Short-term infection of striped bass Morone saxatilis with Mycobacterium marinum.

Striped bass Morone saxatilis were studied in order to characterize their immune responses over the short term following challenge with Mycobacterium marinum. The expression of immunity-related genes (IL-1beta, TNF-alpha, Nramp and TGF-beta) quickly increased following infection with M. marinum, but these genes were subsequently down-regulated despite the fact that bacterial counts remained high. The number of monocytes and neutrophils also initially increased at 1 d postinfection. This confirms the importance of these types of cells in initial inflammation and mycobacterial infection in striped bass. The phagocytic index of splenic leukocytes over these same time frames did not change significantly following infection. The discrete window in which inflammatory mechanisms were stimulated in striped bass may be related to the intracellular nature of this pathogen.

Influence of nutritional state on the progression and severity of mycobacteriosis in striped bass Morone saxatilis.

Challenge studies with Mycobacterium marinum clearly demonstrate that a poor diet affects the progression and severity of mycobacteriosis in striped bass Morone saxatilis. Fish (n = 512 total, wt = 65 +/- 15 g) were inoculated intraperitoneally with 10(4) colony-forming units (CFU) g(-1) body weigth (BW) or a physiological saline solution (controls) and evaluated for 8 mo. Inoculated fish fed a low-ration diet (0.15% BW d(-1)) developed a severe, systemic infection characterized by a high bacterial load (>10(8) CFU g(-1) spleen) and poor granuloma formation, which commonly progressed to mortality by 6 wk. In contrast, inoculated fish fed an adequate ration diet (1% BW d(-1)) developed classic granulomatous inflammation of reduced severity and total body energy similar to that found in uninoculated controls (p > 0.05). After 4 wk, fish fed adequate rations maintained an equilibrium state throughout the study period, even though 10(6) CFU g(-1) spleen mycobacteria were consistently cultured. In a second study, reactivation of an acute inflammatory state was demonstrated by placing previously infected fish on reducing diets (0.073% BW d(-1)). In both studies, the energetic demand of this disease was only appreciable when associated with active, severe, inflammatory states. To our knowledge, this study is the first to demonstrate the interaction of diet and mycobacteriosis in fish.

Improved husbandry to control an outbreak of rainbow trout fry syndrome caused by infection with Flavobacterium psychrophilum.

CASE DESCRIPTION: A cohort of 35,200, 13-week-old, female rainbow trout at a fish farm was evaluated because of a 2-week history of anorexia and lethargy and a mortality rate of approximately 100 fish/d. CLINICAL FINDINGS: Affected fish were lethargic and thin and had disequilibrium, bilateral exophthalmia, pale red gills and kidneys, red-tinged coelomic fluid, and pale brown livers. Some fish were differentially pigmented bilaterally. The presumptive diagnosis was bacterial or viral septicemia. The definitive diagnosis was rainbow trout fry syndrome caused by infection with Flavobacterium psychrophilum. TREATMENT AND OUTCOME: A strategy for controlling the outbreak based on reducing pathogen numbers in affected tanks and reducing pathogen spread among tanks was developed. The option of treating with antimicrobial-medicated feed was discussed with the farmer, but was declined. After changes were made, mortality rate declined quickly, with no more deaths within 10 days after the initial farm visit. CLINICAL RELEVANCE: Bacterial coldwater disease is the most common manifestation of infection with F psychrophilum in fingerling and adult rainbow trout. However, the organism can also cause rainbow trout fry syndrome. This condition should be included on a list of differential diagnoses for septicemia in hatchery-reared rainbow trout fry.

Polysomnography in Bolivian Children Native to High Altitude Compared to Children Native to Low Altitude.

STUDY OBJECTIVES: To compare polysomnographic parameters in high altitude (HA) native Andean children with low altitude (LA) native peers in order to explain the nocturnal oxyhemoglobin saturation (SpO2) instability reported in HA native children and to study the effect on sleep quality. METHODS: Ninety-eight healthy children aged 7-10 y and 13-16 y were recruited at LA (500 m) or HA (3,650 m) above sea level. Physical examination was undertaken and genetic ancestry determined from salivary DNA to determine proportion of European ancestry, a risk factor for poor HA adaptation. Attended polysomnography was carried out over 1 night for 58 children at their resident location. RESULTS: Of 98 children recruited, 85 met inclusion criteria, 58 of 85 (68.2%) completed polysomnography, of which 56 were adequate for analysis: 30 at LA (17 male) and 26 at HA (16 male). There were no altitude differences in genetic ancestry, but a high proportion of European admixture (median 50.6% LA; 44.0% HA). SpO2 was less stable at HA with mean 3% and 4% oxygen desaturation indices greater (both P < 0.001) than at LA. This was not explained by periodic breathing. However, more obstructive hypopnea was observed at HA (P < 0.001), along with a trend toward more central apnea (P = 0.053); neither was explained by clinical findings. There was no difference in sleep quality between altitudes. CONCLUSIONS: HA native Andean children have more respiratory events when scoring relies on SpO2 desaturation due to inherent SpO2 instability. Use of American Academy of Sleep Medicine scoring criteria may yield false-positive results for obstructive sleep-disordered breathing at HA.

Adaptation to Life in the High Andes: Nocturnal Oxyhemoglobin Saturation in Early Development.

STUDY OBJECTIVES: Physiological adaptation to high altitude hypoxia may be impaired in Andeans with significant European ancestry. The respiratory 'burden' of sleep may challenge adaptation, leading to relative nocturnal hypoxia. Developmental aspects of sleep-related breathing in high-altitude native children have not previously been reported. We aimed to determine the influence of development on diurnal-nocturnal oxyhemoglobin differences in children living at high altitude. METHODS: This was a cross-sectional, observational study. Seventy-five healthy Bolivian children aged 6 mo to 17 y, native to low altitude (500 m), moderate high altitude (2,500 m), and high altitude (3,700 m) were recruited. Daytime resting pulse oximetry was compared to overnight recordings using Masimo radical oximeters. Genetic ancestry was determined from DNA samples. RESULTS: Children had mixed European/Amerindian ancestry, with no significant differences between altitudes. Sixty-two participants had ≥ 5 h of nocturnal, artifact-free data. As predicted, diurnal mean oxyhemoglobin saturation decreased across altitudes (infants and children, both P < 0.001), with lowest diurnal values at high altitude in infants. At high altitude, there was a greater drop in nocturnal mean oxyhemoglobin saturation (infants, P < 0.001; children, P = 0.039) and an increase in variability (all P ≤ 0.001) compared to low altitude. Importantly, diurnal to nocturnal altitude differences diminished (P = 0.036), from infancy to childhood, with no further change during adolescence. CONCLUSIONS: Physiological adaptation to high-altitude living in native Andeans is unlikely to compensate for the significant differences we observed between diurnal and nocturnal oxyhemoglobin saturation, most marked in infancy. This vulnerability to sleep-related hypoxia in early childhood has potential lifespan implications. Future studies should characterize the sleep- related respiratory physiology underpinning our observations.

Cognitive performance in high-altitude Andean residents compared with low-altitude populations: from childhood to older age.

OBJECTIVES: To assess cognition in populations born and living at high altitude (HA; 3,700 m) and low altitude (LA; 500 m) in Bolivia, who were similar for both socioeconomic status and genetic ancestry. To determine whether HA hypoxia influences cognitive decline across the life span. METHOD: In total, 191 healthy participants aged 4 to 85 years were assessed at HA (N = 94; 33; 35% male) and LA (N = 97; 46, 47% male) on a battery of cognitive tasks: fluid intelligence, attention, short- and long-term memory, and psychomotor speed. Saliva samples were obtained for evaluation of genetic ancestry. RESULTS: HA participants were significantly slower on measures of processing speed and speed of attention than individuals born and living at LA. HA participants had slightly higher percentage of native Andean ancestry than LA participants, but this was not associated with cognitive performance. CONCLUSIONS: This is the first study of HA residence and neurocognition across the life span. Given the physiological challenges of HA living, the impact on cognition appears to be subtle and related only to the speed of more complex cognitive operations, rather than to their accuracy. Moreover, the impact on cognition does not appear to differ with increasing age or for different degrees of genetic admixture. Further studies recruiting HA participants with a broader range of native Andean ancestry will help to address the issue of to what extent Amerindian ancestry provides neuroprotection to chronic hypoxia in those living at HA.

Neurophysiological evidence for cognitive and brain functional adaptation in adolescents living at high altitude.

OBJECTIVE: Neurophysiological methods were used to study the effects of high altitude living on brain functions in a subgroup of participants of the Bolivian Children Living at Altitude (BoCLA) project. METHODS: Electroencephalogram (EEG), event-related potentials (ERP) and cerebral blood flow velocity (CBFV) were recorded in two groups of adolescents (aged 13-16 years), living either at sea-level or high altitude (~3700m). RESULTS: Neuropsychological testing revealed no deficits in the high altitude group, despite significantly reduced blood oxygen saturation. In agreement, ERPs elicited by oddball target detection and choice reaction time tasks were not different between groups. In contrast, resting state EEG showed reductions in delta and beta frequency amplitudes in adolescents living at high altitude. The EEG attenuations were correlated with lower CBFV, and the EEG group differences diminished during task performance. CONCLUSIONS: No indication was found for negative sequelae of chronic hypoxia in adolescents born and living at an altitude of ~3700m, rather evidence for successful neurophysiological adaptation was found under such conditions. SIGNIFICANCE: Dynamic regulation of metabolic demand is one adaptive mechanism that preserves cognitive development at high altitude.

Expanded range and new host species of Mycobacterium shottsii and M. pseudoshottsii.

Mycobacterium shottsii and M. pseudoshottsii are recently described mycobacteria commonly isolated from Chesapeake Bay striped bass Morone saxatilis. However, their distribution in striped bass outside of the Chesapeake region and their ability to infect alternative hosts have not been described. Mycobacteria identified as M. shottsii (based on fatty acid methyl ester analysis and multigene sequencing) were isolated from striped bass collected in Albemarle Sound, North Carolina, and white perch Morone americana in the Rhode River, Maryland, and detected in striped bass from the New York Bight off Long Island, New York. Mycobacterium pseudoshottsii were isolated from white perch in the Rhode and Corsica rivers, Maryland, and detected in striped bass in the New York Bight. This work demonstrates that these mycobacteria can be found outside of the Chesapeake Bay as well as in hosts other than striped bass.

Mycobacteria as environmental portent in Chesapeake Bay fish species.

Infection with environmental mycobacteria is increasing among many Chesapeake Bay fish species. Prevalence in juvenile Atlantic menhaden differed between tributaries and ranged from 2% to 57%. Mycobacterial infection may be a syndromic sentinel of altered environmental conditions that threaten aquatic animal health.

A novel intronic mutation that may affect genotyping result of CYP2C8 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) is strongly associated with CYP2C8*3 in a South American population.

During the investigation of a CYP2C8*3 genetic polymorphism in a South American population, we obtained a discrepant result using two different polymerase chain reaction (PCR) protocols. A single nucleotide polymorphism (SNP) (IVS3+43 G>C) was identified in the intron 3 region, which was used as a primer-annealing site of one of the two PCR protocols. A genotyping method was developed to enable discrimination of the CYP2C8*1A, CYP2C8*3 (416 G>A), and CYP2C8*3 (416G>A; IVS3+43 G>C) alleles. In a screen of a South American population, we found that individuals carrying the CYP2C8*3 (416 G>A) polymorphism also carried the CYP2C8*3 (416G>A; IVS3+43 G>C). However, we did not find any carriers of CYP2C8*3 (416G>A; IVS3+43 G>C) in a Japanese population.

Genetic polymorphism of CYP2C9 and CYP2C19 in a Bolivian population: an investigative and comparative study.

OBJECTIVE: Several reports of CYP2C genetic polymorphism demonstrate its potential clinical role in determining both inter-individual and inter-ethnic differences in drug efficacy. We estimated the distribution of CYP2C9 and CYP2C19 common variants in the Bolivian population (a South American population), and compared these data with those from Asian, African, Caucasian and Oceanian populations. METHODS: Genomic DNA was obtained from 778 unrelated healthy volunteers from Bolivia. The genotypic status of CYP2C9 and CYP2C19 was determined by means of polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Allelic and genotypic frequencies of CYP2C9 and CYP2C19 were determined for the Bolivian population, and comparison of the data with other ethnic groups revealed a lower CYP2C9*2 frequency (4.8%) than in Caucasians, but a higher frequency than in Asians; frequencies of CYP2C9*3 (3.0%) and CYP2C9 (0.4%) poor metabolizers (PMs) were similar to those seen in Asian populations. Frequencies of CYP2C19*2 (7.8%), CYP2C19*3 (0.1%), and CYP2C19 PMs (1.0%) in the Bolivian population were for the most part lower than in Caucasian, Asian, Oceanian and African populations. CONCLUSION: This is the first study to investigate a South American population for genetic polymorphism in the CYP2C subfamily. The Bolivian population differs from most other ethnic groups in the incidence of CYP2C9 and CYP2C19 common variants that might be influenced by its admixture characteristics.