Gracias a la resurrección de varias enzimas de nuestros antepasados primates se han identificado varias mutaciones que ocurrieron hace, aproximadamente, 10 millones de años, las cuales le confirieron a nuestros antepasados una capacidad mucho mayor para metabolizar etanol. Este episodio de evolución enzimática coincidió con un cambio climático global asociado con la reducción de los bosques africanos y la transición de nuestros antepasados de un estilo de vida arbórea a un estilo de vida terrestre en el cual la fruta altamente fermentada era más común. Estos estudios sugieren que la evolución de las enzimas de nuestros antepasados pueden haberles permitido explotar una fuente alternativa de alimento cuando la comida era escasa. / We have resurrected ancient enzymes from our primate ancestors and identified several mutations occurring approximately 10 million years ago that endowed our ancestors with an enhanced capacity to metabolize ethanol.  This episode of enzyme evolution coincided with a global climate change associated with shrinking African forests and our ancestor’s transition from an arboreal lifestyle to a terrestrial lifestyle where highly fermented fruit is more common. These studies suggest that the evolution of our ancestor’s enzymes may have enabled our ancestors to exploit an alternative source of nourishment during a time when food was scarce.

This longitudinal investigation examined motives for alcohol use, alcohol consumption, and alcohol-related consequences in a Vancouver, British Columbia youth sample (n = 405). Secondary analyses were performed on data that were collected at two time points (1995-1996 and 2003-2004). Sociodemographic variables included age, gender, adoption status, parent education, household moves, and family net worth. Bivariate correlations and structural equation modeling were used to examine associations between social, enhancement, and coping motives, alcohol consumption and alcohol-related consequences. The social motives included drinking to be sociable and drinking to add to the enjoyment of meals. Enhancement motives included drinking to feel good. Coping motives included: drinking to help you relax, drinking to forget worries, and drinking to feel less shy and inhibited. In the final longitudinal structural equation model combining T1 motives and both T1 and T2 alcohol consumption and alcohol-related consequences, results showed endorsement at T1 of drinking to forget worries was predictive of the alcohol-related consequences latent factor at T1. Moreover, T1 consequences were predictive of alcohol-related consequences at T2. The data show a positive relationship between T1 endorsement of drinking to feel good and the alcohol consumption latent variables at both T1 and T2, but no relationship between drinking to feel good and the alcohol-related consequences emerged. Additionally, the data yielded a negative relationship between the variable, “drink to be sociable” and the alcohol-related consequences latent factor at T1. Certain self-identified motives for drinking may be risk factors for continued alcohol use and subsequent misuse. Therefore, differentiating between specific motives for alcohol use may be a helpful marker for Child and Youth Care workers and other professionals to initiate conversations about alcohol use and consequences. / Graduate

This thesis describes the reactions of mercury-sensitized isopropyl alcohol when bombarded with 2537 Angstrom radiation.

Indiana University-Purdue University Indianapolis (IUPUI) / Continued consumption of alcohol despite the knowledge of negative consequences is a hallmark of alcohol use disorder (AUD), yet much remains unknown about what motivates these behaviors. Compulsive drinking may require motivational resources that are not necessary when drinking in unchallenged conditions in order to counteract the addition of these negative consequences. Increased sensitivity to drug-paired stimuli via associative learning processes may provide this additional motivation. To evaluate if alcohol-paired stimuli enhance alcohol seeking, selectively bred crossed High Alcohol Preferring mice experienced Pavlovian conditioning procedures with an alcohol unconditioned stimulus. We hypothesized that after repeated pairings, alcohol cues would elicit seeking conditioned responses. Then, to determine if the motivation provided by these cues influenced responding, mice were trained to respond for alcohol and tested in the presence of alcohol cues. Finally, to test if alcohol-paired cues influence compulsive drinking, this same test was repeated with the addition of response-contingent footshock. We hypothesized the cue paired with alcohol would increase responding for alcohol in unchallenged conditions, but especially in challenged conditions, contributing to compulsivity. An auditory stimulus paired with alcohol did elicit enhanced seeking responses, but contrary to hypothesis, we observed no effect of these same cues on instrumental responding. To validate these findings, training and testing procedures must be optimized to ensure conditioning has properly occurred and compulsivity is being appropriately measured.

College campuses are a common location for individuals to experience alcohol consequences. Those consequences: health, legal, and/or academic, could cause short- or long-term repercussions on the student. Students likely have been provided education about these consequences from a range of sources (e.g., parents, friends, health courses). It is important to understand what knowledge of alcohol-related information students retain and how that information may impact their decisions around risk behavior engagement. The Student Alcohol Questionnaire (SAQ; Engs &Hanson, 1973), contains 4 subscales: drinking patterns, problems related to alcohol, knowledge of alcohol, and alcohol attitudes. This measure provided an important model for assessment of students' understanding of alcohol use consequences, however the questionnaire the language had not been updated since it was created. The current study had two aims; 1) to revise the SAQ with language that would be more accessible to current students and reflective of modern drinking trends, and 2) to examine the factor structure of the drinking problems subscale. The revision process was completed in four steps. First, the SAQ was checked overall on what needed to be rewritten or removed. After the first researcher made these changes, it was looked at by multiple raters of different levels of education (i.e., undergraduates, graduates, and faculty). These raters gave a new perspective and new ideas of what could be added for the drinking problems section. The scale was reconfigured to be shorter and to reflect today’s language. This study (i.e., the factor analysis) is the fourth step in the process to validate the questionnaire. Participants (N=255) were 18- to 58-year-olds (Mage = 20.2, SD = 4.152). Participants were directed to the SONA research site to complete the SAQ and, upon completion, were given credit to use in classes that either required or had extra credit opportunities for the student. Data was collected through RedCap and analyzed on SPSS. The Kaiser-Meyer-Olkin measure of sample adequacy was .91, and Bartlett’s test of sphericity was significant (X 2 (351) = 5428.14, p < .001). Since the KMO and Bartlett’s test were both significant, this meant that it was appropriate to run an exploratory factor analysis. Factor analysis extracted two factors, high-risk drinking consequences, and hangover/blackouts, both with eigenvalues above one. A reliability analysis reported that factor one had a Cronbach's Alpha of .96, and factor two had a Cronbach's Alpha of .87. These results that the revisions to the SAQ resulted in the drinking problems subscale to now reflect two separate factors. All drinking problems questions were retained as meaningful to the model, with a hangover and blackout-related questions forming their own new factor separate from general drinking consequences. The next step in our study will be to examine the correspondence between the scales other three factors and these two factors of the drinking problems subscale. Future research should also be conducted on a larger sample size to examine the stability of factor analytic findings.

Thesis (M. A. (Social Work)) --University of Limpopo, 2019. / The study was aimed at exploring the family member‟s experiences of living with people who consume home brewed alcohol (spayoni) in Oakley. Oakley is a village based in Ehlanzeni district, Mpumalanga province. The researcher looked into the financial management, balancing of the work-family nexus and the manner in which people that consume spayoni deal with and conduct themselves in violent situations. A qualitative research approach was used by the researcher through an exploratory design. A total number of nine (9) respondents took part in the study. They were identified by the use of a purposive and snowball sampling method. Furthermore, the researcher used a semi-structured interview to collect data which was analysed by a thematic analysis structure. Data obtained from the study reveals that people that consume spayoni spend less time with family members as they are either out at work or drinking spayoni throughout the day. They leave home very early in the morning and come back late at night. Family roles and relationships are negatively affected by their routines. The people that consume spayoni mostly rely in piece jobs hence they don‟t have stable income. Nonetheless, the little money that they get is spent solely on the purchase of spayoni. They do not prioritise financial contribution towards household needs. The study also identified that people that consume spayoni are generally disrespectful when drunk but refrain from violent situations. In order to combat the challenges faced by the family members, internal and external measures should be put in place. The use of community awareness campaigns is one method which can help in reducing the demand of spayoni in Oakley village. Involvement of monitoring bodies such as the Liquor control boards and the local traditional authorities will assist the community to have regulations governing the supply of home brewed alcohol. Family members should also develop platforms of open communication between each other to avoid misunderstandings and build a more positive family environment.

Prenatal alcohol exposure (PAE) is associated with a range of physical, growth, and neurobehavioral deficits characteristic of individuals with fetal alcohol spectrum disorders (FASD). Although declarative memory impairment is a key feature of the neurocognitive profile of FASD, the mechanisms underlying this deficit require further clarification. The aim of this cross-sectional research was to examine, both directly and indirectly (via bottom-up and top-down processes), a critical cognitive mechanism that supports successful declarative memory functioning (viz., memory encoding), in children with FASD. Data were collected from a sample (N = 88) of South African children with and without PAE. In Study I, I used a blocked design functional magnetic resonance imaging (fMRI) paradigm to investigate neural activation during visual perception, a lower-order cognitive process essential to memory encoding. The task elicited bilateral category-specific activation during the visual perception of objects and scenes in all participants. The absence of between-group differences suggests that functional recruitment of brain regions during basic visual perception is less susceptible to the effects of PAE than during higher-order processes supporting memory encoding. In Study II, I used an event-related fMRI paradigm to investigate neural activation during memory encoding itself. All participants demonstrated similar memory performance accuracy and recruited extensive bilateral networks during memory encoding. However, participants with a diagnosis of fetal alcohol syndrome (FAS) or partial FAS (PFAS) activated additional regions associated with attentional function. Within the FAS/PFAS group, higher exposure levels were associated with smaller activation increases in the parahippocampal gyri and greater activation increases in the right hippocampal formation during encoding. Data from this study therefore suggest that children with FAS/PFAS recruited more extensive neural resources to support successful memory encoding during this task. In Study III, I used a behavioral source memory paradigm to investigate higher-order executive processes essential for memory encoding. Despite similar recognition accuracy across all diagnostic groups, participants in the FAS/PFAS group showed impaired memory for source details. This pattern of impairment was only partially mediated by working memory performance. These three studies provide novel clarification of the neural and cognitive mechanisms underlying declarative memory impairments in children with FASD.

In an attempt to determine mechanisms of certain aspects of ethanol- induced fetal damage, I have established a mouse model of the fetal alcohol syndrome based on the work of Chernoff (1977), using inbred C3H mice. Ethanol or its metabolite, acetaldehyde, was administered to female mice prior to and throughout gestation. Ethanol in doses of 6%, 10% and 20% ethanol derived calories and acetaldehyde 3. 9 mg and 11. 8 mg were administered daily in a nutritionally balanced liquid diet. An acute dose study was also undertaken, in which pregnant C3H mice were given. "binge" doses of 1ml of a 7. 35% solution of ethanol, twice daily through an orogastric tube, on days one and eight or four and twelve of gestation. The mice were sacrificed on day eighteen of gestation and the fetuses weighed and examined macroscopically. Some were sectioned using Wilson's method of free-hand razor blade sectioning (Barrow and Taylor, 1969), and the skeletons of the others were examined using a modified Dawson's method of skeletal preparation (Richmond and Bennett, 1938). A separate in vitro model based on the work of New (1967) was established, in which embryos of eight or nine days' gestation were explanted with visceral yolk sac intact from normal C3H mice. They were cultured for twenty-eight hours in rat serum containing various concentrations of ethanol or acetaldehyde (ethanol 1500, 3000 and 6000mg/l and acetaldehyde 7.4, 19. 7 and 39.4mg/l). During the last four hours of the culture period the embryos were labelled with one microcurie of tritiated thymidine (specific activity 5curies/mmol). At the end of the culture period the embryos were assessed morphologically, and then prepared for liquid-scintillation counting to determine DNA synthesis by measuring tritiated thymidine uptake. Small numbers of embryos from each group were used for autoradiographic studies in an attempt to quantitate the uptake of label in the various parts of the embryo. I found that ethanol given in chronic dosage in vivo was embryotoxic in all three doses studied. There was no evidence of ma tern al toxicity other than hyperactivity at the highest dose used and maternal jaundice in a small number of the 10% EDC and 20% EDC mice. Acetaldehyde given in chronic dosage in vivo produced no toxic effects on mothers or fetuses, other than a reduction in placental weights. Acute "binge" ethanol dosage of mothers on days one and eight or four and twelve of gestation did not appear to have any adverse effects on mothers or fetuses, apart from changes in placental weights. These findings should be viewed with caution, as the in vitro studies did not produce a corresponding result. In the latter study there was a marked time-related response, particularly for acetaldehyde. Ethanol given in vitro produced little evidence of toxicity except at dose levels which in the corresponding in vivo situation were extremely toxic to the mothers. Acetaldehyde, given in vitro in minute fractions of the harmless doses given to mothers in vivo, proved to be highly toxic to 8-day embryos and relatively non-toxic to 9-day embryos. This difference in sensitivity indicates that there must be some protective factor intervening between eight and ten days gestation - possibly the developing placenta may have a role here. From these findings I would suggest that acetaldehyde is a true teratogen, and the abnormalities produced in the chronic ethanol in vivo study were probably largely due to the action of acetaldehyde.

Epidemiological studies have demonstrated a positive relationship between heavy alcohol use and hypertension, but few studies have directly addressed the role of drinking pattern. This study was designed to investigate the association of current alcohol consumption and aspects of drinking pattern with hypertension risk in a sample of 2609 white men and women from western New York, aged 35 to 80 years, and free from other cardiovascular diseases. Hypertension was defined by systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or use of antihypertensive medication. Odds ratios (95% confidence intervals) were computed after adjustment for several covariates. Compared with lifetime abstainers, participants reporting drinking on a daily basis (1.75 [1.13 to 2.72]) or mostly without food (1.64 [1.08 to 2.51]) exhibited significantly higher risk of hypertension. When analyses were restricted to current drinkers, daily drinkers and participants consuming alcohol without food exhibited a significantly higher risk of hypertension compared with those drinking less than weekly (1.65 [1.18 to 2.30]) and those drinking mostly with food (1.49 [1.10 to 2.00]), respectively. After additional adjustment for the amount of alcohol consumed in the past 30 days, the results were follows: 0.90 (0.58 to 1.41) for daily drinkers and 1.41 (1.04 to 1.91) for drinkers without food. For predominant beverage preference, no consistent association with hypertension risk was found across the various types of beverages considered (beer, wine, and liquor). In conclusion, drinking outside meals appears to have a significant effect on hypertension risk independent of the amount of alcohol consumed.

Indiana University-Purdue University Indianapolis (IUPUI) / Alcohol-paired cues invigorate alcohol-seeking and drinking behaviors in both rodents and individuals with alcohol use disorder (AUD). Additionally, genetic susceptibility plays a key role in alcohol addiction behaviors. Alcohol preferring (P) rats model both genetic vulnerability and symptoms of AUD. The basolateral amygdala (BLA), prefrontal cortex (PFC), hippocampus (HC) and nucleus accumbens (NA) are important brain regions involved in cued alcohol seeking. These regions are interconnected and their functional connections are hypothesized to be critical in the expression of motivated behaviors. Electrophysiological recordings in these four regions were collected in P rats engaged in a cued alcohol task. Data were filtered in the theta band (5-11 Hz) and segregated by behavioral epoch. The phase locking index γ was computed and used to measure strength of phase locking between signals from any two brain regions. The cross correlation between the amplitude of two signals was used to determine directionality. PFC-NA synchrony increased after stimuli presentation and remained elevated, relative to baseline synchrony. PFC-NA synchrony was also stronger for trials in which the animal made three or more lever presses (rewarded; R), compared to trials in which the animal responded fewer than three times (not-rewarded; NR). During lever pressing, PFC-BLA, NA-HC and PFC-HC synchrony was stronger after presentation of the DS+, in R compared to NR trials. NA-HC and PFC-BLA synchrony was stronger when responses were withheld in extinction, relative to conditioning. These data inform our knowledge of how corticolimbic connections are involved in cued ethanol seeking behaviors.