A scoping review and critique of the Input-Output subtyping dimension of spatial neglect.

Spatial neglect is a common and debilitating disorder after stroke whereby individuals have difficulty reporting, orienting, and/or responding to the contralesional side of space. Given the heterogeneity of neglect symptom presentation, various neglect subtypes have been proposed to better characterize the disorder. This review focuses on the distinction between Input neglect (i.e., difficulty perceiving and/or attending to contralesional stimuli) and Output neglect (i.e., difficulty planning and/or executing movements toward contralesional stimuli). Conceptualizations of Input and Output neglect have varied considerably. We provide a novel summary of the terminology, measurement approaches, and neural correlates of these subtypes. A protocol detailing our systematic scoping review strategy is registered on the Open Science Framework (https://osf.io/bvtxf/). For feasibility and greater comparability across studies, we limited our inclusion criteria to tasks focused on visual stimuli and upper-limb movements. A total of 110 articles were included in the review. Subtyping tasks were categorized based on whether they mainly manipulated aspects of the input (i.e., congruence of visual input with motor output, presence of visual input) or the output (i.e., modality, goal, or direction of output) to produce an Input-Output subtype dissociation. We used our review results to identify four main critiques of this literature: 1) lack of consistency/clarity in conceptual models; 2) methodological issues of dissociating Input and Output subtypes; 3) a need for updated neural theories; and 4) barriers to clinical application. We discuss the lessons learned from this subtyping dimension that can be applied to future research on neglect subtype assessment and treatment.

Nonoptimal bacteria species induce neutrophil-driven inflammation and barrier disruption in the female genital tract.

Neutrophil recruitment and activation within the female genital tract are often associated with tissue inflammation, loss of vaginal epithelial barrier integrity, and increased risk for sexually transmitted infections, such as HIV-1. However, the direct role of neutrophils on vaginal epithelial barrier function during genital inflammation in vivo remains unclear. Using complementary proteome and immunological analyses, we show high neutrophil influx into the lower female genital tract in response to physiological surges in progesterone, stimulating distinct stromal, immunological, and metabolic signaling pathways. However, despite the release of extracellular matrix-modifying proteases and inflammatory mediators, neutrophils contributed little to physiological mucosal remodeling events such as epithelial shedding or re-epithelialization during transition from diestrus to estrus phase. In contrast, the presence of bacterial vaginosis-associated bacteria resulted in a rapid and sustained neutrophil recruitment, resulting in vaginal epithelial barrier leakage and decreased cell-cell junction protein expression in vivo. Thus, neutrophils are important mucosal sentinels that rapidly respond to various biological cues within the female genital tract, dictating the magnitude and duration of the ensuing inflammatory response at steady state and during disease processes.

Notch and Schwann cell transformation.

Benign plexiform neurofibromas in NF1 patients can transform spontaneously into malignant peripheral nerve sheath tumors (MPNSTs). Although mutations in the p53 gene have been found in a subset of MPNSTs and mouse models support a role for p53 mutations in malignant conversion, we found that each of three Schwann cell lines derived from human MPNSTs possessed active p53. One of the lines expressed the Notch intracellular domain (NICD), indicative of ongoing Notch signaling. Consistent with a role in malignancy, NICD was able to transform primary rat Schwann cells. Transformation was robust--NICD-transduced cells generated tumors in nude rats--and was associated with the loss of markers associated with Schwann cell differentiation. These data suggest that aberrant Notch signaling may contribute to the conversion of benign neurofibromas to MPNSTs.