Exploration of barriers and facilitators to publishing local public health findings: A mixed methods protocol

Background: Worldwide, the US accounts for a large proportion of journals related to public health. Although the American Public Health Association (APHA) includes 54 affiliated regional and state associations, little is known about their capacity to support public health scholarship. The aim of this study is to assess barriers and facilitators to operation of state journals for the dissemination of local public health research and practices. Methods: A mixed methods approach will be used to complete the 12-month study. Affiliate websites will be accessed through the APHA membership portal to evaluate organizational infrastructure and ascertain the presence/absence of a journal. The leader of each affiliate will be contacted via email containing a link to a 12-question on-line survey to collect his/her perceptions of scholarly journals and the publication of local health data. To determine barriers and facilitators to publication of local public health findings, 30-minute semi-structured telephone interviews will focus on the infrastructure of the association, perceptions of the leader about the journal (if in place), and its operation. Results: We anticipate that 54 affiliate websites will be reviewed to complete the extraction checklist, that 74% of affiliate leaders will respond to the survey, and that 11 semi-structured interviews will be conducted. A limited number of state/regional public health associations will operate journals and a small percentage of those without journals may express an interest in implementing them. Barriers to operation of journals may include lack of resources (i.e., personnel, funding), and low prioritization of publication of state and local public health findings. Facilitators may include strong affiliate-academic relationships, affiliate leadership with experience in publications, and affiliate relationships with state and local departments of health. Conclusions: The research proposed in this protocol may stimulate other state public health associations and other academic public health programs to follow suit; it would not be the first time that an observational research study served as an intervention

Inclusion of \u3b1-bisabolol into PLGA nanoparticles enhances its pro-apoptotic activity in human tumoral pancreatic cells.

Alfa-Bisabolol (figure 1), a sesquiterpene alcohol present in essential oils derived from a variety of plants, presents pro-apoptotic activity against several human cancer cell lines. Its poor aqueous solubility limits in vitro and in vivo tests. Herein we report a study of the formulation and characterization of alfa-Bisabolol using poly lactide-co-glycolid acid copolymer nanoparticles (PLGA/B). The human therapeutic treatment of PLGA is approved by US Food and Drug Administration (USFDA) thanks to its biocompatibility. This copolymer is one of the most successfully used in nanomedicine applications since it is hydrolyzed in the body to produce the biodegradable lactic and glycolic acid monomer

Clinical characteristics of 80 subjects with KCNQ2-related encephalopathy: Results from a family-driven survey

Variants of KCNQ2 are associated with a wide spectrum of disorders, ranging from Self-limiting Neonatal Epilepsy (SelNE) to Early Onset Developmental and Epileptic Encephalopathy (KCNQ2-DEE). Comorbidities associated with this end of the spectrum have been seldomly described and their impact on the life of patients and their families is yet to be investigated. Collaborating with caregivers from different European family associations, we have developed a questionnaire aimed at investigating the onset and frequency of epileptic seizures, anti-seizure medications (ASM), hospitalizations, stages of development, and comorbidities. Responses from 80 patients, 40 males, from 14 countries have been collected. Median age 7.6 years (4 months - 43.6 years). Of 76 epileptic patients (93.6%), 55.3% were seizure-free with a mean age at last seizure of 26.7 months. Among patients with active epilepsy, those older have a lower frequency of seizures (p > 0.05). We were able to identify three different clusters of varying severity (Mild, Severe, Profound), based on neurodevelopmental features and symptoms, excluding epilepsy. Patients in a higher severity cluster had a higher mean number of comorbidities, which had a higher impact on families. Notably, patients in different clusters presented different epilepsy onset and courses. This study constitutes the most extensive data collection of patients with KCNQ2-DEE, with a focus on comorbidities in a wide age group. The participation of caregivers helps to define the impact of the disease on the lives of patients and families and can help identify new primary and secondary outcomes beyond seizures in future studies

neuroimaging changes in menkes disease part 2

SUMMARY: This is the second part of a retrospective and review MR imaging study aiming to define the frequency rate, timing, imaging features, and evolution of gray matter changes in Menkes disease, a rare multisystem X-linked disorder of copper metabolism characterized by early, severe, and progressive neurologic involvement. According to our analysis, neurodegenerative changes and focal basal ganglia lesions already appear in the early phases of the disease. Subdural collections are less common than generally thought; however, their presence remains important because they might challenge the differential diagnosis with child abuse and might precipitate the clinical deterioration. Anecdotal findings in our large sample seem to provide interesting clues about the protean mechanisms of brain injury in this rare disease and further highlight the broad spectrum of MR imaging findings that might be expected while imaging a child with the suspicion of or a known diagnosis of Menkes disease

neuroimaging changes in menkes disease part 1

SUMMARY: Menkes disease is a rare multisystem X-linked disorder of copper metabolism. Despite an early, severe, and progressive neurologic involvement, our knowledge of brain involvement remains unsatisfactory. The first part of this retrospective and review MR imaging study aims to define the frequency rate, timing, imaging features, and evolution of intracranial vascular and white matter changes. According to our analysis, striking but also poorly evolutive vascular abnormalities characterize the very early phases of disease. After the first months, myelination delay becomes evident, often in association with protean focal white matter lesions, some of which reveal an age-specific brain vulnerability. In later phases of the disease, concomitant progressive neurodegeneration might hinder the myelination progression. The currently enriched knowledge of neuroradiologic finding evolution provides valuable clues for early diagnosis, identifies possible MR imaging biomarkers of new treatment efficacy, and improves our comprehension of possible mechanisms of brain injury in Menkes disease

Gait abnormalities in people with Dravet syndrome: A cross-sectional multi-center study

Objective: To quantify gait abnormalities in people with Dravet syndrome (DS). Methods: Individuals with a confirmed diagnosis of DS were enrolled, and stratified according to knee flexion at initial contact (IC) and range of motion (ROM) during stance (atypical crouch: knee flexion >20\ub0 at IC and knee ROM >15\ub0 during stance; straight: knee flexion <20\ub0 at IC). A 1D ANOVA (\u3b1 = 0.05) was used to test statistical differences among the joint kinematics and spatio\u2013temporal parameters of the cohort and an age-matched control group. Clinical (neurological and orthopaedic evaluation) and anamnestic data (seizure type, drugs, genetic mutation) were collected; distribution between the two gait phenotypes was assessed with the Fisher exact test and, for mutation, with the chi-squared test (p < 0.05). Linear regression between maximum knee flexion and normalised walking speed was calculated. Results: Seventy-one subjects were enrolled and evaluated with instrumented gait analysis. Fifty-two were included in final analysis (mean age 13.8 \ub1 7.3; M 26). Two gait patterns were detected: an atypical crouch gait (34.6%) with increased ankle, knee and hip flexion during stance, and reduced walking speed and stride length not associated with muscle-tendon retractions; and a pattern resembling those of healthy age-matched controls, but still showing reduced walking speed and stride length. No differences in clinical or anamnestic data emerged between the two groups. Significance: Objectively quantified gait in DS shows two gait patterns with no clear-cut relation to clinical data. Kinematics abnormalities may be related to stabilization issues. These findings may guide rehabilitative and preventive measures

Working together to implement a Pre-Qualifying Skills Passport in Wales: Report of a pilot project

Midwives are required to undertake a wide range of hands-on skills. Immediately upon qualification, they will be expected to use these skills safely and effectively as part of their practice. Therefore, student midwives must be supported to develop competence and confidence in such skills. Currently, many practical midwifery skills are not specifically identified in the Nursing and Midwifery Council (NMC, 2009) Standards for pre-registration midwifery education. Over time, it has become clear that some midwives were qualifying from universities in Wales and entering their new posts feeling unprepared to undertake a number of important midwifery skills, such as the administration of intramuscular vitamin K to babies. This article describes how heads of midwifery education and lead midwives for education worked together with heads of midwifery to develop and implement an All Wales Midwifery Pre-Qualifying Skills Passport, to address these shortcomings

Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly

The genetic causes of malformations of cortical development (MCD) remain largely unknown. Here we report the discovery of multiple pathogenic missense mutations in TUBG1, DYNC1H1 and KIF2A, as well as a single germline mosaic mutation in KIF5C, in subjects with MCD. We found a frequent recurrence of mutations in DYNC1H1, implying that this gene is a major locus for unexplained MCD. We further show that the mutations in KIF5C, KIF2A and DYNC1H1 affect ATP hydrolysis, productive protein folding and microtubule binding, respectively. In addition, we show that suppression of mouse Tubg1 expression in vivo interferes with proper neuronal migration, whereas expression of altered gamma-tubulin proteins in Saccharomyces cerevisiae disrupts normal microtubule behavior. Our data reinforce the importance of centrosomal and microtubule-related proteins in cortical development and strongly suggest that microtubule-dependent mitotic and postmitotic processes are major contributors to the pathogenesis of MCD

S-Glutathionylation at Cys328 and Cys542 Impairs STAT3 Phosphorylation.

STAT3 is a latent transcription factor that promotes cell survival and proliferation and is often constitutively active in cancers. Although many reports provide evidence that STAT3 is a direct target of oxidative stress, its redox regulation is poorly understood. Under oxidative conditions STAT3 activity can be modulated by S-glutathionylation, a reversible redox modification of cysteine residues. This suggests the possible cross-talk between phosphorylation and glutathionylation and points out that STAT3 is susceptible to redox regulation. Recently, we reported that decreasing the GSH content in different cell lines induces inhibition of STAT3 activity through the reversible oxidation of thiol groups. In the present work, we demonstrate that GSH/diamide treatment induces S-glutathionylation of STAT3 in the recombinant purified form. This effect was completely reversed by treatment with the reducing agent dithiothreitol, indicating that S-glutathionylation of STAT3 was related to formation of protein-mixed disulfides. Moreover, addition of the bulky negatively charged GSH moiety impairs JAK2-mediated STAT3 phosphorylation, very likely interfering with tyrosine accessibility and thus affecting protein structure and function. Mass mapping analysis identifies two glutathionylated cysteine residues, Cys328 and Cys542, within the DNA-binding domain and the linker domain, respectively. Site direct mutagenesis and in vitro kinase assay confirm the importance of both cysteine residues in the complex redox regulatory mechanism of STAT3. Cells expressing mutant were resistant in this regard. The data presented herein confirmed the occurrence of a redox-dependent regulation of STAT3, identified the more redox-sensitive cysteines within STAT3 structure, and may have important implications for development of new drugs