Memory impairments and heightened prefrontal cortical (PFC) activity are hallmarks of cognitive and neurobiological human aging. While structural integrity of PFC gray matter and interregional white matter tracts are thought to impact memory processing, the balance of neurotransmitters within the PFC itself is less well understood. We used fMRI to establish whole-brain networks involved in a memory encoding task and dynamic causal models (DCMs) for fMRI to determine the causal relationships between these areas. These data revealed enhanced connectivity from PFC to medial temporal cortex that negatively correlated with recall ability. To better understand the intrinsic activity within the PFC, DCM for EEG was employed after continuous theta burst transcranial magnetic stimulation (TMS) to the PFC to assess the effect on excitatory/inhibitory (E/I) synaptic ratios and behavior. These data revealed that the young cohort had a stable E/I ratio that was unaffected by the TMS intervention, while the aged cohort exhibited lower E/I ratios driven by a greater intrinsic inhibitory tone. TMS to the aged cohort resulted in decreased intrinsic inhibition and a decrement in memory performance. These results demonstrate increased top-down influence of PFC upon medial temporal lobe in healthy aging that is associated with decreased memory and may be due to unstable local inhibitory tone within the PFC.

Lumbar degenerative disc disease is a pathologic process that affects a large portion of our aging population. In the recent past, surgical treatment has involved fusion procedures. However, lumbar disc arthroplasty and replacement provides an alternative for carefully selected patients. It provides the major advantage of motion preservation and thus keeps adjacent segments from significantly progressive degeneration. The history of lumbar disc replacement has roots that start in the 1960s with the implantation of stainless-steel balls. Decades later, multiple implants with different material design and biomechanical properties were introduced to the market. New third-generation implants have made great strides in improved biomechanics and clinical outcomes. Although there is room for further advancement and studies are warranted to assess the long-term durability and sustainability of lumbar disc arthroplasty, it has certainly proven to be a very acceptable alternative within the surgical armamentarium that should be offered to patients who meet indications. In this review we present an overview of lumbar disc arthroplasty including its history, indications, biomechanics, challenges, and future directions.

Immunotherapy with antigen-specific T cells is a promising, targeted therapeutic option for patients with cancer as well as for immunocompromised patients with virus infections. In this review, we characterize and compare current manufacturing protocols for the generation of T cells specific to viral and non-viral tumor-associated antigens. Specifically, we discuss: (1) the different methodologies to expand virus-specific T cell and non-viral tumor-associated antigen-specific T cell products, (2) an overview of the immunological principles involved when developing such manufacturing protocols, and (3) proposed standardized methodologies for the generation of polyclonal, polyfunctional antigen-specific T cells irrespective of donor source. Ex vivo expanded cells have been safely administered to treat numerous patients with virus-associated malignancies, hematologic malignancies, and solid tumors. Hence, we have performed a comprehensive review of the clinical trial results evaluating the safety, feasibility, and efficacy of these products in the clinic. In summary, this review seeks to provide new insights regarding antigen-specific T cell technology to benefit a rapidly expanding T cell therapy field.