Editors’ Introduction

This special section focuses on genocide and related mass violence in Latin America. Clearly there is a long history of genocide of indigenous peoples, from the arrival of Columbus and other conquerors to the present day. Perpetrated first by European colonial powers, particularly Spain and Portugal, genocidal activities continued in postcolonial settler states following the revolutions of the nineteenth century. Government shifted from Europe to local Euro-American, as well as in some cases indigenous, elites, who shared economic and thus political power with imperialist international actors—including, in many cases, the United States and some of its large corporations. Human-rights abuses continued. In the second half of the twentieth century, the Cold War–era National Security Doctrine, as well as state- specific tensions and agendas, played out in various Latin American contexts in a new round of repression, genocide, and other forms of mass violence. The Guate- malan Genocide of the 1980s and systematic killings and general military repression under dictatorships in Chile and Argentina in the 1970s and 1980s are perhaps the best-known cases, but others abound

The Drėlingas case, the limits of law, and new avenues for repair of and resistance to genocide

The Drėlingas decision corrected the failure of the Vasiliauskas case to establish that the Soviet Union committed genocide through its targeting of Lithuanian resisters to a campaign of denationalization. This approach was required because of the UN Genocide Convention’s limitations, but the cost of success was ignoring the political aspect of this genocide, which is inseparable from its national aspect. The decision also reinforced the Convention’s flawed focus on individuals rather than the social formations that actually commit genocide – in this case, the Soviet Union. The most significant implication of Drėlingas, however, is its determination that those who engaged in armed resistance to a process less than genocidal could themselves be victims of genocide. The Drėlingas decision thus provides a profoundly important counterbalance to the prevailing tendency to treat resistance to oppression as participation in a mutual conflict disallowing genocidal victimization and the pervasive prejudicial preference for helpless victims

A contrapelo: reflexiones críticas sobre el presente y el futuro de los estudios sobre genocidio

Este artículo propone una crítica a ciertas tendencias dentro de los estudios sobre genocidio, entre las que aparecen el abuso del prestigio y de la obra de Lemkin, el alejamiento frente a las posturas del activismo académico contra el genocidio, el tono displicente con el que se aborda la agencia política de los grupos de víctimas, las tendencias relativistas del concepto de “políticas de la memoria” y su implementación, la creciente institucionalización del campo, el concepto de “generocidio” y la imagen opaca que supone la violencia genocida dirigida contra mujeres y niñas, el foco en la deshumanización como condición para el genocidio y el énfasis en las advertencias tempranas. El artículo también discute una nueva estrategia negacionista del genocidio. A la luz de ello, las advertencias tempranas sobre el genocidio son, en gran medida, inoperantes. Más allá de la indiferencia política que explica la existencia de genocidios perpetrados incluso en la actualidad, la preeminencia de este delito se debe al hecho de que el orden mundial del presente y muchas sociedades específicas fueron moldeados por el genocidio y la violación en masa y la opresión vinculadas con ese primer crimen. El artículo sostiene que un proceso global de reparación podría ayudar a encauzar el mundo y alejarlo de los fundamentos y tendencias genocidas

Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease

Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung

In this study, we detail a novel approach that combines bacterial fitness fluorescent reporter strains with scRNA-seq to simultaneously acquire the host transcriptome, surface marker expression, and bacterial phenotype for each infected cell. This approach facilitates the dissection of the functional heterogeneity of M. tuberculosis-infected alveolar (AMs) and interstitial macrophages (IMs) in vivo. We identify clusters of pro-inflammatory AMs associated with stressed bacteria, in addition to three different populations of IMs with heterogeneous bacterial phenotypes. Finally, we show that the main macrophage populations in the lung are epigenetically constrained in their response to infection, while inter-species comparison reveals that most AMs subsets are conserved between mice and humans. This conceptual approach is readily transferable to other infectious disease agents with the potential for an increased understanding of the roles that different host cell populations play during the course of an infection

Metabolic changes in concussed American football players during the acute and chronic post-injury phases

<p>Abstract</p> <p>Background</p> <p>Despite negative neuroimaging findings many athletes display neurophysiological alterations and post-concussion symptoms that may be attributable to neurometabolic alterations.</p> <p>Methods</p> <p>The present study investigated the effects of sports concussion on brain metabolism using ¹H-MR Spectroscopy by comparing a group of 10 non-concussed athletes with a group of 10 concussed athletes of the same age (mean: 22.5 years) and education (mean: 16 years) within both the acute and chronic post-injury phases. All athletes were scanned 1-6 days post-concussion and again 6-months later in a 3T Siemens MRI.</p> <p>Results</p> <p>Concussed athletes demonstrated neurometabolic impairment in prefrontal and motor (M1) cortices in the acute phase where NAA:Cr levels remained depressed relative to controls. There was some recovery observed in the chronic phase where Glu:Cr levels returned to those of control athletes; however, there was a pathological increase of m-I:Cr levels in M1 that was only present in the chronic phase.</p> <p>Conclusions</p> <p>These results confirm cortical neurometabolic changes in the acute post-concussion phase as well as recovery and continued metabolic abnormalities in the chronic phase. The results indicate that complex pathophysiological processes differ depending on the post-injury phase and the neurometabolite in question.</p

Post-translational modifications of voltage-gated sodium channels in chronic pain syndromes.

In the peripheral sensory nervous system the neuronal expression of voltage-gated sodium channels (Navs) is very important for the transmission of nociceptive information since they give rise to the upstroke of the action potential (AP). Navs are composed of nine different isoforms with distinct biophysical properties. Studying the mutations associated with the increase or absence of pain sensitivity in humans, as well as other expression studies, have highlighted Nav1.7, Nav1.8, and Nav1.9 as being the most important contributors to the control of nociceptive neuronal electrogenesis. Modulating their expression and/or function can impact the shape of the AP and consequently modify nociceptive transmission, a process that is observed in persistent pain conditions. Post-translational modification (PTM) of Navs is a well-known process that modifies their expression and function. In chronic pain syndromes, the release of inflammatory molecules into the direct environment of dorsal root ganglia (DRG) sensory neurons leads to an abnormal activation of enzymes that induce Navs PTM. The addition of small molecules, i.e., peptides, phosphoryl groups, ubiquitin moieties and/or carbohydrates, can modify the function of Navs in two different ways: via direct physical interference with Nav gating, or via the control of Nav trafficking. Both mechanisms have a profound impact on neuronal excitability. In this review we will discuss the role of Protein Kinase A, B, and C, Mitogen Activated Protein Kinases and Ca++/Calmodulin-dependent Kinase II in peripheral chronic pain syndromes. We will also discuss more recent findings that the ubiquitination of Nav1.7 by Nedd4-2 and the effect of methylglyoxal on Nav1.8 are also implicated in the development of experimental neuropathic pain. We will address the potential roles of other PTMs in chronic pain and highlight the need for further investigation of PTMs of Navs in order to develop new pharmacological tools to alleviate pain

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.Peer reviewe