Using axenic and gnotobiotic insects to examine the role of different microbes on the development and reproduction of the kissing bug Rhodnius prolixus (Hemiptera: Reduviidae).

Kissing bugs (Hempitera: Reduviidae) are obligately and exclusively blood feeding insects. Vertebrate blood is thought to provide insufficient B vitamins to insects, which rely on symbiotic relationships with bacteria that provision these nutrients. Kissing bugs harbour environmentally acquired bacteria in their gut lumen, without which they are unable to develop to adulthood. Rhodococcus rhodnii was initially identified as the sole symbiont of Rhodnius prolixus, but modern studies of the kissing bug microbiome suggest that R. rhodnii is not always present or abundant in wild-caught individuals. We asked whether R. rhodnii or other bacteria alone could function as symbionts of R. prolixus. We produced insects with no bacteria (axenic) or with known microbiomes (gnotobiotic). Gnotobiotic insects harbouring R. rhodnii alone developed faster, had higher survival, and laid more eggs than those harbouring other bacterial monocultures, including other described symbionts of kissing bugs. R. rhodnii grew to high titre in the guts of R. prolixus while other tested species were found at much lower abundance. Rhodococcus species tested had nearly identical B vitamin biosynthesis genes, and dietary supplementation of B vitamins had a relatively minor effect on development and survival of gnotobiotic R. prolixus. Our results indicate that R. prolixus have a higher fitness when harbouring R. rhodnii than other bacteria tested, that this may be due to R. rhodnii existing at higher titres and providing more B vitamins to the host, and that symbiont B vitamin synthesis is probably a necessary but not sufficient function of gut bacteria in kissing bugs.

The implementation of a multi-level reflective consultation model in a statewide infant & early childcare education professional development system: Evaluation of a pilot.

The growth in professional development for the infant-early childhood workforce has necessitated the implementation of novel, sustainable approaches to meet infant early childhood mental health (IECMH) training and reflective supervision consultation (RSC) needs. The 12-month pilot of a US statewide reflective consultation (RC) group model included IECMH consultants, grant specialists, supervisors, and program managers (n = 38) and their group reflective consultants (n = 6). The pilot evaluation provided an opportunity to design a study that assessed the impact of RC on infant-early childhood professionals. The mixed-methods study included an assessment of consultees' reflective practice skills and experience of their work. Findings included consultees' self-reported increased reflective practice self-efficacy and increased use of reflective practice skills. While there were no changes in the Maslach Burnout Inventory (MBI) personal accomplishment, emotional exhaustion, or depersonalization results, qualitative findings indicated a decrease in burnout and an increase in relationship-based practice across professional roles. This unique pilot provides an example of an organizational approach to instituting RC with a broad spectrum of infant-early childhood professionals and yields valuable information about the impacts of RC models on such professionals' work experience and professional practice.

El crecimiento en cuanto al desarrollo profesional para los trabajadores del área de infancia y temprana niñez ha necesitado de la implementación de acercamientos novedosos y sostenibles para cumplir con las necesidades de entrenamiento y consulta de supervisión con reflexión (RSC) del campo de la salud mental en la infancia y temprana niñez (IECMH). El plan piloto de 12 meses de un modelo de grupo de consulta con reflexión (RC) a lo largo y ancho de los estados de Estados Unidos incluyó consultores de IECMH, especialistas en fondos de financiación, supervisores y directores de programas (n = 38) y los consultores d reflexión de sus grupos (n = 6). L evaluación del plan piloto proveyó una oportunidad para diseñar un estudio que evaluara los impactos que RC tiene en los profesionales de infancia y temprana niñez. El estudio de métodos combinados incluyó una evaluación de las habilidades prácticas y experiencias reflexivas de trabajo de los consultantes. Los resultados incluyen los auto reportes de los consultantes sobre el aumento de la práctica reflexiva de auto eficacia y el aumento del uso de las habilidades de la práctica con reflexión. Aunque no se dieron cambios en cuanto a los logros personales, el agotamiento emocional o los resultados de despersonalización en el Inventario de Agotamiento de Maslach (MBI), los resultados cualitativos indicaron una baja en el agotamiento y un aumento en la práctica basada en la relación a lo largo de los roles profesionales. Este plan piloto único ofrece un ejemplo de un acercamiento organizacional para instituir RC con un enfoque amplio de los profesionales de la infancia y temprana niñez y aporta información de valor acerca de los impactos que los modelos RC tienen sobre las experiencias de trabajo y la práctica profesional de esos profesionales.

La croissance de la formation professionnelle pour les professionnels de la santé des nourrissons et de la petite enfance a nécessité la mise en place d'approches innovatrices et durables afin de remplir les besoins de formation et de consultation de supervision réflective (RSC) de la santé mentale du nourrisson et de la petite enfance (IECMH). Une étude pilote de 12 mois d'un modèle de groupe de consultation réflective (abrégé RC en anglaise) dans un état des Etats-Unis a inclus des consultants IECMH, des spécialistes des subventions, des superviseurs et des gestionnaires de programme (n = 38) et leurs consultants de groupe de réflexion (n = 6). Cette évaluation pilote a présenté l'opportunité de concevoir une étude évaluant les impacts de la RC sur les professionnels de la santé des nourrissons et de la petite enfance. Cette méthode d'étude mixte a inclus une évaluation des compétences en pratique réflective des personnes consultées et de leurs expériences de leur travail. Les résultats ont inclus une pratique d'auto-efficacité réflective plus élevée (auto-rapportée par les consultés) et une utilisation de compétences de pratique de réflexion plus élevée. Bien qu'il n'y ait pas eu de changements dans la réalisation personnelle, l'épuisement émotionnel ou les résultats de dépersonnalisation de l'Inventaire de Burnout de Maslach (MBI) les résultats qualitatifs ont indiqué une baisse du burnout et une augmentation de la pratique basée sur la relation au travers des rôles professionnels. Cette étude pilote unique offre un exemple d'une approche organisationnelle de l'institution de la RC avec un grand éventail de professionnels de la santé des nourrissons et de la petite enfance et offre des renseignements très utiles sur les impacts des modèles de RC sur l'expérience du travail de tels professionnels et leur pratique professionnelle.

Open-label pilot study of oral methylprednisolone for the treatment of patients with friedreich ataxia.

INTRODUCTION: In this study we assessed the effect of methylprednisolone on safety, tolerability, and ability in Friedreich ataxia (FRDA). METHODS: The study was an open-label trial of pulse methylprednisolone on 11 participants with FRDA. All participants followed a 28-day treatment cycle, repeated 7 times. Patients were assessed with the timed 25-foot walk (T25FW), 1-minute walk (1MW), the Friedreich Ataxia Rating Scale (FARS), and the 9-hole peg test (9HPT). Efficacy was tested by comparing baseline and week 26 visits, separated into adult and pediatric groups. RESULTS: In comparisons of participants' baseline and week 26 visits, only the pediatric cohort's 1MW score showed change (P < 0.05). The T25FW, the primary outcome measure, did not change significantly. DISCUSSION: Pediatric participants improved their gait distance in the 1MW, but did not significantly improve in other measures in this overall negative study. Methylprednisolone was generally well tolerated, suggesting that it may be useful for ambulatory children with FRDA if benefit is found with further study.

Body Mass Index and Height in the Friedreich Ataxia Clinical Outcome Measures Study.

BACKGROUND AND OBJECTIVES: Body mass index (BMI) and height are important indices of health. We tested the association between these outcomes and clinical characteristics in Friedreich ataxia (FRDA), a progressive neuromuscular disorder. METHODS: Participants (N = 961) were enrolled in a prospective natural history study (Friedreich Ataxia Clinical Outcome Measure Study). Age- and sex-specific BMI and height Z-scores were calculated using CDC 2000 references for participants younger than 18 years. For adults aged 18 years or older, height Z-scores were also calculated, and absolute BMI was reported. Univariate and multivariate linear regression analyses tested the associations between exposures, covariates, and BMI or height measured at the baseline visit. In children, the superimposition by translation and rotation analysis method was used to compare linear growth trajectories between FRDA and a healthy reference cohort, the Bone Mineral Density in Childhood Study (n = 1,535 used for analysis). RESULTS: Median age at the baseline was 20 years (IQR, 13-33 years); 49% (n = 475) were women. A substantial proportion of children (17%) were underweight (BMI-Z < fifth percentile), and female sex was associated with lower BMI-Z (ß = -0.34, p < 0.05). In adults, older age was associated with higher BMI (ß = 0.09, p < 0.05). Regarding height, in children, older age (ß -0.06, p < 0.05) and worse modified Friedreich Ataxia Rating Scale (mFARS) scores (ß = -1.05 for fourth quartile vs first quartile, p < 0.01) were associated with shorter stature. In girls, the magnitude of the pubertal growth spurt was less, and in boys, the pubertal growth spurt occurred later (p < 0.001 for both) than in a healthy reference cohort. In adults, in unadjusted analyses, both earlier age of FRDA symptom onset (=0.09, p < 0.05) and longer guanine-adenine-adenine repeat length (shorter of the 2 GAA repeats, ß = -0.12, p < 0.01) were associated with shorter stature. Both adults and children with higher mFARS scores and/or who were nonambulatory were less likely to have height and weight measurements recorded at clinical visits. DISCUSSION: FRDA affects both weight gain and linear growth. These insights will inform assessments of affected individuals in both research and clinical settings.

Randomized, double-blind, placebo-controlled study of interferon-γ 1b in Friedreich Ataxia.

Objective: In vitro, in vivo, and open-label studies suggest that interferon gamma (IFN-γ 1b) may improve clinical features in Friedreich Ataxia through an increase in frataxin levels. The present study evaluates the efficacy and safety of IFN-γ 1b in the treatment of Friedreich Ataxia through a double-blind, multicenter, placebo-controlled trial. Methods: Ninety-two subjects with FRDA between 10 and 25 years of age were enrolled. Subjects received either IFN-γ 1b or placebo for 6 months. The primary outcome measure was the modified Friedreich Ataxia Rating Scale (mFARS). Results: No difference was noted between the groups after 6 months of treatment in the mFARS or secondary outcome measures. No change was noted in buccal cell or whole blood frataxin levels. However, during an open-label extension period, subjects had a more stable course than expected based on natural history data. Conclusions: This study provides no direct evidence for a beneficial effect of IFN-γ1b in FRDA. The modest stabilization compared to natural history data leaves open the possibility that longer studies may demonstrate benefit.

Pediatric Ataxia: Focus on Chronic Disorders.

Evaluation of a pediatric patient presenting with ataxia can be expensive and time consuming. Acute causes tend to have a clear developmental paradigm, but chronic presentations are more likely to be secondary to a genetic disorder, either one that primarily causes ataxia or that presents ataxia as one of a multitude of symptoms. Evaluation should focus on a quick diagnosis for those that have treatment options and for those that require other systemic monitoring. Friedreich ataxia is the most common, and genetic testing can easily confirm the suspicion. Testing for vitamin E (for ataxia with isolated vitamin E deficiency) and alpha fetoprotein (for Ataxia Telangiectasia or AT) are important, as is empiric treatment with coenzyme Q10 for those genetic abnormalities that can lead to coenzyme Q deficiency. Clear family history, disease progression, physical examination focusing on type of ataxia and other associated neurologic features, and investigation of systemic involvement can help in focusing clinical assessment.

Improvement in Quality Metrics Outcomes and Patient and Family Satisfaction in a Neurosciences Intensive Care Unit after Creation of a Dedicated Neurocritical Care Team.

INTRODUCTION: Dedicated neurointensivists have been shown to improve outcome measurements in the neurosciences intensive care unit (NSICU). Quality outcome data in relation to patient and family satisfaction is lacking. This study evaluated the impact of newly appointed neurointensivists and creation of a neurocritical care team on quality outcome measures including patient satisfaction in a NSICU. METHODS: This is a retrospective study of data over 36 months from a 14-bed NSICU evaluating quality outcome measures and anonymous patient satisfaction questionnaires before and after neurointensivists appointment. RESULTS: After appointment of neurointensivists, patient acuity of the NSICU increased by 33.4% while LOS decreased by 3.5%. There was a decrease in neurosciences mortality (35.8%), catheter-associated urinary tract infection (50%), central line associated bloodstream infection (100%), and ventilator-associated pneumonia (50%). During the same time, patient satisfaction increased by 28.3% on physicians/nurses consistency (p = 0.025), by 69.5% in confidence/trust in physicians (p < 0.0001), by 78.3% on physicians treated me with courtesy/respect (p < 0.0001), and by 46.4% on physicians' attentiveness (p < 0.0001). Ultimately, patients recommending the hospital to others increased by 67.5% (p < 0.0001). CONCLUSION: Dedicated neurointensivists and the subsequent development of a neurocritical care team positively impacted quality outcome metrics, particularly significantly improving patient satisfaction.

Pharmacological therapeutics in Friedreich ataxia: the present state.

INTRODUCTION: Friedreich ataxia (FRDA) is a progressive, inherited, neurodegenerative disease for which there is currently no cure or approved treatment. FRDA is caused by deficits in the production and expression of frataxin, a protein found in the mitochondria that is most likely responsible for regulating iron-sulfur cluster enzymes within the cell. A decrease in frataxin causes dysfunction of adenosine triphosphate synthesis, accumulation of mitochondrial iron, and other events leading to downstream cellular dysfunction. Areas covered: Therapeutic development for FRDA currently focuses on improving mitochondrial function and finding ways to increase frataxin expression. Additionally, the authors will review potential approaches aimed at iron modulation and genetic modulation. Finally, gene therapy is progressing rapidly and is being explored as a treatment for FRDA. Expert commentary: The collection of multiple therapeutic approaches provides many possible ways to treat FRDA. Although the mitochondrial approaches are not thought to be curative, as the primary frataxin deficit will remain, they may still produce improvements in quality of life and slowing of progression. Therapies aimed at frataxin restoration are more likely to truly modify the disease, with gene therapy as the best possibility to alter the course of the disease from both a cardiac and neurological perspective.

Impact of diabetes in the Friedreich ataxia clinical outcome measures study.

OBJECTIVE: Friedreich ataxia (FA) is a progressive neuromuscular disorder caused by GAA triplet repeat expansions or point mutations in the FXN gene. FA is associated with increased risk of diabetes mellitus (DM). This study assessed the age-specific prevalence of FA-associated DM and its impact on neurologic outcomes. RESEARCH DESIGN AND METHODS: Participants were 811 individuals with FA from 12 international sites in a prospective natural history study (FA Clinical Outcome Measures Study, FACOMS). Physical function was assessed, using validated instruments. Multivariable regression analyses examined the independent association of DM with outcomes. RESULTS: Mean age of participants was 30.1 years (SD 15.3, range: 7-82), 50% were female, and 94% were non-Hispanic white. 9% (42/459) of adults and 3% (10/352) of children had DM. Individuals with FA-associated DM were older (P < 0.001), had longer GAA repeat length on the least affected FXN allele (P = 0.037), and more severe FA (P = 0.0001). Of individuals with DM, 65% (34/52) were taking insulin. Even after accounting statistically for both age and GAA repeat length, DM was independently associated with greater FA symptom burden (P = 0.010), reduced capacity to perform activities of daily living (P = 0.021), and a decrease of 0.33 SDs on a composite performance measure (95% CI: -0.56-0.11, P = 0.004); the relative impact of DM was most apparent in younger individuals. CONCLUSIONS: DM-associated FA has an independent adverse impact on well-being in affected individuals, particularly at younger ages. In future, evidence-based approaches for identification and management of FA-related DM may improve both health and function.

Cardiac transplantation in Friedreich Ataxia: Extended follow-up.

Friedreich Ataxia (FRDA) is an autosomal recessive neurodegenerative disorder most commonly caused by guanine-adenine-adenine (GAA) trinucleotide repeat expansions in both alleles of the FXN gene. Although progressive ataxia remains the hallmark clinical feature, patients with FRDA are at high risk of developing cardiomyopathy, often resulting in premature death. There is no specific treatment for FRDA-associated cardiomyopathy; even in advanced cardiac failure cardiac transplantation is not commonly pursued. This case series describes extended follow-up of three FRDA cases with end-stage heart failure but mild neurologic disease who underwent successful heart transplantation. We also review and examine the ethical considerations for heart transplantation in the setting of neurodegenerative disease.

End-of-life decision making and implementation in recipients of a destination left ventricular assist device.

BACKGROUND: The use of left ventricular assist devices (LVADs) as destination therapy (DT) is increasing and has proven beneficial in prolonging survival and improving quality of life in select patients with end-stage heart failure. Nonetheless, end-of-life (EOL) issues are inevitable and how to approach them underreported. METHODS: Our DT data registry was queried for eligible patients, defined as those individuals who actively participated in EOL decision making. The process from early EOL discussion to palliation and death was reviewed. We recorded the causes leading to EOL discussion, time from EOL decision to withdrawal and from withdrawal to death, and location. Primary caregivers were surveyed to qualify their experience and identify themes relevant to this process. RESULTS: Between 1999 and 2009, 92 DT LVADs were implanted in 69 patients. Twenty patients qualified for inclusion (mean length of support: 833 days). A decrease in quality of life from new/worsening comorbidities usually prompted EOL discussion. Eleven patients died at home, 8 in the hospital and 1 in a nursing home. Time from EOL decision to LVAD withdrawal ranged from <1 day to 2 weeks and from withdrawal until death was <20 minutes in all cases. Palliative care was provided to all patients. Ongoing assistance from the healthcare team facilitated closure and ensured comfort at EOL. CONCLUSIONS: With expanding indications and improved technology, more DT LVADs will be implanted and for longer durations, and more patients will face EOL issues. A multidisciplinary team approach with protocols involving DT patients and their families in EOL decision making allows for continuity of care and ensures dignity and comfort at EOL.