It is well established that tissue damage and functional outcome after experimental or clinical stroke are shaped by biologic sex. We investigated the novel hypothesis that ischemic cell death from neuronally derived nitric oxide (NO) or poly-ADP ribose polymerase (PARP-1) activation is sexually dimorphic and that interruption of these molecular death pathways benefits only the male brain. Female neuronal nitric oxide synthase (nNOS) knockout (nNOSÀ/À) mice exhibited exacerbated histological injury after middle cerebral artery occlusion (MCAO) relative to wild-type (WT) females, unlike the protection observed in male nNOSÀ/À littermates. Similarly, treatment with the nNOS inhibitor (7-nitroindozole, 25 mg/kg) increased infarction in female C57Bl6 WT mice, but protected male mice. The mechanism for this sexually specific response is not mediated through changes in protein expression of endothelial NOS or inducible NOS, or differences in intraischemic cerebral blood flow. Unlike male PARP-1 knockouts (PARP1À/À), female PARP1À/À littermates sustained grossly increased ischemic damage relative to sex-matched WT mice. Treatment with a PARP inhibitor (PJ-34, 10 mg/kg) resulted in identical results. Loss of PARP-1 resulted in reversal of the neuroprotective activity by the female sex steroid, 17b estradiol. These data suggest that the previously described cell death pathways involving NO and PARP ischemic neurotoxicity may be operant solely in male brain and that the integrity of nNO/PARP-1 signaling is paradoxically protective in the female.

US Centers for Disease Control and Prevention (National Institute for Occupational Safety and Health, Agency for Toxic Substances and Disease Registry, and National Center for Environmental Health); New York City Department of Health and Mental Hygiene.

Lay volunteers' poorer health outcomes reflect earlier, more intense exposure to and lack of protection from physical and psychological hazards. There is a need to limit volunteers' exposures during and after disasters, as well as to provide timely screening and health care post-disaster.

BackgroundMany individuals who have 9/11-related physical and mental health symptoms do not use or are unaware of 9/11-related health care services despite extensive education and outreach efforts by the World Trade Center (WTC) Health Registry (the Registry) and various other organizations. This study sought to evaluate Registry enrollees’ perceptions of the relationship between physical and mental health outcomes and 9/11, as well as utilization of and barriers to 9/11-related health care services.MethodsSix focus groups were conducted in January 2010 with diverse subgroups of enrollees, who were likely eligible for 9/11-related treatment services. The 48 participants were of differing race/ethnicities, ages, and boroughs of residence. Qualitative analysis of focus group transcripts was conducted using open coding and the identification of recurring themes.ResultsParticipants described a variety of physical and mental symptoms and conditions, yet their knowledge and utilization of 9/11 health care services were low. Participants highlighted numerous barriers to accessing 9/11 services, including programmatic barriers (lack of program visibility and accessibility), personal barriers such as stigmatization and unfamiliarity with 9/11-related health problems and services, and a lack of referrals from their primary care providers. Moreover, many participants were reluctant to connect their symptoms to the events of 9/11 due to lack of knowledge, the amount of time that had elapsed since 9/11, and the attribution of current health symptoms to the aging process.ConclusionsKnowledge of the barriers to 9/11-related health care has led to improvements in the Registry’s ability to refer eligible enrollees to appropriate treatment programs. These findings highlight areas for consideration in the implementation of the new federal WTC Health Program, now funded under the James Zadroga 9/11 Health and Compensation Act (PL 111-347), which includes provisions for outreach and education.

This manuscript describes the design, implementation and evaluation of the World Trade Center (WTC) Health Registry's Treatment Referral Program (TRP), created to respond to enrollees' self-reported 9/11-related physical and mental health needs and promote the use of WTC-specific health care. In 2009-2011, the TRP conducted personalized outreach, including an individualized educational mailing and telephone follow-up to 7,518 selected enrollees who resided in New York City, did not participate in rescue/recovery work, and reported symptoms of 9/11-related physical conditions or posttraumatic stress disorder (PTSD) on their most recently completed Registry survey. TRP staff spoke with enrollees to address barriers to care and schedule appointments at the WTC Environmental Health Center for those eligible. We assessed three nested outcomes: TRP participation (e.g., contact with TRP staff), scheduling appointments, and keeping scheduled appointments. A total of 1,232 (16.4%) eligible enrollees participated in the TRP; 32% of them scheduled a first-time appointment. We reached 84% of participants who scheduled appointments; 79.4% reported having kept the appointment. Scheduling an appointment, but not keeping it, was associated with self-reported unmet health care need, PTSD, and poor functioning (≥14 days of poor physical or mental health in the past 30 days) ( < 0.05). Neither scheduling nor keeping an appointment was associated with demographic characteristics. Successful outreach to disaster-exposed populations may require a sustained effort that employs a variety of methods in order to encourage and facilitate use of post-disaster services. Findings from this evaluation can inform outreach to the population exposed to 9/11 being conducted by other organizations.