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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 evidence that chronic stress negatively impacts parenting among refugees and other war-affected communities. Persistent parental stress and distress may lead to unresponsive, anxious, or overly harsh parenting and a corresponding increase in emotional and behavior problems among children. Most parenting interventions emphasize the acquisition of knowledge and skills; however, this overlooks the deleterious effects of chronic stress on parenting. The Caregiver Support Intervention (CSI) aims to strengthen quality of parenting skills by lowering stress and improving psychosocial wellbeing among refugee caregivers of children aged 3-12 years, while also increasing knowledge and skills related to positive parenting. The CSI is a nine-session psychosocial group intervention delivered by non-specialist providers. It is intended for all adult primary caregivers of children in high-adversity communities, rather than specifically targeting caregivers already showing signs of elevated distress.Methods/design: The primary objective of this study is to assess the effectiveness of the CSI through a parallel group randomized controlled study with Syrian refugee families in North Lebanon. Participants will be primary caregivers of children aged 3-12 years, with one index child per family. Families will be randomized to the CSI or a waitlist control group. A total of 240 families (480 caregivers) will be recruited into the study. Randomization will be at the family level, and CSI groups will be held separately for women and men. The study will be implemented in two waves. Outcomes for both arms will be assessed at baseline, post-intervention, and at a 3-month follow-up. The primary outcome is quality of parenting skills. Secondary outcomes include parental warmth and sensitivity, harsh parenting, parenting knowledge, and child psychosocial wellbeing. Putative mediators of the CSI on parenting are caregiver stress, distress, psychosocial wellbeing, and stress management.Discussion: This trial may establish the CSI as an effective intervention for strengthening parenting in families living in settings of high adversity, particularly refugee communities.Trial Registration: International Society for the Registration of Clinical Trials, ISRCTN22321773. Registered on 5 August 2019. [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]

The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia (ICG) for regional cardiac control. There is still a knowledge gap, however, about the anatomical location and neurochemical phenotype of sensory neurons inside ICG. In the present study, rat ICG neurons were characterized neurochemically with immunohistochemistry using glutamatergic markers: vesicular glutamate transporters 1 and 2 (VGLUT1; VGLUT2), and glutaminase (GLS), the enzyme essential for glutamate production. Glutamatergic neurons (VGLUT1/VGLUT2/GLS) in the ICG that have axons to the ventricles were identified by retrograde tracing of wheat germ agglutinin–horseradish peroxidase (WGA–HRP) injected in the ventricular wall. Co-labeling of VGLUT1, VGLUT2, and GLS with the vesicular acetylcholine transporter (VAChT) was used to evaluate the relationship between post-ganglionic autonomic neurons and glutamatergic neurons. Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) ICG contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial ICG contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT; (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG neurons could help in better understanding the function of the intrinsic cardiac nervous system. [ABSTRACT FROM AUTHOR]

The article discusses the elaborations and future directions of clinical model for mental health care industry. It highlights the significant of daily stressors and direct exposure concerning mental health status during exposure to war related violence. It also emphasizes the original model discussed by researchers and practitioners during their research of conflict and post conflict settings in 2010.

Following inflammation, primary sensory neurons in the dorsal root ganglion (DRG) alter the production of several proteins. Most DRG neurons are glutamatergic, using glutaminase as the enzyme for glutamate production, but little is known about glutaminase following inflammation. In the present study, adjuvant-induced arthritis (AIA) was produced in rats with complete Freund's adjuvant into the hindpaw. At 7 days of AIA, DRG were examined with glutaminase immunohistochemistry, Western blot immunoreactivity, and enzyme activity. Image analysis revealed that glutaminase was elevated most in small-sized neurons (21%) (P < 0.05). Western blot analysis revealed a 19% increase (P < 0.05) in total glutaminase and 21% in mitochondrial glutaminase (P < 0.05). Glutaminase enzyme activity was elevated 29% (P < 0.001) from 2.20 to 2.83 moles/kg/hr. Elevated glutaminase in primary sensory neurons could lead to increased glutamate production in spinal primary afferent terminals contributing to central sensitization or in the peripheral process contributing to peripheral sensitization. [ABSTRACT FROM AUTHOR]

Abstract: In addition to using glutamate as a neurotransmitter at central synapses, many primary sensory neurons release glutamate from peripheral terminals. Primary sensory neurons with cell bodies in dorsal root or trigeminal ganglia produce glutaminase, the synthetic enzyme for glutamate, and transport the enzyme in mitochondria to peripheral terminals. Vesicular glutamate transporters fill neurotransmitter vesicles with glutamate and they are shipped to peripheral terminals. Intense noxious stimuli or tissue damage causes glutamate to be released from peripheral afferent nerve terminals and augmented release occurs during acute and chronic inflammation. The site of action for glutamate can be at the autologous or nearby nerve terminals. Peripheral nerve terminals contain both ionotropic and metabotropic excitatory amino acid receptors (EAARs) and activation of these receptors can lower the activation threshold and increase the excitability of primary afferents. Antagonism of EAARs can reduce excitability of activated afferents and produce antinociception in many animal models of acute and chronic pain. Glutamate injected into human skin and muscle causes acute pain. Trauma in humans, such as arthritis, myalgia, and tendonitis, elevates glutamate levels in affected tissues. There is evidence that EAAR antagonism at peripheral sites can provide relief in some chronic pain sufferers. [Copyright &y& Elsevier]

Daily stressors may mediate the relation between exposure to disaster-related stressors and psychological and psychosocial distress among youth in disaster-affected countries. A sample of 427 Sri Lankan Sinhalese, Tamil, and Muslim youth (mean age = 14.5) completed a survey with measures of exposure to disaster-related stressors and daily stressors, psychological distress (posttraumatic stress, depression, and anxiety), and psychosocial distress. The results indicated that daily stressors significantly mediated relations between war- and tsunami-related stressors and psychological and psychosocial distress. Some daily stressors not directly related to disaster also predicted functioning. These results point to the need for policies and interventions that focus on reducing proximal daily stressors that are salient to Sri Lankan youth exposed to disasters. [ABSTRACT FROM AUTHOR]

Abstract: In inflamed tissue, the levels of the excitatory amino acid glutamate are increased. Glutamate sensitizes peripheral axons of primary afferent neurons during inflammation leading to decreased firing threshold and hyperexcitability. One proposed source of glutamate is the primary afferent. Antagonizing glutamate receptors on peripheral axons of primary afferents during inflammation provides analgesia in animals and humans. The enzyme glutaminase is used by primary sensory neurons to convert glutamine to glutamate, and peripheral inhibition of glutaminase with 6-diazo-5-oxo-l-norleucine (DON) provides long-lasting analgesia during inflammation. In this study, we measured the effects of glutaminase inhibition on carrageenan-induced spinal Fos expression. Rats were given intraplantar injections of carrageenan and treated locally with either vehicle or DON. After 3h of inflammation, hind paw swelling and spinal expression of Fos were examined. CellProfiler was used to automate Fos nuclei counting in five laminar groupings in the spinal cord (I–II, III–IV, V–VI, VII–IX, X). Carrageenan increased hind paw thickness by ∼70% and spinal Fos expression in superficial (I–II) and deep (V–VI) laminae by 10-fold and 5-fold, respectively. Treatment with DON reduced hind paw swelling by ∼13% and suppressed Fos expression in the laminae I–II by ∼54%, but not the deep laminae. Our results further support the notion of glutamate as a peripheral inflammatory mediator and indicate that glutaminase should be considered as a novel therapeutic target for treatment of inflammatory pain. [Copyright &y& Elsevier]

Abstract: This paper seeks to bridge the divisive split between advocates of trauma-focused and psychosocial approaches to understanding and addressing mental health needs in conflict and post-conflict settings by emphasizing the role that daily stressors play in mediating direct war exposure and mental health outcomes. The authors argue that trauma-focused advocates tend to overemphasize the impact of direct war exposure on mental health, and fail to consider the contribution of stressful social and material conditions (daily stressors). Drawing on the findings of recent studies that have examined the relationship of both war exposure and daily stressors to mental health status, a model is proposed in which daily stressors partially mediate the relationship of war exposure to mental health. Based on that model, and on the growing body of research that supports it, an integrative, sequenced approach to intervention is proposed in which daily stressors are first addressed, and specialized interventions are then provided for individuals whose distress does not abate with the repair of the social ecology. [Copyright &y& Elsevier]

The article presents a study which determines the daily stressors that affect the youth in eastern Sri Lanka using mixed methods approach. The study uses the Children's Daily Stressor Scale (CDSS) to assess the relative contribution of the daily stressors, disaster exposure and war to the psychosocial and mental health of the youth. The result of the study shows that the direct exposure to stress and disaster are not the most crucial determinant of mental health.

This study examined the validity and utility of PTSD among 320 adults in Afghanistan. Findings support the validity of PTSD in this cultural context: PTSD symptoms were highly prevalent, shared common variance, and correlated as expected with exposure to traumatic stress. However, only limited support was found for the clinical utility of PTSD. Other types of psychiatric symptomatology, including depression and a culturally specific measure of general distress, correlated more highly with traumatic stress than did PTSD; and PTSD accounted for limited variance in functioning beyond that explained by depression and general distress. Implications for research and intervention are considered. [ABSTRACT FROM AUTHOR]

Working in Afghanistan's capital city of Kabul, the authors assessed the relative contribution of daily stressors and war-related experiences of violence and loss to levels of depression, PTSD, impaired functioning, and a culturally specific measure of general psychological distress. For women, daily stressors were a better predictor than war experiences of all mental health outcomes except for PTSD; for men, daily stressors were a better predictor of depression and functional impairment, while war experiences and daily stressors were similarly predictive of general distress. For men, daily stressors moderated the relationship between war experiences and PTSD, which was significant only under conditions of low daily stress. The study's implications for research and intervention in conflict and post-conflict settings are considered. [ABSTRACT FROM AUTHOR]

The article focuses on the recommendations to enhance the Inter-Agency Standing Committee (IASC) Guidelines on Mental Health and Psychosocial Support in Emergency Settings epidemiological assessments. It states that the IASC assessments have limited functions including the narrow focus on post traumatic stress disorder, and failure to distinguish between distress reactions and actual disorder. It mentions that the recommendations would be of great help in assessing mental health.

This article describes a methodology for developing culturally grounded assessment measures in conflict and postconflict situations. A mixed-method design was used in Kabul, Afghanistan, to identify local indicators of distress and develop the 22-item Afghan Symptom Checklist (ASCL). The ASCL contains several indigenous items and items familiar to Western mental health professionals. The ASCL was pilot tested and subsequently administered to 324 adults in 8 districts of Kabul. It demonstrated excellent reliability (alpha=.93) and good construct validity, correlating strongly with a measure of exposure to war-related violence and loss (r=.70). Results of the survey indicate moderate levels of distress among Afghan men and markedly higher levels of distress and impaired functioning among women (and widows in particular). [ABSTRACT FROM AUTHOR]

This article examines the centrality of trauma-focused psychiatric epidemiology (TFPE) in research with war-affected populations. The authors question the utility of the dominant focus on posttraumatic stress disorder and other disorders of Western psychiatry, and they identify a set of critical research foci related to mental health work with communities affected by political violence. Core assumptions of TFPE and its roots in logical positivism and the biomedical model of contemporary psychiatry are explored. The authors suggest that an alternative framework—social constructivism—can serve as a bridge between researchers and practitioners by helping to refocus research efforts in ways that are conceptually and methodologically more attuned to the needs of war-affected communities and those working to address their mental health needs. [ABSTRACT FROM AUTHOR]

Findings are presented from a narrative study that examined the use of interpreters in psychotherapy with refugees. Fifteen therapists and 15 interpreters were interviewed at 14 refugee mental health treatment centers in the United States. Core findings concerned the impact of interpreters on the therapeutic alliance, the complex emotional reactions that may arise within the therapy triad, the effects of interpreting on interpreters' own well-being, the multiple roles that interpreters play in addition to translating language, and the training and supervision needs of interpreters and of therapists who work with them. Implications of these findings for agencies that use interpreters in their clinical work with refugees are considered, and specific recommendations are made concerning the hiring, training, and support of interpreting staff. [ABSTRACT FROM AUTHOR]

This paper examines the role of trust and the concept of access as they affect the relational context in which community research, and research with refugee communities in particular, is conducted. Sociologist Irving Goffman's metaphor of frontstage and backstage behavior is used to illustrate the complexity and importance of developing of relations of trust, and thereby gaining "backstage" access, in communities that are generally closed to outsiders. It is argued that gaining authentic ("backstage") access to refugee communities, as well as other communities that have developed a self-protective insularity, is essential if we are to gather data that accurately reflect the actual beliefs, feelings, and experiences of community members. The paper then examines the puzzling lack of discussion regarding issues of trust, access, and the relational context in the literature on refugee mental health. Explanations for this apparent inattention are sought in the influence of the prevailing scientific paradigm that guides most research with refugees, and that shapes the values of the field's "gatekeepers," the editors and reviewers of scholarly journals. Throughout the paper, key points are illustrated with examples drawn from the author's research with refugees from Guatemala, Bosnia, and Afghanistan. [ABSTRACT FROM AUTHOR]

Field-reversed configurations (FRCs) are created and sustained using a rotating magnetic field (RMF) in the Translation Confinement and Sustainment experiment. Normally this experiment is operated in a manner where the RMF only partially penetrates the plasma column. This method of operation may have significant advantages in producing less disturbances to the bulk of the FRC, but requires driving an overall radially inward flow to maintain E[sub θ](r)=0 everywhere (through the V[sub r]B[sub z] term in the generalized Ohm’s law). However, some RMF penetration is still required at the field null R, where B[sub z]=0. For some experimental conditions it appears that the RMF does not even penetrate as far as the null, raising the question as to how E[sub θ](r=R) can be maintained at zero despite a finite η[sub ⊥]j[sub θ](r=R). Numerical simulations with a resistivity profile that is sharply peaked near the plasma edge yield similar profiles, and provide insight into this physical process. An inner magnetic structure forms, which rotates at a much lower frequency than the RMF. A tearing and reconnection process produces a torque transfer from the outer RMF to the inner structure, allowing it to act as an RMF downshifted to a lower frequency, and thus provide current drive to the inner region of the FRC. This mode of RMF current drive is being called “edge-driven mode.” © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

This study examined the relative contribution of 2 exile-related variables—social isolation and daily activity level—and war experiences of violence and loss, to levels of PTSD and depressive symptomatology in 2 groups of Bosnian refugees, 1 clinical group (N = 59) and the other a nonclinical community (N = 40) group. As hypothesized, exposure to war-related violence was highly predictive of PTSD symptoms in both groups; in addition, social isolation was significantly related to PTSD symptomatology in the community group. In contrast, depressive symptomatology was accounted for primarily by the exile-related stressors. For the clinical group, depressive symptoms were also accounted for by experiences of war-related loss. The implications of these findings for mental health interventions with refugees are considered. [ABSTRACT FROM AUTHOR]

Supporting glial cells of the peripheral nervous system include satellite cells of dorsal root ganglia and Schwann cells of peripheral nerves. In the central nervous system, glial cells contain enzymes related to the tricarboxylic acid and glutamine cycles: pyruvate carboxylase, glutamate dehydrogenase, and glutamine synthetase. The present study used immunohistochemistry in the rat peripheral nervous system to determine the cellular distribution of these enzymes along with glutamine. In dorsal root ganglia and peripheral nerves, glutamine and glutamine related enzymes were enriched in satellite and Schwann cells. In the dorsal root ganglia, immunoreactive satellite cells surrounded neurons of all sizes. In peripheral nerve, immunoreactive Schwann cells were most easily observed surrounding large diameter, myelinated axons. These Schwann cells contained immunoreactivity in their cell bodies, nodes of Ranvier, and the rim of cytoplasm outside the myelin sheath. Myelin sheaths were non-immunoreactive. The peripheral glial tricarboxylic and glutamine cycles may be used to produce glutamine for neuronal cell uptake and conversion to glutamate for synaptic transmission. Alternatively, these cycles may function in peripheral glia similar to central nervous system astrocytes for supporting the energy demands of neurons. [Copyright &y& Elsevier]

The authors used semistructured interviews to examine exile-related stressors affecting a sample of 28 adult Bosnian refugees in Chicago. The interviews covered 3 areas: life in prewar Bosnia, the journey of exile, and, most centrally, life in Chicago. Primary sources of exile-related distress included social isolation and the loss of community, separation from family members, the loss of important life projects, a lack of environmental mastery, poverty and related stressors such as inadequate housing, and the loss of valued social roles. The implications of these findings for mental health interventions with refugees are considered, and the value of narrative methods in research with refugee communities is discussed. [ABSTRACT FROM AUTHOR]

This article examines the recent Graça Machel Study, The Impact of Armed Conflict on Children, with a focus on the mental health of internally displaced and refugee children. Observations of the Machel Study are located within the context of the current psychological literature on refugee and displaced children and families. Gaps in our current knowledge that might be the focus of future research efforts are considered, and several issues are identified that are not discussed in the Machel Study, but that are particularly salient for psychologists working in this area. [ABSTRACT FROM AUTHOR]

Examines the mental health and psychosocial development of 58 Guatemalan Mayan Indian children in two refugee camps in Chiapas, Mexico. Background of the Guatemalan refugees in Chiapas; Refugee camps; Examination of children's understanding and feelings regarding their situation; Images of violence upon leaving Guatemala; Coping behavior of refugee children.

Discusses the adaptation and implementation of the Playing to Grow primary health intervention program based on work with children in Guatemalan refugee camps. Use of expressive arts techniques; Goals of the program; Training of camp teachers; Limitations of the program; Positive effects of the program on teachers and students.

The impact of armed conflict and displacement on children's mental health is strongly mediated by compromised parenting stemming from persistently high caregiver stress. Parenting interventions for refugees emphasize the acquisition of parenting knowledge and skills, while overlooking the deleterious effects of chronic stress on parenting. War Child Holland's Caregiver Support Intervention (CSI) aims to strengthen parenting by lowering stress and improving psychosocial wellbeing among refugee parents, while also increasing knowledge and skill related to positive parenting. The CSI is a nine-session group intervention delivered by non-specialist providers. We describe the findings of a two-arm pilot randomized controlled trial of the CSI with Syrian refugees in Lebanon. The primary aim was to test the feasibility of our study methodology prior to conducting a definitive RCT. We recruited 78 families (151 parents), who were randomized to the CSI or a waitlist control group. Data were collected at baseline and post-intervention. Randomization was successful, retention was high (99 %), as was intervention completion (95 % among women, 86 % among men). Implementation fidelity was excellent. Blinding was largely, though not completely effective. The CSI group showed significantly increased parental warmth and responsiveness, decreased harsh parenting, lowered stress and distress, improved psychosocial wellbeing, and improved stress management. CSI parents reported increased child psychosocial wellbeing. Control families showed no significant change on any variable. Findings demonstrate the feasibility of our methodology for a definitive RCT, and suggest that the CSI shows promise as a scalable approach to strengthening parenting in refugee communities. Trial registration # ISRCTN33665023 [ABSTRACT FROM AUTHOR]

• Neuronal Nuclei (NeuN) protein is expressed in the nucleus and cytoplasm of DRG neurons. • Increased NeuN/FOX-3 expression indicates a robust DRG neuronal response at the peak swelling timepoint of CFA-induced acute inflammation. • No morphologic signs of nuclear shrinking, chromatin condensation, or DNA fragmentation were observed in DRG neurons of any inflammatory group. • These data suggest that there are no signs of DRG neuronal suffering or injury at the 48-h timepoint of the AIA model in the hind paw of the rat. Pseudo-unipolar cell bodies of somatosensory primary neurons are located in the dorsal root ganglia (DRG). The somatic and peripheral domains of DRG neurons are often studied in sensory pain research to understand molecular mechanisms involved in the activation of pain and maintenance of inflammation. Adjuvant-induced arthritis (AIA) is an inflammatory model that elicits a robust and rapid onset immune response with a maximal swelling period of 24−48 h and persisting for several weeks. The AIA model in the hind paw of the rat elicits a potent inflammatory response of the dermis and epidermis, leading to protein expression changes for sensitization of many DRG neurons; however, it is unknown if the AIA model in the hind paw of the rat induces DRG neuronal injury, necrosis, or apoptosis at the somatic level. Neuronal nuclei (NeuN) antigen is a biomarker for post-mitotic neurons, neuronal identification, protein alterations, injury, and loss. Calcitonin gene-related peptide (CGRP) is expressed in C and Aδ DRG neurons, a subset of DRG neurons known to play a role in peripheral sensitization. The focus of this research was to evaluate the expression pattern of NeuN immunoreactivity, in size (soma) and CGRP subpopulations of DRG neurons in naïve and inflamed groups. Confirmed by both immunofluorescence and immunoprecipitation, DRG neuronal expression of NeuN was localized to nuclear and cytoplasmic subcellular compartments. NeuN increased within the nucleus of small CGRP positive DRG neurons during inflammation, indicating a potential role for NeuN in a subset of nociceptive neurons. [ABSTRACT FROM AUTHOR]

Immunohistochemistry (IHC) is a valuable tool in clinical and biological research for evaluating proteins and other antigens in spatially bound tissue. In neuroinflammatory pain research, primary afferent neurons of the dorsal root ganglion (DRG) are studied to understand molecular signaling mechanisms involved in nociception (pain) and inflammation. Measuring IHC (immunofluorescence) in DRG neurons requires manual hand tracing of nuclear and somatic boundaries, which is laborious, error-prone, and may require several weeks to collect the appropriate sample size with a mouse or pen-input display monitor. To overcome these limitations and increase standardization of sampling and measurement, we employed a reliable neuronal cytoplasmic reporter, exclusive to DRG neuronal soma, in a semi-automated algorithm-based approach of Image Cytometry in rat DRG (IC-DRG). The resulting output images are binary nuclear and somatic masks of DRG neurons, defining boundaries of measurement for CellProfiler and manually scored at 94% accurate. Herein, we successfully show a novel approach of automated image analysis for DRG neurons using a robust ImageJ/FIJI script, overcoming morphological variability and imaging artifacts native to imaging frozen tissue sections processed with immunofluorescence. [Display omitted] • Manual measurement of immunofluorescence can be laborious and require several weeks to collect the appropriate sample size. • To overcome these limitations, we employed a reliable neuronal cytoplasmic reporter to identify the population of interest. • The resulting output images are automatically generated binary nuclear and somatic masks of DRG neurons. • Herein, we successfully show a novel approach of automated image analysis for DRG neurons in slide-mounted cryostat sections. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine how upper thoracic spinal neurons responded to activation and desensitization of cardiac transient receptor potential vanilloid-1 (TRPV1)-containing afferent fibers. Extracellular potentials of single T3 spinal neurons were recorded in pentobarbital-anesthetized, paralyzed, and ventilated male rats. To activate cardiac nociceptive receptors, a catheter was placed in the pericardial sac to administer various chemicals: bradykinin (BK; 10 µg/ml, 0.2 ml), capsaicin (CAP, 10 µg/ml, 0.2 ml), or a mixture of algesic chemicals (AC; 0.2 ml) containing adenosine 10-3 M, BK, serotonin, histamine, and PGE2, 10-5 M for each. Spinal neurons that responded to intrapericardial BK and/or CAP were used in this study. Results showed that 81% (35/43) of the neurons had excitatory responses to both intrapericardial BK and CAP, and the remainder responded to either BK or CAP. Intrapericardial resiniferatoxin (RTX) (0.2 µg/ml, 0.2 ml, 1 min), which desensitizes TRPV1-containing nerve endings, abolished excitatory responses to both BK (n = 8) and CAP (n = 7), and to AC (n = 5) but not to somatic stimuli. Intrapericardial capsazepine (1 mg/ml, 0.2 ml, 3 min), a specific antagonist of TRPV1, sharply attenuated excitatory responses to CAP in 5/5 neurons, but responses to BK in 5/5 neurons was maintained. Additionally, intrapericardial capsazepine had no significant effect on excitatory responses to AC in 3/3 neurons. These data indicated that intrapericardial BK-initiated spinal neuronal responses were linked to cardiac TRPV1-containing afferent fibers, but were not dependent on TRPV1. Intraspinal signaling for cardiac nociception was mediated through CAP-sensitive afferent fibers innervating the heart. [ABSTRACT FROM AUTHOR]

Abstract: Complications of diabetes mellitus within the nervous system are peripheral and central neuropathy. In peripheral neuropathy, defects in neurofilament and microtubules have been demonstrated. In this study, we examined the effects of insulin deficiency within the brain in insulin knockout mice (I(−/−)). The I(−/−) exhibited hyperphosphorylation of tau, at threonine 231, and neurofilament. In addition, we showed hyperphosphorylation of c-Jun N-terminal kinase (JNK) and glycogen synthase kinase 3 β (GSK-3 β) at serine 9. Extracellular signal-regulated kinase 1 (ERK 1) showed decrease in phosphorylation, whereas ERK 2 showed no changes. Ultrastructural examination demonstrated swollen mitochondria, endoplasmic reticulum, and Golgi apparatus, and dispersion of the nuclear chromatin. Microtubules showed decrease in the number of intermicrotubule bridges and neurofilament presented as bunches. Thus, lack of insulin brain stimulation induces JNK hyperphosphorylation followed by hyperphosphorylation of tau and neurofilament, and ultrastructural cellular damage, that over time may induce decrease in cognition and learning disabilities. [Copyright &y& Elsevier]

Some evidence shows that the upper cervical spinal cord might play an important role in propriospinal processing as a sensory filter and modulator for visceral afferents. The aims of this study were to determine (1) the responses of C1–C2 spinal neurons to gastric distension and (2) the relative contribution of vagal and spinal visceral afferent pathways for transmission of gastric input to the upper cervical spinal cord. Extracellular potentials of single C1–C2 spinal neurons were recorded in pentobarbital anesthetized male rats. Graded gastric distension (20–80 mm Hg) was produced by air inflation of a latex balloon surgically placed in the stomach. Sixteen percent of the neurons (32/198) responded to gastric distension; 17 neurons were excited and 15 neurons were inhibited by gastric distension. Spontaneous activity of neurons with inhibitory responses was higher than those neurons with excitatory responses (18.1±2.7 vs. 3.8±1.7 impulses s−1, p<0.001). Twenty-eight of thirty-two (87.5%) neurons responded to mechanical stimulation of somatic fields on head, neck, ears or shoulder. Most lesion sites of neurons with excitatory responses were found in laminae V, VII; however, neurons with inhibitory responses were in laminae III, IV. Bilateral cervical vagotomy abolished responses of 4/8 neurons tested. Spinal transection at C6–C7 abolished responses of the other four neurons that still responded to gastric distension after bilateral vagotomy. Results of these data supported the concept that a group of C1–C2 spinal neurons might play a role in processing sensory information from the stomach that travels in vagal and spinal visceral afferent fibers. [Copyright &y& Elsevier]

The purposes of this study were to examine responses of superficial (depth <300 μm) and deeper thoracic spinal neurons to chemical stimulation of cardiac afferents and effects of descending influences on these neurons. Extracellular potentials of single T3–T4 neurons were recorded in pentobarbital anesthetized, paralyzed and ventilated male rats. A catheter was placed in the pericardial sac to administer 0.2 ml of a mixture of algogenic chemicals that contained adenosine (10−3 M), bradykinin, histamine, serotonin, prostaglandin E2 (10−5 M). Fifteen of 55 (27%) superficial neurons responsive to intrapericardial chemicals were compared to 80/169 (47%) deeper neurons. All 15 superficial neurons that responded to cardiac afferents were excited (E), whereas 66 deeper neurons were excited, ten were inhibited and four showed excitation–inhibition. Spontaneous activity of superficial neurons with short-lasting excitatory responses was significantly lower than that of deeper neurons (P<0.05). Somatic receptive fields on chest, axilla, arm and upper back areas were found for 77/95 (81%) neurons that responded to intrapericardial chemicals. The proportion of somatic field properties and their sizes in superficial neurons were similar to deeper neurons. After cervical spinal transection, both spontaneous activity and responses to chemical stimulation of cardiac afferents significantly increased in six out of six neurons excited by intrapericardial injections. Results showed that chemical stimulation of cardiac afferents excited superficial T3–T4 spinal neurons, whereas deeper neurons exhibited multiple patterns of responses. Some characteristics of subgroups of superficial neurons were quantitatively different from deeper neurons. Thoracic spinal neurons processing cardiac nociceptive information were under tonic descending inhibition. [Copyright &y& Elsevier]

Background: Syrian refugees and asylum seekers (SRAs) face multiple stressors after flight, which may vary due to different geographic, economic, cultural and socio-political contexts in the host countries. Past research has recognised the importance of participants' own perspectives. The aims of this multi-country study were to identify and compare self-reported problems of SRAs between various settings.Methods: A semi-structured client-generated outcome measurement was used to collect data among adult SRAs in Jordan (N = 61), Turkey (N = 46) and Switzerland (N = 57) between September 2018 and November 2019. Answers were analysed following thematic analysis.Results: Over half of the participants reported practical problems with an emphasis on camp-related problems (Jordan), finances (Turkey), employment (Jordan and Switzerland) and government regulations (Switzerland), followed by psychological, and social issues.Conclusion: This study highlights the impact of local contextual factors on wellbeing. The findings emphasise that planning preventative procedures and mental health care services for SRAs need to consider local challenges affecting the population in specific countries. [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]

Darfur refugees face hardships associated with chronic displacement, including lack of basic needs and safety concerns. Psychiatric research on refugees has focused on trauma, but daily stressors may contribute more to variance in distress. This article reports rates of past trauma and current stressors among Darfur refugees and gauges the contribution of each to psychological distress and functional impairment. A representative sample of 848 Darfuris in 2 refugee camps were interviewed about traumatic events, stressors faced in the camps, psychological distress, and functional impairment. Basic needs and safety concerns were more strongly correlated with measures of distress ( rs = .19–.31) than were war-related traumatic events ( rs = .09–.20). Hierarchical regression supported models in which effects of trauma on distress were mediated by current stressors. Although war-related traumatic events are the initial causes of refugees’ hardship, findings suggest that the day-to-day challenges and concerns in camps mediate psychological distress associated with these events. [ABSTRACT FROM AUTHOR]

β-Arrestin-1 (βArr1) plays a major role in the desensitization and internalization of G protein-coupled receptors. We previously localized βArr1 in the sensory neurons of rat lumbar 4 and 5 dorsal root ganglia (DRG) and reported the predominant presence of βArr1 in the small-diameter DRG neurons that are often implicated with nociception. Because of βArr1’s crucial role in regulating the initiation of cellular signaling, in the current study we evaluated the distribution of βArr1 in the peripheral sensory terminals where various receptors are present. Western blotting confirmed the presence of βArr1 immunoreactivity in the rat skin. Sciatic nerve ligation demonstrated that βArr1 is transported peripherally from the DRG, and immunohistochemistry showed βArr1 immunoreactivity in the glabrous skin of the rat hindpaw. In the glabrous skin, strong βArr1 immunoreactivity was detected in nerve fibers in the dermal nerve plexus and dermal papillae. Fine varicose immunoreactive fibers were found in the epidermis. In addition, βArr1 was observed in specialized sensory receptors such as Meissner corpuscles. Our observations thus indicate that βArr1 may be involved in modulation of specific tactile stimulation from the skin in addition to nociception. [Copyright &y& Elsevier]

Abstract Members of arrestin/β-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors, including rhodopsin and β2 -adrenergic receptor. Unlike in human and cow, splice variants of this protein family in rat have not been studied extensively, and there has been no report on their existence at protein level. Hence, a previous report by others on the localization of both β-arrestin-1 and -2 in a wide range of innervated rat tissues could imply their broad receptor specificity. In this report we show the presence of two alternatively spliced forms of β-arrestin-1 in several rat tissues using both reverse transcription–polymerase chain reaction and Western immunoblot. Splicing of β-arrestin-1 pre-mRNA appears to be subject to differential regulation between the rat CNS and peripheral tissues. In contrast, we detected no splice variants of β-arrestin-2 in rat. A comparison of the genomic DNA sequences of bovine and rat β-arrestin-2, where the splicing of bovine β-arrestin-2 mRNA has been reported, revealed a high degree of homology in their organization of exons and introns as well as certain differences that might be responsible for the different processing of β-arrestin-2 mRNA in the two species. Our two-dimensional isoelectric focusing gels using rat spinal cord and heart tissues demonstrate isoelectric heterogeneity of rat β-arrestin-1, suggesting that β-arrestin-1 is subject to post-translational modification unlike β-arrestin-2. [ABSTRACT FROM AUTHOR]