Due to 40% higher enzymatic activity of the Val compared to Met allele , homozygote carriers of the Val allele metabolize PFC DA at a more efficient rate, resulting in lower levels of DA in the synapse, whereas those with Met/Met genotype have the lowest rate of DA clearance, resulting in higher level of DA in the synapse. As METH substantially augments the concentration of extracellular DA, we hypothesized that COMT genotype would be a relevant predictor of brain consequences of METH exposure. COMT Val158Met has been examined in many contexts relevant to catecholamine function. With regard to cognition, it has been linked most consistently to differences in executive function , although some controversy remains about the replicability of findings . In healthy adults, the Val allele has been linked to executive dysfunction , whereas the Met allele is associated with enhanced executive function . Some evidence suggests this effect may be specific to men . The Met-associated cognitive advantage is likely due to higher DA bio-availability in the PFC resulting from slower clearance coded by Met. Other findings point to an inverted U-shape relationship between DA activity in the PFC and cognitive performance such that the relationship between COMT and PFC function is likely to be context dependent and more complex than a simple dichotomy in which a Val allele is harmful and a Met allele is protective. For example, under conditions of DA excess, such as after METH administration, the greater metabolic activity conferred by Val alleles may be more advantageous in restoring the brain to homeostasis. In an earlier study of COMT Val158Met and executive dysfunction in the context of HIV disease and METH dependence, we found that, regardless of HIV status,grow rack individuals with Met/Met genotype had better executive function compared to Val carriers, except if they were METH users, and this effect did not generalize to other cognitive domains .

Although increased bio-availability of cortical DA associated with the Met/Met genotype is thought to enhance executive function under physiologically normal conditions, in the hyperdopaminergic state induced by METH, slow DA clearance can result in neurotoxicity, possibly via DA auto-oxidation , thus attenuating any advantage, or posing a liability for executive function in METH-using Met/Met individuals. Here, we aim to examine whether variability in COMT Val158Met contributes to individual differences in executive deficits reported after heavy chronic METH exposure, with the goal to potentially identify genotype groups that are at higher risk of METH-associated executive dysfunction. In this investigation, we are focusing on a more homogenous sample than in our prior work, reducing variability associated with sex and racial background, as well as HIV status, since HIV can also affect dopaminergic circuitry. Our analyses will examine the main and interactive effects of COMT genotype and METH dependence on a three-test composite of executive function . Follow-up analyses will examine the effects of COMT genotype and METH dependence on each test of executive function. We hypothesize that, contrary to its effect in the general population, among individuals with METH dependence, slower DA clearance in the PFC conferred by the Met/Met genotype, in conjunction with METH induced dopaminergic excess, will be associated with worse executive function, while Val carriers will show comparatively better executive function. Participants were 85 METH dependent and 64 non-drug dependent comparison research volunteers evaluated at the University of California, San Diego All were HIV- non-Hispanic White men. We limited our sample to a demographically narrow group for the purpose of genetic analyses, as some sex and race differences in COMT effects and allele frequencies have been reported , and we did not have sufficient numbers of women or non-White participants to conduct separate analyses. Participants were excluded if: they met DSM-IV criteria for lifetime dependence on any drugs other than METH or cannabis within the last 5 years, or alcohol dependence within the last 12 months; they reported abuse of any substances other than METH within the last 12 months, with the exception of cannabis, alcohol and nicotine, given their high prevalence in this population; or they had a history of neurologic, psychiatric, or developmental disorders of sufficient severity to confound neuropsychological test results.

The Wide Range Achievement Test version 3 or 4 reading subtest was used as an estimate of preexisting cognitive ability. Participants who had WRAT reading scores below 80 were excluded to limit the confounding contribution of preexisting low intellectual functioning. Participants gave written informed consent prior to enrollment and collection of neuropsychological, neuropsychiatric, medical and genetic information. HIV status was determined using enzyme linked immunosorbent assays with a confirmatory test. Hepatitis C status was also determined and, while slightly more frequent in METH+, hepatitis C seropositivity did not differ significantly among the COMT genotypes. All procedures were approved by the Human Research Protection Program at UCSD.DNA for genotyping was isolated from 0.2 ml whole blood stored at −70°C using the Qiagen QIAamp DNA Mini Kit and QiaCube Robotic workstation for automated DNA purification. The COMT Val158Met SNP was assayed using an addiction-relevant gene array . All participants were genotyped for COMT Val158Met by standard procedures. Genotyping involved hybridization of a locus-specific oligonucleotide and two allele-specific oligonucleotides to target genomic DNA, extension and ligation reactions, followed by PCR with common dye-labeled PCR primers . The PCR products were hybridized to the universal array, and imaged using a high-resolution scanner. Finally, the images were analyzed using software for automated genotype clustering and calling within Bead Studio software. Participants completed three tests of executive function: Wisconsin Card Sorting Test 64-item-computerized version , Stroop Color-Word Test , and Trail Making Test Part B . The executive function composite consisted of number of perseverative responses on the WCST, reflecting untimed ability to perceive complex pattern set-shifting; score obtained in 45 seconds on the Stroop Color-Word interference condition, reflecting timed ability to selectively inhibit information and manage cognitive interference; and time to complete Trails B, reflecting timed ability to switch and maintain attention between ongoing sequences. Raw scores from the component tests were converted to T-scores adjusted for age, education, and gender according to published test norms, and then averaged across tests to form the EF composite T-score. Variables that differed significantly across the six groups were included as covariates in primary analyses.

Groups differed significantly by years of education, reading level , days since last alcohol use, and lifetime average drinks per day. Thus, these variables were included as covariates in subsequent models for executive function. Years of education was not included as a covariate given that the outcome variables of executive function are demo graphically adjusted for years of education. We used multi-variable linear regression analyses to examine the effects of COMT genotype, METH dependence, and their interaction on the executive function composite,greenhouse grow tables controlling for significant covariates. COMT genotype was coded with Val/Met as the reference group, given that it is the largest genotype group in our analyses and the most common in the general population, including White populations . In order to probe significant COMT*METH interactions and assess the differential influence of each predictor on executive function, we conducted follow-up analyses stratified by COMT genotype and separately, stratified by METH dependence. Similar analyses examined the same predictors in multi-variable linear regression analyses with the individual tests of executive function as outcomes. For these three individual tests, stratified analyses that followed-up on COMT*METH interaction effects were interpreted using a Bonferroni-adjusted α-threshold of .0167 .Participants were all non-Hispanic White men, ranged in age from 18 to 66 years old , and had an average of 12.6 years of formal education . Table 1 provides sample demographic and lifetime substance use characteristics by METH status and COMT genotype group. Across the six groups, METH+ participants had significantly fewer years of formal education, lower WRAT reading scores, more days since last alcohol use and higher average lifetime alcohol drinks per day compared to METH- participants. Importantly, within each METH group, COMT genotype groups had comparable background characteristics , substance use histories, and proportion of hepatitis C seropositivity . This risk is highest for large breed dogs and those over 10 years of age.Cancer and its treatments cause disruptions in nutritional status, such as loss of appetite and cachexia in many species. In humans undergoing or surviving beyond treatment, evidence for the effectiveness of dietary strategies is inconsistent, which might reflect the complexity of the relationships among various nutritional factors, cancer biology, and both general and cancer-specific outcomes. Overall, research data in humans suggest general healthy diet and lifestyle measures are beneficial after diagnosis and during treatment of cancer, including healthy weight management, exercise, increased fruit and vegetable consumption, and avoidance of red or processed meats.

Little evidence is available to support using specific nutritional strategies for dogs with cancer. Nonetheless, recommendations for specific commercial diets as well as home-prepared diet recipes for dogs with cancer are readily accessible by pet owners, although the latter do not typically meet nutritional standards.Dogs with cancer are more likely to receive home-prepared foods, with more than half of diet alterations after a cancer diagnosis involving the addition of home-prepared components. Owners of dogs with cancer are more likely to give supplements.Given the importance of nutrition in dogs with cancer, and because owners might change the diets after diagnosis, it is important that clinicians collect information on what owners are feeding their dogs and how a cancer diagnosis affects this. There is limited data on alterations relating to supplement usage or specific diet strategies, such as grain-free or organic. Diet history information, including supplement and treat use, is essential for performing the nutritional assessment, and understanding why certain changes are being made is important for client counseling and to develop sound treatment plans.This is especially relevant in cases where owners are switching to potentially unbalanced home-prepared diets or adding raw animal products that carry the risk of contamination with pathogenic bacteria.This study sought to determine how dog owners altered diet and supplement usage in response to a cancer diagnosis. Owners were surveyed on diets and supplements given both before and after diagnosis, in addition to current treat usage. Reasons for alterations as well as informational resources used by owners of dogs with cancer were also queried. Based on previous studies, we expected that the most common changes would involve the initiation of supplements as well as the reduction or discontinuation of commercial diet products in favor of home-prepared foods.Dog owners were surveyed if their dog presented, for the first time, to the UC Davis Veterinary Medical Teaching Hospital’s Oncology Service for the treatment or further diagnosis of a tumor between December of 2020 and March of 2022. Dogs presenting to the service for the first time with recurrence or that had a previous, different type of cancer were excluded. Surveys were sent out in groups every 2 to 3 weeks. During this period, we reviewed the appointment schedule for newly presenting dogs and sent out surveys to owners upon identifying recruitment eligibility. A link to the Qualtrics survey was distributed to eligible dog owners via the email address that they provided during registration of their dog at the hospital. Consent to participate was obtained through the first question of the survey. Participants were then asked if they would prefer to take the survey by telephone; if the participant selected this option, the online survey would end, and we attempted to collect responses via telephone call. Owners were excluded if they did not consent to the survey.An early draft of the survey was piloted with several dog owners. The final version of the survey had 62 possible questions, many of which were conditionally shown based on previous answers . Survey data were matched to each dog’s medical record to collect information regarding signalment, diagnosis, time from diagnosis to survey response, and estimated household income based on census tract. The bulk of the survey consisted of 3 sections: diet, supplements, and treats. All eligible responses with information on diet, supplements, or treats were retained for analysis. The diet section asked what owners were currently feeding their dogs, including specific characteristics and if the diets were commercially available, home prepared, or a combination of the 2. For commercial diets, the brand name and form of diet was collected.