Early Investigations and Recent Advances in Intraperitoneal Immunotherapy for Peritoneal Metastasis.

Peritoneal metastasis (PM) is an advanced stage malignancy largely refractory to modern therapy. Intraperitoneal (IP) immunotherapy offers a novel approach for the control of regional disease of the peritoneal cavity by breaking immune tolerance. These strategies include heightening T-cell response and vaccine induction of anti-cancer memory against tumor-associated antigens. Early investigations with chimeric antigen receptor T cells (CAR-T cells), vaccine-based therapies, dendritic cells (DCs) in combination with pro-inflammatory cytokines and natural killer cells (NKs), adoptive cell transfer, and immune checkpoint inhibitors represent significant advances in the treatment of PM. IP delivery of CAR-T cells has shown demonstrable suppression of tumors expressing carcinoembryonic antigen. This response was enhanced when IP injected CAR-T cells were combined with anti-PD-L1 or anti-Gr1. Similarly, CAR-T cells against folate receptor α expressing tumors improved T-cell tumor localization and survival when combined with CD137 co-stimulatory signaling. Moreover, IP immunotherapy with catumaxomab, a trifunctional antibody approved in Europe, targets epithelial cell adhesion molecule (EpCAM) and has shown considerable promise with control of malignant ascites. Herein, we discuss immunologic approaches under investigation for treatment of PM

Revival of the American Labor Movement: Issues, Problems, Prospects

[Excerpt] The purpose of this book is to examine union revitalization efforts: to identify central developments, to analyze strengths and weaknesses in the new initiatives, and to assessprogress made and prospects for the future. We ask questions such as: Can union decline be reversed? Are there serious indications of revitalization beyond new leadership and publicity? What accounts for successes and failures so far, and what strategies have shown the most promise for future success? Can innovations in areas such as vocational training consortia contribute to labor movement revitalization? Are there ways to reconcile the contradictions between an organizing model of unionism and the traditional member-focused servicing model of the postwar era? Can unions successfully target relevant groups (beyond the existing blue-collar and public-sector bases) such as women, minorities, service employees, semiprofessionals, and professionals? Can political action and legislative campaigns on issues such as trade contribute to reversing the decline, or is this only a way to hold the line (or even worse, an inadequate strategy of the past)? This book is designed to target these and related questions by bringing together the work of highly regarded experts whose research and analysis indicate contrasting answers and perspectives. There is, to be sure, a great deal of opinion trumpeting on many of these questions; the focus here, by contrast, is on research: hard evidence and causal analysis provide grounded answers and realistic perspectives. We hope that the analysis presented will offer meaningful signposts for future research as well as for policymakers and union leaders regarding what is and is not possible, what may and may not work

Depression in Right Hemisphere Disorder

Between 25-79% of stroke survivors suffer depression, which can lead to limited recovery, decreased quality of life, and increased mortality. In adults with right hemisphere disorder (RHD), the cause(s) of depression have been unclear. Our results showed that significantly more adults with RHD were depressed than normal controls, and that adults with RHD were significantly more depressed than normal controls. In both groups, depression was significantly related with loneliness. In adults with RHD, depression was also significantly related with social support. No demographic or lesion-related variables were associated with increased depression in our samples. Suggestions for treatment research are offered

Risk Factors for Depression in Aphasia: Clinical Implications

Between 25-79% of stroke survivors suffer depression, which can limit recovery, decrease quality of life, and increase mortality. In adults with aphasia, the cause(s) of depression, and thus the means by which it can be addressed, have been unclear. Our participants with aphasia did not differ from our normal controls in presence or severity of depression. However, possible causes of depression differed between groups. In both groups, loneliness was a significant factor. In adults with aphasia, other significant factors were time poststroke, severity of language impairment, and desired control over every day events. Suggestions for research and treatment are offered

Tidal controls on the lithospheric thickness and topography of Io from magmatic segregation and volcanism modelling

Tidal heating is expected to impart significant, non-spherically-symmetric structure to Jupiter's volcanic moon Io. A signature of spatially variable tidal heating is generally sought in observations of surface heat fluxes or volcanic activity, an exploration complicated by the transient nature of volcanic events. The thickness of the lithosphere is expected to change over much longer timescales, and so may provide a robust link between surface observations and the tidal heating distribution. To predict long-wavelength lithospheric thickness variations, we couple three-dimensional tidal heating calculations to a suite of one-dimensional models of magmatic segregation and volcanic eruption. We find that the lithospheric thickness could either be correlated with the radially integrated heating rate, or weakly anti-correlated. Lithospheric thickness is correlated with radially integrated heating rate if magmatic intrusions form at a constant rate in the lithosphere, but is weakly anti-correlated if intrusions form at a rate proportional to the flux through volcanic conduits. Utilising a simple isostasy model we show how variations in lithospheric thickness can predict long-wavelength topography. The relationship between lithospheric thickness and topography depends on the difference in chemical density between the lithosphere and mantle. Assuming that this difference is small, we find that long-wavelength topography anti-correlates with lithospheric thickness. These results will allow future observations to critically evaluate models for Io's lithospheric structure, and enable their use in constraining the distribution of tidal heating.Comment: Published in Icaru

In-vivo Vomeronasal Stimulation Reveals Sensory Encoding of Conspecific and Allospecific Cues by the Mouse Accessory Olfactory Bulb

The rodent vomeronasal system plays a critical role in mediating pheromone-evoked social and sexual behaviors. Recent studies of the anatomical and molecular architecture of the vomeronasal organ (VNO) and of its synaptic target, the accessory olfactory bulb (AOB), have suggested that unique features underlie vomeronasal sensory processing. However, the neuronal representation of pheromonal information leading to specific behavioral and endocrine responses has remained largely unexplored due to the experimental difficulty of precise stimulus delivery to the VNO. To determine the basic rules of information processing in the vomeronasal system, we developed a unique preparation that allows controlled and repeated stimulus delivery to the VNO and combined this approach with multisite recordings of neuronal activity in the AOB. We found that urine, a well-characterized pheromone source in mammals, as well as saliva, activates AOB neurons in a manner that reliably encodes the donor animal’s sexual and genetic status. We also identified a significant fraction of AOB neurons that respond robustly and selectively to predator cues, suggesting an expanded role for the vomeronasal system in both conspecific and interspecific recognition. Further analysis reveals that mixed stimuli from distinct sources evoke synergistic responses in AOB neurons, thereby supporting the notion of integrative processing of chemosensory information.Molecular and Cellular Biolog

The effect of cyclosporine A on survival time in salicylate-poisoned rats.

Salicylate (SAL) produces mitochondrial membrane permeability transition (MPT) with resultant oxidative phosphorylation uncoupling. Cyclosporine A (CSA) inhibits SAL-induced MPT. This study determined if CSA pretreatment prolonged survival time in SAL-poisoned rats. Twenty-nine rats were randomized to receive pre-treatment with either 30 mg/kg CSA or equal volume of control diluent intraperitoneally (i.p.). Four hours later, all rats received 1700 mg/kg sodium salicylate i.p. Survival time, whole blood CSA ([CSA]), and serum sodium ([Na]), glucose and SAL ([SAL]) concentrations were determined. The results showed median survival time for controls was 18 min (95% CI 14-22 min) and for CSA animals was 14 min (95% CI 13-15 min). Univariate and multivariate analyses and Cox proportional hazard regression revealed CSA treatment was associated with higher [SAL], which was associated with shortened survival times. The CSA group also demonstrated shorter survival times for a given [SAL]. In conclusion, CSA pre-treatment shortened survival in SAL-poisoned rats

An intelligent computer-based spelling task for chronic aphasic patients

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Microaphasiology and the Computerized Clinician

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A Computerized Treatment System for Chronic Aphasic Patients

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