Stable transduction of the neonatal mouse liver using a hybrid rAAV/sleeping beauty transposon gene delivery system.

Background: Conventional adeno-associated viral (AAV) vectors, while highly effective in quiescent cells such as hepatocytes in the adult liver, confer less durable transgene expression in proliferating cells owing to episome loss. Sustained therapeutic success is therefore less likely in liver disorders requiring early intervention. We have previously developed a hybrid, dual virion approach, recombinant AAV (rAAV)/piggyBac transposon system capable of achieving stable gene transfer in proliferating hepatocytes at levels many fold above conventional AAV vectors.

Sleeping Beauty mRNA-LNP enables stable rAAV transgene expression in mouse and NHP hepatocytes and improves vector potency.

Recombinant adeno-associated virus (rAAV) vector gene delivery systems have demonstrated great promise in clinical trials but continue to face durability and dose-related challenges. Unlike rAAV gene therapy, integrating gene addition approaches can provide curative expression in mitotically active cells and pediatric populations. We explored a novel in vivo delivery approach based on an engineered transposase, Sleeping Beauty (SB100X), delivered as an mRNA within a lipid nanoparticle (LNP), in combination with an rAAV-delivered transposable transgene.

AAV-delivered hepato-adrenal cooperativity in steroidogenesis: Implications for gene therapy for congenital adrenal hyperplasia.

Despite the availability of life-saving corticosteroids for 70 years, treatment for adrenal insufficiency is not able to recapitulate physiological diurnal cortisol secretion and results in numerous complications. Gene therapy is an attractive possibility for monogenic adrenocortical disorders such as congenital adrenal hyperplasia; however, requires further development of gene transfer/editing technologies and knowledge of the target progenitor cell populations. Vectors based on adeno-associated virus are the leading system for direct gene delivery but have limitations in targeting replicating cell populations such as in the adrenal cortex.

Hand preference predicts behavioral responses to threats in Barbary macaques.

The structure and functioning of the brain are lateralized-the right hemisphere processes unexpected stimuli and controls spontaneous behavior, while the left deals with familiar stimuli and routine responses. Hemispheric dominance, the predisposition of an individual using one hemisphere over the other, may lead to behavioral differences; particularly, an individual may be programed to act in a certain way concerning hemispheric dominance. Hand preference is a robust estimator of hemispheric dominance in primates, as each hemisphere controls the opposing side of the body.

Sick or Sad? A Qualitative Study on How Dutch GPs Deal With Sadness Complaints Among Young Adults.

Feelings of sadness among young adults related to a certain phase of life or to societal factors run the risk of being interpreted as an individual medical problem. Therefore, healthcare professionals should more often widen their perspective and consider de-medicalization as being part of their professional responsibility too. This article presents results from a qualitative interview conducted with 13 GPs in different phases of their career to get more insight into the way they deal with complaints of sadness among young adults.

Development of a Prognostic Survival Algorithm for Patients with Metastatic Spine Disease.

Background: Current prognostication models for survival estimation in patients with metastatic spine disease lack accuracy. Identifying new risk factors could improve existing models. We assessed factors associated with survival in patients surgically treated for spine metastases, created a classic scoring algorithm, nomogram, and boosting algorithm, and tested the predictive accuracy of the three created algorithms at estimating survival.

Validation of the Spine Oncology Study Group-Outcomes Questionnaire to assess quality of life in patients with metastatic spine disease.

Background Context: General questionnaires are often used to assess quality of life in patients with spine metastases, although a disease-specific survey did not exist until recently. The Spine Oncology Study Group has developed an outcomes questionnaire (SOSG-OQ) to measure quality of life in these patients. However, a scoring system was not developed, and the questionnaire was not validated in a group of patients, nor was it compared with other general quality of life questionnaires such as the EuroQol 5 Dimensions (EQ-5D) questionnaire.