CSF proteomic profiling with amyloid/tau positivity identifies distinctive sex-different alteration of multiple proteins involved in Alzheimer's disease.

In Alzheimer's disease (AD), the most common cause of dementia, females have higher prevalence and faster progression, but sex-specific molecular findings in AD are limited. Here, we comprehensively examined and validated 7,006 aptamers targeting 6,162 proteins in cerebral spinal fluid (CSF) from 2,077 amyloid/tau positive cases and controls to identify sex-specific proteomic signatures of AD. In discovery (N=1,766), we identified 330 male-specific and 121 female-specific proteomic alternations in CSF (FDR <0.05). These sex-specific proteins strongly predicted amyloid/tau positivity (AUC=0.98 in males; 0.99 in females), significantly higher than those with age, sex, and APOE-ε4 (AUC=0.85). The identified sex-specific proteins were well validated (r≥0.5) in the Stanford study (N=108) and Emory study (N=148). Biological follow-up of these proteins led to sex differences in cell-type specificity, pathways, interaction networks, and drug targets. Male-specific proteins, enriched in astrocytes and oligodendrocytes, were involved in postsynaptic and axon-genesis. The male network exhibited direct connections among 152 proteins and highlighted PTEN, NOTCH1, FYN, and MAPK8 as hubs. Drug target suggested melatonin (used for sleep-wake cycle regulation), nabumetone (used for pain), daunorubicin, and verteporfin for treating AD males. In contrast, female-specific proteins, enriched in neurons, were involved in phosphoserine residue binding including cytokine activities. The female network exhibits strong connections among 51 proteins and highlighted JUN and 14-3-3 proteins (YWHAG and YWHAZ) as hubs. Drug target suggested biperiden (for muscle control of Parkinson's disease), nimodipine (for cerebral vasospasm), quinostatin and ethaverine for treating AD females. Together, our findings provide mechanistic understanding of sex differences for AD risk and insights into clinically translatable interventions.

Clinical Diagnosis and Management of Fetal Alcohol Spectrum Disorder and Sensory Processing Disorder in Children.

Fetal alcohol spectrum disorder (FASD) is commonly misdiagnosed because of the complexity of presentation and multiple diagnostic criteria. FASD includes four categorical entities (fetal alcohol syndrome, partial fetal alcohol syndrome, alcohol related neurodevelopmental disorder, and alcohol related birth defects). The four FASD diagnostic criteria are facial dysmorphology, growth deficiency, central nervous system dysfunction, and prenatal alcohol exposure. Sensory processing disorders (SPDs) are common in FASD and are observed as inappropriate behavioral responses to environmental stimuli. These can be either a sensory-based motor disorder, sensory discrimination disorder, or sensory modulation disorder. A child with SPD may experience challenges with their fine motor coordination, gross motor coordination, organizational challenges, or behavioral regulation impairments. FASD requires a multidimensional approach to intervention. Although FASD cannot be cured, symptoms can be managed with sleep-based therapies, sensory integration, and cognitive therapies. This paper reviews SPDs in FASD and the interventions that can be used by practitioners to help improve their therapeutic management, although it is unlikely that any single intervention will be the right choice for all patients.

Nutrition Guidelines for Improved Clinical Care.

Given the importance of poor nutrition as a cause for human chronic disease, it is surprising that nutrition receives so little attention during medical school training and in clinical practice. Specific vitamins, minerals, fatty acids, amino acids and water in the diet are essential for health, and deficiencies lead or contribute to many diseases. Proper use of the dietary guidelines and nutrition facts labeling can improve nutritional status and lead to the consumption of a healthy diet. COVID-19 has altered access to nutritious foods for millions and increased awareness of the importance of diet and immune function. An improved appreciation for nutrition will improve the outcomes of clinical care.

Effect of Walnut Predinner Snack on Mealtime Hunger and Nutrient Intake Among University Students.

Freshman-15 is a phenomenon of first-year university students resulting in weight gain partly due to new cafeteria eating patterns and stress. This study determined if a premeal walnut snack alters planned eating behavior and mealtime nutrient intake during a subsequent buffet-model meal. Healthy university students (n = 36; 18.1 ± 0.5 years; body mass index: 23.6 ± 3.9) received three treatments (90 min premeal) in randomized order on 3 consecutive days: (1) snack of 190 Cal (1 oz) of walnuts (WS), (2) snack of 190 Cal of gummy candy (GS), or (3) no snack (NS; control) before a standard cafeteria dinner (1760 Cal). Visual analog scale (VAS) surveys were administered before and after dinner, and caloric intake was determined. Premeal VAS desire to eat was lower after WS and GS than NS, whereas the sense of hunger and sense of fullness were higher after WS and GS compared with NS. Postmeal VAS was not different between treatments. Mealtime calories, total fat, saturated fat, cholesterol, protein, sodium, fiber, and sugar consumed after WS were significantly less than NS. Total fat and sodium consumed after GS did not significantly differ from NS. Mealtime total fat, sodium, and fiber for WS were significantly less than GC, and a trend was observed for total calories. Differences in calorie intake were not observed between treatments when snack calories were included as part of the mealtime caloric intake. These findings could be helpful for promoting WS and to a lesser degree GS for increased satiety before meals possibly leading to reduced food intake during dinner by university students.

Non-Nutritive (Artificial) Sweetener Knowledge among University Students.

This study determined non-nutritive sweetener (NNS; artificial sweetener) depth of knowledge among university health and science students. An online survey was delivered to 1248 science students and completed by 493 respondents (19.0 ± 2.2 years old), evaluating ability to provide an NNS description/definition, examples of NNS from memory, and evaluate NNS word familiarity with a click-drag-box to identify six NNS by chemical name (CN) and six NNS by trade name (TN), relative to six decoy NNS, six caloric sweeteners, and six food items (mean ± standard deviation). NNS definitions contained 1.1 ± 1.1 of four previously defined elements suggestive of knowledge depth, with highest scores among self-described non-NNS users and food ingredient label users. Knowledge depth was not correlated with gender, age, American College Test score, or history of weight loss attempts. Without prompting, respondents could name 0.9 ± 1.1 NNS from memory, with highest scores among self-described non-NNS users (1.4 ± 0.8) and food ingredient label users (1.4 ± 0.8). NNS example memory was not correlated with gender, age, ACT score, or history of weight loss attempts. With the click-drag-box exercise, NNS were correctly identified 4.9 ± 1.0 times by TN and significantly less by CN (3.9 ± 1.9 times). Decoy NNS were incorrectly identified as being a real NNS 4.7 ± 1.3 times, while caloric sweeteners and food items were incorrectly identified as NNS 1.7 ± 1.7 times and 1.0 ± 1.5 times, (TN and Decoy NNS > CN > caloric sweetener and food item). NNS knowledge among university students may be inadequate for understanding what NNS are, if they consume NNS, or whether NNS are important for dietary health.

Urinary Clearance of Cranberry Flavonol Glycosides in Humans.

Cranberry is reported to have health benefits, including prevention of urinary tract infections and other chronic diseases, due to the high content of polyphenols, including flavonols and flavan-3-ols. The aim of this study was to determine the clearance of flavonol glycosides and flavan-3-ols and/or their metabolites in human urine. Ten healthy women volunteers ingested 240 mL of cranberry juice containing flavonol glycosides. Urine samples were collected at 0, 90, 225, and 360 min postingestion. While flavan-3-ols were not detected, five flavonol glycosides common in cranberry were identified. Quercetin-3-galactoside, the most abundant cranberry flavonol, exhibited the highest peak urine concentration (Cmax) of 1315 pg/mg creatinine, followed by quercetin-3-rhamnoside, quercetin-3-arabinoside, myricetin-3-arabinoside, and myricetin-3-galactoside. Quercetin-3-arabinoside showed delayed clearance, Cmax at 237 min (Tmax), relative to other flavonols (90-151 min). Both aglycone and the conjugated sugar moiety structure mediate the flavonol's bioavailability. Interindividual variation for bioavailability and clearance is also apparent. Metabolites, e.g. glucoronides, were not detected.

Prognostic value of resting pulmonary function in heart failure.

BACKGROUND: The heart and lungs are intimately linked anatomically and physiologically, and, as a result, heart failure (HF) patients often develop changes in pulmonary function. This study examined the prognostic value of resting pulmonary function (PF) in HF. METHODS AND RESULTS: In all, 134 HF patients (enrolled from January 1, 1999 Through December 31, 2005; ejection fraction (EF) = 29% ± 11%; mean age = 55 ± 12 years; 65% male) were followed for 67 ± 34 months with death/transplant confirmed via the Social Security Index and Mayo Clinic registry. PF included forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), diffusing capacity of the lungs for carbon monoxide (DLCO), and alveolar volume (VA). Patients were divided in tertiles according to PF with survival analysis via log-rank Mantel-Cox test with chi-square analysis. Groups for FVC included (1) >96%, (2) 96% to 81%, and (3) <81% predicted (chi-square = 18.9, P < 0.001). Bonferroni correction for multiple comparisons (BC) suggested differences between groups 1 and 3 (P < 0.001) and 2 and 3 (P = 0.008). Groups for FEV1 included (1) >94%, (2) 94% to 77%, and (3) <77% predicted (chi-square = 17.3, P <0.001). BC suggested differences between groups 1 and 3 (P <0.001). Groups for DLCO included (1) >90%, (2) 90% to 75%, and (3) <75% predicted (chi-square = 11.9, P = 0.003). BC suggested differences between groups 1 and 3 (P < 0.001). Groups for VA included (1) >97%, (2) 97% to 87%, and (3) <87% predicted (Chi-square = 8.5, P = 0.01). BC suggested differences between groups 1 and 2 (P = 0.014) and 1 and 3 (P = 0.003). CONCLUSIONS: In a well-defined cohort of HF patients, resting measures of PF are predictive of all-cause mortality.

Relaxation breathing improves human glycemic response.

OBJECTIVES: This study evaluated a simple relaxation breathing exercise for acute improvement of postprandial glycemic and insulinemic status. DESIGN: Healthy human subjects were randomized to control breathing (CB; n=13) or a relaxation breathing exercise (RB; n=13) that was repeated every 10 minutes for the 30 minutes before and 90 minutes after consuming a glucose challenge (oral glucose tolerance test; OGTT; 75 g/240 mL). Blood samples were collected before, and 30, 60, and 90 minutes post OGTT for glucose and insulin analysis. RESULTS: Blood glucose at 0 minutes (pre-OGTT), and 30, 60, and 90 minutes post-OGTT with continued RB was 93.7±1.9, 136.5±8.1, 165.7±8.1, and 130.2±6.9 mg/dL, and 97.1±2.4, 173.1±8.4, 158.7±11.1, and 137.1±10.1 with CB, respectively. RB blood glucose was significantly lower at 30 minutes than CB. Glucose area under the curve (AUC) for CB and RB were not significantly different. Plasma insulin for both CB and RB was significantly increased relative to baseline at 30, 60, and 90 minutes. Insulin values for RB tended to be higher than CB at 30 and 60 minutes, although the difference was not statistically significant. Insulin AUC for CB and RB was not significantly different. CONCLUSIONS: Relaxation breathing acutely improves the glycemic response of healthy subjects, and breathing pattern could be important for interpretation of glycemic index measurements.

Geriatric obesity: evaluating the evidence for the use of flavonoids to promote weight loss.

Obesity is a rapidly growing epidemic that now affects approximately 30% of the adult population in the United States. The prevalence of obesity in the geriatric population makes it one of the fastest growing groups due to aging baby boomers. Because of the limited number of available treatments for obese adults, they often turn to supplements and alternative medicine sources to help them lose weight. One such group of supplements contains plant metabolites flavonoids, which includes catechins from tea, quercetin from fruits and vegetables, and isoflavones from soy products. Some flavonoids such as catechins and soy isoflavones can modestly reduce weight. This review examined the clinical evidence for catechins, quercetin, and soy isoflavones for the treatment of obesity and explored the mechanisms of action as related to obesity. Furthermore, flavonoids were evaluated for the treatment of obesity in geriatric populations as well as for safety concerns.

Effect of Red Bull energy drink on cardiovascular and renal function.

Energy drink consumption has been anecdotally linked to the development of adverse cardiovascular effects in consumers, although clinical trials to support this link are lacking. The effects of Red Bull energy drink on cardiovascular and neurologic functions were examined in college-aged students enrolled at Winona State University. In a double-blind experiment where normal calorie and low calorie Red Bull were compared to normal and low calorie placebos, no changes in overall cardiovascular function nor blood glucose (mg/dL) were recorded in any participant (n = 68) throughout a 2-h test period. However, in the second experiment, nine male and twelve female participants subjected to a cold pressor test (CPT) before and after Red Bull consumption showed a significant increase in blood sugar levels pre- and post Red Bull consumption. There was a significant increase in diastolic blood pressure of the male volunteers immediately after submersion of the hand in the 5 degrees C water for the CPT. Under the influence of Red Bull, the increase in diastolic pressure for the male participants during the CPT was negated. There were no significant changes in the blood pressure of the female participants for the CPT with or without Red Bull. Finally, the CPT was used to evaluate pain threshold and pain tolerance before and after Red Bull consumption. Red Bull consumption was associated with a significant increase in pain tolerance in all participants. These findings suggest that Red Bull consumption ameliorates changes in blood pressure during stressful experiences and increases the participants' pain tolerance.

Glycemic responses to sweetened dried and raw cranberries in humans with type 2 diabetes.

This study assessed the metabolic response to sweetened dried cranberries (SDC), raw cranberries (RC), and white bread (WB) in humans with type 2 diabetes. Development of palatable cranberry preparations associated with lower glycemic responses may be useful for improving fruit consumption and glycemic control among those with diabetes. In this trial, type 2 diabetics (n= 13) received WB (57 g, 160 cal, 1 g fiber), RC (55 g, 21 cal, 1 g fiber), SDC (40 g, 138 cal, 2.1 g fiber), and SDC containing less sugar (SDC-LS, 40 g, 113 cal, 1.8 g fiber + 10 g polydextrose). Plasma glucose (mmol/L) peaked significantly at 60 min for WB, and at 30 min for RC, SDC, and SDC-LS at 9.6 ± 0.4, 7.0 ± 0.4, 9.6 ± 0.5, and 8.7 ± 0.5, respectively, WB remained significantly elevated from the other treatments at 120 min. Plasma insulin (pmol/mL) peaked at 60 min for WB and SDC and at 30 min for RC and SDC-LS at 157 ± 15, 142 ± 27, 61 ± 8, and 97 ± 11, respectively. Plasma insulin for SDC-LS was significantly lower at 60 min than either WB or SDC. Insulin area under the curve (AUC) values for RC and SDC-LS were both significantly lower than WB or SDC. Phenolic content of SDC and SDC-LS was determined following extraction with 80% acetone prior to high-performance liquid chromatography (HPLC) and electronspray ionization-mass spectrometry (ESI-MS) and found to be rich in 5-caffeoylquinic cid, quercetin-3-galactoside, and quercetin-3-galactoside, and the proanthocyanidin dimer epicatechin. In conclusion, SDC-LS was associated with a favorable glycemic and insulinemic response in type 2 diabetics. Practical Application: This study compares phenolic content and glycemic responses among different cranberry products. The study seeks to expand the palatable and portable healthy food choices for persons with type 2 diabetes. The novel use of polydextrose as a bulking agent making possible a reduction in caloric content and potential glycemic response is also characterized in this study.

Advising consumers about dietary supplements: lessons from cranberry products.

Consumers are continuing to incorporate dietary supplements as part of their routine health care. Yet, even as the market continues to grow, questions regarding safety, efficacy, and quality remain. Clinicians are increasingly being asked to advise their patients about the safe and efficacious use of such products. Cranberry is a commonly encountered supplement that has been studied comprehensively. We review some of the findings from the evaluation of cranberry as a dietary supplement and suggest how such findings can be shared effectively with patients and consumers.

Human glycemic response and phenolic content of unsweetened cranberry juice.

This cross-sectional study determined the phenolic composition of an over-the-counter cranberry juice (CBJ) with high-performance liquid chromatography and examined the effects of low- and normal-calorie CBJ formulations on the postprandial glycemic response in healthy humans. The CBJ used in this study contained seven phenolic acids, with 3- and 5-caffeoylquinic acid being the primary components, and 15 flavonol glycosides, with myricetin-3-galactoside and quercetin-3-galactoside being the most prevalent. CBJ proanthocyanidins consisted of three different tetramers and a heptamer, which were confirmed with matrix-assisted laser desorption ionization-time of flight-mass spectrometry analysis. Participants received one of the following six treatments: nothing (no water/beverage), water (480 mL), unsweetened low-calorie CBJ (38 Cal/480 mL), normal-calorie CBJ (280 Cal/480 mL), isocaloric normal calorie (high fructose corn syrup [HFCS]), or isocaloric low-calorie beverages. No significant differences in postprandial blood glucose or insulin were observed in the groups receiving nothing, water, or low-calorie treatments. In contrast, the ingestion of normal-calorie CBJ and normal-calorie control beverage resulted in significantly higher blood glucose concentrations 30 minutes postprandially, although the differences were no longer significant after 180 minutes. Plasma insulin of normal-calorie CBJ and control (HFCS) recipients was significantly higher 60 minutes postprandially, but not significantly different 120 minutes postprandially. CBJ ingestion did not affect heart rate or blood pressure. This study suggests that the consumption of a low-calorie CBJ rich in previously uncharacterized trimer and heptamer proanthocyanidins is associated with a favorable glycemic response and may be beneficial for persons with impaired glucose tolerance.

Effects of low carbohydrate diets high in red meats or poultry, fish and shellfish on plasma lipids and weight loss.

BACKGROUND: Low carbohydrate diets (LCDs) have been demonstrated to be effective tools for promoting weight loss and an improved plasma lipid profile. Such diets are often associated with increased meat consumption, either poultry, fish, and shellfish (PFS), which are generally high in polyunsaturated fat (PUFA) or red meats (RM), generally high in saturated fat (SFA). The fatty acid profile and content of a diet may influence the plasma lipid profile of humans. This study examined whether the type of meat consumed could influence the outcome of an LCD. METHODS: Moderately obese subjects consumed two different LCDs as part of a weight loss regimen: 1) a diet high in foods of mammalian origin (RM) intended to contain more SFA, or 2) a diet high in PFS intended to contain more PUFA. Diet dependent changes in body weight, nutritional intake, and plasma lipids were evaluated during a 28 day study period. RESULTS: Both diets were associated with significant weight loss after 28 days, -5.26 +/- 0.84 kg and -5.74 +/- 0.63 kg for RM and PFS groups, respectively. The PFS diet was associated with a significantly higher intake of PUFA and cholesterol. Despite high cholesterol and fat intakes, neither diet was associated with significant changes in plasma cholesterol or the plasma lipoprotein cholesterol profile. While plasma triglycerides were reduced in both groups, the effect was only statistically significant for the PFS diet.

Reading the tea leaves: anticarcinogenic properties of (-)-epigallocatechin-3-gallate.

Green tea is an extremely popular beverage worldwide. Derivatives of green tea, particularly (-)-epigallocatechin-3-gallate (EGCG), have been proposed to have anticarcinogenic properties based on preclinical, observational, and clinical trial data. To summarize, clarify, and extend current knowledge, we conducted a comprehensive search of the PubMed database and other secondary data sources, as appropriate, regarding the chemopreventive potential of EGCG. Apparently, EGCG functions as an antioxidant, preventing oxidative damage in healthy cells, but also as an antiangiogenic agent, preventing tumors from developing a blood supply needed to grow larger. Furthermore, EGCG may stimulate apoptosis in cancerous cells by negatively regulating the cell cycle to prevent continued division. Finally, EGCG exhibits antibacterial activity, which may be implicated in the prevention of gastric cancer. Although in vitro research of the anticarcinogenic properties of EGCG seems promising, many diverse and unknown factors may influence its in vivo activity in animal and human models. Some epidemiological studies suggest that green tea compounds could protect against cancer, but existing data are inconsistent, and limitations in study design hinder full interpretation and generalizability of the published observational findings. Several clinical trials with green tea derivatives are ongoing, and further research should help to clarify the clinical potential of EGCG for chemoprevention and/or chemotherapy applications.

The GRR1 gene of Candida albicans is involved in the negative control of pseudohyphal morphogenesis.

The opportunistic fungal pathogen Candida albicans can grow as yeast, pseudohyphae or true hyphae. C. albicans can switch between these morphologies in response to various environmental stimuli and this ability to switch is thought to be an important virulence trait. In Saccharomyces cerevisiae, the Grr1 protein is the substrate recognition component of an SCF ubiquitin ligase that regulates cell cycle progression, cell polarity and nutrient signaling. In this study, we have characterized the GRR1 gene of C. albicans. Deletion of GRR1 from the C. albicans genome results in a highly filamentous, pseudohyphal morphology under conditions that normally promote the yeast form of growth. Under hypha-inducing conditions, most cells lacking GRR1 retain a pseudohyphal morphology, but some cells appear to switch to hyphal-like growth and express the hypha-specific genes HWP1 and ECE1. The C. albicans GRR1 gene also complements the elongated cell morphology phenotype of an S. cerevisiae grr1Delta mutant, indicating that C. albicans GRR1 encodes a true orthologue of S. cerevisaie Grr1. These results support the hypothesis that the Grr1 protein of C. albicans, presumably as the F-box subunit of an SCF ubiquitin ligase, has an essential role in preventing the switch from the yeast cell morphology to a pseudohyphal morphology.

Transgenic corn for control of the European corn borer and corn rootworms: a survey of Midwestern farmers' practices and perceptions.

In 2001, a self-administered questionnaire was sent to 1000 corn, Zea mays L., farmers in each of five states (Illinois, Indiana, Iowa, Minnesota, and Nebraska) to evaluate their perceptions of transgenic corn designed to control the European corn borer, Ostrinia nubilalis (Hübner), and corn rootworms, Diabrotica spp. Respondents returned 1,313 surveys (26.2%). Farmers with small acreages planted a greater portion of their corn (54.5%) with transgenic corn for control of European corn borer than farmers with large farms (39.2%). The majority (75.2%) of farmers use crop rotation to control the corn rootworm. Nine insecticides comprised 92.2% of the commercial soil insecticides used for control of corn rootworm larvae. More than one-third of the farmers in Illinois (33.5%) and Indiana (39.4%) treated first-year corn for corn rootworm, primarily due to western corn rootworm egg laying in soybean, Glycine max (L.). When asked whether they would plant transgenic corn protected against the corn rootworm, 35.0% of farmers responded they would, whereas 40.5% said they were unsure. The two greatest farmer concerns about transgenic corn were the ability to sell harvested grain (59.3%) and additional technology fees (54.8%). Respondents indicated that less farmer exposure to insecticide (69.9%) and less insecticide in the environment (68.5%) were the primary benefits of transgenic corn. Farmers who had no concerns about transgenic corn for rootworm control were more likely to purchase the product (46.8%). The most common refuge-planting options farmers favored were adjacent fields (30.9%) and split fields (29.9%). Farmers (21.1%) observed a yield increase (23.7 bu/ha [9.6 bu/acre]) when using transgenic corn for European corn borer control compared with non-transgenic corn. These data can help in understanding farmers' knowledge and concerns regarding transgenic corn. This information may be of value to guide researchers, extension specialists, and policy makers in designing insect resistance management and integrated pest management programs.