Factors in an Auto-Brewery Syndrome group compared to an American Gut Project group: a case-control study.

Background: Auto-Brewery Syndrome (ABS), also known as Gut Fermentation Syndrome, is a rare but underdiagnosed condition. While scores of case studies of ABS are published, only one previous study examined ABS patients' demographics, health history, lifestyle factors, and diet compared to a control group of household members. Methods: We designed a case-control study to identify factors that individuals with a diagnosis of ABS and those who live with them might have that differ from a larger general group. We administered a survey to 46 patients known to have a diagnosis of ABS and their household members. Here, we compare our group of survey takers to a cohort of the American Gut Project (AGP) participants (N=11,297) for the 30 questions that were identical. Results: With a response rate of 88% and using Rank Sum Tests, the data demonstrate that patients with ABS and their household members are more likely than participants of the AGP to own a pet (p=.03 for cat; p=.0001 for dog), get less sleep (p=.0001), and have lesser quality of bowel movements (p=.03). In addition, the ABS group consumes more water (p=.02) and less alcohol (p=.0004), eats at home more often (p=.0056), and reports more aversion to sweets (p=.01). The most striking difference is a higher presence of non-food allergies in all five subcategories of the survey in the ABS group compared to the AGP group. Conclusion: Patients with ABS and their household members show several significant differences in their lifestyle and health, diet, and medical history compared to a large group of AGP participants. These differences lead to several hypotheses about co-morbidities that warrant further research.

Case-Control Research Study of Auto-Brewery Syndrome.

BACKGROUND: Auto-brewery syndrome (ABS), also known as Gut Fermentation Syndrome and Endogenous Ethanol Fermentation, is afflicting people worldwide, but little is known about ABS patients' demographics, health history, lifestyle factors, and diet. METHOD: We conducted a broad-based case-control survey study on 52 patients known to have a diagnosis of ABS and their household members. The research compares the symptomatic group (N = 28) to the asymptomatic group (N = 18) regarding lifestyle and health, diet, and medical history. RESULTS: With a response rate of 88% and using rank-sum tests, the data demonstrate that patients with ABS have significant differences compared to people without ABS in lower quality bowel movements (P = .048), more frequent bowel movements (P = .038), more reports of malodorous breath (P = .0001), and self-classify as having poorer health (P = .009). Furthermore, participants with ABS consume more water (P = .038), consume less tea and coffee (P = .033), eat fewer dairy products (P = .0185), eat less candy (P = .032), eat out less and rely on food prepared at home (P = .043), have more aversion to starch (P = .008), and have more food sensitivities (P = .043) than the group without ABS. The ABS group also reports more diarrhea (P = .048), higher amounts of yeast in their gastrointestinal tract (P = .015), and using acne medication for a longer time (P = .037) than the control group. CONCLUSION: Patients with ABS have significant differences in their lifestyle and health, diet, and medical history compared to non-ABS participants and these differences warrant further research.

The effect of tea tree oil (Melaleuca alternifolia) on wound healing using a dressing model.

Numerous studies have shown the promising antibacterial effects of Melaleuca alternifolia, or tea tree essential oil. The study detailed here replicates in humans a 2004 in vitro study that used a dressing model over Petri dishes to determine the antimicrobial effects of the fumes of tea tree essential oil. The current study used the same dressing model with patients who had wounds infected with Staphylococcus aureus. Ten participants volunteered for the quasi-experimental study, and four of the 10 were used as matched participants to compare wound healing times between conventional treatment alone and conventional treatment plus fumes of tea tree essential oil. The results demonstrated decreased healing time in all but one of the participants treated with tea tree oil. The differences between the matched participants were striking. The results of this small investigational study indicate that additional study is warranted.

The effects of aromatherapy on nicotine craving on a U.S. campus: a small comparison study.

OBJECTIVES: To evaluate the effect of two inhaled essential oils (black pepper or angelica) on the nicotine habits of students, staff, and faculty on a U.S. college campus. DESIGN: Comparative study with pre-/post-test measures. SETTING: Community college in rural East Texas. PARTICIPANTS: Convenience sample of 20 volunteers from the college community (students, faculty, and staff) who were regular (daily) users of nicotine (cigarettes, snuff, or chewing tobacco). INTERVENTIONS: Inhalation of one drop of essential oil on a tissue for 2 minutes when participant was craving nicotine. OUTCOME MEASURES: (1) Pre-inhalation journal recording of self-assessed level of craving for nicotine on a 0-10 scale, (2) post-inhalation journal recording of self-assessed level of craving for nicotine on a 0-10 scale, and (3) minutes that participant waited from start of inhalation until next use of tobacco. RESULTS: Both black pepper and angelica reduced the level of nicotine craving and allowed a longer delay before next use of tobacco. However, black pepper reduced the level of craving more than did angelica, and angelica allowed for a longer delay than did black pepper. CONCLUSIONS: Aromatherapy may be useful in nicotine withdrawal. Further studies are warranted.

Application of the M technique to two severely disabled children in Belarus.

Following the early-morning explosion of reactor four at the Chernobyl nuclear plant on 26 April 1986, radioactive fallout fell over 80% of Belarus. More than 2.2 million people were affected, including thousands of children. As a result, there are now over 50,000 children in 600 orphanages in Belarus. Many of the orphanages are without basic amenities and are operating in dire circumstances. This article outlines two case studies of orphaned children with profound disabilities in one of these orphanages. The first author, a nurse volunteer from Ireland, used a method of touch called the 'M technique' to calm and soothe the children. The M technique is a gentle repetitive method of touch that can be learnt in a few hours. The results suggest that even when the situation appears very challenging, simple touch can have a beneficial effect.

A regional academic partnership for the early identification and retention of at-risk nursing students.

UNLABELLED: In a 2006 Texas Higher Education Coordinating Board report (Increasing RN Graduates in Texas: A Report to the 79th Legislature), nursing programs in Texas were challenged to increase the number of graduates to deal with the nursing shortage. This article describes the East Texas region's efforts to identify and intervene in the nursing student attrition rates of participating partners nursing programs. The primary purpose of this study was to identify and intervene with students at risk for attrition. Nine nursing programs participated in the study. METHODS: Online surveys were used to assess variables associated with attrition. Online interventions and an intensive test review protocol were used as intervention methods. RESULTS: Across the nine nursing programs, 898 students participated in the study. Regression and categorical data analysis revealed that lack of reading comprehension was the best predictor of a student being off track or out of a nursing program (P < .0001). Two other highly predictive variables of attrition were entrance examination composite scores (P = .0271) and a student's grades in anatomy and physiology (P = .005). Grant intervention protocols were effective in reducing the attrition rate (P = .0002) between students who participated during the grant period and those prior to implementation of the grant.

Gene expression profile of the PDAPP mouse model for Alzheimer's disease with and without Apolipoprotein E.

The APOE epsilon 4 allele is a strong risk factor for Alzheimer's disease (AD). However, the molecular basis for this effect remains unclear. We examined expression of approximately 12,000 genes and expressed sequence tags in the hippocampus and cortex of PDAPP (APP(V717)) mice modeling AD that show extensive amyloid beta (A beta) deposition, and in PDAPP mice lacking murine APOE expression, which show marked attenuation of A beta deposition in the brain. Wild type and APOE knockout animals were also examined. Expression levels were determined at the initial stage of A beta deposition, as well as in older animals showing extensive neuropathological changes. Fifty-four transcripts were identified using our statistical analysis as differentially regulated between the PDAPP and PDAPP/APOE ko mice, whereas 31 transcripts were classified as differentially regulated among PDAPP mice and WT animals, and seven transcripts were identified as regulated between the PDAPP/APOE ko animals and the APOE ko animals. Interestingly, many of the differentially regulated genes we detected can be related to biological processes previously shown to be important in AD pathophysiology, including inflammation, calcium homeostasis, cholesterol transport and uptake, kinases and phosphatases involved in tau phosphorylation and dephosphorylation, mitochondrial energy metabolism, protein degradation, neuronal growth, endoplasmic reticulum (ER) stress related proteins, antioxidant activity, cytoskeletal organization, and presenilin binding proteins. Regulated genes also included some not directly associated with AD in the past but likely to be involved in known AD pathophysiologic mechanisms, and others that may represent completely novel factors in the pathogenesis of AD. These results provide a global molecular profile of hippocampal and cortical gene expression during the initial and intermediate stages Abeta deposition, and the effects of APOE deletion on this process.

Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors.

The synthesis, evaluation, and structure-activity relationships of a series of succinoyl lactam inhibitors of the Alzheimer's disease gamma-secretase are described. Beginning with a screening hit with broad proteinase activity, optimization provided compounds with both high selectivity for inhibition of gamma-secretase and high potency in cellular assays of A beta reduction. The SAR and early in vivo properties of this series of inhibitors will be presented.

Positive and negative regulation of APP amyloidogenesis by sumoylation.

Amyloid beta peptide (Abeta) generated from amyloid precursor protein (APP) is central to Alzheimer's disease (AD). Signaling pathways affecting APP amyloidogenesis play critical roles in AD pathogenesis and can be exploited for therapeutic intervention. Here, we show that sumoylation, covalent modification of cellular proteins by small ubiquitin-like modifier (SUMO) proteins, regulates Abeta generation. Increased protein sumoylation resulting from overexpression of SUMO-3 dramatically reduces Abeta production. Conversely, reducing endogenous protein sumoylation with dominant-negative SUMO-3 mutants significantly increases Abeta production. We also show that mutant SUMO-3, K11R, which can only be monomerically conjugated to target proteins, has an opposite effect on Abeta generation to that by SUMO-3, which can form polymeric chains on target proteins. In addition, SUMO-3 immunoreactivity is predominantly detected in neurons in brains from AD, Down's syndrome, and nondemented humans. Therefore, polysumoylation reduces whereas monosumoylation or undersumoylation enhances Abeta generation. These findings provide a regulatory mechanism in APP amyloidogenesis and suggest that components in the sumoylation pathway may be critical in AD onset or progression.

Secretion of apolipoprotein E by brain glia requires protein prenylation and is suppressed by statins.

Apolipoprotein E (ApoE) genotype modulates the risk of Alzheimer's disease. ApoE has been shown essential for amyloid beta-peptide fibrillogenesis and deposition, a defining pathological feature of this disease. Because astrocytes and microglia represent the major source of extracellular apoE in brain, we investigated apoE secretion by glia. We determined that protein prenylation is required for apoE release from a continuous microglial cell line, primary mixed glia, and from organotypic hippocampal cultures. Using selective protein prenylation inhibitors, apoE secretion was found to require protein geranylgeranylation. This prenylation involved a protein critical to apoE secretion, not apoE proper. ApoE secretion could also be suppressed by inhibiting synthesis of mevalonate, the precursor to both types of protein prenylation, using hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors (statins). Recent reports have described the beneficial effects of statins on the risk of dementia. Our finding that protein geranylgeranylation is required for apoE secretion in the brain parenchyma provides another contributing mechanism to explain the effective properties of statins against the development of dementia. In this model, statin-mediated inhibition of mevalonate synthesis, an essential reaction in forming geranylgeranyl lipid, would lower extracellular levels of parenchymal apoE. Because apoE has been found necessary for plaque development in transgenic models of Alzheimer's disease, suppressing apoE secretion by statins could reduce plaques and, in turn, improve cognitive function.

Amyloid forming proteases: therapeutic targets for Alzheimer's disease.

Alzheimer's disease is an age-related neurodegenerative disease which causes global loss of cognitive function. Drug treatment for Alzheimer's disease has been limited to agents that ameliorate behavioral symptoms but these agents are without effect on disease progression. Rational drug design for the treatment of Alzheimer's disease now seems possible. As a result of major advances in medical research in this area, knowledge of the etiology of Alzheimer's disease is rapidly being understood. This information has uncovered relevant and novel targets for treatment. At the center of the etiological progression of this disease is beta-amyloid. A substantial body of evidence strongly suggests that this small protein is critical to the development of Alzheimer's disease. The beta-amyloid protein is generated by two different proteolytic cleavages. Recently, the proteases responsible for producing the beta-amyloid protein have been identified. The proteases represent viable targets for therapeutic intervention against Alzheimer's disease. In this review, we describe the biological characteristics of the beta-amyloid-forming proteases in the context of pharmaceutical development.

Structural and functional characterization of the upstream regulatory region of the human gene encoding prostate apoptosis response factor-4.

Prostate apoptosis response factor-4 (Par-4) is critical to cell growth and apoptosis. Induction of Par-4 expression has been shown to be required for apoptosis in a diversity of cellular systems, including neurons. Neuronal populations in individuals with degenerative disorders show elevated levels of Par-4 protein in advance of cellular and functional loss. To understand the regulation of par-4 expression, we isolated and characterized 5.7 kb of the human par-4 promoter. We demonstrated that the isolated promoter was functional. Similar to the endogenous par-4 gene, par-4 expression could be induced upon apoptotic insult with thapsigargin following introduction of the promoter DNA into human A375 cells. Also, increased levels of the atypical protein kinase C, zetaPKC, was shown to negatively regulate expression from the ectopic par-4 promoter. A 550 bp sequence immediately upstream to the 5'-untranslated region of the gene was found to be responsible for par-4 promoter induction to apoptosis by thapsigargin.