Community-Based Approach to Promote Rational Use of Antibiotics in Indonesia: The Development and Assessment of an Education Program for Cadres.

BACKGROUND: Cadres play an important part in providing community-based education. This study developed and assessed an education program for cadres in Malang, Indonesia, as 'change agents' to promote rational antibiotic use. METHODS: In-depth-interviews with stakeholders (N = 55) and a subsequent group discussion with key personnel (N = 5) were conducted to develop a relevant education tool for cadres. This was followed with a pilot study with cadres (N = 40) to assess the effectiveness and acceptability of the new tool. RESULTS: Consensus was reached on the education tool media: an audio-recording (containing full information) with a pocketbook (containing key information) as a supplement. A pilot study on the new tool reported its effectiveness in improving knowledge (p < 0.001) and demonstrated a high acceptability (all respondents stated 'Strongly Agree' or 'Agree' on all statements). CONCLUSION: This study has created a model for an education tool which can potentially be implemented for cadres to educate their communities about antibiotics in the Indonesian context.

Effect of probiotic supplementation on cognitive function in children and adolescents: a systematic review of randomised trials.

Available reviews have shown potential effects of probiotics on neurobehavioral outcomes through 'gut-brain axis' mechanism in adults. However, reviews on cognitive function in children and adolescents are lacking. Therefore, we conducted a systematic review of randomised controlled trials (RCTs) of the effect of probiotic supplementation on cognitive function in children and adolescents. A search of four databases (Cochrane Central Register of Controlled Trials, PsycARTICLES, Scopus, PubMed) was conducted to identify RCTs published from January 1990 to December 2018. Seven studies met the inclusion criteria and their cognitive outcomes were analysed. Only one study found a positive result with Lactobacillus rhamnosus GG (LGG) 1×1010 cfu supplementation with outcomes on attention deficit hyperactivity disorder (ADHD) or Asperger syndrome (AS) manifestations as diagnosed using the International Classification of Diseases-10 criteria. The supplementations were administered to Finnish mothers for 4 weeks before delivery and continuously given for 6 months after delivery if they breastfed, or to the children. ADHD or AS was diagnosed at the age of 13 years in 17.1% children in the placebo and none in the probiotic group (P=0.008). This study found significant differences in species composition and number of cells belonging to the genus Bifidobacterium between healthy children and children who later developed ADHD or AS at different time points. Six remaining studies with varying strains, durations of intervention, start-time of administration, and outcomes demonstrated no difference in cognition after probiotic supplementation. Metagenomic analyses on gut microbiota composition were not performed in any of these studies. In conclusion, the favourable effect of probiotic supplementation on cognitive function in children and adolescents was observed in one study with LGG supplementation by a risk reduction of developing ADHD or AS (i.e. autism). More long-term and follow-up trials using probiotics identifying the effect on cognition are warranted before routine use.

Neuroinflammation in healthy aging: a PET study using a novel Translocator Protein 18kDa (TSPO) radioligand, [(18)F]-FEPPA.

One of the cellular markers of neuroinflammation is increased microglia activation, characterized by overexpression of mitochondrial 18kDa Translocator Protein (TSPO). TSPO expression can be quantified in-vivo using the positron emission tomography (PET) radioligand [(18)F]-FEPPA. This study examined microglial activation as measured with [(18)F]-FEPPA PET across the adult lifespan in a group of healthy volunteers. We performed genotyping for the rs6971 TS.PO gene polymorphism to control for the known variability in binding affinity. Thirty-three healthy volunteers (age range: 19-82years; 22 high affinity binders (HAB), 11 mixed affinity binders (MAB)) underwent [(18)F]-FEPPA PET scans, acquired on the High Resolution Research Tomograph (HRRT) and analyzed using a 2-tissue compartment model. Regression analyses were performed to examine the effect of age adjusting for genetic status on [(18)F]-FEPPA total distribution volumes (VT) in the hippocampus, temporal, and prefrontal cortex. We found no significant effect of age on [(18)F]-FEPPA VT (F (1,30)=0.918; p=0.346), and a significant effect of genetic polymorphism (F (1,30)=8.767; p=0.006). This is the first in-vivo study to evaluate age-related changes in TSPO binding, using the new generation TSPO radioligands. Increased neuroinflammation, as measured with [(18)F]-FEPPA PET was not associated with normal aging, suggesting that healthy elderly individuals may serve as useful benchmark against patients with neurodegenerative disorders where neuroinflammation may be present.

Fetal glucocorticoid exposure and hypothalamo-pituitary-adrenal (HPA) function after birth.

The fetus may be exposed to increased endogenous glucocorticoid or synthetic glucocorticoid in late gestation. Indeed, 7-10% of pregnant women in Europe and North America are treated with synthetic glucocorticoid to promote lung maturation in fetuses at risk of preterm delivery. Such therapy is effective in reducing respiratory complications. However, very little is known about the mechanisms by which synthetic glucocorticoid or prenatal stress influence neurodevelopment in the human, or whether specific time windows of increased sensitivity exist. Glucocorticoids are essential for many aspects of normal brain development. However, there is growing evidence that exposure of the fetal brain to excess glucocorticoid can have lifelong effects on neuroendocrine function and behavior. We have shown that both endogenous glucocorticoid and synthetic glucocorticoid exposure has a number of rapid effects in the fetal brain in late gestation, including modification of neurotransmitter systems and transcriptional machinery. Such fetal exposure permanently alters hypothalamo-pituitary-adrenal (HPA) function in prepubertal, postpubertal, and aging offspring, in a sex-dependent manner. These effects are linked to changes in central glucocorticoid feedback machinery after birth. Prenatal glucocorticoid manipulation also leads to modification of HPA-associated behaviors, brain and organ morphology, as well as altered regulation of other endocrine systems. Permanent changes in endocrine function will have a long-term impact on health, since elevated cumulative exposure to endogenous glucocorticoid is linked to the premature onset of pathologies associated with aging.