Context Of Therapeutic Interventions Research Articles

An implementation science systematic review of neurophysiological evidence indicates the tinnitus core network as a therapeutic target

Identifying and implementing an effective tinnitus treatment has been a challenge. Despite efforts over many decades, there is no definitive cure for tinnitus yet. Implementation science may assist audiology practitioners and end-user patients in their pursuit of a cure by identifying ways to maximize the use of research findings. Within the context of therapeutic interventions, implementation science is the study of a successful treatment–system fit evidenced by use. Research evidence for tinnitus treatment efficacy is dominated by behavioral questionnaires as they are a pragmatic source of patient-driven data. Neurophysiological evidence of the underlying neural network change correlated with these behavioral findings enhances research conclusions and potential use. This implementation science review systematically sourced and analyzed neurophysiological evidence from 29 studies to find that targeting tinnitus core network neuroplasticity may be the most effective tinnitus treatment. Narrow-band sound treatment has the greatest body of correlated neurophysiological-behavioral evidence. This is the first tinnitus implementation science systematic review. It is hoped that new or improved treatments may emerge from pivoting the evidential lens toward the pragmatic use of neurophysiological evidence.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022335201.

Confessions of a mind-wandering MBSR student: remembering social amnesia

Based upon a first-person experience of a Mindfulness-Based Stress Reduction (MBSR) program, this article provides a critical reflection on this clinical intervention within the context of late capitalist society. It draws inspiration from Russell Jacoby's critique of contemporary psychology, what he referred to as ‘social amnesia’, a form of collective forgetting, manifesting as a tendency to repress, forget, and exclude the larger social, historical, and political context of therapeutic interventions. With its fetishization of the present moment, MBSR is predicated on a politics of subjectivity that assumes stress is localized to the failure of the individual to regulate their emotions.

Reduced AKT/mTOR signaling and protein synthesis dysregulation in a Rett syndrome animal model

Rett syndrome (RTT) is a neurodevelopmental disorder with no efficient treatment that is caused in the majority of cases by mutations in the gene methyl-CpG binding-protein 2 (MECP2). RTT becomes manifest after a period of apparently normal development and causes growth deceleration, severe psychomotor impairment and mental retardation. Effective animal models for RTT are available and show morphofunctional abnormalities of synaptic connectivity. However, the molecular consequences of MeCP2 disruption leading to neuronal and synaptic alterations are not known. Protein synthesis regulation via the mammalian target of the rapamycin (mTOR) pathway is crucial for synaptic organization, and its disruption is involved in a number of neurodevelopmental diseases. We investigated the phosphorylation of the ribosomal protein (rp) S6, whose activation is highly dependent from mTOR activity. Immunohistochemistry showed that rpS6 phosphorylation is severely affected in neurons across the cortical areas of Mecp2 mutants and that this alteration precedes the severe symptomatic phase of the disease. Moreover, we found a severe defect of the initiation of protein synthesis in the brain of presymptomatic Mecp2 mutant that was not restricted to a specific subset of transcripts. Finally, we provide evidence for a general dysfunction of the Akt/mTOR, but not extracellular-regulated kinase, signaling associated with the disease progression in mutant brains. Our results indicate that defects in the AKT/mTOR pathway are responsible for the altered translational control in Mecp2 mutant neurons and disclosed a novel putative biomarker of the pathological process. Importantly, this study provides a novel context of therapeutic interventions that can be designed to successfully restrain or ameliorate the development of RTT.

Ionizing radiation effects on the KG1a primitive hematopoietic cell line

Better understanding of radiation-induced effects on the hematopoietic system is important in both the context of therapeutic intervention and accidental exposure. However, direct study of these effects on the hematopoietic stem cell pool is hampered by the small number of accessible cells. We, thus, studied radiation-induced effects on the KG1a stem cell line. We confirmed and extended the immunophenotype of KG1a with monoclonal antibodies, established a radiation survival curve, and quantified mRNAs by Northern blotting 30 min after 1, 2, and 3 Gy of ionizing radiation (IR) and followed for up to 48 h after a 3 Gy dose. Cell cycle status and apoptosis were assessed by fluorescent-activated cell sorter (FACS) analysis, cell morphology, and DNA fragmentation. KG1a was found to be CD34+, CD7+, Thy1 low, CD38 low, lineage negative (neg), C-KITneg and HLA-DRneg, a phenotype consistent with a primitive hematopoietic origin. This immunophenotype was not altered by x-ray irradiation. The D0 value was 1.75 Gy. We showed a time-dependent variation of c-jun mRNA expression with an early and transient dose-dependent induction followed by a second increase at 24 and 48 h: a biphasic dose-dependent variation of bcl-2 expression 30 min after irradiation with a reduction of mRNA level at 1 Gy, and a normalization at higher doses and stable levels of mRNA for c-fos, c-myc, G-CSF, GM-CSF, IL-6, TNF-alpha, TGF-beta, and MIP-1 alpha genes. Cell cycle analysis showed the absence of G1/S phase arrest, a point consistent with the absence of detection of P53 mRNA by Northern blot analysis. The dose-dependent G2/M phase arrest was not followed by significant apoptotic cell death. Taken together, this data indicates that radiation-induced cell death of KG1a, a cell line that has a relatively high D0 value, does not seem to be the result of the apoptotic pathway but occurs subsequent to a G2/M phase arrest.