Type-2-diabetes alters CSF but not plasma metabolomic and AD risk profiles in vervet monkeys

Epidemiological studies suggest that individuals with type 2 diabetes (T2D) have a twofold to fourfold increased risk for developing Alzheimer's disease (AD), however, the exact mechanisms linking the two diseases are unknown. In both conditions, the majority of pathophysiological changes, including glucose and insulin dysregulation, insulin resistance, and AD-related changes in Aβ and tau, occur decades before the onset of clinical symptoms and diagnosis. In this study, we investigated the relationship between metabolic biomarkers associated with T2D and amyloid pathology including Aβ levels, from cerebrospinal fluid (CSF) and fasting plasma of healthy, pre-diabetic (PreD), and T2D vervet monkeys (Chlorocebus aethiops sabaeus). Consistent with the human disease, T2D monkeys have increased plasma and CSF glucose levels as they transition from normoglycemia to PreD and diabetic states. Although plasma levels of acylcarnitines and amino acids remained largely unchanged, peripheral hyperglycemia correlated with decreased CSF acylcarnitines and CSF amino acids, including branched chain amino acid (BCAA) concentrations, suggesting profound changes in cerebral metabolism coincident with systemic glucose dysregulation. Moreover, CSF Aβ 40 and CSF Aβ 42 levels decreased in T2D monkeys, a phenomenon observed in the human course of AD which coincides with increased amyloid deposition within the brain. In agreement with previous studies in mice, CSF Aβ 40 and CSF Aβ 42 were highly correlated with CSF glucose levels, suggesting that glucose levels in the brain are associated with changes in Aβ metabolism. Interestingly, CSF Aβ 40 and CSF Aβ 42 levels were also highly correlated with plasma but not CSF lactate levels, suggesting that plasma lactate might serve as a potential biomarker of disease progression in AD. Moreover, CSF glucose and plasma lactate levels were correlated with CSF amino acid and acylcarnitine levels, demonstrating alterations in cerebral metabolism occurring with the onset of T2D. Together, these data suggest that peripheral metabolic changes associated with the development of T2D produce alterations in brain metabolism that lead to early changes in the amyloid cascade, similar to those observed in pre-symptomatic AD

Genome-Wide Interaction Analyses of Serum Calcium on Ventricular Repolarization Time in 125 393 Participants

Background: Ventricular repolarization time (ECG QT and JT intervals) is associated with malignant arrhythmia. Genome-wide association studies have identified 230 independent loci for QT and JT; however, 50% of their heritability remains unexplained. Previous work supports a causal effect of lower serum calcium concentrations on longer ventricular repolarization time. We hypothesized calcium interactions with QT and JT variant associations could explain a proportion of the missing heritability. Methods and Results: We performed genome-wide calcium interaction analyses for QT and JT intervals. Participants were stratified by their calcium level relative to the study distribution (top or bottom 20%). We performed a 2-stage analysis (genome-wide discovery [N=62 532] and replication [N=59 861] of lead variants) and a single-stage genome-wide meta-analysis (N=122 393, [European ancestry N=117 581, African ancestry N=4812]). We also calculated 2-degrees of freedom joint main and interaction and 1-degree of freedom interaction P values. In 2-stage and single-stage analyses, 50 and 98 independent loci, respectively, were associated with either QT or JT intervals (2-degrees of freedom joint main and interaction P value <5x10(-8)). No lead variant had a significant interaction result after correcting for multiple testing and sensitivity analyses provided similar findings. Two loci in the single-stage meta-analysis were not reported previously (SPPL2B and RFX6). Conclusions: We have found limited support for an interaction effect of serum calcium on QT and JT variant associations despite sample sizes with suitable power to detect relevant effects. Therefore, such effects are unlikely to explain a meaningful proportion of the heritability of QT and JT, and factors including rare variation and other environmental interactions need to be considered

Knowledge of Bovine Tuberculosis, Cattle Husbandry and Dairy Practices amongst Pastoralists and Small-Scale Dairy Farmers in Cameroon

BACKGROUND:Control of bovine tuberculosis (bTB) and zoonotic tuberculosis (zTB) has relied upon surveillance and slaughter of infected cattle, milk pasteurisation and public health education. In Cameroon, like many other sub-Saharan African countries, there is limited understanding of current cattle husbandry or milk processing practices or livestock keepers awareness of bTB. This paper describes husbandry and milk processing practices within different Cameroonian cattle keeping communities and bTB awareness in comparison to other infectious diseases. STUDY DESIGN:A population based cross-sectional sample of herdsmen and a questionnaire were used to gather data from pastoralists and dairy farmers in the North West Region and Vina Division of Cameroon. RESULTS:Pastoralists were predominately male Fulanis who had kept cattle for over a decade. Dairy farmers were non-Fulani and nearly half were female. Pastoralists went on transhumance with their cattle and came into contact with other herds and potential wildlife reservoirs of bTB. Dairy farmers housed their cattle and had little contact with other herds or wildlife. Pastoralists were aware of bTB and other infectious diseases such as foot-and-mouth disease and fasciolosis. These pastoralists were also able to identify clinical signs of these diseases. A similar proportion of dairy farmers were aware of bTB but fewer were aware of foot-and-mouth and fasciolosis. In general, dairy farmers were unable to identify any clinical signs for any of these diseases. Importantly most pastoralists and dairy farmers were unaware that bTB could be transmitted to people by consuming milk. CONCLUSIONS:Current cattle husbandry practices make the control of bTB in cattle challenging especially in mobile pastoralist herds. Routine test and slaughter control in dairy herds would be tractable but would have profound impact on dairy farmer livelihoods. Prevention of transmission in milk offers the best approach for human risk mitigation in Cameroon but requires strategies that improved risk awareness amongst producers and consumers

Assessment of Tertiary Education Readiness of the Pioneering Senior High School Graduates in a Private Higher Education Institution in Northern Mindanao, Philippines

Secondary school graduates entering tertiary education must possess the skills and knowledge to adapt rapidly to the ever-changing landscape of a knowledge-based economy. This study assessed the cognitive and non-cognitive college readiness levels of the 127 pioneering senior high school graduates of the Philippine K-12 Program enrolled as first-year college students in a private Higher Education Institution (HEI) in Northern Mindanao, Philippines. Data gathered for this descriptive research were collected using two standardized tests (OLSAT and 16PF). Results revealed that many students had a below-average cognitive level and average non-cognitive skills implying that they were not ready for the tertiary level cognitively but were college-prepared non-cognitively. It was concluded that assessing students' college readiness levels proved imperative to ensure that standards of the chosen programs are met vis-à-vis students' skills. The researchers recommend that Higher Education Institutions strengthen and institutionalize readiness assessment that will serve as a basis for bridging and remediation program for identified cognitively unprepared college students

Training considerations for optimising endurance development: an alternate concurrent training perspective

Whilst the "acute hypothesis" was originally coined to describe the detrimental effects of concurrent training on strength development, similar physiological processes may occur when endurance training adaptations are compromised. There is a growing body of research indicating that typical resistance exercises impair neuromuscular function and endurance performance during periods of resistance training-induced muscle damage. Furthermore, recent evidence suggests that the attenuating effects of resistance training-induced muscle damage on endurance performance are influenced by exercise intensity, exercise mode, exercise sequence, recovery and contraction velocity of resistance training. By understanding the influence that training variables have on the level of resistance training-induced muscle damage and its subsequent attenuating effects on endurance performance, concurrent training programs could be prescribed in such a way that minimises fatigue between modes of training and optimises the quality of endurance training sessions. Therefore, this review will provide considerations for concurrent training prescription for endurance development based on scientific evidence. Furthermore, recommendations will be provided for future research by identifying training variables that may impact on endurance development as a result of concurrent training

Attitudes of parents towards the immunization of their children in Sampaloc II, Dasmarinas City, Cavite.

The focus of the study is to determine the attitude of parents in Sampaloc II, Dasmariñas City, Cavite towards the immunization of their children in view of the three (3) domains of attitude - affective, behavioral, and cognitive. The respondents were parents of children ages 6-12 years old. Demographic variables were age, civil status, educational attainment, and monthly family income. Descriptive survey method using a validated self-made tool was utilized to determine the respondents\u27 attitude. Using quota sampling method, questionnaire was personally handed by the researchers to 362 respondents. The respondents are those who were the most involved parent of children 6 to 12 years old in their child\u27s immunization. Percentage, mean, and ANOVA were the statistical measures used in the study. The study concluded that majority of the respondents were young adults, married, attained high school level, and belonged to low economic status; the attitude of the respondents towards immunization was positive when categorized among domains, namely affective, behavioral, and cognitive, and cognitive. Therefore, the parents had a favourable disposition when it comes to their child\u27s immunization. Regardless of age, civil status, educational attainment, and monthly family income the respondents had the same attitude towards their child’s immunization