The inflammatory response to birth requires MyD88 and is driven by both mother and offspring.

Birth is an inflammatory event for the newborn, characterized by elevations in interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α peripherally and/or centrally, as well as changes in brain microglia. However, the mechanism(s) underlying these responses is unknown. Toll-like receptors (TLRs) play crucial roles in innate immunity and initiate inflammatory cascades upon recognition of endogenous or exogenous antigens. Most TLR signaling depends on the adaptor molecule myeloid differentiation primary response 88 (MyD88). We independently varied MyD88 gene status in mouse dams and their offspring to determine whether the inflammatory response to birth depends on MyD88 signaling and, if so, whether that signaling occurs in the offspring, the mother, or both. We find that the perinatal surges in plasma IL-6 and brain expression of TNF-α depend solely on MyD88 gene status of the offspring, whereas postnatal increases in plasma IL-10 and TNF-α depend on MyD88 in both the pup and dam. Interestingly, MyD88 genotype of the dam primarily drives differences in offspring brain microglial density and has robust effects on developmental neuronal cell death. Milk cytokines were evaluated as a possible source of postnatal maternal influence; although we found high levels of CXCL1/GROα and several other cytokines in ingested post-partum milk, their presence did not require MyD88. Thus, the inflammatory response previously described in the late-term fetus and newborn depends on MyD88 (and, by extension, TLRs), with signaling in both the dam and offspring contributing. Unexpectedly, naturally-occuring neuronal cell death in the newborn is modulated primarily by maternal MyD88 gene status.

A patient-initiated DMARD self-monitoring service for people with rheumatoid or psoriatic arthritis: a cost-effectiveness analysis.

OBJECTIVE: To determine whether a patient-initiated DMARD self-monitoring service for people on MTX is a cost-effective model of care for patients with RA or PsA. METHODS: An economic evaluation was undertaken alongside a randomized controlled trial involving 100 patients. Outcome measures were quality of life and ESR assessed at baseline and post-intervention. Costs were calculated for healthcare usage using a United Kingdom National Health Service economic perspective. Sensitivity analysis was performed to explore the impact of nurse-led telephone helplines. Uncertainty around the cost-effectiveness ratios was estimated by bootstrapping and analysing the cost-effectiveness planes. RESULTS: Fifty-two patients received the intervention and 48 usual care. The difference in mean cost per case indicated that the intervention was £263 more expensive (P < 0.001; 95% CI: £149.14, £375.86) when the helpline costs were accounted for and £94 cheaper (P = 0.08; 95% CI: -£199.26, £10.41) when these costs were absorbed by the usual service. There were, however, statistically significant savings for the patient (P = 0.02; 95% CI: -£28.98, £3.00). When costs and effectiveness measures of ESR and quality of life measured, using the Short Form-12v1, were combined this did not show the patient-initiated service to be cost-effective at a statistically significant level. CONCLUSION: This patient-initiated service led to reductions in primary and secondary healthcare services that translated into reduced costs, in comparison with usual care, but were not cost-effective. Further work is needed to establish how nurse-led telephone triage services are integrated into rheumatology services and the associated costs of setting up and delivering them. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, ISRCTN21613721.

A patient-initiated DMARD self-monitoring service for people with rheumatoid or psoriatic arthritis on methotrexate: a randomised controlled trial.

OBJECTIVE: To determine the effectiveness of a patient-initiated disease-modifying antirheumatic drugs (DMARD) self-monitoring service for people with rheumatoid (RA) or psoriatic arthritis (PsA) on methotrexate. METHODS: A two-arm, single-centre, randomised controlled trial assessing superiority in relation to healthcare use, clinical and psychosocial outcomes. Participants were 100 adults with either RA or PsA on a stable dose of methotrexate, randomly assigned to usual care or the patient-initiated service. Intervention participants were trained how to understand and interpret their blood tests and use this information to initiate care from their clinical nurse specialist (CNS). The primary outcome was the number of outpatient visits to the CNS during the trial period. Differences between groups were analysed using Poisson regression models. Secondary outcomes were collected at baseline and after the third and sixth blood tests. Disease activity was measured using either the Disease Activity Score in 28 joints or Psoriatic Arthritis Response Criteria (PsARC), pain and fatigue using a visual numeric scale and the Health Assessment Question-II, Hospital Anxiety and Depression Scale and SF12 were completed to assess disability, mood and quality of life, respectively. Differences between groups over time on secondary outcomes were analysed using multilevel models. RESULTS: The patient-initiated DMARD self-monitoring service was associated with 54.55% fewer visits to the CNS (p<0.0001), 6.80% fewer visits to the rheumatologist (p=0.23) and 38.80% fewer visits to the general practitioner (p=0.07), compared with control participants. There was no association between trial arm and any of the clinical or psychosocial outcomes. CONCLUSIONS: The results suggest that a patient-initiated service that incorporates patients' self-monitoring DMARD therapy can lead to significant reductions in healthcare use, while maintaining clinical and psychosocial well-being. TRIAL REGISTRATION NUMBER: ISRCTN21613721.

An unusual case of weight loss in a patient with refractory rheumatoid arthritis.

We describe a case of metastatic malignant melanoma with no primary cutaneous lesion presenting as weight loss in a man with refractory, seropositive rheumatoid arthritis (RA). The patient had undergone multiple investigations previously and the case highlights the importance of repeat assessment in elderly patients presenting with unexplained weight loss.

Parvocellular subparafascicular thalamic nucleus in the rat: anatomical and functional compartmentalization.

The parvocellular subparafascicular thalamic nucleus (SPFp) is located in the posterior thalamus, consists of horizontally oriented cells, and extends from rostromedial to caudolateral, fusing with the posterior intralaminar nucleus and the peripeduncular nucleus. The present study demonstrates a chemoarchitechtonic and functional parcellation of the rat SPFp. Analysis of the distributions of the neuropeptides galanin, calcitonin gene related peptide (CGRP), substance P, and calbindin revealed the existence of a medial and lateral subdivision within SPFp, and a possible intermediate subdivision. The medial subdivision contains a dense population of galanin-immunoreactive fibers, originating from galanin neurons in the lumbosacral spinal cord. In contrast, the lateral subdivision contains CGRP-positive fibers and neurons. The presence of substance P and calbindin immunoreactivity throughout the entire nucleus suggests that these are separate subdivisions of SPFp, rather than different subnuclei. The present study also investigated the functional association of the separate subdivisions of SPFp for male and female rat sexual behavior. In the medial subdivision, Fos-positive neurons were activated in males by display of ejaculation and in females by vaginocervical stimulation. Thus, Fos induction in medial SPFp appears to reflect processing of inputs related to those events. In contrast, sexual behavior did not induce Fos in the lateral SPFp. Taken together, the present results indicate the existence of separate subdivisions in SPFp that are involved in different behavioral functions. The medial SPFp may process inputs important for sexual behavior, whereas the lateral SPFp may be involved in convergence of auditory and nociceptive inputs important for conditioned fear responses.

Activation of a subset of lumbar spinothalamic neurons after copulatory behavior in male but not female rats.

The precise pathways that convey copulation-related information to forebrain regions activated during male and female sexual behavior are poorly understood. Previous work from our laboratory and others has demonstrated the existence of a spinothalamic pathway that is a candidate to relay information to these areas. This pathway originates from a population of spinothalamic neurons in the lumbar spinal cord containing several neuropeptides including galanin, located in laminas 7 and 10 of the lumbar segments 3 and 4. To investigate the involvement of these lumbar spinothalamic neurons in conveying copulation-related information, we tested the hypothesis that these cells are activated after ejaculation in male rats and vaginocervical stimulation in female rats. This was assessed using galanin or cholecystokinin as a marker for this subset of spinothalamic neurons and Fos-immunoreactivity as a marker for neuronal activation. The results demonstrated that activation of these spinothalamic neurons is triggered by stimuli associated with ejaculation. Fos induction was specifically associated with ejaculation, because mounts or intromissions did not trigger expression. Moreover, these spinothalamic neurons were not activated by vaginocervical stimulation in female rats. Spinothalamic neurons have generally been associated with signaling pain and temperature information. The present findings demonstrate that a specific subpopulation of spinothalamic neurons signals information associated with ejaculation.