to the maintenance of cool-induced dormancy on a phyD background. Effects of seed-maturation temperature were much stronger than effects of seed-maturation photoperiod. PHYB contributed to germination somewhat more strongly in seeds matured under short days, whereas PHYD contributed to germination somewhat more strongly in seeds matured under long days. The variable contributions of different phytochromes to germination as a function of seed-maturation conditions reveal further functional diversification of the phytochromes during the process of germination. This study identifies among the first genes to be associated with maternal environmental effects on germination.

Leydig cells are the major source of androgen in the male mammal. We describe here for the first time the development of the Leydig cell in a macropodid marsupial, the tammar wallaby, Macropus eugenii. Leydig cells are first recognized morphologically 2 days after birth with the appearance of lipid droplets in the cytoplasm of certain interstitial cells. Lipid content closely matches the steroid content of the developing testis and marks the maturation of the steroid synthesis pathway in the tammar testis. Morphologically mature Leydig cells, marked by distinct mitochondria with tubular cristae and an extensive anastomosing network of smooth endoplasmic reticulum, are developed by day 10 after birth - the time of peak testosterone content in perinatal tammar testes. The volume percentage of each cell type in the testis does not change over time so the growth of each cellular component keeps pace with growth of the whole testis. There was no morphological or quantitative evidence of a change from one population of Leydig cells to another in the tammar testis as has been reported in several other species including the rat, mouse and human. Maturation of the testis is also marked by the development of tight junctions between the cell membranes of adjacent Sertoli cells. These appear around day 30 after birth and coincide with the onset of mitotic arrest in male germ cells. Overall, the development of the Leydig cell in the tammar wallaby follows a similar pattern to that seen in other mammals, although the start of Leydig cell differentiation is, like many other organ systems in marsupials, post natal, not fetal and there appears to be only a single population of Leydig cells.

We identified a new role of phytochrome in mediating germination responses to seasonal cues and thereby identified for the first time a gene involved in maternal environmental effects on germination. We examined the germination responses of a mutant, hy2-1, which is deficient in the phytochrome chromophore. The background genotype, Landsberg erecta (Ler), lacked dormancy in most treatments, while hy2-1 required cold stratification for germination in a manner that resembled a more dormant ecotype, Columbia (Col). Unlike Col, hy2-1 was not induced into dormancy by warm stratification. Therefore, the down-regulation of phytochrome-mediated germination pathways results in sensitivity to cold, but we found no evidence that reduced phytochrome activity enables the warm-induction of dormancy. Cool temperatures during seed maturation induced dormancy. The hy2-1 mutants did not overcome this dormancy, indicating that phytochrome-mediated pathways are required to break cold-induced dormancy. Ler did not respond to post-stratification temperature, but hy2-1 did respond, suggesting phytochrome pathways are involved in germination responses to temperature. In summary, phytochromes mediate dormancy and germination responses to seasonal cues experienced both during seed maturation and after dispersal. Phytochromes therefore appear to be involved in mediating seasonal germination timing, a trait of great ecological importance and one that is under strong natural selection.

In this longitudinal study, the authors investigated individual differences in how families adapt to a child's congenital disorder. Family impact, maternal grief resolution, and child attachment were assessed among 74 mothers and their toddlers with a neurological disorder or disfigurement. Fifty dyads were reevaluated 16 months later. For children with neurological compared with disfigurement diagnoses, there was a greater likelihood of negative impact on family, unresolved maternal grief, and insecure attachment at Time 1. Children classified as secure were significantly more likely to have mothers classified as resolved regarding their reactions to their children's diagnosis. Maternal grief resolution was significantly stable (77%) over time and mediated the relation between type of diagnosis and child security. With time, negative impact of child condition on the family decreased and percentage of children classified as secure increased, suggesting that on average families improved. Results suggest that helping parents come to terms emotionally and cognitively with their child's condition may be a useful focus for intervention., (Copyright 2006 APA, all rights reserved.)

Over the last ten years a fatal syndrome associated with immunodeficiency and severe anaemia has been reported in young Fell pony foals in the UK. Affected foals are usually normal at birth but from the age of 2-4 weeks they progressively lose condition and become severely anaemic. Signs of immunodeficiency become apparent at around 3-4 weeks of age. Morbidity is low but mortality is 100% despite intensive treatment. Affected foals die or are euthanized usually before they reach the age of 3 months. A single autosomal recessive gene is suggested to be on the basis of the syndrome. Recently, affected Fell pony foals have been identified in the Netherlands and between June 2003 and August 2005, six affected Fell pony foals were referred to the Faculty of Veterinary Medicine for investigation.

This review discusses the literature on B. burgdorferi infections in view of the rising incidence of this infection in general and the increasing concerns of horse owners and equine practitioners. Lyme disease, the clinical expression of Borrelia infections in man is an important health problem. The geographic distribution of B. burgdorferi infections in equidae should resemble that of human cases because the vector tick involved, Ixodes ricinus, feeds on both species and, indeed, the infection has been established many times in horses. However, a definite diagnosis of the disease "Lyme borreliosis" in human beings as well as in horses and other animals is often difficult to accomplish. Although a broad spectrum of clinical signs has been attributed to B. burgdorferi infections in horses, indisputable cases of equine Lyme borreliosis are extremely rare so far, if they exist at all.

Piroplasmosis, a disease endemic to most tropical and subtropical areas, appears to be spreading to more temperate zones. This article gives a review of equine piroplasmosis and describes an acute case of infection with Babesia caballi in a Dutch Standard bred foal after a short stay at a stud in Normandy (France). A 3-month-old stallion foal was presented with lethargy, fever of 41 degrees C, and pale mucosal membranes. Haematology revealed a low packed cell volume (14 l/l) leucytosis (25 G/l) and a high blood urea nitrogen concentration (20.1mmol/l). Infection with B. caballi was diagnosed on the basis of Giemsa staining blood smears and was confirmed by polymerase chain reaction in combination with RLB. Treatment with imidocarb dipropionate and a blood transfusion resolved the haemolytic crisis.

The activin growth factors consist of dimeric proteins made up of activin beta subunits and have been shown to be essential regulators of diverse systems in physiology. Four subunits are known to be expressed in mammalian cells: betaA, betaB, betaC, and betaE. Surprisingly, deletion of activin betaC and betaE subunits in vivo does not affect embryonic development or adult physiology which has led to the activin betaC and betaE subunits being regarded as non-essential and unimportant. The steady accumulation of circumstantial evidence to the contrary has led this lab to reassess the role of the activin betaC subunit. Activin betaC protein is expressed more widely than indicated by mRNA localisation. Experiments overexpressing activin betaC subunit or adding exogenous Activin C in vitro are contradictory but suggest roles for activin betaC in regulating Activin A action in apoptosis and homeostasis. Sequestration of betaA subunits by dimerisation with betaC subunits to form Activin AC represents an intracellular regulator of Activin A bioactivity. Activins play a pivotal role in normal physiology and carcinogenesis, so any molecule, such as the activin betaC subunit, that can affect activin action is potentially significant. Advancing our understanding of the physiological role of the activin betaC subunit requires new tools and reagents. Direct detection of the Activin AC dimer will be essential and will necessitate the purification of heteromeric Activin AC protein. In addition, there is a need for the development of an in vivo model of activin betaC subunit overexpression. With development of these tools, research into activin action in development and physiology can expand to include the less well understood members of the activin family such as activin betaC.

Umbilical hernias are common in foals. This article provides a review of the literature and presents a case of an 1.5-year-old Friesian mare with an incarcerated umbilical hernia. After reposition of the incarcerated intestine (with a lot of effort), the practising veterinarian referred the mare to the Department of Equine Sciences. Preperforative peritonitis was diagnosed, presumed to be caused by necrotic bowel. After laparotomy, this tentative diagnosis was confirmed. The necrotic part of the small intestine was resected and intensive medical treatment was started. Initially, the mare recovered well, but seven days after surgery her general condition deteriorated and she had to be euthanized. At necropsy, impaction of the stomach and rupture of the stomach wall were found. The impaction was probably a result of the generalized peritonitis.

Polychlorinated biphenyls (PCBs) are ubiquitous highly persistent manufactured chemicals known to bioaccumulate in the food chain. Exposure to PCBs has been implicated in a wide range of human health effects, including altering normal endocrine processes and reproductive function. However, very little is understood regarding the specific mechanisms by which PCBs may exert their effects in biological systems. We have examined the ability of PCBs to interfere with transcriptional activation of the androgen receptor (AR) and glucocorticoid receptor (GR) in an in vitro transcription-based reporter assay system. Four Aroclor PCB mixtures were found to antagonize AR-mediated transcription in the presence of the natural AR ligand dihydrotestosterone (DHT). The antagonistic activity of Aroclor mixtures increased in the following order: 1260 < 1242 < 1254 < 1248. These Aroclor mixtures had no discernible effect on GR activity. Aroclor 1254 in the absence of DHT exhibited weak agonistic responses in a dose-dependent manner with AR. Within a series of individual congeners, congeners 42, 128, and 138 are shown to antagonize AR activity. These congeners all share a common core chlorine substitution pattern. Ligand-binding studies demonstrate that endocrine activities of PCB mixtures and congeners on AR are likely due to direct and specific binding to AR ligand-binding domain., (Copyright 2002 Elsevier Science (USA).)

The development of the phallus from the indifferent stage to sexual dimorphism has not been described in any marsupial. This study describes the morphological and histological changes occurring in the development of the phallus of the tammar wallaby. The development of the penis and clitoris in the tammar closely follow the most widely accepted model for the development of the same organs in eutherian mammals. The urogenital plate that is present in both sexes at birth hollows out to form a urogenital groove at approximately 70 days postpartum (p.p.). There is then greater growth of the phallus in males than in females, which results in sexual dimorphism in length approximately 100 days p.p. In males, the urogenital groove secondarily closes over at this time and fuses in the midline and by 128 days p.p. the penile urethra is fully formed. In females, the groove remains open. The clitoris changes little morphologically from the time of formation of the urogenital groove until adulthood. The pattern of development of the penis in the tammar is similar to that seen in eutherian mammals. There is strong evidence that penis development is androgen-dependent in the tammar, yet unusually it becomes sexually dimorphic at a time when androgen content of the developing testis is low.

In the marsupial tammar wallaby, virilization begins approximately 3 wk after the onset of testosterone synthesis. In the eutherian mammal, in contrast, the onset of virilization of the male urogenital tract occurs shortly after the onset of androgen synthesis. Androgen action requires the presence of the androgen receptor to mediate a response in target tissues. We therefore investigated the developmental expression of the androgen receptor (AR) in both sexes of the tammar wallaby. AR gene transcript was detected in fetal gonad and brain as early as Day 19 of the 26.5-day gestation, 7 days earlier than the first rise in testicular testosterone (Days 0-5 postpartum [p.p.]). Immunoreactive AR was identified in the male urogenital sinus (UGS) 2 days before birth and in the female UGS and mammary glands by the day of birth. AR was present in the UGS, vagina, and prostate until Day 152 p.p., the oldest age examined. AR was identified in the gubernaculum testis at Day 2 p.p. and became more abundant by Day 32. In the phallus of both sexes, AR was identified by Day 4 p.p. and until Day 157, the oldest age examined. AR was not detected in the scrotum at any age from the day of birth to Day 157. Maturation of the phallus, wolffian duct, and epididymis was marked by appearance of epithelial immunostaining. AR was localized in the epithelium of the UGS in females by Day 50 p.p. but was not found in the epithelium of the male UGS up to Day 152 p.p., the oldest examined. AR were found in the mesenchyme of the UGS of male and female tammars 3-4 wk before virilization is first evident in the male at Day 25 p.p. We conclude that the presence of AR is not the initiating signal for virilization of the UGS in this marsupial male.

The development of the prostate and the normal descent of the testes in the tammar wallaby (Macropus eugenii) were influenced by treatment with the non-steroidal anti-androgen flutamide. Male pouch young were treated daily from day 9 to day 45, or from day 20 to day 45, of pouch life. Prostate development was inhibited in both treatment groups to a similar extent. Since prostatic buds do not form until day 25 of pouch life, these results suggest that there is a window of androgen sensitivity operating between day 20 and day 25 of pouch life. The number of prostatic buds was significantly lower, but despite the duration of treatment there was never complete abolition of prostate development. Although testes had descended to the same position in treated and control pouch young, inguinal hernias developed in three of four animals treated with flutamide from day 9. These data demonstrate that virilization of the male reproductive tract in this marsupial is dependent on a relatively brief exposure to androgens. Blocking androgen receptor action interferes with normal development of the inguinal canal, which suggests that it is this aspect of inguinoscrotal testicular descent that is androgen dependent.

This study examines the role of dihydrotestosterone in virilization of the developing male tammar. The onset of prostate differentiation in this marsupial species normally occurs around 25 days postpartum, long after the onset of testicular testosterone production immediately after birth and the appearance of 5 alpha-reductase in the urogenital sinus before day 10. Males treated with the 5 alpha-reductase inhibitor Finasteride had reduced prostatic growth and development, and their testicular structure was disorganized. Exogenous testosterone in males enhanced the development of prostatic buds but also caused damage to the testis structure. Treatment of female tammars with testosterone between days 20-30 postpartum stimulated prostatic tissue formation and Wolffian duct development, confirming that prostatic differentiation is initiated by androgens and occurs over a relatively narrow window of time. Testosterone had a deleterious effect on the ovary, destroying the germ cells. Although treatment with testosterone damaged gonadal cellular structure in both male and female tammar young, dihydrotestosterone is apparently necessary for stability of the seminiferous tubules in the testis. Taken together, these results suggest that dihydrotostesterone initiates prostatic development between days 20 and 25 after birth in this marsupial.

Background: Articles were identified from a literature search based on Index Medicus from 1983 onwards with additional, as yet, unpublished data obtained directly from ongoing research at The Middlesex Hospital Vascular Laboratory. Original scientific articles were selected if they addressed the mechanisms causing venous ulceration in relation to the events in the microcirculation., Objective: To review the mechanisms proposed recently to explain the pathogenesis of venous ulceration., Results: Recent data suggest that there is a systemic inflammatory response associated with the presence of venous disease in the lower limb, as indicated by measuring plasma neutrophil elastase and lactoferrin. In volunteers without venous disease white cell activation may be produced by experimental venous hypertension lasting 30 minutes, produced by applying a venous tourniquet to the lower limb or by standing without moving for 30 minutes., Conclusion: Inflammatory mechanisms play a significant role in the pathogenesis of venous disease but the exact mechanisms producing venous ulceration remain to be elucidated.

Incisions for vascular access at the groin are usually vertical. Because such incisions cross the moist skin-crease area and disrupt lymphatics, they may be more prone to infection than oblique incisions placed above and parallel to the groin crease. To determine whether this was the case, 149 patients undergoing vascular reconstruction through a groin incision over a period of 30 months were studied. Those with previous groin incisions were excluded, and where an incision was necessary in both groins, each wound was studied separately. Over a 10-day postoperative period 5 of 85 vertical wounds developed infection with purulent discharge, whereas no oblique wounds (n = 82) became infected (P = 0.032). Oblique incisions for vascular access at the groin are associated with a decreased incidence of wound infection compared with conventional vertical incisions.

Light reflection rheography is a simple non-invasive technique for assessing venous function in the leg. One hundred and twenty-four patients referred for venography with a clinically suspected deep venous thrombosis were investigated by light reflection rheography to determine the accuracy of the technique in diagnosing acute thrombosis. In half of the patients venography confirmed a deep venous thrombosis. Light reflection rheography had a sensitivity of 92 per cent and a specificity of 84 per cent in detecting acute thrombosis. The technique had a negative predictive value of 92 per cent in selecting those patients with no thrombosis. Light reflection rheography can be performed at the bedside or in the radiography department which makes it a suitable technique for screening patients with suspected deep venous thrombosis.

An 18-month-old infant required six hospital admissions in a period of six months for episodes consisting of coughing, respiratory depression, hematemesis, coma, dehydration, and lesions about the mouth. A negative history of ingestion of toxins was repeatedly obtained from the family and two home inspection by the local Health Department failed to identify potential toxins. Metabolic work-up was entirely negative. Utilizing methods of GC-MS, metabolites of a-terpineol were isolated from infant urine on two admissions to the hospital. These metabolites were confirmed by mass spectrometry to be the same metabolites excreted by Sprague-Dawley rats injected with a-terpineol or pine oil. The child had no additional episodes after physical separation from the home environment.

A simplified mathematical model is described for the measurement of regional cerebral blood flow by positron emission tomography in man, based on a modification of the autoradiographic strategy originally developed for experimental animal studies. A modified ramp intravenous infusion of radiolabeled tracer is used; this results in a monotonically increasing curvilinear arterial activity curve that may be accurately described by a polynomial of low degree (= zeta). Integrated cranial activity CB is measured in regions of interest during the latter portion of the tracer infusion period (times T1 to T2). It is shown that (See formula: text) where each of the terms A chi is a readily evaluated function of the blood flow rate constant kappa, the brain:blood partition coefficient for the tracer, the cranial activity integration limits T1 and T2, the coefficients of the polynomial describing the arterial curve, and an iteration factor n that is chosen to yield the desired degree of precision. This relationship permits generation of a table of CB vs. kappa, thus facilitating on-line computer solution for blood flow. This in vivo autoradiographic paradigm was validated in a series of rats by comparing it to the classical autoradiographic strategy developed by Kety and associates. Excellent agreement was demonstrated between blood flow values obtained by the two methods: CBF in vivo = CBF classical X 0.99 - 0.02 (units in ml g-1 min-1; correlation coefficient r = 0.966).

The effects on tissue oxygenation of postoperative adjuvant oxygen have been studied in a group of 20 patients undergoing below-knee (BK) amputation for vascular disease. Ten patients received no therapy, the remainder receiving 28% oxygen for 48 hours following surgery. The results showed that the transcutaneous pO2 in the amputation flaps fell significantly by some 20 mmHg (p less than 0.01) following surgery and that this fall was prevented by the use of adjuvant oxygen. The fall was not observed in the non-amputated limbs. TcpO2 took almost two weeks to reach its pre-operative levels in the amputated limbs. The effect on stump healing of adjuvant oxygen therapy was investigated in a randomized controlled trial in a series of 39 patients undergoing BK amputation. There were 22 patients in the control (untreated) group and 17 in the treated group (adjuvant oxygen for 48 hours). In the treated group 14 patients healed primarily and three amputations failed. In the untreated group 14 limbs healed primarily, one secondarily and there were 7 failures. The pre-operative transcutaneous values in the stumps which failed (26 mmHg +/- 14) was significantly lower (p less than 0.005) than in those which healed (40 mmHg +/- 9). The mean pre-operative TcpO2 in the patients in whom healing occurred in the treated group (35 mmHg +/- 10) was significantly lower (p less than 0.001) than the mean pressure observed in the untreated group (44 mmHg +/- 9).

Gas chromatograph/mass spectrometer/computer systems can be used to quantify a wide variety of compounds of clinical interest. A quadrupole instrument operated in the chemical ionization (Cl) mode was used in these studies. Because of the sensitivity and specificity of selective ion detection, it is possible to make measurements routinely in the nanogram to picogram range, with 0.1-1.0 ml samples of plasma and 1-5 ml samples or urine. Internal standards, preferably stable-isotope-labeled compounds, were added to the biological samples before isolation was begun. We describe clinical applications of these procedures to problems in toxicology, pharmacokinetics, and perinatal pharmacology.