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During obstructive sleep apnea, elevation of CO2 during apneas contributes to awakening and restoring airway patency. We previously found that glutamatergic neurons in the external lateral parabrachial nucleus (PBel) containing calcitonin gene related peptide (PBelCGRP neurons) are critical for causing arousal during hypercapnia. However, others found that genetic deletion of serotonin (5HT) neurons in the brainstem also prevented arousal from hypercapnia. To examine interactions between the two systems, we showed that dorsal raphe (DR) 5HT neurons selectively targeted the PBel. Either genetically directed deletion or acute optogenetic silencing of DRSert neurons dramatically increased the latency of mice to arouse during hypercapnia, as did silencing DRSert terminals in the PBel. This effect was mediated by 5HT2a receptors which are expressed by PBelCGRP neurons. Our results indicate that the serotonergic input from the DR to the PBel via 5HT2a receptors is critical for modulating the sensitivity of the PBelCGRP neurons that cause arousal to rising levels of blood CO2.

Optogenetics and chemogenetics are powerful tools, allowing the specific activation or inhibition of targeted neuronal subpopulations. Application of these techniques to sleep and circadian research has resulted in the unveiling of several neuronal populations that are involved in sleep-wake control, and allowed a comprehensive interrogation of the circuitry through which these nodes are coordinated to orchestrate the sleep-wake cycle. In this review, we discuss six recently described sleep-wake and circadian circuits that show promise as therapeutic targets for sleep medicine. The parafacial zone (PZ) and the ventral tegmental area (VTA) are potential druggable targets for the treatment of insomnia. The brainstem circuit underlying rapid eye movement sleep behavior disorder (RBD) offers new possibilities for treating RBD and neurodegenerative synucleinopathies, whereas the parabrachial nucleus, as a nexus linking arousal state control and breathing, is a promising target for developing treatments for sleep apnea. Therapies that act upon the hypothalamic circuitry underlying the circadian regulation of aggression or the photic regulation of arousal and mood pathway carry enormous potential for helping to reduce the socioeconomic burden of neuropsychiatric and neurodegenerative disorders on society. Intriguingly, the development of chemogenetics as a therapeutic strategy is now well underway and such an approach has the capacity to lead to more focused and less invasive therapies for treating sleep-wake disorders and related comorbidities.

Urban poor children have low vegetable consumption due to food insecurities leading to limited access to vegetables. Children's involvement in gardening may improve their vegetable consumption and connection with nature. This qualitative study explored the potential facilitators and barriers related to vegetable consumption and gardening among urban poor children in Kuala Lumpur, Malaysia. Four focus group discussions were conducted among 20 randomly selected children aged 9–12 years, residing in selected low‐cost flats in Kuala Lumpur, Malaysia, from November 2021 to January 2022. Thematic analysis via NVivo software was conducted to analyse the transcripts. Children reported several barriers to eating vegetables, such as disliking taste, sensory and appearance, limited accessibility and vegetable availability at home. Most children felt positive and interested to join gardening. The findings are useful in planning nutrition intervention programmes that incorporate gardening as one of the elements to improve vegetable consumption. [ABSTRACT FROM AUTHOR]

'Sundowning' in dementia and Alzheimer's disease is characterized by early-evening agitation and aggression. While such periodicity suggests a circadian origin, whether the circadian clock directly regulates aggressive behavior is unknown. We demonstrate that a daily rhythm in aggression propensity in male mice is gated by GABAergic subparaventricular zone (SPZGABA) neurons, the major postsynaptic targets of the central circadian clock, the suprachiasmatic nucleus. Optogenetic mapping revealed that SPZGABA neurons receive input from vasoactive intestinal polypeptide suprachiasmatic nucleus neurons and innervate neurons in the ventrolateral part of the ventromedial hypothalamus (VMH), which is known to regulate aggression. Additionally, VMH-projecting dorsal SPZ neurons are more active during early day than early night, and acute chemogenetic inhibition of SPZGABA transmission phase-dependently increases aggression. Finally, SPZGABA-recipient central VMH neurons directly innervate ventrolateral VMH neurons, and activation of this intra-VMH circuit drove attack behavior. Altogether, we reveal a functional polysynaptic circuit by which the suprachiasmatic nucleus clock regulates aggression.

The precise neural circuitry that mediates arousal during sleep apnea is not known. We previously found that glutamatergic neurons in the external lateral parabrachial nucleus (PBel) play a critical role in arousal to elevated CO2 or hypoxia. Because many of the PBel neurons that respond to CO2 express calcitonin gene-related peptide (CGRP), we hypothesized that CGRP may provide a molecular identifier of the CO2 arousal circuit. Here, we report that selective chemogenetic and optogenetic activation of PBelCGRP neurons caused wakefulness, whereas optogenetic inhibition of PBelCGRP neurons prevented arousal to CO2, but not to an acoustic tone or shaking. Optogenetic inhibition of PBelCGRP terminals identified a network of forebrain sites under the control of a PBelCGRP switch that is necessary to arouse animals from hypercapnia. Our findings define a novel cellular target for interventions that may prevent sleep fragmentation and the attendant cardiovascular and cognitive consequences seen in obstructive sleep apnea. VIDEO ABSTRACT.

Background: Anaemia has been identified as a major public health problem that affects both developed and developing countries, including Malaysia. To prevent anaemia, knowledge is a key parameter for changing attitudes and practices. Aim: This present study aims to determine the association of knowledge and practices in preventing nutritional anaemia with anaemia status of urban poor adolescents in Kuala Lumpur, Malaysia. Methods: A total of 209 urban poor adolescents (50.7% males and 49.3% females) aged 10 to 17 years old were recruited from eight low-cost flats (People Housing Programme) in Kuala Lumpur, Malaysia. A self-administered questionnaire was used to assess the sociodemographic characteristics, knowledge and practices in preventing nutritional anaemia. Anaemia status from the haemoglobin level concentration was determined using HemoCue® 201 + hemoglobinometer. Results: The prevalence of anaemia among urban poor adolescents was 58.4%, particularly prevalent among females (p < 0.001) and household size of six and above (p = 0.036). Only 29.2% and 10.0% of them were found to have good levels of knowledge and practices in preventing nutritional anaemia, respectively. Adolescents with high knowledge level tended to be anaemic as compared to poor knowledge level (AOR(95% CI) = 2.20 (1.02, 5.61), p < 0.05) after adjusting for sex, household size and monthly household income. Conclusion: Findings showed high prevalence of anaemia and low levels of knowledge and practices of nutritional anaemia prevention among the urban poor adolescents. Nutrition education and intervention are needed to improve the anaemia status of the urban poor adolescents. [ABSTRACT FROM AUTHOR]