The impact of a produce prescription programme on healthy food purchasing and diabetes-related health outcomes.

OBJECTIVE: To evaluate a Produce Prescription Programme's utilisation and its effects on healthy food purchasing and diabetes control among participants with type 2 diabetes. DESIGN: Prospective cohort study using participants' electronic health records and food transaction data. Participants were categorised as 'Frequent Spenders' and 'Sometimes Spenders' based on utilisation frequency. Multivariate regressions assessed utilisation predictors and programme effects on fruit/vegetable purchasing (spending, expenditure share and variety) and on diabetes-related outcomes (HbA1c, BMI and blood pressure). SETTING: Patients enrolled by clinics in Durham, North Carolina, USA. Participants received $40 monthly for fruits and vegetables at a grocery store chain. PARTICIPANTS: A total of 699 food-insecure participants (353 with diabetes). RESULTS: Being female and older was associated with higher programme utilisation; hospitalisations were negatively associated with programme utilisation. Frequent Spender status was associated with $8·77 more in fruit/vegetable spending (P < 0·001), 3·3 % increase in expenditure share (P = 0·007) and variety increase of 2·52 fruits and vegetables (P < 0·001). For $10 of Produce Prescription Dollars spent, there was an $8·00 increase in fruit/vegetable spending (P < 0·001), 4·1 % increase in expenditure share and variety increase of 2·3 fruits/vegetables (P < 0·001). For the 353 participants with diabetes, there were no statistically significant relationships between programme utilisation and diabetes control. CONCLUSIONS: Programme utilisation was associated with healthier food purchasing, but the relatively short study period and modest intervention prevent making conclusions about health outcomes. Produce Prescription Programmes can increase healthy food purchasing among food-insecure people, which may improve chronic disease care.

Direct activation of G-protein-gated inward rectifying K+ channels promotes nonrapid eye movement sleep.

STUDY OBJECTIVES: A major challenge in treating insomnia is to find effective medicines with fewer side effects. Activation of G-protein-gated inward rectifying K+ channels (GIRKs) by GABAB agonists baclofen or γ-hydroxybutyric acid (GHB) promotes nonrapid eye movement (NREM) sleep and consolidates sleep. However, baclofen has poor brain penetration, GHB possesses abuse liability, and in rodents both drugs cause spike-wave discharges (SWDs), an absence seizure activity. We tested the hypothesis that direct GIRK activation promotes sleep without inducing SWD using ML297, a potent and selective GIRK activator. METHODS: Whole-cell patch-clamp recordings from hypocretin/orexin or hippocampal neurons in mouse brain slices were made to study neuronal excitability and synaptic activity; spontaneous activity, locomotion, contextual and tone-conditioned memory, and novel object recognition were assessed. Electroencephalogram/electromyogram (EEG/EMG) recordings were used to study GIRK modulation of sleep. RESULTS: ML297, like baclofen, caused membrane hyperpolarization, decreased input resistance, and blockade of spontaneous action potentials. Unlike baclofen, ML297 (5-10 µM) did not cause significant depression of postsynaptic excitatory and inhibitory currents (EPSCs-IPSCs), indicating preferential postsynaptic inhibition. ML297 (30 mg/kg, i.p.) inhibited wake activity and locomotion, and preferentially increased NREM sleep without altering EEG delta power, REM sleep, inducing SWDs, or impairing conditioned memory and novel object recognition. CONCLUSIONS: This study finds that direct activation of neuronal GIRK channels modulates postsynaptic membrane excitability and prolongs NREM sleep without changing sleep intensity, inducing SWDs, or impairing memory in rodents. These results suggest that direct GIRK activation with a selective compound may present an innovative approach for the treatment of chronic insomnia.

Analgesic Microneedle Patch for Neuropathic Pain Therapy.

Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain. Local analgesic effects were evaluated in rats by testing behavioral pain sensitivity in response to thermal and mechanical stimuli using neuropathic pain models such as spared-nerve injury and diabetic neuropathy pain, as well as neurogenic inflammatory pain model induced by ultraviolet B (UVB) radiation. Unlike several conventional therapies, the AMN patches produced effective analgesia on neuropathic pain without disturbing the normal nociception and motor function of the rat, resulting from the high specificity of the delivered peptide against CGRP receptors. The AMN patches did not cause skin irritation or systemic side effects. These results demonstrate that dissolvable microneedle patches delivering CGRP antagonist peptide provide an effective, safe, and simple approach to mitigate neuropathic pain with significant advantages over current treatments.

Hypocretin/orexin neurons contribute to hippocampus-dependent social memory and synaptic plasticity in mice.

Hypocretin/orexin (Hcrt)-producing neurons in the lateral hypothalamus project throughout the brain, including to the hippocampus, where Hcrt receptors are widely expressed. Hcrt neurons activate these targets to orchestrate global arousal state, wake-sleep architecture, energy homeostasis, stress adaptation, and reward behaviors. Recently, Hcrt has been implicated in cognitive functions and social interaction. In the present study, we tested the hypothesis that Hcrt neurons are critical to social interaction, particularly social memory, using neurobehavioral assessment and electrophysiological approaches. The validated "two-enclosure homecage test" devices and procedure were used to test sociability, preference for social novelty (social novelty), and recognition memory. A conventional direct contact social test was conducted to corroborate the findings. We found that adult orexin/ataxin-3-transgenic (AT) mice, in which Hcrt neurons degenerate by 3 months of age, displayed normal sociability and social novelty with respect to their wild-type littermates. However, AT mice displayed deficits in long-term social memory. Nasal administration of exogenous Hcrt-1 restored social memory to an extent in AT mice. Hippocampal slices taken from AT mice exhibited decreases in degree of paired-pulse facilitation and magnitude of long-term potentiation, despite displaying normal basal synaptic neurotransmission in the CA1 area compared to wild-type hippocampal slices. AT hippocampi had lower levels of phosphorylated cAMP response element-binding protein (pCREB), an activity-dependent transcription factor important for synaptic plasticity and long-term memory storage. Our studies demonstrate that Hcrt neurons play an important role in the consolidation of social recognition memory, at least in part through enhancements of hippocampal synaptic plasticity and cAMP response element-binding protein phosphorylation.

Rodent motor and neuropsychological behaviour measured in home cages using the integrated modular platform SmartCage™.

1. To facilitate investigation of diverse rodent behaviours in rodents' home cages, we have developed an integrated modular platform, the SmartCage(™) system (AfaSci, Inc. Burlingame, CA, USA), which enables automated neurobehavioural phenotypic analysis and in vivo drug screening in a relatively higher-throughput and more objective manner. 2, The individual platform consists of an infrared array, a vibration floor sensor and a variety of modular devices. One computer can simultaneously operate up to 16 platforms via USB cables. 3. The SmartCage(™) detects drug-induced increases and decreases in activity levels, as well as changes in movement patterns. Wake and sleep states of mice can be detected using the vibration floor sensor. The arousal state classification achieved up to 98% accuracy compared with results obtained by electroencephalography and electromyography. More complex behaviours, including motor coordination, anxiety-related behaviours and social approach behaviour, can be assessed using appropriate modular devices and the results obtained are comparable with results obtained using conventional methods. 4. In conclusion, the SmartCage(™) system provides an automated and accurate tool to quantify various rodent behaviours in a 'stress-free' environment. This system, combined with the validated testing protocols, offers powerful a tool kit for transgenic phenotyping and in vivo drug screening.