Cell and gene therapy: a snapshot of investor perspectives.

In a collaborative effort between the Commercialization Committee of the International Society for Cell & Gene Therapy (ISCT) and Bloomberg Intelligence, a broad survey of the investment community was executed in order to understand investor perceptions of companies that develop cell and gene therapies (CGTs) and gauge the trajectory of future investment. A broad spectrum of investors responded to the survey, including both health care specialists and generalist investors across a wide range of fund sizes and geographies. A majority of survey respondents have limited exposure to CGTs in their health care portfolios today, which highlights the opportunity to increase awareness of this burgeoning field in the investment community.

Rehabilitation Needs of the Elderly Patient with Cancer.

Physiatrist taking care of the geriatric patient with cancer should be able to manage an array of conditions that might present from diagnosis throughout completion of treatments and beyond. The elderly cancer population is at greater risk of functional impairments. The physician should anticipate changes in clinical status and must adjust rehabilitation goals accordingly.

Treatment of Chemotherapy-Induced Peripheral Neuropathy in Integrative Oncology: A Survey of Acupuncture and Oriental Medicine Practitioners.

Objectives: Complementary and alternative medicine is increasingly integrated into cancer care. We sought detail on the treatment of chemotherapy-induced peripheral neuropathy (CIPN) with acupuncture and oriental medicine (AOM) by surveying practitioners at integrative oncology (IO) sites across the United States.

Design: Online survey of licensed acupuncturists.

Feasibility of the Tailored Activity Program for Hospitalized (TAP-H) Patients With Behavioral Symptoms.

Purpose Of The Study: To evaluate feasibility of implementing the Tailored Activity Program for Hospitals (TAP-H) to improve engagement in patients with dementia admitted for behavioral disturbances.

Design And Methods: TAP-H involves up to 11 in-hospital sessions to develop activities tailored to patient interests and capabilities and train staff/families in their use. Interventionists (occupational therapists) recorded session lengths, patient engagement (N = 20), and staff (N = 4) readiness to use activities.

Knowing versus doing: education and training needs of staff in a chronic care hospital unit for individuals with dementia.

Hospital clinical staff routinely confront challenging behaviors in patients with dementia with limited training in prevention and management. The authors of the current article conducted a survey of staff on a chronic care hospital unit concerning knowledge about dementia, perceived educational needs, and the care environment. The overall mean score for a 27-item knowledge scale was 24.

Feeder-independent culture systems for human pluripotent stem cells.

The continued success of pluripotent stem cell research is ultimately dependent on access to reliable and defined reagents for the consistent culture and cryopreservation of undifferentiated, pluripotent cells. The development of defined and feeder-independent culture media has provided a platform for greater reproducibility and standardization in this field. Here we provide detailed protocols for the use of mTeSR™1 and TeSR™2 with various cell culture matrices as well as defined cryopreservation protocols for human embryonic and human induced pluripotent stem cells.

Clinimetrics corner: the many faces of selection bias.

Selection bias, also known as susceptibility bias in an intervention study or spectrum bias in a diagnostic accuracy study, is present throughout clinically applicable evidence in various forms. Selection bias implies that the intervention or diagnostic test has been studied in a less representative sample population, which can lead to inflated overall effect sizes and/or inaccurate findings. Within the literature, there are over 40 forms of selection bias that can influence the external validity of results.

Mitochondrial loss, dysfunction and altered dynamics in Huntington's disease.

Although a direct causative pathway from the gene mutation to the selective neostriatal neurodegeneration remains unclear in Huntington's disease (HD), one putative pathological mechanism reported to play a prominent role in the pathogenesis of this neurological disorder is mitochondrial dysfunction. We examined mitochondria in preferentially vulnerable striatal calbindin-positive neurons in moderate-to-severe grade HD patients, using antisera against mitochondrial markers of COX2, SOD2 and cytochrome c. Combined calbindin and mitochondrial marker immunofluorescence showed a significant and progressive grade-dependent reduction in the number of mitochondria in spiny striatal neurons, with marked alteration in size.

Uridine ameliorates the pathological phenotype in transgenic G93A-ALS mice.

There is strong evidence from studies in humans and animal models to suggest the involvement of energy metabolism defects in neurodegenerative diseases. Uridine, a pyrimidine nucleoside, has been suggested to be neuroprotective in neurological disorders by improving bioenergetic effects, increasing ATP levels and enhancing glycolytic energy production. We assessed whether uridine treatment extended survival and improved the behavioral and neuropathological phenotype observed in G93A-ALS mice.

Reduced creatine kinase as a central and peripheral biomarker in Huntington's disease.

A major goal of current clinical research in Huntington's disease (HD) has been to identify preclinical and manifest disease biomarkers, as these may improve both diagnosis and the power for therapeutic trials. Although the underlying biochemical alterations and the mechanisms of neuronal degeneration remain unknown, energy metabolism defects in HD have been chronicled for many years. We report that the brain isoenzyme of creatine kinase (CK-BB), an enzyme important in buffering energy stores, was significantly reduced in presymptomatic and manifest disease in brain and blood buffy coat specimens in HD mice and HD patients.

Endoglin is not critical for hematopoietic stem cell engraftment and reconstitution but regulates adult erythroid development.

Endoglin is a transforming growth factor-beta (TGF-beta) accessory receptor recently identified as being highly expressed on long-term repopulating hematopoietic stem cells (HSC). However, little is known regarding its function in these cells. We have used two complementary approaches toward understanding endoglin's role in HSC biology: one that efficiently knocks down expression via lentiviral-driven short hairpin RNA and another that uses retroviral-mediated overexpression.

Smad4 is critical for self-renewal of hematopoietic stem cells.

Members of the transforming growth factor beta (TGF-beta) superfamily of growth factors have been shown to regulate the in vitro proliferation and maintenance of hematopoietic stem cells (HSCs). Working at a common level of convergence for all TGF-beta superfamily signals, Smad4 is key in orchestrating these effects. The role of Smad4 in HSC function has remained elusive because of the early embryonic lethality of the conventional knockout.

Smad7 promotes self-renewal of hematopoietic stem cells.

The Smad-signaling pathway downstream of the transforming growth factor-beta superfamily of ligands is an evolutionarily conserved signaling circuitry with critical functions in a wide variety of biologic processes. To investigate the role of this pathway in the regulation of hematopoietic stem cells (HSCs), we have blocked Smad signaling by retroviral gene transfer of the inhibitory Smad7 to murine HSCs. We report here that the self-renewal capacity of HSCs is promoted in vivo upon blocking of the entire Smad pathway, as shown by both primary and secondary bone marrow (BM) transplantations.

Smad5 is dispensable for adult murine hematopoiesis.

Smad5 is known to transduce intracellular signals from bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-beta (TGF-beta) superfamily and are involved in the regulation of hematopoiesis. Recent findings suggest that BMP4 stimulates proliferation of human primitive hematopoietic progenitors in vitro, while early progenitors from mice deficient in Smad5 display increased self-renewal capacity in murine embryonic hematopoiesis. Here, we evaluate the role of Smad5 in the regulation of hematopoietic stem cell (HSC) fate decisions in adult mice by using an inducible MxCre-mediated conditional knockout model.

Anemia, thrombocytopenia, leukocytosis, extramedullary hematopoiesis, and impaired progenitor function in Pten+/-SHIP-/- mice: a novel model of myelodysplasia.

The myeloproliferative disorder of mice lacking the Src homology 2 (SH2)-containing 5' phosphoinositol phosphatase, SHIP, underscores the need for closely regulating phosphatidylinositol 3-kinase (PI3K) pathway activity, and hence levels of phosphatidylinositol species during hematopoiesis. The role of the 3' phosphoinositol phosphatase Pten in this process is less clear, as its absence leads to embryonic lethality. Despite Pten heterozygosity being associated with a lymphoproliferative disorder, we found no evidence of a hematopoietic defect in Pten(+/-) mice.