Freezing tolerance and survival experiments with various intertidal organisms from Kachemak Bay, Alaska

Thesis (M.S.) University of Alaska Fairbanks, 2004Intertidal organisms at high latitudes experience multiple stresses created by freezing, including ischemia, free water reduction, and distortion and destruction of cells, and in response have adapted behavioral and physiological solutions. This study examined the response of intertidal organisms in Kachemak Bay, Alaska to freezing through laboratory experiments and field studies. Mytilus trossulus, Balanus glandula, Protothaca staminea and various limpets (Lottidae) survived freezing conditions to -10 and -20°C, depending on the season. Mytilus trossulus and B. glandula survived multiple freeze events at -10°C. Seasonal freeze response was not induced by exposure to low air temperature in M trossulus. Exposure to O⁰C was not fatal to any of the species studied: M trossulus, B. glandula, P. staminea, limpets, Fusitriton oregonensis, Katharina tunicata and Leptasterias hexactis. Preliminary results suggest that M trossulus and P. staminea have an ice nucleator. Freezing avoidance may be one cause for the differences seen in seasonal distribution patterns of F. oregonensis, Nucella lima, Onchidella borealis, Siphonaria thersites and Littorina sitkana. The current study demonstrated that intertidal organisms in this region exhibit differing responses to freezing. Some organisms survive freezing conditions by freeze tolerance, while others may avoid it by moving lower in the intertidal

Self-Feeding Interventions for Adults with Tremors

This research analysis was completed in collaboration with Carol Schramek, OTR/L, who works at a skilled nursing facility (SNF) in Iowa run by ABCM corporations. A systematic review of literature was conducted to explore the research question: What evidence-based interventions have been shown to be effective for reducing tremors, improving occupational performance, and/or increasing client satisfaction during self-feeding in adults with resting and/or action tremors? After initial review of 73 articles based on title, 33 articles met our inclusion criteria and were included in our critical appraisal of our topic (CAT). We found there to be a lack of research specifically on self-feeding interventions for adults with an upper-extremity tremor. Due to this gap in research, inferences on the effectiveness of the non-functional interventions for occupation-based tasks in our critical appraisal for self-feeding were made. After reviewing the 33 articles, 8 intervention categories prevailed that had positive impacts on occupational performance for clients with tremor including: limb temperature, positioning of the upper extremity, electrical stimulation, vibration, orthoses, muscular therapy, behavioral training, and various eating devices. After meeting with our collaborator to discuss options for disseminating our findings from the CAT analysis, it was determined that a digital booklet containing basic information ( description, methods, cost, photos) on each intervention category would be most useful for Schramek and her occupational therapy (OT) practitioner colleagues to use when learning about and selecting interventions to use. The booklet was created and sent via email in a pdf and Microsoft Word document to reference and print at her convenience. The purpose of providing a Microsoft Word version, was to enable editing of the files for client-centered customization. To measure the efficacy and benefits of the booklet for the OT practitioners, pre and post surveys were created to assess the OT practitioners\u27 current usage, knowledge, and familiarity of self-feeding interventions for adults with tremor before and after reading through our booklet. Results from our surveys and collaborator feedback indicated that the booklet provided useful information for practitioners to utilize and increased their knowledge on options for interventions to address self-feeding in adults with tremor. OT practitioners should consider all supports and barriers the client has for self-feeding when determining if an intervention included in this critical appraisal is appropriate for their clients with tremor. More research is needed to determine if these interventions are appropriate for OT practitioners to implement for clients with tremors

No Need for Lopinavir Dose Adjustment during Pregnancy: a Population Pharmacokinetic and Exposure-Response Analysis in Pregnant and Nonpregnant HIV-Infected Subjects

ABSTRACT Lopinavir-ritonavir is frequently prescribed to HIV-1-infected women during pregnancy. Decreased lopinavir exposure has been reported during pregnancy, but the clinical significance of this reduction is uncertain. This analysis aimed to evaluate the need for lopinavir dose adjustment during pregnancy. We conducted a population pharmacokinetic analysis of lopinavir and ritonavir concentrations collected from 84 pregnant and 595 nonpregnant treatment-naive and -experienced HIV-1-infected subjects enrolled in six clinical studies. Lopinavir-ritonavir doses in the studies ranged between 400/100 and 600/150 mg twice daily. In addition, linear mixed-effect analysis was used to compare the area under the concentration-time curve from 0 to 12 h (AUC 0–12 ) and concentration prior to dosing ( C predose ) in pregnant women and nonpregnant subjects. The relationship between lopinavir exposure and virologic suppression in pregnant women and nonpregnant subjects was evaluated. Population pharmacokinetic analysis estimated 17% higher lopinavir clearance in pregnant women than in nonpregnant subjects. Lopinavir clearance values postpartum were 26.4% and 37.1% lower than in nonpregnant subjects and pregnant women, respectively. As the tablet formulation was estimated to be 20% more bioavailable than the capsule formulation, no statistically significant differences between lopinavir exposure in pregnant women receiving the tablet formulation and nonpregnant subjects receiving the capsule formulation were identified. In the range of lopinavir AUC 0–12 or C predose values observed in the third trimester, there was no correlation between lopinavir exposure and viral load or proportion of subjects with virologic suppression. Similar efficacy was observed between pregnant women and nonpregnant subjects receiving lopinavir-ritonavir at 400/100 mg twice daily. The pharmacokinetic and pharmacodynamic results support the use of a lopinavir-ritonavir 400/100-mg twice-daily dose during pregnancy

Elevated frequencies of micronucleated erythrocytes in infants exposed to zidovudine in utero and postpartum to prevent mother-to-child transmission of HIV

Zidovudine-based antiretroviral therapies (ART) for treatment of HIV-infected pregnant women have markedly reduced mother-to-child transmission of the human immunodeficiency virus (HIV-1) from ~25% to <1%. However, zidovudine (ZDV; AZT), a nucleoside analogue, induces chromosomal damage, gene mutations, and cancer in animals following direct or transplacental exposures. To determine if chromosomal damage is induced by ZDV in infants exposed transplacentally, we evaluated micronucleated reticulocyte frequencies (%MN-RET) in 16 HIV-infected ART-treated mother-infant pairs. Thirteen women received prenatal ART containing ZDV; 3 received ART without ZDV. All infants received ZDV for 6 weeks postpartum. Venous blood was obtained from women at delivery, and from infants at 1–3 days, 4–6 weeks, and 4–6 months of life; cord blood was collected immediately after delivery. Ten cord blood samples (controls) were obtained from infants of HIV-uninfected women who did not receive ART. %MN-RET was measured using a single laser 3-color flow cytometric system. Ten-fold increases in %MN-RET were seen in women and infants who received ZDV-containing ART prenatally; no increases were detected in 3 women and infants who received prenatal ART without ZDV. Specifically, mean %MN-RET in cord blood of ZDV-exposed infants was 1.67±0.34 compared with 0.16±0.06 in non-ZDV ART-exposed infants (P=0.006) and 0.12±0.02 in control cord bloods (p<0.0001). %MN-RET in ZDV-exposed newborns decreased over the first 6 months of life to levels comparable to cord blood controls. These results demonstrate that transplacental ZDV exposure is genotoxic in humans. Long-term monitoring of HIV-uninfected ZDV-exposed infants is recommended to ensure their continued health

Assimilation of Oil-Derived Elements by Oysters Due to the Deepwater Horizon Oil Spill

During and after the Deepwater Horizon Oil Spill (DWHOS), oysters (Crassostrea virginica) were exposed to oil and susceptible to incidental consumption of surface and subsurface oil materials. We determined the contribution of oil materials from the DWHOS to diet of oysters by comparing carbon (C) and nitrogen (N) stable isotope ratios in oyster shell to ratios in suspended particulate matter (SPM) and in fresh and weathered oil. Average δ13C and δ15N values in oyster shell (−21 ± 1‰ and 9−11‰, respectively) were consistent with consumption of naturally available SPM as opposed to values in oil (−27 ± 0.2‰, 1.6 ± 0.4‰). Stable isotope ratios in oyster adductor muscle were similar to shell for δ15N but not δ13C, suggesting either a recent shift in diet composition or differential assimilation of C between tissue types. We found no evidence of assimilation of oil-derived C and N and, therefore, no evidence of an oyster-based conduit to higher trophic levels. Trace elements in shell were inconclusive to corroborate oil exposure. These findings are not an indication that oysters were not exposed to oil; rather they imply oysters either did not consume oil-derived materials or consumed too little to be detectable compared to natural diet

Treatment Responses in Antiretroviral Treatment (ART) Naïve Pre- and Post-menopausal HIV-infected Women: An Analysis from ACTG Studies

Menopause may affect antiretroviral treatment (ART) response. Immunologic and virologic responses to ART were compared in 220 pre- and 47 post-menopausal women enrolled in two ART-naive studies. Changes in CD4 counts or HIV-1 RNA were similar at 24, 48, or 96 weeks. Treatment-naïve women should respond to ART regardless of menopausal status

Carboxyl terminus of Hsp70-interacting protein (CHIP) is required to modulate cardiac hypertrophy and attenuate autophagy during exercise

The carboxyl terminus of HSP70-interacting protein (CHIP) is a ubiquitin ligase/co-chaperone critical for the maintenance of cardiac function. Mice lacking CHIP (CHIP −/−) suffer decreased survival, enhanced myocardial injury, and increased arrhythmias compared to wild type controls following challenge with cardiac ischemia reperfusion injury. Recent evidence implicates a role for CHIP in chaperone-assisted selective autophagy, a process that is associated with exercise-induced cardioprotection. To determine whether CHIP is involved in cardiac autophagy, we challenged CHIP −/− mice with voluntary exercise. CHIP −/− mice respond to exercise with an enhanced autophagic response that is associated with an exaggerated cardiac hypertrophy phenotype. No impairment of function was identified in the CHIP −/− mice by serial echocardiography over the five weeks of running, indicating that the cardiac hypertrophy was physiologic not pathologic in nature. It was further determined that CHIP plays a role in inhibiting Akt signaling and autophagy determined by autophagic flux in cardiomyocytes and in the intact heart. Taken together, cardiac CHIP appears to play a role in regulating autophagy during the development of cardiac hypertrophy, possibly by its role in supporting Akt signaling, induced by voluntary running in vivo

Genetic myostatin decrease in the golden retriever muscular dystrophy model does not significantly affect the ubiquitin proteasome system despite enhancing the severity of disease

Recent studies suggest that inhibiting the protein myostatin, a negative regulator of skeletal muscle mass, may improve outcomes in patients with Duchenne muscular dystrophy by enhancing muscle mass. When the dystrophin-deficient golden retriever muscular dystrophy (GRMD) dog was bred with whippets having a heterozygous mutation for the myostatin gene, affected GRMD dogs with decreased myostatin (GRippets) demonstrated an accelerated physical decline compared to related affected GRMD dogs with full myostatin. To examine the role of the ubiquitin proteasome and calpain systems in this accelerated decline, we determined the expression of the muscle ubiquitin ligases MuRF1, Atrogin-1, RNF25, RNF11, and CHIP: the proteasome subunits PSMA6, PSMB4, and PSME1: and calpain 1/2 by real time PCR in the cranial sartorius and vastus lateralis muscles in control, affected GRMD, and GRippet dogs. While individual affected GRMD and GRippet dogs contributed to an increased variability seen in ubiquitin ligase expression, neither group was significantly different from the control group. The affected GRMD dogs demonstrated significant increases in caspase-like and trypsin-like activity in the cranial sartorius; however, all three proteasome activities in the GRippet muscles did not differ from controls. Increased variability in calpain 1 and calpain 2 expression and activity in the affected GRMD and GRippet groups were identified, but no statistical differences from the control group were seen. These studies suggest a role of myostatin in the disease progression of GRMD, which does not significantly involve key components of the ubiquitin proteasome and calpain systems involved in the protein quality control of sarcomere and other structural skeletal muscle proteins

Immune Activation While on Potent Antiretroviral Therapy Can Predict Subsequent CD4+ T-Cell Increases Through 15 Years of Treatment

While persistent T-cell activation has been cross-sectionally associated with poor CD4+ T-cell restoration in HIV-infected individuals maintaining antiretroviral treatment (ART)–mediated viral suppression, it remains unclear whether CD8+ T-cell activation is of predictive effect on CD4+ T-cell recovery