Assessment of the impact of a personalised nutrition intervention in impaired glucose regulation over 26 weeks: a randomised controlled trial.

Dietary interventions can reduce progression to type 2 diabetes mellitus (T2DM) in people with non-diabetic hyperglycaemia. In this study we aimed to determine the impact of a DNA-personalised nutrition intervention in people with non-diabetic hyperglycaemia over 26 weeks. ASPIRE-DNA was a pilot study. Participants were randomised into three arms to receive either (i) Control arm: standard care (NICE guidelines) (n = 51), (ii) Intervention arm: DNA-personalised dietary advice (n = 50), or (iii) Exploratory arm: DNA-personalised dietary advice via a self-guided app and wearable device (n = 46). The primary outcome was the difference in fasting plasma glucose (FPG) between the Control and Intervention arms after 6 weeks. 180 people were recruited, of whom 148 people were randomised, mean age of 59 years (SD = 11), 69% of whom were female. There was no significant difference in the FPG change between the Control and Intervention arms at 6 weeks (- 0.13 mmol/L (95% CI [- 0.37, 0.11]), p = 0.29), however, we found that a DNA-personalised dietary intervention led to a significant reduction of FPG at 26 weeks in the Intervention arm when compared to standard care (- 0.019 (SD = 0.008), p = 0.01), as did the Exploratory arm (- 0.021 (SD = 0.008), p = 0.006). HbA1c at 26 weeks was significantly reduced in the Intervention arm when compared to standard care (- 0.038 (SD = 0.018), p = 0.04). There was some evidence suggesting prevention of progression to T2DM across the groups that received a DNA-based intervention (p = 0.06). Personalisation of dietary advice based on DNA did not result in glucose changes within the first 6 weeks but was associated with significant reduction of FPG and HbA1c at 26 weeks when compared to standard care. The DNA-based diet was effective regardless of intervention type, though results should be interpreted with caution due to the low sample size. These findings suggest that DNA-based dietary guidance is an effective intervention compared to standard care, but there is still a minimum timeframe of adherence to the intervention before changes in clinical outcomes become apparent.Trial Registration: www.clinicaltrials.gov.uk Ref: NCT03702465.

Psilocybin reduces low frequency oscillatory power and neuronal phase-locking in the anterior cingulate cortex of awake rodents.

Psilocybin is a hallucinogenic compound that is showing promise in the ability to treat neurological conditions such as depression and post-traumatic stress disorder. There have been several investigations into the neural correlates of psilocybin administration using non-invasive methods, however, there has yet to be an invasive study of the mechanism of action in awake rodents. Using multi-unit extracellular recordings, we recorded local field potential and spiking activity from populations of neurons in the anterior cingulate cortex of awake mice during the administration of psilocybin (2 mg/kg). The power of low frequency bands in the local field potential was found to significantly decrease in response to psilocybin administration, whilst gamma band activity trended towards an increase. The population firing rate was found to increase overall, with just under half of individual neurons showing a significant increase. Psilocybin significantly decreased the level of phase modulation of cells with each neural frequency band except high-gamma oscillations, consistent with a desynchronization of cortical populations. Furthermore, bursting behavior was altered in a subset of cells, with both positive and negative changes in the rate of bursting. Neurons that increased their burst firing following psilocybin administration were highly likely to transition from a phase-modulated to a phase unmodulated state. Taken together, psilocybin reduces low frequency oscillatory power, increases overall firing rates and desynchronizes local neural activity. These findings are consistent with dissolution of the default mode network under psilocybin, and may be indicative of disruption of top-down processing in the acute psychedelic state.

The association between sedentary behaviour, physical activity and type 2 diabetes markers: A systematic review of mixed analytic approaches.

The negative effect of sedentary behaviour on type 2 diabetes markers is established, but the interaction with measures of physical activity is still largely unknown. Previous studies have analysed associations with single-activity models, which ignore the interaction with other behaviours. By including results from various analytical approaches, this review critically summarises the effects of sedentary behaviour on diabetes markers and the benefits of substitutions and compositions of physical activity. Ovid Medline, Embase and Cochrane Library databases were systematically searched. Studies were selected if sedentary behaviour and physical activity were measured by accelerometer in the general population, and if associations were reported with glucose, insulin, HOMA-IR, insulin sensitivity, HbA1c, diabetes incidence, CRP and IL-6. Forty-five studies were included in the review. Conclusive detrimental associations with sedentary behaviour were determined for 2-h insulin (6/12 studies found associations), fasting insulin (15/19 studies), insulin sensitivity (4/6 studies), diabetes (3/4 studies) and IL-6 (2/3 studies). Reallocating sedentary behaviour to light or moderate-to-vigorous activity has a beneficial effect for 2-h glucose (1/1 studies), fasting insulin (3/3 studies), HOMA-IR (1/1 studies) and insulin sensitivity (1/1 studies). Compositional measures of sedentary behaviour were found to affect 2-h glucose (1/1 studies), fasting insulin (2/3 studies), 2-h insulin (1/1 studies), HOMA-IR (2/2 studies) and CRP (1/1 studies). Different analytical methods produced conflicting results for fasting glucose, 2-h glucose, 2-h insulin, insulin sensitivity, HOMA-IR, diabetes, hbA1c, CRP and IL-6. Studies analysing data by quartiles report independent associations between sedentary behaviour and fasting insulin, HOMA-IR and diabetes only for high duration of sedentary time (7-9 hours/day). However, this review could not provide sufficient evidence for a time-specific cut-off of sedentary behaviour for diabetes biomarkers. While substituting sedentary behaviour with moderate-to-vigorous activity brings greater improvements for health, light activity also benefits metabolic health. Future research should elucidate the effects of substituting and combining different activity durations and modalities.

Closed-Loop Implantable Therapeutic Neuromodulation Systems Based on Neurochemical Monitoring.

Closed-loop or intelligent neuromodulation allows adjustable, personalized neuromodulation which usually incorporates the recording of a biomarker, followed by implementation of an algorithm which decides the timing (when?) and strength (how much?) of stimulation. Closed-loop neuromodulation has been shown to have greater benefits compared to open-loop neuromodulation, particularly for therapeutic applications such as pharmacoresistant epilepsy, movement disorders and potentially for psychological disorders such as depression or drug addiction. However, an important aspect of the technique is selection of an appropriate, preferably neural biomarker. Neurochemical sensing can provide high resolution biomarker monitoring for various neurological disorders as well as offer deeper insight into neurological mechanisms. The chemicals of interest being measured, could be ions such as potassium (K+), sodium (Na+), calcium (Ca2+), chloride (Cl-), hydrogen (H+) or neurotransmitters such as dopamine, serotonin and glutamate. This review focusses on the different building blocks necessary for a neurochemical, closed-loop neuromodulation system including biomarkers, sensors and data processing algorithms. Furthermore, it also highlights the merits and drawbacks of using this biomarker modality.

Chorionic villus sampling: a distinctive teratogenic effect on fingers?

BACKGROUND: An increased frequency of major limb malformations, especially terminal transverse limb defects, have been described in several studies of birth defects in children who had been exposed to the prenatal diagnosis procedure known as chorionic villus sampling (CVS). Vascular disruption has been proposed as the mechanism behind the fetal effect. We postulate that this mechanism is more likely to affect one or two middle fingers, rather than all five fingers. A recent report of the frequency of defects in any or all fingers in an unexposed control population enabled us to assess whether CVS is associated with an increased frequency of defects involving one or two fingers, as well as terminal transverse limb defects. METHODS: The frequency of limb-reduction defects affecting one or more fingers or toes, including those with constriction rings and tissue loss, in published studies of 20,236 children who had been exposed to CVS was compared with the frequency in 161,252 newborn infants who had not been exposed to CVS. Children with recognized genetic disorders were excluded. RESULTS: Several aspects of the limb deficiencies were more common in the CVS-exposed infants than in unexposed controls. The former were more likely to have: 1) any type of limb deficiency involving one or more fingers (p < .001); 2) absence/ hypoplasia of two fingers (p < .001); and 3) absence/hypoplasia of all five fingers (p = .015). The absence of the distal portion of the third finger was a distinctive type of limb-reduction defect in CVS-exposed infants. CONCLUSIONS: The occurrence of deficiencies in one or two fingers, including those designated as "amniotic band deformities," are as common as terminal transverse limb defects in CVS-exposed infants, and both are much more common than in unexposed infants. The absence of the distal portion of the third finger, with tapering and stiff joints, appears to be a distinctive effect of exposure to CVS.