The Duquesne Emergency Preparedness Project: An Examination of Existing Citizen Preparedness Guides and an Exploration of Community Perceptions and Emergency Preparedness Needs

Vulnerable populations and communities lacking resources may be disproportionately affected in the event of a public health emergency. Preexisting social conditions among vulnerable populations including low socioeconomic status and poor educational systems, contribute to the vulnerability of communities in the face of disaster. The Duquesne City, Pennsylvania community is a vulnerable population likely to be disproportionately affected in the event of an emergency. The primary objectives for the Duquesne Emergency Preparedness Project were to: 1) Examine the literacy level and assumptions underlying existing preparedness guides; 2) Define risk perceptions and understand information-seeking behaviors of residents in Duquesne, PA; 3) Better understand the challenges faced by low-resource populations in utilizing emergency preparedness materials and use this understanding to make recommendations for the development of educational preparedness materials and a community-based model for emergency preparedness. The literacy level and assumptions underlying existing emergency preparedness educational guides were assessed and evaluated for their relevance for the Duquesne community. In order to make recommendations for the development of emergency preparedness educational materials relevant to low literacy and resource poor communities, the Project also investigated the risk perceptions and information seeking behaviors of Duquesne community members and explored existing strengths, weaknesses and perceived individual and community emergency capabilities through focus group discussions and surveying. Study conclusions include: 1) People in Duquesne and surrounding areas do not view emergencies or disasters as impending high-risk events; 2) A serious communication disconnect exists between local officials, agencies and the public; and 3) Individuals are largely unfamiliar with existing citizen preparedness materials, perhaps because this information has not percolated into these communities, tends to focus on low-probability and abstract events, exceeds the literacy level of these populations and is not consistent with the needs of vulnerable populations. A paucity of information on the emergency preparedness needs of low-resource populations exist in the literature and understanding these needs is essential for community-based public health preparedness. Conclusions of the Duquesne Emergency Preparedness Project reveal important insights about the emergency preparedness needs of vulnerable populations and have important implications for public health approaches to preparedness for low-resource communities

The control of alternative splicing by SRSF1 in myelinated afferents contributes to the development of neuropathic pain

Neuropathic pain results from neuroplasticity in nociceptive neuronal networks. Here we demonstrate that control of alternative pre-mRNA splicing, through the splice factor serine-arginine splice factor 1 (SRSF1), is integral to the processing of nociceptive information in the spinal cord. Neuropathic pain develops following a partial saphenous nerve ligation injury, at which time SRSF1 is activated in damaged myelinated primary afferent neurons, with minimal found in small diameter (IB4 positive) dorsal root ganglia neurons. Serine arginine protein kinase 1 (SRPK1) is the principal route of SRSF1 activation. Spinal SRPK1 inhibition attenuated SRSF1 activity, abolished neuropathic pain behaviors and suppressed central sensitization. SRSF1 was principally expressed in large diameter myelinated (NF200-rich) dorsal root ganglia sensory neurons and their excitatory central terminals (vGLUT1 + ve) within the dorsal horn of the lumbar spinal cord. Expression of pro-nociceptive VEGF-Axxxa within the spinal cord was increased after nerve injury, and this was prevented by SRPK1 inhibition. Additionally, expression of anti-nociceptive VEGF-Axxxb isoforms was elevated, and this was associated with reduced neuropathic pain behaviors. Inhibition of VEGF receptor-2 signaling in the spinal cord attenuated behavioral nociceptive responses to mechanical, heat and formalin stimuli, indicating that spinal VEGF receptor-2 activation has potent pro-nociceptive actions. Furthermore, intrathecal VEGF-A165a resulted in mechanical and heat hyperalgesia, whereas the sister inhibitory isoform VEGF-A165b resulted in anti-nociception. These results support a role for myelinated fiber pathways, and alternative pre-mRNA splicing of factors such as VEGF-A in the spinal processing of neuropathic pain. They also indicate that targeting pre-mRNA splicing at the spinal level could lead to a novel target for analgesic development

FOX-2 Dependent Splicing of Ataxin-2 Transcript Is Affected by Ataxin-1 Overexpression

Alternative splicing is a fundamental posttranscriptional mechanism for controlling gene expression, and splicing defects have been linked to various human disorders. The splicing factor FOX-2 is part of a main protein interaction hub in a network related to human inherited ataxias, however, its impact remains to be elucidated. Here, we focused on the reported interaction between FOX-2 and ataxin-1, the disease-causing protein in spinocerebellar ataxia type 1. In this line, we further evaluated this interaction by yeast-2-hybrid analyses and co-immunoprecipitation experiments in mammalian cells. Interestingly, we discovered that FOX-2 localization and splicing activity is affected in the presence of nuclear ataxin-1 inclusions. Moreover, we observed that FOX-2 directly interacts with ataxin-2, a protein modulating spinocerebellar ataxia type 1 pathogenesis. Finally, we provide evidence that splicing of pre-mRNA of ataxin-2 depends on FOX-2 activity, since reduction of FOX-2 levels led to increased skipping of exon 18 in ataxin-2 transcripts. Most striking, we observed that ataxin-1 overexpression has an effect on this splicing event as well. Thus, our results demonstrate that FOX-2 is involved in splicing of ataxin-2 transcripts and that this splicing event is altered by overexpression of ataxin-1

Familial Forms of Cushing Syndrome in Primary Pigmented Nodular Adrenocortical Disease Presenting with Short Stature and Insidious Symptoms: A Clinical Series.

Cushing syndrome (CS) is a rare disease in children, frequently associated with subtle or periodic symptoms that may delay its diagnosis. Weight gain and growth failure, the hallmarks of hypercortisolism in pediatrics, may be inconsistent, especially in ACTH-independent forms of CS. Primary pigmented nodular adrenocortical disease (PPNAD) is the rarest form of ACTH-independent CS, and can be associated with endocrine and nonendocrine tumors, forming the Carney complex (CNC). Recently, phenotype/genotype correlations have been described with particular forms of CNC where PPNAD is isolated or associated only with skin lesions. We present four familial series of CS due to isolated PPNAD, and compare them to available data from the literature. We discuss the clinical and molecular findings, and underline challenges in diagnosing PPNAD in childhood