Haplosporidium acetes n. sp. infecting the hepatopancreas of jelly prawns Acetes sibogae australis from Moreton Bay, Australia.

Wild Acetes sibogae australis from northern Moreton Bay, Australia displaying opacity of the hepatopancreas were sampled and examined histologically, revealing infection by multinucleate plasmodia of a haplosporidian-like parasite in the epithelial cells of the hepatopancreas. A morphological and phylogenetic investigation identified the parasite as a novel species of the order Haplosporida, and the parasite is described as Haplosporidium acetes n. sp. This is the first report of disease caused by a haplosporidian in wild Australian decapod crustaceans, and the first record of haplosporidiosis in sergestid shrimp. Infections of H. acetes were observed in all cell types (R, B, F and E) within the hepatopancreas. Infected epithelial cells became hypertrophied as they filled with haplosporidian parasites and, in heavy infections, caused almost complete displacement of normal hepatopancreas tissue. Although sporulation was not observed, infected jelly prawns appeared terminally diseased. Infections became grossly evident in around 5% of wild prawns during early autumn at a time of year when jelly prawn populations decline rapidly with decreasing water temperatures, however histopathology indicated at least 13% of apparently normal jelly prawns were also infected. Further studies are required in order to determine if this parasite influences jelly prawn population dynamics. In addition, we report co-infection of a novel microsporidian parasite in the Enterocytozoon Group Microsporidia (EGM) infecting nuclei of hepatopancreatic epithelial cells. The microsporidian was phylogenetically distinct from Enterocytozoon hepatopenaei (EHP) known to infect penaeid shrimp in Asia.

Investigation into white spots in the carapace of a moribund mud crab (Scylla serrata) from a white spot syndrome virus (WSSV) positive zone in Moreton Bay, Australia.

BACKGROUND: A freshly deceased mud crab (Scylla serrata) exhibiting multiple white spots under the carapace was found in Pumicestone Passage, northern Moreton Bay in May 2018. This crab was taken from within a biosecurity zone established due to a recent incursion of White Spot Syndrome Virus (WSSV) into populations of wild penaeids (Penaeus spp., Metapenaeus spp.) and crabs (Thalamita crenata) in the area. Because grossly visible white spots have been previously observed under the carapace of moribund S. serrata with white spot disease (WSD) in India, an investigation into the cause of death was undertaken. CASE REPORT: The affected S. serrata was negative for WSSV DNA when gill samples were tested by real-time PCR. Histopathology found no evidence of WSD lesions in the form of basophilic hypertrophied intranuclear inclusions in any tissues of ectodermal or mesodermal origin. Histopathology of the affected carapace showed that the white spots consisted of multiple lighter coloured foci in the exocuticle formed from concentric crystalline-like rings, which extended into the endocuticle. These were interpreted as evidence of mineral mobilisation within the carapace during the pre-moult (D1 or D2) stage of the moult cycle. The cause of death in this case therefore may have been due to moult-related complications. CONCLUSION: These observations confirm that formation of grossly visible white spots under the carapace of S. serrata are not pathognomonic for infection with WSSV. Similar observations in previous studies where WSSV was detected by PCR in this same host may have been incidental findings.

WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3-24.1, a region frequently affected in breast cancer.

Studies were conducted with the final goal of identifying genes of interest mapping to the chromosome region 16q23.3-24.1, an area commonly affected by allelic losses in breast cancer. To this end we generated a detailed physical map of the genomic region spanning between sequence-tagged site markers D16S518 and D16S516. To identify candidate genes, we used shotgun genomic sequencing as well as isolation and analysis of transcripts mapping to the area of interest. We identified and cloned a novel gene, the genomic structure of which spans the whole region of interest. We named this gene WWOX because it contains two WW domains coupled to a region with high homology to the short-chain dehydrogenase/reductase family of enzymes. The ORF of WWOX is 1245 bp long, encoding a 414-amino acid protein. This gene is composed of nine exons. We performed a mutation screening of WWOX exons in a panel of breast cancer lines, most of which are hemizygous for the 16q genomic region indicated. We found no evidence of mutations, thus indicating that WWOX is probably not a tumor suppressor gene. However, we observed that one case of homozygous deletion as well as two previously described translocation breakpoints map to intronic regions of this gene. We speculate that WWOX may span the yet uncharacterized common fragile site FRA16D region. In expression studies we found overexpression of WWOX in breast cancer cell lines when compared with normal breast cells and tissues. The highest normal expression of WWOX was observed in hormonally regulated tissues such as testis, ovary, and prostate. This expression pattern and the presence of a short-chain dehydrogenase/reductase domain and specific amino acid features suggest a role for WWOX in steroid metabolism. Interestingly, the presence of WW domains in the structure of WWOX indicate the likelihood that this protein physically interacts with other proteins. The unique features of WWOX and its possible association with cancer processes make it an interesting target for further investigation.

Effects of estrogen on global gene expression: identification of novel targets of estrogen action.

The important role played by the sex hormone estrogen in disease and physiological processes has been well documented. However, the mechanisms by which this hormone elicits many of its normal as well as pathological effects are unclear. To identify both known and unknown genes that are regulated by or associated with estrogen action, we performed serial analysis of gene expression on estrogen-responsive breast cancer cells after exposure to this hormone. We examined approximately 190,000 mRNA transcripts and monitored the expression behavior of 12,550 genes. Expression levels for the vast majority of those transcripts were observed to remain constant upon 17beta estradiol (E2) treatment. Only approximately 0.4% of the genes showed an increase in expression of > or =3-fold by 3 h post-E2 treatment. We cloned five novel genes (E2IG1-5), which were observed up-regulated by the hormonal treatment. Of these the most highly induced transcript, E2IG1, appears to be a novel member of the family of small heat shock proteins. The E2IG4 gene is a new member of the large family of leucine-rich repeat-containing proteins. On the basis of architectural and domain homology, this gene appears to be a good candidate for secretion in the extracellular environment and, therefore, may play a role in breast tissue remodeling and/or epithelium-stroma interactions. Several interesting genes with a potential role in the regulation of cell cycle progression were also identified to increase in expression, including Pescadillo and chaperonin CCT2. Two putative paracrine/autocrine factors of potential importance in the regulation of the growth of breast cancer cells were identified to be highly up-regulated by E2: stanniocalcin 2, a calcium/phosphate homeostatic hormone; and inhibin-beta B, a TGF-beta-like factor. Interestingly, we also determined that E2IG1 and stanniocalcin 2 were exclusively overexpressed in estrogen-receptor-positive breast cancer lines, and thus they have the potential to serve as breast cancer biomarkers. This data provides a comprehensive view of the changes induced by E2 on the transcriptional program of human E2-responsive cells, and it also identifies novel and previously unsuspected gene targets whose expression is affected by this hormone.

Cyclosporine pharmacokinetics in cats following topical ocular administration.

Topical ocular administration of two forms of cyclosporine were studied in the cat. Both forms were able to produce measurable whole-blood levels capable of suppressing in vitro lymphocyte stimulation. The kinetics of cyclosporine following administration of either oral solution or cyclosporine in olive oil were variable, with peak concentrations ranging from 450 to 1033 ng/ml and 288 to 648 ng/ml, respectively. Absorption lag time ranged from 0 to 1.34 hr for oral solution, and 0.27 to 1.2 hr for cyclosporine in olive oil. The half-life of elimination ranged from 2.41 to 10.04 hr, and 3.09 to 15.75 hr, respectively. When compared with the commercially available oral solution, cyclosporine dissolved in olive oil was better tolerated during administration. Topical ocular administration of cyclosporine in cats offers a possible alternative method of treatment for individuals intolerant of oral administration. Topical ocular administration might also replace the need for intravenous administration of cyclosporine during perioperative periods or during periods of vomiting and nausea associated with rejection or other illnesses. Due to individual variation in absorption and elimination of topically applied cyclosporine, dosages in each cat must be determined by monitoring blood, plasma, or serum levels.

California Verbal Learning Test practice effects in a schizophrenia sample.

Practice effects on the California Verbal Learning Test (CVLT; >Delis et al., 1987), a measure of new learning and memory, were evaluated in a sample of patients with schizophrenia who were administered the CVLT at baseline, week 10, and week 14 in the context of a study of the effects of a non-pharmacological intervention on psychiatric status. Large effects attributable to prior exposure to the test were evident at weeks 10 and 14. These effects indicate that caution must be exercised in interpreting serial performances on this commonly used test, whether in research or clinical circumstances. Additionally, although the exact nature of the learning involved is unclear, the influence of prior exposure on later performance reveals considerable retention over time of new information in this sample of persons with schizophrenia.

Normal neurocognitive performance after extended practice in patients with schizophrenia.

This study evaluated new methods for improving the performance of patients with schizophrenia on specific neurocognitive tasks. Patients (n = 22) practiced sustained perceptual, memory and motor tasks 5 times/week for 10 weeks. Tasks were initially easy enough for patients to do well, but were made gradually more difficult over the 10 weeks. Patients received base pay and performance-based monetary supplements. No coaching or ongoing instruction was provided, and performance gains were assumed to depend upon implicit learning. High functioning healthy controls (n = 5) were given the same tasks at difficulty levels comparable to those achieved by patients after 10 weeks of practice. After 10 weeks of practice, 16 of the 22 patients performed as well or better than the best control on the perceptual and memory tasks, and 11 patients performed within the range of control subjects on the motor task. Half of the patients retested 6 months after training maintained supranormal performance, while the others showed marked performance declines. Patients with schizophrenia appear to have greater potential for neurocognitive improvement, and potentially for employment, than generally appreciated.

Factorial structure of the Scale of Prodromal Symptoms.

Data from the Scale of Prodromal Symptoms (SOPS) [Early Intervention in Psychotic Disorders, pp. 135-150] on 94 hitherto never-psychotic individuals were entered into a principal components analysis, revealing six components with an eigenvalue greater than 1.0. Based upon scree-plot analysis, further extractions were limited to three, then two, factors. Varimax rotation of the three-component extraction revealed factors with reasonable congruence with a priori content areas. All symptoms labeled as negative in the SOPS loaded on one factor, and four of five symptoms labeled as positive loaded on another. The remaining positive symptom, conceptual disorganization, has been found not to load with other positive-labeled symptoms in studies of schizophrenia using applicable instruments. All symptoms labeled as "general" in the SOPS loaded on a third factor, which appears to reflect the nonspecific psychological distress that might be expected in psychosis-naïve individuals experiencing the preliminary stages of a serious psychiatric disorder. The independence of this component from the positive and negative symptom factors suggests that the structure obtained suggests a clinical continuity between the at-risk presentations seen in this sample and established schizophrenia.

Estimated yield of early detection of prodromal or first episode patients by screening first degree relatives of schizophrenic patients.

Screening a population of relatives of current schizophrenic patients could be an efficient means to accrue a sample of early first episode or prodromal patients for a prediction study or an intervention study. The risk of new onset schizophrenia cases in any one year in a population of relatives depends on the number of schizophrenic probands and three additional factors: (1) the age of onset distribution for schizophrenia; (2) the lifetime risk of the at-risk group of relatives selected; and (3) the number of at-risk relatives per proband and their age distribution. Estimates are made for each of these parameters, and calculations are presented. The base model suggests that screening all siblings and children of patients with schizophrenia would yield approximately 19 new cases of schizophrenia per year per 10,000 relatives screened. The results of the calculation are relatively insensitive to reasonable variation of most model parameter estimates. The yield of new cases obtained by screening relatives of current patients appears to be low if the purpose is to recruit a sample for an early intervention study over a relatively short period of time.

Neuropsychological status of subjects at high risk for a first episode of psychosis.

Thirty-six subjects aged 16 years or older judged at risk for a first episode of psychosis within a North American multi-site study of the schizophrenia prodrome [McGlashan et al., Schizophr. Res. (2003); Miller et al., Schizophr. Res. (2003)] performed at levels intermediate to population norms and data reported for schizophrenia samples on a comprehensive neuropsychological exam. In the context of normal intelligence, this intermediate status suggests that, as a group, these subjects are not fully normal in neuropsychological functioning. Conversely, the finding that they do not show the levels of impairment commonly observed in schizophrenia, including within the first episode, suggests that prodromal interventions might conceivably prevent, delay, or lessen the severity of declines associated with first psychotic episodes.

The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. I. Study rationale and design.

The first double-blind placebo-controlled clinical trial of an atypical neuroleptic medication is being conducted in symptomatic treatment-seeking patients meeting new diagnostic criteria for a putative prodromal syndrome. This identifies them as being at high risk for developing psychosis in the near future. The study aims include prevention of psychosis onset and disability, as well as palliation of ongoing symptomatology. This report presents the study rationale and design. Recent studies will be reviewed that have advanced our knowledge about the early course of schizophrenia and our ability to predict onset prospectively, advances that have rendered prodromal intervention research feasible and ethical. The study design has many novel features. It tests for prevention versus delay in psychosis onset, as well as for efficacy and safety in a newly defined clinical population. This has required the development of innovative clinical research assessment instruments and a new operational definition of psychosis onset. The integration of these novel elements into an otherwise typical clinical trial design is detailed. The companion report will address sample recruitment and the clinical phenomenology at baseline of this putative "prodromal" entity.

The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. II. Baseline characteristics of the "prodromal" sample.

The first double-blind placebo-controlled clinical trial of an atypical neuroleptic medication is being conducted in symptomatic treatment-seeking patients meeting new diagnostic criteria for a putative prodromal syndrome. This identifies them as being at high risk for developing psychosis in the near future. The study aims include prevention of psychosis onset and disability, as well as palliation of ongoing symptomatology. The purpose of this report is to describe the study's "prodromally symptomatic" sample at baseline, i.e., at intake immediately prior to randomization and prior to receiving study medication. Sixty treatment-seeking patients meeting prodromal inclusion criteria were recruited across four sites: New Haven, CT (n=39), Toronto, Ontario (n=9), Calgary, Alberta (n=6), and Chapel Hill, NC (n=6). The sample was young (median age 16), largely male (65%), and came from families with high titers of serious mental illness (44%). Most patients (93%) met criteria for the Attenuated Positive Symptom (APS) prodromal syndrome and presented with significant but nonpsychotic suspiciousness, perceptual aberrations, unusual thought content, and conceptual disorganization. They presented with minimal to mild affective symptoms and substance use/abuse, but they were quite functionally compromised (mean Global Assessment of Functioning (GAF) score=42). The prodromal sample was compared with other clinical-trial samples of adolescent depression, adolescent mania, and first episode schizophrenia. Prodromal patients proved not to be depressed or manic. They were less severely ill than untreated first episode schizophrenia but more severely ill than treated first episode schizophrenia. While not psychotically disabled, these patients nevertheless present with a clinical syndrome. Subsequent reports will detail the effects of drug versus placebo on prodromal symptoms, neuropsychological profile, and the rate of conversion to psychosis.

Can line clinicians master the conceptual complexities of dialectical behavior therapy? An evaluation of a State Department of Mental Health training program.

Dialectical behavior therapy for borderline personality disorder has rapidly attained wide-spread popularity, with one indication being the development of training initiatives by the Department of Mental Health within at least two States in USA. Efficacy data published by the originator of the treatment, Marsha Linehan, and her colleagues, probably accounts at least in part for this popularity. However, the complexity of DBT raises a fundamental question regarding these broader applications: can clinicians of diverse backgrounds acquire a shared and sophisticated understanding of the treatment theory? The clinical utility of a treatment rests heavily upon ease of dissemination (APA, Template for developing guidelines: Interventions for mental disorders and psychosocial aspects of physical disorders. Washington, DC: Author, 1995), and in that regard DBT--a complicated, multifaceted approach--could appear vulnerable. This vulnerability is heightened when institutional adoption involves the collaboration of numerous clinicians, who, despite occupying diverse roles, must nevertheless develop a shared understanding of the treatment. Using a detailed examination of DBT knowledge, we evaluated the conceptual mastery of 109 clinicians trained via a State Department of Mental Health initiative. Performance on the examination correlated specifically with DBT training. Prior education or background in behavior therapy accounted for little variance, indicating that clinicians occupying diverse roles acquired reasonable intellectual mastery over this complex model.

Working memory, attention, and communication disturbances in schizophrenia.

The authors hypothesized that schizophrenic communication disturbances reflect specific cognitive deficits in the areas of working memory and attention. They examined the cognitive correlates of communication disturbances, as measured by linguistic reference performance, in schizophrenic (n = 48), bipolar (n = 24), and nonpsychiatric control (n = 23) individuals. Reference performance ratings in the schizophrenic patients were associated with scores on tests of working memory and attention and were not related to performance on concept formation or verbal fluency tests. In contrast, in the bipolar and nonpsychiatric individuals, reference performance was associated with concept formation and verbal fluency test scores but was not related to performance on tests of working memory. Implications with respect to the processes underlying schizophrenic communication disturbances are discussed.

Experimental and natural infection with Bartonella henselae in domestic cats.

Domestic cats were experimentally infected with culture propagated Bartonella henselae by intradermal (i.d.) and intravenous (i.v.) routes. Cats were more efficiently infected by the i.d. (8/8 cats) than by the i.v. (2/16) route. Bacteremia was detected 1-3 weeks following inoculation and lasted for most cats for 1-8 months. However, one naturally infected cat was observed for 24 months and was found to be cyclically bacteremic, with bacterial levels varying one hundred fold or more from one period to another. No clinical or hematologic abnormalities were observed in any of the infected cats, even at the peak of bacteremia. Two cats that had become abacteremic were resistant to reinfection when inoculated with B. henselae a second time. Horizontal transmission through intimate contact between bacteremic and susceptible cats did not occur, and antibody positive bacteremic queens did not transmit the infection to their kittens in utero, peri-partum or post-partum. Only four of the 18 kittens acquired detectable levels of maternal antibody following nursing, which disappeared by 6 weeks of age. These studies indicate that B. henselae exists in an almost perfect host-parasite relationship with its feline host, but that most cats can ultimately rid themselves of the infection. The susceptibility of cats to intradermal infection and the lack of direct cat-cat transmission are compatible with possible arthropod vectors.

Homologous protection but lack of heterologous-protection by various species and types of Bartonella in specific pathogen-free cats.

Cat-scratch disease (CSD) is caused by Bartonella henselae, and possibly by B. clarridgeiae. In immuno-compromised persons, B. henselae is one of the agents causing bacillary angiomatosis. Domestic cats are the main reservoir of these bacteria, which are transmitted primarily from cat to cat by fleas. Possible strategies to prevent the spread of infection among cats are to eliminate flea infestation or to prophylactically immunize cats. In order to develop an appropriate vaccine, it is important to determine if cats become resistant to re-infection by the same strain or various types or species of Bartonella. In a series of experiments, 21 SPF cats were experimentally infected by the intradermal route with 10(5)-10(10) colony-forming units/ml of either B. henselae type II (17 cats), or a new strain 'Humboldt' isolated from a mountain lion (4 cats). The cats were bled weekly to every other week for determination of bacteremia and specific antibody production. After they cleared their infection, they were challenged by a homologous or heterologous strain of Bartonella: 10 cats were challenged with B. henselae type II, three cats with B. henselae type I, four cats with B. clarridgeiae and four cats with the 'Humboldt' strain. Seven of these cats received a third inoculum dose resulting in three cats sequentially infected with sequence B. henselae type II/B. henselae type II/'Humboldt', two cats with sequence B. henselae type II/'Humboldt'/B. clarridgeiae, and two cats with the sequence 'Humboldt'/B. henselae type II/'Humboldt'. All cats challenged with a homologous strain remained abacteremic after challenge and had an increased IgG antibody titer. All cats challenged with either a different Bartonella species or type became bacteremic. The few cats receiving a third inoculum with a strain homologous to the initial strain remained abacteremicafter that challenge. All cats infected with B. clarridgeiae suffered relapsing bacteremia compared to only 36% of the B. henselae infected cats and 22% of the 'Humboldt'-infected cats (p=0.008). The duration of bacteremia was significantly longer in B. henselae primary-infected cats (mean: 34 weeks) than B. henselae heterologously challenged cats (mean: 9 weeks) (p=0.014). These data clearly indicate the lack of cross-protection between B. henselae and B. clarridgeiae and furthermore, indicate the lack of protection between B. henselae types I and II, and a wildlife isolate. A vaccine strategy for CSD prevention in domestic cats will require a multivalent vaccine approach.

Continuation of high-risk behavior by HIV-positive drug users. Treatment implications.

Drug users who are positive for the human immunodeficiency virus (HIV) represent a major vector of HIV transmission, yet relatively little is known about their continued drug- and sex-related HIV-risk behavior, which may impede the development of effective risk-reduction interventions. In this study, 50 HIV-seropositive injection drug users entering methadone maintenance treatment completed a comprehensive risk assessment battery, including self-report of HIV-risk behavior since learning HIV serostatus, and measures of risk-reduction information, motivation, and behavioral skills. We found that a disconcertingly high proportion of patients (66%) reported having engaged in HIV-risk behavior since learning their HIV-seropositive status. Level of HIV-related knowledge did not predict high-risk behavior. Drug-related risk behavior was predicted by psychiatric severity and poor behavioral skills. Sex-related risk was predicted by low levels of motivation and poor behavioral skills. Implications of these findings for treatment are discussed.

Normative implications of the relationship between reading vocabulary and Boston Naming Test performance.

The 60-item Boston Naming Test (BNT) was published in 1983 with norms described as provisional. One recent finding (Thompson & Heaton, 1989) suggests that verbal intelligence, and the Wechsler Adult Intelligence Scale (WA1S)-Revised Vocabulary subtest, in particular, is strongly correlated with BNT performance, and that education is moderately so. High false-positive rates for naming deficit may conceivably result from the application of the published norms with subjects of lower verbal abilities or limited educational backgrounds. To further explore the relationship of naming to other verbal abilities, analyses were undertaken of the correlations between Level 7-9 Gates-MacGinite Reading Vocabulary Test (G-MRVT) and BNT data from 97 schizophrenic, bipolar, and normal subjects. Reading vocabulary is strongly correlated with BNT performance, and the nature of this relationship is essentially the same across the three diagnostic groups. Application of the published norms would have resulted in a high false-positive rate for naming deficit in all groups among subjects with reading vocabularies equivalent to twelfth grade or less. As a word-recognition based reading exercise, the G-MRVT is likely to provide a brain-compromise-resistant index against which the adequacy of naming performances can be assessed. Accordingly, G-MRVT based BNT performance expectation guidelines are presented for use as a complement to the published norms. Other implications are discussed.

Limitations of cognitive status exams: a case-based discussion.

Despite their extensive use in psychiatric and medical settings, brief mental status examinations have significant limitations that are easily overlooked in the pressure-cooker environments within which they are commonly used. Although undoubtedly of value as quick screening devices, the sheer brevity of these instruments all but guarantees limited validity. Brief examinations perform best with grossly impaired cases, alerting clinicians to the fact that something is badly amiss in patients who are significantly confused, disoriented, aphasic, or otherwise severely impaired. Very poor scores are accordingly frequently useful. Moderate or even perfect scores, however, will frequently be misleading, because patients with compromised brains often obtain them (Nelson et al. 1986). One such case follows.

Genetic association of impulsivity in young adults: a multivariate study.

Impulsivity is a heritable, multifaceted construct with clinically relevant links to multiple psychopathologies. We assessed impulsivity in young adult (N~2100) participants in a longitudinal study, using self-report questionnaires and computer-based behavioral tasks. Analysis was restricted to the subset (N=426) who underwent genotyping. Multivariate association between impulsivity measures and single-nucleotide polymorphism data was implemented using parallel independent component analysis (Para-ICA). Pathways associated with multiple genes in components that correlated significantly with impulsivity phenotypes were then identified using a pathway enrichment analysis. Para-ICA revealed two significantly correlated genotype-phenotype component pairs. One impulsivity component included the reward responsiveness subscale and behavioral inhibition scale of the Behavioral-Inhibition System/Behavioral-Activation System scale, and the second impulsivity component included the non-planning subscale of the Barratt Impulsiveness Scale and the Experiential Discounting Task. Pathway analysis identified processes related to neurogenesis, nervous system signal generation/amplification, neurotransmission and immune response. We identified various genes and gene regulatory pathways associated with empirically derived impulsivity components. Our study suggests that gene networks implicated previously in brain development, neurotransmission and immune response are related to impulsive tendencies and behaviors.