Expression pattern of protein kinase C δ during mouse embryogenesis

BACKGROUND: The members of the protein kinase C (PKC) family consist of serine/threonine kinases classified according to their regulatory domain. Those that belong to the novel PKC subfamily, such as PKCδ, are dependent on diacylglycerol but not Calcium when considering their catalytic activity. Although several studies have shown the importance of PKCδ in different cellular events in health and disease, the overall in vivo distribution of this PKC isoform during development is still lacking. Through Lac Z and antibody staining procedures, we show here the in vivo expression of PKCδ during mouse embryogenesis. RESULTS: Ganglia were the domains with most prominent expression of PKCδ in most of the stages analysed, although PKCδ could also be detected in heart and somites at earlier stages, and cartilage primordium and skin among other sites in older embryos. CONCLUSIONS: The strong expression of PKCδ in ganglia during murine development shown in this study suggests a significant role of this isoform as well as redundancy with other PKCs within the nervous system, since PKCδ deficient mice develop normally

Evolution of Geriatric Medicine: Midcareer Faculty Continuing the Dialogue

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137692/1/jgs14842_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137692/2/jgs14842.pd

Introduction

Species categories are not simply an invention of the human mind. Plants, animals, fungi, and viruses engage in species making by mingling and separating.1 Yet, at the same time, the boundaries that define or differentiate species are not simply natural ; they are actively made, maintained, politically charged, and fashioned to serve some needs more than others, inviting new essentialisms even as they alert us to important differences. Like other rubrics for organizing social worlds—race, ethnicity, gender, age, ability—the concept of species and the alternative classifications it invites are complicated and controversial. Whether wild or domestic, pet or pest, such categories are subject to temporally fluctuating human motives, shifting values, and cultural diversities

Introduction

Species categories are not simply an invention of the human mind. Plants, animals, fungi, and viruses engage in species making by mingling and separating.1 Yet, at the same time, the boundaries that define or differentiate species are not simply natural ; they are actively made, maintained, politically charged, and fashioned to serve some needs more than others, inviting new essentialisms even as they alert us to important differences. Like other rubrics for organizing social worlds—race, ethnicity, gender, age, ability—the concept of species and the alternative classifications it invites are complicated and controversial. Whether wild or domestic, pet or pest, such categories are subject to temporally fluctuating human motives, shifting values, and cultural diversities

Precision treatment of Singleton Merten syndrome with ruxolitinib: a case report.

BACKGROUND Singleton-Merten syndrome 1 (SGMRT1) is a rare type I interferonopathy caused by heterozygous mutations in the IFIH1 gene. IFIH1 encodes the pattern recognition receptor MDA5 which senses viral dsRNA and activates antiviral type I interferon (IFN) signaling. In SGMRT1, IFIH1 mutations confer a gain-of-function which causes overactivation of type I interferon (IFN) signaling leading to autoinflammation. CASE PRESENTATION We report the case of a nine year old child who initially presented with a slowly progressive decline of gross motor skill development and muscular weakness. At the age of five years, he developed osteoporosis, acro-osteolysis, alveolar bone loss and severe psoriasis. Whole exome sequencing revealed a pathogenic de novo IFIH1 mutation, confirming the diagnosis of SGMRT1. Consistent with constitutive type I interferon activation, patient blood cells exhibited a strong IFN signature as shown by marked up-regulation of IFN-stimulated genes. The patient was started on the Janus kinase (JAK) inhibitor, ruxolitinib, which inhibits signaling at the IFN-α/β receptor. Within days of treatment, psoriatic skin lesions resolved completely and the IFN signature normalized. Therapeutic efficacy was sustained and over the course muscular weakness, osteopenia and growth also improved. CONCLUSIONS JAK inhibition represents a valuable therapeutic option for patients with SGMRT1. Our findings also highlight the potential of a patient-tailored therapeutic approach based on pathogenetic insight

Exploring the mechanisms underlying the effectiveness of psychosocial aftercare in pediatric chronic pain treatment: a qualitative approach

A newly developed specialized psychosocial aftercare program (PAC) for pediatric patients with chronic pain following an intensive interdisciplinary pain treatment (IIPT) was found to be significantly more effective than IIPT alone. This qualitative study aimed to gain further insight into the mechanisms and prerequisites for the effectiveness of this specialized aftercare program. We conducted structured telephone interviews with patients, parents, and health care professionals conducting PAC. A total of 16 interviews were conducted—seven interviews with parents, six interviews with patients, and three interviews with health care professionals—and transcribed verbatim. Data were analyzed using reflexive thematic analysis. Four major themes consisting of 20 subcategories were identified, namely (1) frame conditions, (2) person factors, (3) stabilization and (4) catalyst. The foundations of treatment success are frame conditions, such as flexibility or constancy, and person factors, such as respect or expertise. Based on these foundations, stabilization is achieved through security, mediation, orientation and support. Altogether, these components of PAC reveal their potential as catalysts for further improvement even after discharge from IIPT. Overall, patients and their families emphasized widespread personal relevance and acceptance of the PAC program. The findings of this study may be employed in the development of other aftercare programs or interventions involving families in the context of psychotherapeutic and psychosocial health care

Results From a Survey of American Geriatrics Society Members’ Views on Physician‐Assisted Suicide

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152741/1/jgs16245_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152741/2/jgs16245-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152741/3/jgs16245.pd

AGS Position Statement: Making Medical Treatment Decisions for Unbefriended Older Adults

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135987/1/jgs14586_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135987/2/jgs14586.pd

Determining the pathogenicity of CFTR missense variants : multiple comparisons of in silico predictors and variant annotation databases

Pathogenic variants in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) are responsible for cystic fibrosis (CF), the commonest monogenic autosomal recessive disease, and CFTR-related disorders in infants and youth. Diagnosis of such diseases relies on clinical, functional, and molecular studies. To date, over 2,000 variants have been described on CFTR (~40% missense). Since few of them have confirmed pathogenicity, in silico analysis could help molecular diagnosis and genetic counseling. Here, the pathogenicity of 779 CFTR missense variants was predicted by consensus predictor PredictSNP and compared to annotations on CFTR2 and ClinVar. Sensitivity and specificity analysis was divided into modeling and validation phases using just variants annotated on CFTR2 and/or ClinVar that were not in the validation datasets of the analyzed predictors. After validation phase, MAPP and PhDSNP achieved maximum specificity but low sensitivity. Otherwise, SNAP had maximum sensitivity but null specificity. PredictSNP, PolyPhen-1, PolyPhen-2, SIFT, nsSNPAnalyzer had either low sensitivity or specificity, or both. Results showed that most predictors were not reliable when analyzing CFTR missense variants, ratifying the importance of clinical information when asserting the pathogenicity of CFTR missense variants. Our results should contribute to clarify decision making when classifying the pathogenicity of CFTR missense variants