Diving deeper into individual foraging specializations of a large marine predator, the southern sea lion.

Despite global declines in the abundance of marine predators, knowledge of foraging ecology, necessary to predict the ecological consequences of large changes in marine predator abundance, remains enigmatic for many species. Given that populations suffering severe declines are of conservation concern, we examined the foraging ecology of southern sea lions (SSL) (Otaria flavescens)-one of the least studied otariids (fur seal and sea lions)-which have declined by over 90% at the Falkland Islands since the 1930s. Using a combination of biologging devices and stable isotope analysis of vibrissae, we redress major gaps in the knowledge of SSL ecology and quantify patterns of individual specialization. Specifically, we revealed two discrete foraging strategies, these being inshore (coastal) and offshore (outer Patagonian Shelf). The majority of adult female SSL (72% or n = 21 of 29 SSL) foraged offshore. Adult female SSL that foraged offshore travelled further (92 ± 20 vs. 10 ± 4 km) and dived deeper (75 ± 23 vs. 21 ± 8 m) when compared to those that foraged inshore. Stable isotope analysis revealed long-term fidelity (years) to these discrete foraging habitats. In addition, we found further specialization within the offshore group, with adult female SSL separated into two clusters on the basis of benthic or mixed (benthic and pelagic) dive behavior (benthic dive proportion was 76 ± 9 vs. 51 ± 8%, respectively). We suggest that foraging specialization in depleted populations such as SSL breeding at the Falkland Islands, are influenced by foraging site fidelity, and could be independent of intraspecific competition. Finally, the behavioral differences we describe are crucial to understanding population-level dynamics, impediments to population recovery, and threats to population persistence.

The association of HIV viral load with indirect markers of liver injury.

This study assessed the association of HIV RNA with indirect markers of liver injury including FIB-4 index, liver enzymes and platelet counts in a high-risk Hispanic population. The data were derived from a prospective study that included 138 HIV/hepatitis C (HCV)-coinfected and 68 HIV-infected participants without hepatitis C or B co-infection (mono-infected). In unadjusted analyses, detectable HIV viral load (vs undetectable, <400 copies/mL) was associated with a 40% greater odds (OR 1.4, 95% CI: 1.1-1.9, P = 0.016) of FIB-4 > 1.45 in the HIV/HCV-coinfected group and 70% greater odds of FIB-4 > 1.45 (OR 1.7, 95% CI: 1.0-2.8; P = 0.046) in the HIV-mono-infected group. In multivariable analyses, a 1 log(10) increase in HIV RNA was associated with a median increase in FIB-4 of 12% in the HIV/HCV-coinfected group and 11% in the HIV-mono-infected group (P < 0.0001). Among the HIV/HCV-coinfected group, the elevating effect of HIV RNA on FIB-4 was strongest at low CD4 counts (P = 0.0037). Among the HIV-mono-infected group, the association between HIV RNA and FIB-4 was independent of CD4 cell counts. HIV RNA was associated with alterations in both liver enzymes and platelet counts. HIV antiretroviral therapy was not associated with any measure of liver injury examined. This study suggests that HIV may have direct, injurious effects on the liver and that HIV viral load should be considered when these indirect markers are used to assess liver function.

Targeting histone deacetylase 6 mediates a dual anti-melanoma effect: Enhanced antitumor immunity and impaired cell proliferation.

The median survival for metastatic melanoma is in the realm of 8-16 months and there are few therapies that offer significant improvement in overall survival. One of the recent advances in cancer treatment focuses on epigenetic modifiers to alter the survivability and immunogenicity of cancer cells. Our group and others have previously demonstrated that pan-HDAC inhibitors induce apoptosis, cell cycle arrest and changes in the immunogenicity of melanoma cells. Here we interrogated specific HDACs which may be responsible for this effect. We found that both genetic abrogation and pharmacologic inhibition of HDAC6 decreases in vitro proliferation and induces G1 arrest of melanoma cell lines without inducing apoptosis. Moreover, targeting this molecule led to an important upregulation in the expression of tumor associated antigens and MHC class I, suggesting a potential improvement in the immunogenicity of these cells. Of note, this anti-melanoma activity was operative regardless of mutational status of the cells. These effects translated into a pronounced delay of in vivo melanoma tumor growth which was, at least in part, dependent on intact immunity as evidenced by the restoration of tumor growth after CD4+ and CD8+ depletion. Given our findings, we provide the initial rationale for the further development of selective HDAC6 inhibitors as potential therapeutic anti-melanoma agents.

Elevated resting energy expenditure among HIV-seropositive persons receiving highly active antiretroviral therapy.

OBJECTIVES: To ascertain the relationships between resting energy expenditure (REE), HIV RNA in plasma, and highly active antiretroviral therapy (HAART). DESIGN: Cross-sectional analysis using data of a large cohort study of nutrition in relation to HIV disease. METHODS: HIV RNA in plasma, REE, fat-free mass (FFM), and medication regimens were assessed at 530 visits among 372 participants in a cohort study of HIV-seropositive men and women. RESULTS: HIV RNA in plasma was directly correlated with REE. After adjustment for FFM, age, CD4 cell count and HAART use, there was an increase in REE of 90 kJ/day per log10 copies/ml increase in HIV RNA [95% confidence interval (CI) 16-164; P = 0.02). HAART use had an independent effect on REE. In patients reporting HAART use, adjusted REE was 339 kJ/day higher than in those not reporting HAART use (95% CI 177-501; P = 0.0001). CONCLUSIONS: Viral load and HAART appear to exert independent effects on REE. Although HAART may decrease metabolic rate by lowering viral burden, it appears to increase metabolic demands through some mechanism(s) independent of its effect on viral burden. This may result in elevated REE despite control of viral replication.

The effect of protease inhibitors on weight and body composition in HIV-infected patients.

OBJECTIVES: To determine the nutritional changes that occur in HIV-infected patients receiving protease inhibitor (PI) therapy and to determine the effects of PI treatment on physical functioning and health perceptions in patients with HIV infection. DESIGN: Longitudinal data analysis of 38 patients from a large Nutrition and HIV cohort. METHODS: Patients were included if they had started PI therapy after enrollment in the cohort, if they had taken the drug for at least 4 months without interruption and if data on weight, body composition and viral loads were available. RESULTS: Mean person-months of follow-up was 8.1 months before and 12.2 months after PI treatment. Weight (1.54 kg, P < 0.0001), body mass index (0.50 kg/m2, P < 0.0001), physical functioning (8.52 points, P = 0.0006) and current health perception (6.7 points, P = 0.01) increased significantly, and the daily caloric intake increase was close to significance (915.5 kJ/day, P = 0.06), after treatment with PI. Lean body mass did not change. Patients who responded to PI therapy with decreased viral load (n = 28) had significantly greater weight gain per month than non-responders. CONCLUSIONS: PI therapy of HIV infection is associated with weight gain and improvement in quality of life indices. The weight gain is mainly in fat mass, with no change in lean body mass (skeletal muscle). Optimal therapy of HIV-infected patients with weight loss may require highly active antiretroviral therapy combined with an anabolic stimulus such as exercise, anabolic steroids or human growth hormone.

Role of acquired immune deficiency syndrome-defining conditions in human immunodeficiency virus-associated wasting.

To evaluate the contribution of acquired immune deficiency syndrome-defining conditions (ADCs) in human immunodeficiency virus (HIV)-associated wasting, we analyzed longitudinal data from 671 participants in a nutrition and HIV cohort study. Data on ADCs, height, and weight were collected at baseline and during 6 monthly study visits. The frequency of ADCs decreased over time, but the relative risk (RR) of wasting (decrease in body mass index [BMI] to <20 kg/m(2)) increased with a history of >1 ADC; the RR of wasting increased 1.3-fold with each additional historical ADC. Any ADC during the 6 months prior to a study visit was associated with a decrease in BMI to <20 kg/m(2). The risk of wasting increased 2.7-fold with each additional recent ADC. These risks were not altered when adjusted for socioeconomic status, CD4 cell count, energy intake, or baseline BMI. Although ADCs contribute to the development of wasting, their contribution is relatively small.

Influence of reduced neuron pool on the magnitude of naturally occurring motor neuron death.

The present investigation was undertaken to examine the role of peripheral competition in survival of motor neurons during development. A loss of approximately half of the trochlear motor neurons in duck and quail occurs during the course of normal embryogenesis. The number of motor neurons in the nucleus of quail prior to the onset of cell death is identical to the final number of survivors in the nucleus of duck embryos (about 1,300 neurons). In the present study competition at the peripheral target was decreased by reducing the number of trochlear motor neurons initially projecting to their target muscle. This was accomplished by substituting the midbrain of duck embryos with the same neural tissue from quail embryos. Midbrain transplantation was performed before motor axon outgrowth and normal cell death begin. The development of the motor neurons and their sole target of innervation, the superior oblique muscle, was examined by using a variety of techniques. The source of the grafted motor neurons and of a reduction in the size of the motor neuron pool was confirmed from histological sections and cell counts. The grafted motor neurons projected their axons into the appropriate peripheral target, which was determined by the use of HRP tracing technique. Counts of muscle fibers, motor endplates, and acetylcholine receptors and measurement of total muscle protein indicated that the size of the superior oblique muscle in the chimera embryos was similar to that of the normal duck but significantly larger than the muscle in quail embryos. Electrophysiological observations indicated that the grafted trochlear motor neurons made functional connections with the superior oblique muscle. Counts of the trochlear motor neurons after the period of cell death indicated an average of 1,310 neurons in the nucleus of duck, 772 in quail, and 690 in the chimera embryos. The number of motor neurons in the chimera embryos is not significantly different from that in the normal quail. In other words, in spite of reduced peripheral competition trochlear motor neuron death of normal magnitude occurred. Lack of increased cell survival in our study suggests that trochlear motor neurons do not compete for survival at the peripheral target.

Development of the trochlear nucleus in quail and comparative study of the trochlear nucleus, nerve, and innervation of the superior oblique muscle in quail, chick, and duck.

The present study was undertaken to examine the development of the trochlear nucleus in quail and to compare the mature trochlear nucleus, nerve, and their sole target of innervation, the superior oblique muscle, in quail, chick, and duck. Study of the trochlear nucleus in quail from embryonic day 5 through hatching shows a maximum of 1,248 neurons on embryonic day 10 followed by spontaneous degeneration of 40% of the neurons between days 10 and 16. Previous studies have shown that although the initial and final number of neurons is different in chick and duck, the magnitude of trochlear cell loss in both species is about 40%. This study shows the average number of neurons in the nucleus of quail, chick, and duck, 2 weeks post-hatching, to be 658, 743 and 1,459, respectively. Fiber counts in the trochlear nerve from electron micrograph montages at the same period indicated a ratio of about 1:1 between neurons and axons. While a majority of the fibers in these nerves are myelinated, an average of 3-6% of the fibers are unmyelinated. The nucleus in the quail not only contains the smallest number of neurons but it also innervates the smallest muscle in terms of total number of muscle cells and endplates. However, the opposite relationship does not hold true. The nucleus in duck contains the largest number of neurons, yet the largest number of muscle cells and endplates were found in the chick. The ratios between the neurons and muscle cells as well as between neurons and endplates are about the same in quail and duck. These ratios are much higher in the chick, reflecting the relatively small neuron pool destined for a relatively large target. In spite of variations in the number of neurons, muscle fibers, and endplates the average number of endplates per muscle fiber is relatively constant among the three species.

Effect of highly active antiretroviral therapy on fat, lean, and bone mass in HIV-seropositive men and women.

BACKGROUND: Alterations in body composition have been reported in HIV-positive adults receiving highly active antiretroviral therapy (HAART), but the magnitude and potential determinants of these changes are unclear. OBJECTIVE: We compared total and regional body composition, as measured by dual-energy X-ray absorptiometry, in 203 HIV-positive men and 62 HIV-positive women according to HAART. DESIGN: This was a cross-sectional analysis of a cohort study of nutrition and HIV infection. RESULTS: After adjustment for age, weight, race, and exercise habits, total weight and fat mass did not differ significantly in men or women by HAART. Trunk fat was greater in men (1.0 kg; P < 0.001) and women (1.4 kg; P = 0.005) and leg fat was lower in men (-1.0 kg; P < 0.001) and women (-1.5 kg, P = 0.005) receiving HAART than in those not. This corresponded to a greater percentage of total fat mass located in the trunk (men: 7.5%, P < 0.001; women: 5.1%, P = 0.02). Lean mass was also greater with longer duration of HAART in men (P < 0.002). In men receiving HAART, total and regional bone mineral content were less than in the men not receiving HAART (P < 0.001). These effects increased with longer duration of HAART. Protease inhibitors were associated with the largest differences in regional fat. CONCLUSIONS: HAART is associated with redistribution of fat mass from the legs to the trunk, despite no significant differences in total fat mass or weight. In men, HAART is also associated with a reduction in bone mineral content, suggesting that HAART increases the risk of central obesity and osteoporosis.

Calcium absorption in elderly subjects on high- and low-fiber diets: effect of gastric acidity.

In vitro studies suggest that the effect of fiber in inhibiting calcium absorption is pH dependent. In nine normal, elderly control subjects and eight elderly subjects with achlorhydria, 47Ca was ingested with three test meals: a low-fiber meal (0.5 g dietary fiber), a high-fiber meal (10.5 g), and a high-fiber meal with 120 mL of 0.1 mol HC/L. In control subjects calcium retention, measured in a whole-body counter, was 25.7 +/- 4.0% (mean +/- SD) with the low-fiber meal, 19.1 +/- 1.9% with the high-fiber meal (P less than 0.002 vs low fiber), and 18.9 +/- 3.3% with the high-fiber-plus-acid meal (P less than 0.002 vs low fiber, NS vs high fiber). Calcium absorption in achlorhydric subjects was not different from control subjects: 26.2 +/- 8.0% with low fiber, 19.6 +/- 4.1% with high fiber (P less than 0.04 vs low fiber), and 21.0 +/- 5.8% with high fiber plus acid (P less than 0.04 vs low fiber, NS vs high fiber). We conclude that, in humans, the reduction in calcium absorption with high fiber intake is unaffected by gastric pH.

Colonic mucosal concentrations of folate correlate well with blood measurements of folate status in persons with colorectal polyps.

BACKGROUND: Estimates of habitual dietary folate intake are known to be imprecisely correlated with systemic measures of folate status. Furthermore, measurements of blood folate concentrations may not accurately reflect the concentration of folate in tissues of interest. This issue is important for assessing folate status in the colorectal mucosa because low dietary intake or blood concentrations of folate are associated with an increased risk of colorectal neoplasia. OBJECTIVE: We examined whether conventional measures of folate in blood and a more sensitive, inverse indicator of systemic folate status, serum homocysteine, accurately reflected folate concentrations in human colonic mucosa obtained by endoscopic biopsy. DESIGN: In 30 persons with colorectal polyps, blood samples were taken and biopsies of normal rectosigmoid mucosa performed at the time of colonoscopic polypectomy. Serum, red blood cell, and colonic mucosal folate and serum homocysteine concentrations were measured. RESULTS: Serum and red blood cell folate and serum homocysteine concentrations accurately reflected colonic mucosal folate concentrations; among these, serum homocysteine correlated best with mucosal concentrations. Folate concentrations in the normal rectosigmoid mucosa were significantly lower in persons with adenomatous polyps than in those with hyperplastic polyps (P=0.04). Conventional measures of systemic folate status were not significantly lower in those with adenomas, although serum homocysteine was mildly elevated (P=0.04). CONCLUSIONS: Our data underscore the ability of systemic measures of folate status, particularly serum homocysteine, to reflect folate concentrations in the colonic mucosa. Nevertheless, future studies that examine the ability of folate to modulate colorectal carcinogenesis may benefit from direct measurement of folate in the colon.

Colonic mucosal concentrations of folate are accurately predicted by blood measurements of folate status among individuals ingesting physiologic quantities of folate.

Folate status is inversely related to the risk of colorectal cancer. Whether conventional blood measurements of folate status accurately reflect folate concentrations in the colorectal mucosa has been a controversial topic. This is an important issue because accurate measures of folate status in the colorectal mucosa are important for ascertaining the risk of colorectal cancer in epidemiological studies and for determining the effects of folate supplementation in clinical trials. We examined whether conventional blood measurements of folate and a more sensitive, inverse indicator of systemic folate status, serum homocysteine, accurately reflect folate concentrations in human colonic mucosa obtained by endoscopic biopsy. Study subjects (n = 20) were participants in a randomized trial that investigated the effect of folate supplementation (5 mg daily for 1 year) on provisional molecular markers of colon cancer. Blood samples and biopsies of normal rectosigmoid mucosa were obtained at baseline, at 6 months, and at 1 year. Serum, RBC, and colonic mucosal folate and serum homocysteine concentrations were determined. Colonic mucosal folate concentrations correlated directly with serum folate concentrators at each time point (r = 0.572-0.845; P < 0.015) and with RBC folate concentrations at 6 months and 1 year (r = 0.747-0.771; P < 0.001). Colonic mucosal folate concentrations correlated inversely with serum homocysteine concentrations at each time point (r = -0.622-0.666; P < 0.008). Systemic measures of folate status did not correlate with colonic mucosal folate concentrations among individuals receiving supplemental folate. Our observations indicate that colonic mucosal concentrations of folate may be predicted accurately by blood measurements of folate status only among individuals not ingesting supraphysiological quantities of folate.

Interactions between nutrition and infection with human immunodeficiency virus.

Nutritional status is severely compromised in persons infected with the human immunodeficiency virus (HIV). One or a combination of several disease-related factors can contribute to substantial weight loss and malnutrition, accelerating the downhill course of the disease. Efforts to prevent weight loss should include early intervention aimed at appetite stimulation, nutritional supplementation with high-calorie, high-protein oral supplements, and diagnosis and treatment of underlying infections and malabsorption. Although enteral or parenteral feedings may be warranted, these forms of nutritional support pose special problems in HIV-infected persons, and the ultimate benefits of these measures are not yet clear. The recent use of pharmacologic agents to stimulate appetite or improve body composition shows promise, but more research is needed before these drugs can be widely recommended as adjuncts to therapy. In general, unproven remedies should be avoided, as their risks may well outweigh their benefits.

Acute fatty liver of pregnancy in triplet gestation.

BACKGROUND: Acute fatty liver is reported to be more common in twin than in singleton pregnancies. We report three cases of biopsy-proven acute fatty liver in triplet gestations. CASES: In all three cases of acute fatty liver complicating triplet pregnancies, the presenting features were vague abdominal complaints with elevated hepatic aminotransferase levels. A liver biopsy was performed in each case, and cesareans were performed immediately after the diagnosis was confirmed histologically. Clinical resolution occurred in all cases, and all infants did well in the neonatal period. CONCLUSION: Patients with triplet gestations should be monitored closely for the early signs of acute fatty liver. Triplet gestations may contribute to the onset of acute fatty liver by further stressing the fatty acid oxidation capabilities of the susceptible woman.

Evaluation of abnormal liver function in pregnancy.

Liver disease in pregnancy may present in a subtle or dramatic fashion. An approach using the pattern of liver function abnormalities, time of gestation, and constellation of symptoms will narrow the diagnostic possibilities. Diagnostic tests, including serology, ultrasonography of the hepatobiliary tree, and liver biopsy, can make a definitive diagnosis.

Bioelectrical impedance methods in clinical research: a follow-up to the NIH Technology Assessment Conference.

In 1994, the National Institutes of Health (NIH) convened a Technology Assessment Conference "to provide physicians with a responsible assessment of bioelectrical impedance analysis (BIA) technology for body composition measurement." In 1997, Serono Symposia USA, Inc., organized an invited panel of scientists and clinicians, with extensive research and clinical experience with BIA, to provide an update. Panel members presented reviews based on their own work and published studies for the intervening years. Updates were provided on the single and multifrequency BIA methods and models; continued clinical research experiences; efforts toward establishing population reference norms; and the feasibility of establishing guidelines for potential diagnostic use of BIA in a clinical setting. This report provides a summary of the panel's findings including a consensus on several technical and clinical issues related to the research use of BIA, and those areas that are still in need of additional study.

Enhanced vector competence of Aedes aegypti (Diptera: Culicidae) from the Torres Strait compared with mainland Australia for dengue 2 and 4 viruses.

Australian Aedes aegypti (L.) mosquitoes colonized from the Torres Strait and three mainland localities (Charters Towers, Townsville, and Cairns) were fed on blood suspensions containing dengue virus type 2 (DEN-2) or dengue virus type 4 (DEN-4). Variation was found in oral susceptibility to DEN-2 (59 -99% infection) and DEN-4 (28-79% infection) among Ae. aegypti assayed for virus at 8, 12, 16, or 20 d after ingestion of infected blood. Torres Strait Ae. aegypti were the most susceptible to DEN-2 and were significantly more efficient in transmission to capillary tube at 16 d (76% transmission) than mainland Ae. aegypti populations (20-28% transmission). Torres Strait Ae. aegypti were also the most susceptible to DEN-4, although transmission did not vary significantly from mainland populations at 16 d (12% compared with 0-4%) or 20 d (16% compared with 4-16%). Disseminated infection (i.e., leg infection) with either DEN-2 or DEN-4 was not an accurate predictor of transmission potential. This study demonstrates differences among Australian Ae. aegypti populations in vector competence for DEN-2 and DEN-4. Torres Strait Ae. aegypti were more frequently infected and able to transmit DEN-2 at higher rates than mainland populations. These data indicate that the Torres Strait region is potentially more receptive to dengue transmission than mainland localities, a finding discussed with respect to past outbreaks.

Endoscopic ultrasound of the upper gastrointestinal tract.

Endoscopic ultrasound (EUS) is an evolving technique used by gastroenterologists to examine lesions that are located either within or adjacent to the walls of the upper gastrointestinal (GI) tract; this topic is relatively unknown to most radiologists. Proper use of this modality is benefited by a cooperative effort between gastroenterologists and radiologists specializing in ultrasound and cross-sectional imaging. This article informs radiologists of the applications of this procedure. Most patients are examined with EUS after a biopsy of a mucosal tumor has been performed. A smaller number are performed to evaluate submucosal masses or when pancreatic disease is suspected but not diagnosed. The examinations can be performed either with dedicated flexible echoendoscopes or with catheter-based probes passed through a conventional endoscope. The exact location of abnormalities associated with the upper GI tract can be observed. Known anatomic landmarks are sought. Abnormalities of structures outside the upper GI tract will occasionally be found during these examinations. The specific layers of the walls of the gut are examined, and the T and N-classification of upper GI tumors can be determined accurately. The performance of an EUS examination requires advanced skills, and in many medical centers, it is the imaging modality of choice to stage cancers, to evaluate submucosal masses, and to investigate both malignant and benign pancreaticobiliary disease. Endoscopic ultrasound is sensitive but not specific, and biopsy is necessary to establish a diagnosis. Therapeutic applications of EUS are evolving. Specialized applications with catheter-based probes are also being developed.