Rare homozygous nonsense variant in AIMP1 causing Early Onset Epileptic Encephalopathy with Burst Suppression (EOEE-BS).

Pathogenic variants in AIMP1 gene are rare causes of neurologic disorders. Homozygous frameshift and nonsense variants in AIMP1 have been described in severe neurodegenerative disease. This is the third report of a homozygous nonsense variant in AIMP1 [c.115 C > T (p.Gln39*)] in a girl with severe neonatal onset epileptic encephalopathy. Like the two other cases reported, our patient is also of Filipino descent. Clinical features include microcephaly, poor visual motor development, shallow breathing, severe hypertonia in extremities, severe global developmental delay, poor gag and suck reflex, failure to thrive in the neonatal period, and early onset intractable seizures. Brain MRI showed hypoplasia of corpus callosum as well as cerebellar vermis, global volume loss and diminished myelination for her age. Electroencephalogram at four months of age showed background consisting of synchronous and asynchronous intervals of burst suppression with intermittent multifocal spikes predominantly in the bi-temporal region, suggestive of Early Onset Epileptic Encephalopathy with Burst Suppression (EOEE-BS) which has not been previously associated with the c.115 C > T variant in AIMP1. Of note, she presented to us in super refractory status epilepticus which was eventually controlled after administration of ketogenic diet and Epidiolex (cannabidiol). This report expands the genetic landscape of EOEE-BS. This is the first case of this specific variant in which Epidiolex was administered, which along with Ketogenic diet aided in controlling patient's super refractory status epilepticus.

[Risk factors for the development and recurrence of pressure ulcers in patients with spinal cord injury: A systematic review.] / Factores de riesgo para la aparición y/o recurrencia de úlceras por presión en sujetos con lesión medular: revisión sistemática.

Introduction: A spinal cord injury refers to the damage suffered in the spinal cord as a result of trauma, disease or degeneration. Every person with spinal cord injury is at risk of developing pressure ulcers, and almost everyone will develop at least one ulcer due to severe pressure during his or her life. Objective: To identify the studies that detected risk factors for the development and recurrence of pressure ulcers in patients with spinal cord injury; and, if possible, synthesize the evidence to determine whether an association exists between them. Methods: A systematic search was conducted in Medline, LILACS, SciELO and Cochrane until December 4, 2018. The following studies were included: observational studies, case-control studies, and prospective or retrospective cohort studies, which provided an adjusted analysis of the risk factors associated with the development and recurrence of pressure ulcers in patients with spinal cord injury. Results: 25 articles met the eligibility criteria and were included for analysis. A total of 30 risk factors were identified: 4 were demographic factors, 8 were related to the injury, 5 belonged to medical comorbidities, 3 to nutritional factors, 9 were psychological, cognitive, contextual and social factors and 1 was related to support surface. As regards the factors, 56.67 percent of them were classified as non-modifiable. Conclusion: 30 risk factors were identified for the development and recurrence of pressure ulcers in patients with spinal cord injury. However, we were not able to synthesize the evidence due to the heterogeneity of the articles included in this review.

Introducción: Una lesión medular hace referencia a los daños sufridos en la médula espinal a consecuencia de un traumatismo, enfermedad o degeneración. Todas las personas con lesión medular corren riesgo de desarrollar úlceras por presión y casi todas desarrollarán al menos una úlcera por presión grave durante su vida. Objetivo: Identificar los estudios que detectaron factores de riesgo para la aparición y/o recurrencia de úlceras por presión en sujetos con lesión medular. Y de ser posible, sintetizar la evidencia para detectar asociación entre los mismos. Método: Se realizó una búsqueda sistemática en Medline, LILACS, SciELO y Cochrane hasta el 4 de diciembre del año 2018. Se incluyeron estudios observacionales, casos-controles y de cohorte, retrospectivos o prospectivos, que realizaron un análisis ajustado de los factores de riesgo para el desarrollo y/o recurrencia de úlceras por presión en sujetos con lesión medular. Resultados: 25 artículos cumplieron los criterios de elegibilidad y fueron incluidos para el análisis. Se identificaron un total de 30 factores de riesgo, de los cuales 4 fueron factores demográficos, 8 relacionados con la lesión, 5 pertenecieron a comorbilidades médicas, 3 a factores nutricionales, 9 fueron factores psicológicos, cognitivos, contextuales y sociales y 1 estuvo relacionado con la superficie de apoyo. El 56,67% se clasificaron como no modificables. Conclusión: Se identificaron 30 factores de riesgo para la aparición y/o recurrencia de úlceras por presión en sujetos con lesión medular. No fue posible sintetizar la evidencia debido a la heterogeneidad presentada por los artículos incluidos en la presente revisión.

Mutation update for the SATB2 gene.

SATB2-associated syndrome (SAS) is an autosomal dominant neurodevelopmental disorder caused by alterations in the SATB2 gene. Here we present a review of published pathogenic variants in the SATB2 gene to date and report 38 novel alterations found in 57 additional previously unreported individuals. Overall, we present a compilation of 120 unique variants identified in 155 unrelated families ranging from single nucleotide coding variants to genomic rearrangements distributed throughout the entire coding region of SATB2. Single nucleotide variants predicted to result in the occurrence of a premature stop codon were the most commonly seen (51/120 = 42.5%) followed by missense variants (31/120 = 25.8%). We review the rather limited functional characterization of pathogenic variants and discuss current understanding of the consequences of the different molecular alterations. We present an expansive phenotypic review along with novel genotype-phenotype correlations. Lastly, we discuss current knowledge of animal models and present future prospects. This review should help provide better guidance for the care of individuals diagnosed with SAS.

mRCC Outcome in the Treatment of Metastatic Renal Cell Carcinoma - A German Single-center Real-world Experience.

BACKGROUND/AIM: Since the advent of targeted therapeutics, paradigms in metastatic renal cell carcinoma (mRCC) treatment have changed. We investigated if efficacy and safety data from randomized controlled trials can be transferred into real-world settings. PATIENTS AND METHODS: All patients with mRCC treated from 2006-2015 at the Department of Urology (Marburg-Germany) were retrospectively analyzed. Collected data include: Patient demographics, tumor characteristics, efficacy, safety, and used therapy sequences. RESULTS: In total, 197 patients with mRCC were identified. About one third of patients reached third-line therapy. Median overall survival in real-world amounted to 25.8 months with a five-year survival rate of 30% with significant differences between IMDC risk groups (p<0.01). Response rates were highest using tyrosine kinase inhibitor (TKI). Patients with response to therapy showed significantly improved survival (p<0.05). Side-effects in each therapy line were manageable in daily practice. CONCLUSION: Our data suggest that targeted therapy in the treatment of mRCC is effective and safe in daily clinical practice and for real-world patients.

Covert Stuttering: Investigation of the Paradigm Shift From Covertly Stuttering to Overtly Stuttering.

Purpose: Covert stuttering is a type of stuttering experience that occurs when a person who stutters conceals his or her stutter from others, attempting to be perceived as a nonstuttering individual. A person who covertly stutters experiences the cognitive and emotional elements of stuttering with minimum overt behavioral symptoms. Individuals who covertly stutter are able to provide insight into their experiences in attempting to be perceived as nonstuttering individuals. Covert stuttering is a topic that continues to be in need of a formal definition. The current investigation is utilizing thematic analysis to provide a detail-rich investigation of the paradigm shift from covertly stuttering to overtly stuttering. Method: The current investigation is a qualitative analysis of individuals' transition process from covertly stuttering to overtly stuttering. Real-time video interviews were conducted with the use of open-ended phenomenological interview questions. Interviews were transcribed, and thematic analysis of interview transcripts was conducted to investigate the covertly to overtly stuttering process for participants. Results: The findings provide insight into a paradigm shift that occurs when individuals who covertly stutter begin to outwardly identify themselves and allow for overt stuttering. The primary theme was a paradigm shift in the 6 participants' mindset regarding stuttering; additional details are provided in the subthemes: attending speech therapy, meeting other people who stutter, and a psychological low point. The details of the covert-to-overt stuttering conversion are documented with the use of direct quotations. Conclusion: The evidence suggests the various intricacies of the experiences of persons who are covert. Clinical implications of these findings for assessing and treating individuals who covertly stutter are discussed.

Postpartum relapse to cigarette smoking in inner city women.

Past studies suggest that African American women who quit smoking during pregnancy are more likely to relapse during the postpartum period than white women, although it is not intuitively clear why this should be the case. To shed further light on this issue, two studies were carried out to determine factors that influence smoking cessation during pregnancy and postpartum relapse to smoking in a predominantly low-income African American population. In Study 1, the women were asked to fill out a written survey, and in Study 2, women participated in a structured interview. The same variables that influence smoking cessation and postpartum relapse in the general population, such as nicotine addiction levels, smoking by other members of the household, lack of social support, stress, weight gain, behavioral intentions to quit temporarily, and quitting for others, as opposed to one's self, influenced the behavior of low-income inner city residents. These findings suggest that the difference in rates of postpartum relapse to smoking in African American women and the general population is a matter of degree, rather than kind. The implications of these findings for understanding postpartum relapse in general and assisting low-income women in particular were discussed.