Repopulated spinal cord microglia exhibit a unique transcriptome and contribute to pain resolution.

Microglia are implicated as primarily detrimental in pain models; however, they exist across a continuum of states that contribute to homeostasis or pathology depending on timing and context. To clarify the specific contribution of microglia to pain progression, we take advantage of a temporally controlled transgenic approach to transiently deplete microglia. Unexpectedly, we observe complete resolution of pain coinciding with microglial repopulation rather than depletion. We find that repopulated mouse spinal cord microglia are morphologically distinct from control microglia and exhibit a unique transcriptome. Repopulated microglia from males and females express overlapping networks of genes related to phagocytosis and response to stress. We intersect the identified mouse genes with a single-nuclei microglial dataset from human spinal cord to identify human-relevant genes that may ultimately promote pain resolution after injury. This work presents a comprehensive approach to gene discovery in pain and provides datasets for the development of future microglial-targeted therapeutics.

Frequency, compliance, and yield of cardiac testing after high-sensitivity troponin accelerated diagnostic protocol implementation.

BACKGROUND: Among persons presenting to the emergency department with suspected acute myocardial infarction (MI), cardiac troponin (cTn) testing is commonly used to detect acute myocardial injury. Accelerated diagnostic protocols (ADPs) guide clinicians to integrate cTn results with other clinical information to decide whether to order further diagnostic testing. OBJECTIVE: To determine the change in the rate and yield of stress test or coronary CT angiogram following cTn measurement in patients with chest pain presenting to the emergency department pre- and post-transition to a high-sensitivity (hs-cTn) assay in an updated ADP. METHODS: Using electronic health records, we examined visits for chest pain at five emergency departments affiliated with an integrated academic health system 1-year pre- and post-hs-cTn assay transition. Outcomes included stress test or coronary imaging frequency, ADP compliance among those with additional testing, and diagnostic yield (ratio of positive tests to total tests). RESULTS: There were 7564 patient-visits for chest pain, including 3665 in the pre- and 3899 in the post-period. Following the updated ADP using hs-cTn, 862 (23.5 per 100 patient visits) visits led to subsequent testing versus 1085 (27.8 per 100 patient visits) in the pre-hs-cTn period, (P < 0.001). Among those who were tested, the protocol-compliant rate fell from 80.9% to 46.5% (P < 0.001), but the yield of those tests rose from 24.5% to 29.2% (P = 0.07). Among tests that were noncompliant with ADP guidance, yield was similar pre- and post-updated hs-cTn ADP implementation (pre 13.0%, post 15.4% (P = 0.43). CONCLUSION: Implementation of hs-cTn supported by an updated ADP was associated with a lower rate of stress testing and coronary CT angiogram.

A mystery client study of crisis pregnancy center practices in New York State.

OBJECTIVES: To evaluate practices of crisis pregnancy centers (CPCs) in a state with supportive abortion policies. STUDY DESIGN: We called all New York State CPCs regarding their services using a "mystery client" protocol, utilizing checklists and thematic analysis. RESULTS: Of 86 CPCs, 67 (78%) encouraged in-person appointments, offering free medical services and support. Twelve centers (14%) spontaneously disclosed their non-medical status, and 36 (42%) disclosed after direct questioning. Sixty-five (76%) made inaccurate or inflammatory statements about pregnancy or abortion. CONCLUSIONS: In a state without specific barriers to abortion and pregnancy care, CPCs claim to provide support while using inflammatory rhetoric and concealing their organizational status.

Sex-distinct microglial activation and myeloid cell infiltration in the spinal cord after painful peripheral injury.

Chronic pain is a common and often debilitating problem that affects 100 million Americans. A better understanding of pain's molecular mechanisms is necessary for developing safe and effective therapeutics. Microglial activation has been implicated as a mediator of chronic pain in numerous preclinical studies; unfortunately, translational efforts using known glial modulators have largely failed, perhaps at least in part due to poor specificity of the compounds pursued, or an incomplete understanding of microglial reactivity. In order to achieve a more granular understanding of the role of microglia in chronic pain as a means of optimizing translational efforts, we utilized a clinically-informed mouse model of complex regional pain syndrome (CRPS), and monitored microglial activation throughout pain progression. We discovered that while both males and females exhibit spinal cord microglial activation as evidenced by increases in Iba1, activation is attenuated and delayed in females. We further evaluated the expression of the newly identified microglia-specific marker, TMEM119, and identified two distinct populations in the spinal cord parenchyma after peripheral injury: TMEM119+ microglia and TMEM119- infiltrating myeloid lineage cells, which are comprised of Ly6G + neutrophils and Ly6G- macrophages/monocytes. Neurons are sensitized by inflammatory mediators released in the CNS after injury; however, the cellular source of these cytokines remains somewhat unclear. Using multiplex in situ hybridization in combination with immunohistochemistry, we demonstrate that spinal cord TMEM119+ microglia are the cellular source of cytokines IL6 and IL1ß after peripheral injury. Taken together, these data have important implications for translational studies: 1) microglia remain a viable analgesic target for males and females, so long as duration after injury is considered; 2) the analgesic properties of microglial modulators are likely at least in part related to their suppression of microglial-released cytokines, and 3) a limited number of neutrophils and macrophages/monocytes infiltrate the spinal cord after peripheral injury but have unknown impact on pain persistence or resolution. Further studies to uncover glial-targeted therapeutic interventions will need to consider sex, timing after injury, and the exact target population of interest to have the specificity necessary for translation.

Managing public health care policy: who's being forgotten?

The purpose of this paper is to explore the lived experience and perceptions of a sample of caregivers who are providing informal care 24h per day, 7 days per week for those with Alzheimer's disease in New Zealand. A mixed-method research design was used to collect and analyse the data. Semi-structured interviews with five caregivers and the completion of a questionnaire survey by 64 full-time caregivers provided insight into the significant burden carried by voluntary caregivers. However, alongside their experience of negative effects on their mental and psychological health, work and financial status, new perspectives of valued self-development and enhanced support networks in their caregiving role emerged. Despite this exploratory project being limited to a small sample of caregivers, the evidence suggests that they employ coping mechanisms which need to be recognised and supported with adequate and equitable resource allocation, if policy managers desire the current level of dependence on informal caregiving for those with Alzheimer's in this country to be sustained.

Paid maternity and paternity leave: rights and choices.

From April 2007 onwards, maternity leave will be raised to nine months Paid maternity leave is associated with significant health benefits for babies, including reduced infant mortality The Government proposes to increase paid maternity leave to one year and introduce additional paternity leave by around 2009 The U.K's provision for maternity leave and child care is more generous than the U.S.A. or Australia but less than in the Scandinavian countries

Lavender Islands: the New Zealand study.

Lavender Islands: Portrait of the Whole Family is the first national strengths-based study of lesbian, gay, and bisexual (LGB) people in New Zealand. The 133-item survey was made available both by website and paper copy from April to July 2004. Multidisciplinary interest areas were developed by a community reference group, and included identity and self-definition, families of origin, relationships and sexuality, families of choice, immigration and internal migration, wellbeing, politics, income and spending, education, careers and leisure, community connections, challenges, and spirituality. A four-axis model of sexual identity was also tested; 2,269 responses were received. Of these 83% were from the website; 45% of responses were from women and 54% from men. Responses identified a robust, highly educated, relatively high-income, politically active LGB community. Male and female respondents experienced same-sex relationships and identity in significantly different ways.

Anxiety before, during, and after participation in a population-based screening mammography programme in Waikato Province, New Zealand.

AIM: This study investigated anxiety levels before, during and after mammography in the Waikato breast cancer screening pilot. METHOD: A sample of 1085 women on the Waikato database were sent survey questionnaires, which included questions about the anxiety experienced. Data from 584 completed questionnaires were obtained. RESULTS: Two significant findings were identified. The first was that population-based screening can ultimately reduce anxiety for participants who receive a clear result from their mammogram. The second finding was that levels of worry throughout were related to ethnicity. Maori and Pacific Island women reported higher levels of worry than New Zealand European and Asian women about developing breast cancer (p<0.001), while awaiting their appointment (p=0.041) and results (p=0.046). Across all groups, levels of worry about developing breast cancer were also related to level of education (p=0.018), a family history of breast cancer (p=0.002), stress levels during screening mammography (p<0.001), and experience of pain during the procedure (p<0.001). At least some months following receipt of their results, 67% (95% CI 63-71) of all women experienced reassurance from receiving a clear result. CONCLUSIONS: The results show that the population-based screening programme demonstrates greater potential to ultimately relieve (rather then increase) anxiety for participants who receive a clear result from their mammogram.