An open‐label, single‐arm, phase 2 study of single‐agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93582/1/bjh9232.pd

AAPT Diagnostic Criteria for Chronic Cancer Pain Conditions

Chronic cancer pain is a serious complication of malignancy or its treatment. Currently, no comprehensive, universally accepted cancer pain classification system exists. Clarity in classification of common cancer pain syndromes would improve clinical assessment and management. Moreover, an evidence-based taxonomy would enhance cancer pain research efforts by providing consistent diagnostic criteria, ensuring comparability across clinical trials. As part of a collaborative effort between the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) and the American Pain Society (APS), the ACTTION-APS Pain Taxonomy (AAPT) initiative worked to develop the characteristics of an optimal diagnostic system.59, 65 Following the establishment of these characteristics, a working group consisting of clinicians and clinical and basic scientists with expertise in cancer and cancer-related pain was convened to generate core diagnostic criteria for an illustrative sample of 3 chronic pain syndromes associated with cancer (i.e., bone pain and pancreatic cancer pain as models of pain related to a tumor) or its treatment (i.e., chemotherapy-induced peripheral neuropathy). A systematic review and synthesis was conducted to provide evidence for the dimensions that comprise this cancer pain taxonomy. Future efforts will subject these diagnostic categories and criteria to systematic empirical evaluation of their feasibility, reliability and validity and extension to other cancer-related pain syndromes

The search for translational pain outcomes to refine analgesic development: Where did we come from and where are we going?

Pain measures traditionally used in rodents record mere reflexes evoked by sensory stimuli; the results thus may not fully reflect the human pain phenotype. Alterations in physical and emotional functioning, pain-depressed behaviors and facial pain expressions were recently proposed as additional pain outcomes to provide a more accurate measure of clinical pain in rodents, and hence to potentially enhance analgesic drug development. We aimed to review how preclinical pain assessment has evolved since the development of the tail flick test in 1941, with a particular focus on a critical analysis of some nonstandard pain outcomes, and a consideration of how sex differences may affect the performance of these pain surrogates. We tracked original research articles in Medline for the following periods: 1973-1977, 1983-1987, 1993-1997, 2003-2007, and 2014-2018. We identified 606 research articles about alternative surrogate pain measures, 473 of which were published between 2014 and 2018. This indicates that preclinical pain assessment is moving toward the use of these measures, which may soon become standard procedures in preclinical pain laboratories.FPU grant from the Spanish Ministry of Education, Culture and SportsSpanish Ministry of Economy and Competitiveness (MINECO, grant SAF2016-80540-R)Ramón Areces FoundationJunta de Andalucía (grant CTS 109)Esteve PharmaceuticalsEuropean Regional Development Fund (ERDF

Reproductive inequality in humans and other mammals

Data, Materials, and Software Availability: All study data are included in the article and/or supporting information available online at https://www.pnas.org/lookup/doi/10.1073/pnas.2220124120#supplementary-materials .Copyright © 2023 the Author(s). To address claims of human exceptionalism, we determine where humans fit within the greater mammalian distribution of reproductive inequality. We show that humans exhibit lower reproductive skew (i.e., inequality in the number of surviving offspring) among males and smaller sex differences in reproductive skew than most other mammals, while nevertheless falling within the mammalian range. Additionally, female reproductive skew is higher in polygynous human populations than in polygynous nonhumans mammals on average. This patterning of skew can be attributed in part to the prevalence of monogamy in humans compared to the predominance of polygyny in nonhuman mammals, to the limited degree of polygyny in the human societies that practice it, and to the importance of unequally held rival resources to women’s fitness. The muted reproductive inequality observed in humans appears to be linked to several unusual characteristics of our species—including high levels of cooperation among males, high dependence on unequally held rival resources, complementarities between maternal and paternal investment, as well as social and legal institutions that enforce monogamous norms.This work was conducted as a part of the “Emergence of Hierarchy and Leadership in Mammalian Societies” group at the National Institute for Mathematical and Biological Synthesis, supported by NSF Award DBI-1300426 and the University of Tennessee, Knoxville. It was supported by NSF awards SMA-1329089 and SMA-1743019, and the Santa Fe Institute, as well as the Max Planck Institute for Evolutionary Anthropology, Department of Human Behavior, Ecology and Culture. S.G. was supported by the US Army Research Office grants W911NF-14-1-0637, W911NF-17-1-0150, and the Office of Naval Research grant W911NF-18-1-0138. Additional funding for data collection was provided by the Wenner-Gren Foundation for Anthropological Research awards: 8913 and 7970, by NSF awards: BCS-0924630, BCS-0925910, BCS-0848360, BCS-0514559, BCS-0613226, BCS-0827277, SES-9870429, and DDRIG-1357209, by the National Geographic Society awards: HJ-099R-17, 20113909, 8671-09, and 7968-06, by the Kone Foundation awards: 086809, 088423, and 088423, and by the Jacobs Foundation, the UCSB Broom Center for Demography, and the UCSB Department of Anthropology

doi:10.1016/j.neulet.2009.02.031

a b s t r a c t Treatment for cancer has been indicated to negatively impact the quality of life for patients. Specifically, chemotherapy has been associated with fatigue, nausea, and peripheral neuropathy. More recently, chemotherapy has been found to be related to cognitive impairment in various domains including working memory, information processing speed, and visual attention. At this time, the mechanisms underlying cognitive impairment are not understood, and there is currently no treatment for this condition. The purpose of this study was to examine the development of chemotherapy-induced cognitive impairments and symptoms of peripheral neuropathy. While receiving the chemotherapeutic agent Taxol, animals were tested daily in the Five Choice Serial Reaction Time Task (5CSRTT), a task which requires animals to respond to a visually presented stimulus in order to obtain reinforcement. In addition, animals were tested for the development of peripheral neuropathy, measured by changes in sensitivity to mechanical stimulation. The results indicate Taxol treated animals developed mechanical sensitivity within 24 h after the first injection of chemotherapy. However, relative to control animals, Taxol treated animals did not exhibit alterations in cognitive function in the 5CSRTT. These differential findings may provide interesting insight into the mechanisms underlying chemotherapy-related cognitive impairment

The anterior cingulate cortex and pain processing

The neural network that contributes to the suffering which accompanies persistent pain states involves a number of brain regions. Of primary interest is the contribution of the cingulate cortex in processing the affective component of pain. The purpose of this review is to summarize recent data obtained using novel behavioral paradigms in animals based on measuring escape and/or avoidance of a noxious stimulus. These paradigms have successfully been used to study the nature of the neuroanatomical and neurochemical contributions of the anterior cingulate cortex to higher order pain processing in rodents