Whirling disease: re-emergence among wild trout

Summary: Whirling disease of rainbow trout is caused by Myxobolus cerebralis, a myxozoan parasite possessing a life cycle well adapted to the natural environments where salmonid fish are found. Whirling disease was first described in Europe in 1898 among farmed rainbow trout but recent occurrences have been devastating to wild trout in North America. The disease is considered a major threat to survival of wild rainbow trout in the intermountain west of the United States. Difficulties in containing the spread and potentially eliminating the pathogen are tied to features of a complex life cycle involving two hosts, the salmonid fish and an aquatic oligochaete. Details of the morphologic development of the parasite have been described in each host but only now are we beginning to appreciate the breadth of interactions between these developmental forms and the sequential responses of the host. Fundamental mechanisms of the recognition and attachment of the parasite to the hosts, how host immunity is evaded and the unknown influences of environmental factors all contribute to a rather poor understanding of the biology of the parasite. Although the biology and ecology of the salmonid host are better known than for the oligochaete host, our knowledge is inadequate to interpret their complex interactions with the parasite. This uncertainty precludes the development of effective management activities designed to enhance the viability and productivity of wild trout populations in M. cerebralis- positive river systems. Improving our understanding of the hosts, the parasite and the environmental factors determining their interaction should provide for more focused and effective control methods for containing the spread and devastating effects whirling disease is causing to our wild trout populations.     

Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study

BACKGROUND: Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously. METHOD: Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975-1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk. RESULTS: ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences. CONCLUSIONS: Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.     

Comparative genomic hybridization of 49 primary retinoblastoma tumors identifies chromosomal regions associated with histopathology,progression, and patient outcome

Forty-nine primary retinoblastoma (Rb) tumors were analyzed by the use of comparative genomic hybridization (CGH), and clinical/histological correlations were performed. Adverse histological factors were present in 13 patients. Chromosomal imbalance was a frequent phenomenon, seen in 96% of the tumors. Gain of 6p represented the most frequent event (69% of the tumors), whereas +1q was observed in 57%, confirming that these abnormalities are key secondary events in retinoblastoma tumor progression. Loss of 13q and 16 was significantly associated with tumors displaying adverse histo-prognostic factors, whereas -16q was significantly associated with tumors without adverse features. In three patients who developed an extra-ocular relapse, the tumors showed -13q and 2/3 had -5q, suggesting that these abnormalities may be associated with metastasis. Children >or= 36 months of age at enucleation tended to have more CGH abnormalities per tumor than children < 12 months (median numbers 11 vs. 3). In addition, +1q, +13q, -16, and -16q were more frequent in children with an older age at enucleation. Identical CGH changes were found in both tumors from one patient with bilateral tumors, suggesting a common origin. It is possible that tumors displaying loss of 13q and 5q indicate those patients who may suffer an adverse outcome and who would require alternative or more intensive therapy. CGH analysis on larger cohorts and in prospective clinical trials will be invaluable in determining whether a genetic classification of retinoblastoma represents a reliable measure of prognosis.     

Functional effects of eotaxin are selectively upregulated on IL-5 transgenic mouse eosinophils

Synergistic interactions between cytokines, chemokines and adhesion molecules may facilitate the selective recruitment of eosinophils into sites of allergic inflammation. Ovalbumin-sensitized IL5TG mice responded to antigen challenge with robust airway eosinophilia 24 and 72 hr post-exposure. Adhesion molecule expression and functional responsiveness of immune cells derived from IL5TG mice to various inflammatory mediators were evaluated. IL5TG-derived eosinophils, but not neutrophils, expressed higher levels of CD49d and CD11b relative to WT. Functional responsiveness to eotaxin was increased in IL5TG eosinophils as demonstrated by a 10× increase in its potency in producing actin polymerization and 3× increase in CD11b upregulation relative to WT. These data are consistent with increased CCR3 expression on IL5TG eosinophils. Responsiveness of eosinophils to LTB4 or MIP-1 was similar between WT and IL-5TG mice. These data provide evidence of synergy between eosinophil-specific cytokines and chemokines that may promote accumulation of this cell type under conditions of allergic inflammation in vivo.     

Pain in individuals with RASopathies: Prevalence and clinical characterization in a sample of 80 affected patients

Pain in individuals with RASopathies is a neglected topic in literature. In this article, we assessed prevalence and profile of pain in a sample of 80 individuals affected by RASopathies. The study sample included individuals with Noonan syndrome (N = 42), Costello syndrome (N = 17), and cardio‐facio‐cutaneous syndrome (N = 21). A set of standardized questionnaires and scales were administered (VAS/numeric scale, r‐FLACC, Wang‐Baker scale, NPSI, BPI, NCCPC‐R) to detect and characterize acute and chronic pain and to study the influence of pain on quality of life (PEDs‐QL, SF‐36) and sleeping patterns (SDSC); revision of past medical history and multisystemic evaluation was provided. Available clinical data were correlated to the presence of pain. High prevalence of acute (44%) and chronic (61%) pain was documented in the examined sample. Due to age and intellectual disability, acute pain was localized in 18/35 individuals and chronic pain in 33/49. Muscle‐skeletal and abdominal pain was more frequently reported. The intensity of acute and chronic pain interfered with daily activities in 1/3 of the sample. Pain negatively impacted on QoL and sleeping patterns. This work documents that pain is highly prevalent in RASopathies. Future studies including subjective and objective measures of pain are required to discriminate a somatosensory abnormality from an abnormal elaboration of painful stimuli at a central level.     

Lipid screening in HIV-infected veterans

BACKGROUND: Lipid screening is recommended for patients taking protease inhibitors (PIs). METHODS: We examined data from the Veterans Administration Immunology Case Registry to assess lipid screening among HIV-infected veterans who received PIs for at least 6 consecutive months during 1999 and 2001. We estimated crude and adjusted associations between lipid screening and patient characteristics (age, gender, HIV exposure, and race/ethnicity), comorbidities (AIDS, cardiovascular disease, diabetes, hypertension, smoking, and hyperlipidemia), and facility characteristics (urban location, case management, guidelines, and quality improvement programs). RESULTS: Among 4065 patients on PIs, clinicians screened 2395 (59%) for lipids within 6 months of initiating treatment. Adjusting for patient characteristics, comorbidities, facility traits, and clustering, lipid screening was more common among patients who were cared for in urban areas (relative risk [RR] = 1.3, confidence limits: 1.0-1.5), diabetic (RR = 1.2, confidence limits: 1.1-1.3), or previously hyperlipidemic (RR = 1.4, confidence limits: 1.3-1.5) and less common among patients with a history of intravenous drug use (IVDU) (RR = 0.90, confidence limits: 0.79-1.0) or unknown HIV risk (RR = 0.85, confidence limits: 0.75-0.95). CONCLUSIONS: Six in 10 patients taking PIs receive lipid screening within 6 months of PI use. Systemic interventions to improve overall HIV quality of care should also address lipid screening, particularly among patients with unknown or IVDU HIV risk and those cared for in nonurban areas.     

Neural responses to free field and virtual acoustic stimulation in the inferior colliculus of the guinea pig

Virtual auditory space (VAS) stimuli based on outer ear transfer functions became increasingly important in spatial hearing research. However, few studies have investigated the match between responses of auditory neurons to VAS and free-field (FF) stimulation. This study validates acoustic spatial receptive fields (SRFs) of 183 individual midbrain units using both VAS and FF stimuli. The first-spike latency, which varied systematically across SRFs, was 14.9 +/- 8.3 (SD) ms in FF, and 15.1 +/- 8.3 ms in VAS. Spike-count-based SRFs measured 0-20 dB above the neural threshold covered on average 44.5 +/- 18.0% of the recorded sphere in FF and 45.5 +/- 18.7% in VAS. The average deviation of the centroid position of SRFs using FF and VAS stimuli was 7.4 degrees azimuth and 3.3 degrees elevation. The average spike rate remained unchanged. The SRF overlap recorded using FF and VAS stimuli (mean: 71.3 +/- 12.6%) or repeated FF stimuli (70.2 +/- 14.2%) was high and strongly correlated (r = 0.96; P < 0.05). The SRF match observed with FF and VAS stimuli was not significantly altered over a range of stimulus levels (paired t-test P = 0.51; n = 6). Randomized VAS barely affected SRF sizes, centroids, or maximum spike count but decreased the average minimum response to 59% compared with sequential stimulation (paired t-test; P = 0.05; n = 26). SRF recordings in VAS excluding the acoustic distortions of the recording equipment differed from those in VAS incorporating the equipment (paired t-test P = 0.01; n = 5). In conclusion, neurophysiological recordings demonstrate that individualized VAS stimuli provided a good simulation of a FF environment.     

Distribution of putative adhesins in different seropathotypes of Shiga toxin-producing Escherichia coli

The distribution of eight putative adhesins that are not encoded in the locus for enterocyte effacement (LEE) in 139 Shiga toxin-producing Escherichia coli (STEC) of different serotypes was investigated by PCR. Five of the adhesins (Iha, Efa1, LPF(O157/OI-141), LPF(O157/OI-154), and LPF(O113)) are encoded in regions corresponding to genomic O islands of E. coli EDL933, while the other three adhesins have been reported to be encoded in the STEC megaplasmid of various serotypes (ToxB [O157:H7], Saa [O113:H21], and Sfp [O157:NM]). STEC strains were isolated from humans (n = 54), animals (n = 52), and food (n = 33). They were classified into five seropathotypes (A through E) based on the reported occurrence of STEC serotypes in human disease, in outbreaks, and in the hemolytic-uremic syndrome (M. A. Karmali, M. Mascarenhas, S. Shen, K. Ziebell, S. Johnson, R. Reid-Smith, J. Isaac-Renton, C. Clark, K. Rahn, and J. B. Kaper, J. Clin. Microbiol. 41:4930-4940, 2003). The most prevalent adhesin was that encoded by the iha gene (91%; 127 of 139 strains), which was distributed in all seropathotypes. toxB and efa1 were present mainly in strains of seropathotypes A and B, which were LEE positive. saa was present only in strains of seropathotypes C, D, and E, which were LEE negative. Two fimbrial genes, lpfA(O157/OI-141) and lpfA(O157/OI-154), were strongly associated with seropathotype A. The fimbrial gene lpfA(O113) was present in all seropathotypes except for seropathotype A, while sfpA was not present in any of the strains studied. The distribution of STEC adhesins depends mainly on serotypes and not on the source of isolation. Seropathotype A, which is associated with severe disease and frequently is involved in outbreaks, possesses a unique adhesin profile which is not present in the other seropathotypes. The wide distribution of iha in STEC strains suggested that it could be a candidate for vaccine development.     

Which treatment for whom for ADHD? Moderators of treatment response in the MTA

Using receiver operating characteristics, the authors examined outcome predictors (variables associated with outcome regardless of treatment) and moderators (variables identifying subgroups with differential treatment effectiveness) in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD; MTA). Treatment response was determined using parent- and teacher-reported ADHD and oppositional defiant symptoms, with levels near or within the normal range indicating excellent response. Among 9 baseline child and family characteristics, none predicted but 3 moderated treatment response. In medication management and combined treatments, parental depressive symptoms and severity of child ADHD were associated with decreased rates of excellent response; when these 2 characteristics were present, below-average child IQ was an additional moderator. No predictors or moderators emerged for behavioral and community comparison treatments. The authors discuss conceptual and clinical implications of research on treatment moderators.     

Impact of the 1998 World Health Organization/International Society of Urological Pathology classification system for urothelial neoplasms of the kidney.

The classification of urothelial neoplasms of the kidney traditionally has been similar to that of urinary bladder tumors. Several years ago, the classification of papillary urothelial neoplasms was revised. The current study focuses on the application of the 1998 World Health Organization (WHO)/International Society of Urological Pathology classification system to 102 renal pelvic urothelial neoplasms and compares it to the 1973 WHO classification scheme. In this study, all tumors were classified as urothelial carcinomas, and the majority (85%) were papillary. Most patients with papillary tumors presented with 'superficial' disease (< or = pT1). With the 1998 system, most papillary carcinomas were high grade, and were more often invasive as compared to low-grade tumors. Only 34% were low-grade papillary tumors and, of these, most (93%) were noninvasive. With the 1973 system, most papillary tumors were grade 2 or 3, with invasion more common in grade 3 tumors. By 1973 criteria, grade 2 tumors were a heterogeneous group; with 1998 criteria, nearly one-half were high grade and the other half low grade. The grade of papillary urothelial carcinomas with both the 1973 and 1998 grading methods was associated with stage (P=0.001). Our study reveals that papillomas and papillary urothelial neoplasms of low malignant potential are uncommon tumors in the kidney. Renal pelvic papillary urothelial neoplasms are most often carcinomas and are more commonly high grade than low grade. Although both the 1973 and 1998 systems showed a significant association with tumor stage, grade 2 papillary carcinomas are a heterogeneous group by 1973 criteria. The 1998 system provides useful information in that it more clearly defines a papillary tumor's grade and selects for a group of tumors, namely low-grade papillary urothelial carcinomas, for which a low likelihood of invasion can be predicted.