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Background: Parenting interventions in humanitarian settings have prioritized the acquisition of parenting knowledge and skills, while overlooking the adverse effects of stress and distress on parenting—a key mediator of refugee children's mental health. We evaluated the effectiveness of the Caregiver Support Intervention (CSI), which emphasizes caregiver wellbeing together with training in positive parenting. Methods: We conducted a two‐arm randomized controlled trial of the CSI with Syrian refugees in Lebanon, with an intent‐to‐treat design, from September 2019–December 2020. A total of 480 caregivers from 240 families were randomized to the CSI or a waitlist control group (1:1). Retention from baseline to endline was 93%. Data on parenting and caregiver psychological wellbeing were collected at baseline, endline, and three‐month follow‐up. Prospective trial registration: ISRCTN22321773. Results: We did not find a significant change on overall parenting skills at endline (primary outcome endpoint) (d =.11, p =.126) or at follow‐up (Cohen's d =.15, p =.054). We did find a significant effect on overall parenting skills among participants receiving the full intervention—the sub‐sample not interrupted by (COVID‐19) (d = 0.25, p <.05). The CSI showed beneficial effects in the full sample at endline and follow‐up on harsh parenting (d = −.17, p <.05; d =.19, p <.05), parenting knowledge (d =.63, p <.001; d =.50, p <.001), and caregiver distress (d = −.33, p <.001; d =.23, p <.01). We found no effects on parental warmth and responsiveness, psychosocial wellbeing, stress, or stress management. Changes in caregiver wellbeing partially mediated the impact of the CSI on harsh parenting, accounting for 37% of the reduction in harsh parenting. Conclusions: The CSI reduced harsh parenting and caregiver distress, and demonstrated the value of addressing caregiver wellbeing as a pathway to strengthening parenting in adversity. These effects were achieved despite a pandemic‐related lockdown that impacted implementation, a severe economic crisis, and widespread social unrest. Replication under less extreme conditions may more accurately demonstrate the intervention's full potential. [ABSTRACT FROM AUTHOR]

Background. There is robust evidence that compromised parenting, stemming from persistently high stress, mediates the impact of war and displacement on children's mental health and psychosocial wellbeing. Parenting interventions generally prioritize the acquisition of parenting knowledge and skills, while under-attending to parental stress and distress. This paper describes the development of the Caregiver Support Intervention (CSI), a nine-session group intervention for conflict-affected parents of children aged 3-13, that aims to strengthen parenting both indirectly, by lowering stress and improving psychosocial wellbeing among parents, and directly, by increasing knowledge and skill related to positive parenting. Methods. We describe the multi-phase, iterative process by which we developed the CSI, and illustrate the essential role of community input in shaping the intervention and strengthening its cultural fit and perceived usefulness. We used focus group data from participants in successive cycles of implementation, feedback, and revision, as well as quantitative data and expert consultation to develop a culturally and empirically grounded intervention. Results. This mixed-method, iterative approach to intervention development enabled us to develop a psychosocial intervention for conflict-affected caregivers that is feasible, acceptable, and perceived by participants as useful in addressing their own wellbeing and their parenting. Focus group data support the underlying model in which caregiver wellbeing powerfully influences parenting. Conclusions. Programs aimed at strengthening parenting in conflict-affected communities should substantively address caregiver wellbeing. An iterative approach incorporating community feedback can help ensure intervention acceptability and feasibility. We also illustrate the feasibility of involving men in parenting interventions. [ABSTRACT FROM AUTHOR]

Glutamate is a neurotransmitter used at both the peripheral and central terminals of nociceptive primary sensory neurons, yet little is known concerning regulation of glutamate metabolism during peripheral inflammation. Glutaminase (GLS) is an enzyme of the glutamate-glutamine cycle that converts glutamine into glutamate for neurotransmission and is implicated in producing elevated levels of glutamate in central and peripheral terminals. A potential mechanism for increased levels of glutamate is an elevation in GLS expression. We assessed GLS expression after unilateral hind paw inflammation by measuring GLS immunoreactivity (ir) with quantitative image analysis of L4 dorsal root ganglion (DRG) neurons after one, two, four, and eight days of adjuvant-induced arthritis (AIA) compared to saline injected controls. No significant elevation in GLS-ir occurred in the DRG ipsilateral to the inflamed hind paw after one or two days of AIA. After four days AIA, GLS-ir was elevated significantly in all sizes of DRG neurons. After eight days AIA, GLS-ir remained elevated in small (<400 µm²), presumably nociceptive neurons. Western blot analysis of the L4 DRG at day four AIA confirmed the elevated GLS-ir. The present study indicates that GLS expression is increased in the chronic stage of inflammation and may be a target for chronic pain therapy. [ABSTRACT FROM AUTHOR]

Background: Four decades of war, political upheaval, economic deprivation and forced displacement have profoundly affected both in-country and refugee Afghan populations., Aims: We reviewed literature on mental health and psychosocial well-being, to assess the current evidence and describe mental healthcare systems, including government programmes and community-based interventions., Method: In 2022, we conducted a systematic search in Google Scholar, PTSDpubs, PubMed and PsycINFO, and a hand search of grey literature ( N = 214 papers). We identified the main factors driving the epidemiology of mental health problems, culturally salient understandings of psychological distress, coping strategies and help-seeking behaviours, and interventions for mental health and psychosocial support., Results: Mental health problems and psychological distress show higher risks for women, ethnic minorities, people with disabilities and youth. Issues of suicidality and drug use are emerging problems that are understudied. Afghans use specific vocabulary to convey psychological distress, drawing on culturally relevant concepts of body-mind relationships. Coping strategies are largely embedded in one's faith and family. Over the past two decades, concerted efforts were made to integrate mental health into the nation's healthcare system, train cadres of psychosocial counsellors, and develop community-based psychosocial initiatives with the help of non-governmental organisations. A small but growing body of research is emerging around psychological interventions adapted to Afghan contexts and culture., Conclusions: We make four recommendations to promote health equity and sustainable systems of care. Interventions must build cultural relevance, invest in community-based psychosocial support and evidence-based psychological interventions, maintain core mental health services at logical points of access and foster integrated systems of care.

Glutamate is an excitatory neurotransmitter, produced by its synthetic enzyme, glutaminase (GLS), and packaged by vesicular transporters (VGluT2) into synaptic vesicles. Primary sensory peripheral nerve and spinal synaptic terminals release glutamate during nociceptive (pain) signaling. In post-incisional and inflammation models in rats, GLS and VGluT2 production is elevated in dorsal root ganglion neuronal cell bodies and transported to peripheral and spinal terminals for increased glutamate synthesis and release. 6-Diazo-5-oxo-l-norleucine (DON) is a GLS inhibitor that produces long lasting pain relief when applied to the inflamed paw of arthritic rats, but its effect in a post-incisional model has not been evaluated. In this study, we examined the analgesic efficacy of DON in a surgical incision model by measuring thermal latency and mechanical allodynia. Following behavioral evaluation, we examined the skin for VGluT2, GLS and glutamate immunoreactivity (ir). Our findings revealed that VGluT2-ir is elevated in the stratum lucidum by approximately 19%, 64 hours post-surgical incision and attenuated by approximately 5.4% after the administration of DON. During that same period GLS-ir was elevated in dermal nerve fibers by 52% and was attenuated by approximately 27.9% after the application of DON. Additionally, glutamate-ir was elevated in epidermal nerve fibers by 35% after incision and attenuated by approximately 23% after the administration of DON. Behavioral testing 24 and 48 hours after a single local administration of DON showed five out of six animals having an analgesic response to mechanical allodynia, but not to thermal hyperalgesia. Following a surgical incision, the area of injury shows increased VGluT2-, GLS-, glutamate-ir, mechanical allodynia and no change in thermal latency. After the application of the GLS inhibitor, DON, nerve fiber of the skin showed decreased VGluT2, GLS, and glutamate-ir. Furthermore, post-incision DON treated animals exhibited decreased mechanical allodynia with no change in thermal latency when compared to control animals.

Glutamate is an excitatory neurotransmitter, released by primary sensory peripheral nerve and spinal synaptic terminals during nociceptive (pain) signaling. The primary source of neurotransmitter, glutamate, is provided from its synthetic enzyme, glutaminase (GLS). Neurotransmitter glutamate is packaged into synaptic vesicles in nociceptive neurons by the vesicular glutamate transporter 2 (VGluT2). Little is known, however, what effect a surgical incision has on GLS and VGluT2 in primary afferent neurons. In this study, an aseptic, midline incision in the proximal one-third of the rat-tail was examined to determine whether sacral dorsal root ganglia innervate the area of surgical incision, utilizing the retrograde tracer Fluoro-Gold™. Subsequently, the amount of VGluT2 and GLS immunoreactivity (IR) in sacral dorsal root ganglia (DRG) was evaluated using immunofluorescence with image analysis and Western immunoblotting with density analysis. GLS messenger RNA (mRNA) changes were evaluated using real-time reverse transcriptase polymerase chain reaction (RT 2 -PCR). Our findings revealed that sacral-1 (S 1 ) DRG neurons innervate the area of surgical incision. Both GLS and VGluT2-ir are elevated post-surgical incision in S 1 DRG neurons for up to 72 hours, while GLS mRNA levels rapidly decreased post-incision and remain depressed for at least 96 hours. Following a surgical incision of the tail, sacral DRGs rapidly deplete their available supply of GLS mRNA and alter their production of the synthetic enzyme, GLS and the vesicular transporter, VGluT2. The rapid use of GLS mRNA and subsequent elevation of GLS protein, along with VGluT2 protein may result in both increased glutamate production and release at peripheral and central processes contributing to primary and secondary sensitization, respectively., Competing Interests: Authors have no conflicts of interest.

6-diazo-5-oxo-l-norleucine (DON) is a glutamine antagonist produced naturally by Streptomyces . It inhibits several glutamine-dependent enzyme pathways. Of particular note is its inhibitory effect on the mitochondrial enzyme, glutaminase (GLS), the primary producer of neuronal glutamate. Glutamate is an excitatory neurotransmitter released by primary sensory peripheral nerve terminals and spinal synaptic terminals during pain signaling. Previous work using the tail incision and inflammatory models of pain has demonstrated that a single application of the glutaminase inhibitor, DON, into a surgical incision or the paw of arthritic animals results in pain relief. Even though this compound shows promise as a therapeutic agent, limited data exist regarding its dermal toxicity. As a first approach, we evaluated the effect of several concentrations of DON, on the viability, mitochondrial oxidative capacity and proliferation of rat skin fibroblasts, and then examined the effect of DON after incubation with human liver microsomes on proliferation. Finally, we evaluated DON treated rat skin (tail and hind paw) for cellular necrosis, inflammation and mitotic bodies. No significant effects (p > 0.05) of DON were noted on apoptosis, necrosis, and mitochondrial activity in experiments with cultured rat skin fibroblasts. Flow cytometry revealed the absence of apoptosis in cells treated at the IC 50 of 232.5 μM. Enhanced toxicity post-exposure to human microsomes was not observed when compared to DON alone. The H&E staining of the rat skin revealed no obvious pathology in the DON treatment group (10 mM). DON has no/minimal cellular toxicity in vitro on dermal fibroblasts at concentrations that effectively provide analgesia. The local application of concentrations greater than the in vitro IC 50 for DON revealed no in vivo skin toxicity. These data provide results indicating zero-to-minimal cellular toxicity with DON and support the further investigation of DON as an analgesic., Competing Interests: Authors have no conflicts of interest.