"Work with us to make it more accessible". What women with intellectual disabilities want from infant-feeding health resources: an exploratory study.

BACKGROUND: More women with intellectual disabilities are becoming mothers but fewer are known to breastfeed compared with other women. Women with intellectual disabilities are entitled to accessible antenatal and infant feeding information, yet are rarely asked for their views on available resources. This article reports on the final stage of a UK project exploring how women with intellectual disabilities are supported to make infant feeding decisions. The wider project includes a scoping review and interviews with healthcare professionals, here we focus on the voices of the women themselves. METHODS: Four women with an intellectual disability participated in a focus group where they were asked to give their views on the accessibility of currently available infant feeding resources and on alternative representations of infant feeding. All were interested in women's health issues, including infant feeding. Photo-elicitation was used to gather views on videos, bespoke 'Easy Read' material and several alternative representations of infant feeding. A transcription of the discussion was thematically analysed whilst a critical visual analysis was undertaken of the women's preferred images/resources. The study took place in Bristol, UK, during 2022. RESULTS: Two themes were identified from the group discussion: 'The desire for choice' and 'How easy is 'Easy Read'?' The desire for choice was expressed in terms through agreements and disagreements about preferred imagery, differing tastes, and reasons for these preferences. We identified a challenge to 'Easy Read' as a default standard and concerns that some forms of 'Easy Read' can confuse rather than inform. Critical visual analysis identified the importance of the story and social setting of the preferred infant feeding image. CONCLUSIONS: Findings suggest a need for a suite of resources, avoiding the one-size-fits-all approach, including people with an intellectual disability at every stage of the design and production process. Resources should recognise and embrace differences in terms of understanding, visual literacy and cultural taste, as well as being freely available to support women with intellectual disabilities to make informed infant feeding decisions. An accessible film was co-produced, to disseminate the findings from all three stages of the completed project.

Cannabinoid mechanisms contribute to the therapeutic efficacy of the kratom alkaloid mitragynine against neuropathic, but not inflammatory pain.

AIMS: Mitragynine (MG) is an alkaloid found in Mitragyna speciosa (kratom), a plant used to self-treat symptoms of opioid withdrawal and pain. Kratom products are commonly used in combination with cannabis, with the self-treatment of pain being a primary motivator of use. Both cannabinoids and kratom alkaloids have been characterized to alleviate symptoms in preclinical models of neuropathic pain such as chemotherapy-induced peripheral neuropathy (CIPN). However, the potential involvement of cannabinoid mechanisms in MG's efficacy in a rodent model of CIPN have yet to be explored. MAIN METHODS: Prevention of oxaliplatin-induced mechanical hypersensitivity and formalin-induced nociception were assessed following intraperitoneal administration of MG and CB1, CB2, or TRPV1 antagonists in wildtype and cannabinoid receptor knockout mice. The effects of oxaliplatin and MG exposure on the spinal cord endocannabinoid lipidome was assessed by HPLC-MS/MS. KEY FINDINGS: The efficacy of MG on oxaliplatin-induced mechanical hypersensitivity was partially attenuated upon genetic deletion of cannabinoid receptors, and completely blocked upon pharmacological inhibition of CB1, CB2, and TRPV1 channels. This cannabinoid involvement was found to be selective to a model of neuropathic pain, with minimal effects on MG-induced antinociception in a model of formalin-induced pain. Oxaliplatin was found to selectively disrupt the endocannabinoid lipidome in the spinal cord, which was prevented by repeated MG exposure. SIGNIFICANCE: Our findings suggest that cannabinoid mechanisms contribute to the therapeutic efficacy of the kratom alkaloid MG in a model of CIPN, which may result in increased therapeutic efficacy when co-administered with cannabinoids.

Monoacylglycerol Lipase Inhibitor MJN110 Reduces Neuronal Hyperexcitability, Restores Dendritic Arborization Complexity, and Regulates Reward-Related Behavior in Presence of HIV-1 Tat.

While current therapeutic strategies for people living with human immunodeficiency virus type 1 (HIV-1) suppress virus replication peripherally, viral proteins such as transactivator of transcription (Tat) enter the central nervous system early upon infection and contribute to chronic inflammatory conditions even alongside antiretroviral treatment. As demand grows for supplemental strategies to combat virus-associated pathology presenting frequently as HIV-associated neurocognitive disorders (HAND), the present study aimed to characterize the potential utility of inhibiting monoacylglycerol lipase (MAGL) activity to increase inhibitory activity at cannabinoid receptor-type 1 receptors through upregulation of 2-arachidonoylglycerol (2-AG) and downregulation of its degradation into proinflammatory metabolite arachidonic acid (AA). The MAGL inhibitor MJN110 significantly reduced intracellular calcium and increased dendritic branching complexity in Tat-treated primary frontal cortex neuron cultures. Chronic MJN110 administration in vivo increased 2-AG levels in the prefrontal cortex (PFC) and striatum across Tat(+) and Tat(-) groups and restored PFC N-arachidonoylethanolamine (AEA) levels in Tat(+) subjects. While Tat expression significantly increased rate of reward-related behavioral task acquisition in a novel discriminative stimulus learning and cognitive flexibility assay, MJN110 altered reversal acquisition specifically in Tat(+) mice to rates indistinguishable from Tat(-) controls. Collectively, our results suggest a neuroprotective role of MAGL inhibition in reducing neuronal hyperexcitability, restoring dendritic arborization complexity, and mitigating neurocognitive alterations driven by viral proteins associated with latent HIV-1 infection.