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Party vibrancy can help parties reproduce themselves, but many long-lasting parties have exhausted former levels of vibrancy, and many new parties emerge and never form the intense connections that vibrancy entails. Yet while entrepreneurs forming parties under democracy may have the option to sidetrack developing party structures, new parties can and do build extensive grassroots networks. I suspect that many parties that Luna et al. code as fulfilling the core tasks of political parties would generate sufficient attachment from activists that Rosenblatt would code them as being vibrant, while most diminished subtype parties would not. Party History and Organization Ackerman focuses on the opportunities parties have to build connections with the public, and Van Dyck focuses on the incentives that parties have to do so. [Extracted from the article]

Background: The COVID-19 pandemic (March 2020-May 2023) had a profound effect around the world with vulnerable people being particularly affected, including worsening existing health inequalities. This article explores the impact of the pandemic on health services for First Nations people living with HIV (FN-PWLE) in Manitoba, Canada. This study investigated perceptions of both health care providers and FN-PWLE through qualitative interviews occurring between July 2020 and February 2022 to understand their experience and identify lessons learned that could be translated into health system changes. Methods: Using a qualitative, participatory-action, intentional decolonizing approach for this study we included an Indigenous knowledge keeper and Indigenous research associates with lived experience as part of the study team. A total of twenty-five [25] in-depth semi-structured interviews were conducted with eleven healthcare providers (HCPs) and fourteen First Nation people with lived HIV experience (FN-PWLE). In total, 18/25 or 72% of the study participants self-identified as First Nation people. Results: The COVID-19 pandemic negatively impacted health services access for FN-PWLE, a) disrupted relationships between FN-PWLE and healthcare providers, b) disrupted access to testing, in-person appointments, and medications, and c) intersectional stigma was compounded. Though, the COVID-19 pandemic also led to positive effects, including the creation of innovative solutions for the health system overall. Conclusions: The COVID-19 pandemic exaggerated pre-existing barriers and facilitators for Manitoba FN-PWLE accessing and using the healthcare system. COVID-19 impacted health system facilitators such as relationships and supports, particularly for First Nation people who are structurally disadvantaged and needing more wrap-around care to address social determinants of health. Innovations during times of crisis, included novel ways to improve access to care and medications, illustrated how the health system can quickly provide solutions to long-standing barriers, especially for geographical barriers. Lessons learned from the COVID-19 pandemic should be considered for improvements to the health system's HIV cascade of care for FN-PWLE and other health system improvements for First Nations people with other chronic diseases and conditions. Finally, this study illustrates the value of qualitative and First Nation decolonizing research methods. Further studies are needed, working together with First Nations organizations and communities, to apply these recommendations and innovations to change health care and people's lives. [ABSTRACT FROM AUTHOR]

Democracy is weakened when citizens and elites do not criticize actions or actors that undermine its principles. Yet this study documents a widespread pattern of partisan rationalization in how elites and the public evaluate democratic performance in Latin America. Survey data show that those whose party controls the presidency consistently express positive evaluations of the current state of democratic competition and institutions even when democracy in their country is weak. This pattern emerges in both mass survey data and among elected elites. These data have a worrying implication: if only the political opposition is willing to publicly acknowledge and sound the alarm when democracy is under attack, public pressure to protect democracy is likely to be dramatically reduced. [ABSTRACT FROM AUTHOR]

Background: Aging dogs may suffer from canine cognitive dysfunction syndrome (CCDS), a condition in which cognitive decline is associated with amyloid pathology and cortical atrophy. Presumptive diagnosis is made through physical examination, exclusion of systemic/metabolic conditions, and completion of screening questionnaires by owners.Objective: This study aimed to determine whether cognitive function could be quantified in aging pet dogs, and to correlate cognitive testing with validated questionnaires and plasma neurofilament light chain (pNfL) concentration.Methods: Thirty-nine dogs from fifteen breeds were recruited (9.3 to 15.3 years). Owners completed the Canine Dementia Scale (CADES) and Canine Cognitive Dysfunction Rating scale (CCDR). Executive control and social cues were tested, and pNfL was measured with single molecule array assay. Comparisons were made between cognitive testing scores, CADES, CCDR scores, and pNfL.Results: CADES scoring classified five dogs as severe CCDS, six as moderate, ten as mild, and eighteen as normal. CCDR identified seven dogs at risk of CCDS and thirty-two as normal. Cognitive testing was possible in the majority of dogs, although severely affected dogs were unable to learn tasks. CADES score correlated with sustained attention duration (r = -0.47, p = 0.002), inhibitory control (r = -0.51, p = 0.002), detour (r = -0.43, p = 0.001), and pNfL (r = 0.41, p = 0.025). Concentration of pNfL correlated with inhibitory control (r = -0.7, p≤0.001). The CCDR scale correlated with performance on inhibitory control (r = -0.46, p = 0.005).Conclusion: Our findings suggest that a multi-dimensional approach using a combination of questionnaires, specific cognitive tests, and pNfL concentration can be used to quantify cognitive decline in aging pet dogs. [ABSTRACT FROM AUTHOR]

A robust economy is assumed to bolster leaders' standing. This ignores how benefits of growth are distributed. Extending the partisan models of economic voting, we theorize executives are more likely rewarded when gains from growth go to their constituents. Analyses of presidential approval in 18 Latin American countries support our pro-constituency model of accountability. When economic inequality is high, growth concentrates among the rich, and approval of right-of-center presidents is higher. Leftist presidents benefit from growth when gains are more equally distributed. Further analyses show growth and inequality inform perceptions of personal finances differently based on wealth, providing a micro-mechanism behind the aggregate findings. Study results imply that the economy is not purely a valence issue, but also a position issue. [ABSTRACT FROM AUTHOR]

Public evaluations of the economy are key for understanding how citizens develop policy opinions and monitor government performance. But what drives economic evaluations? In this article, we argue the context in which information about the economy is distributed shapes economic perceptions. In high-quality information environments—where policies are transparent, the media is free, and political opposition is robust—mass perceptions closely track economic conditions. In contrast, compromised information environments provide openings for political manipulation, leading perceptions to deviate from business cycle fluctuations. We test our argument with unique data from eight Latin American countries. Results show restrictions on access to information distort the public's view of economic performance. The ability of voters to sanction governments is stronger when democratic institutions and the media protect citizens' access to independent, unbiased information. Our findings highlight the importance of accurate evaluations of the economy for government accountability and democratic responsiveness. [ABSTRACT FROM AUTHOR]

Introduction: Trauma patients who develop indications for therapeutic anticoagulation (TAC) present a challenge due to concern for bleeding. Transfusion requirement has been described as a common complication of TAC after trauma but its clinical relevance is unclear.Objective: Determine risk factors for and clinical outcomes associated with transfusion requirement on TAC after trauma.Methods: All trauma patients admitted to an academic urban level I trauma center from January 2010 to August 2020 who received TAC were included in this retrospective cohort study. Data included injury characteristics; TAC indication and timing; transfusions; and interventions. Patients who required transfusion after TAC were compared to those who did not.Results: Eighty-two patients were included. The most common reasons for TAC were deep vein thrombosis (67.1%) and pulmonary embolism (31.7%). Two (2.4%) patients developed gastrointestinal bleeding. One (1.2%) underwent endoscopic intervention. Two patients (4.9%) had intracranial hemorrhage progression. Blood transfusion after TAC initiation was required in 43.9% of patients. Patients who were transfused started TAC more quickly after traumatic injury (5.5 vs 10.0 days, P = .03), had fewer hospital-free days (54 vs 64 days, P < .01), ICU-free days (8.5 vs 16.5 days, P = .01), and higher mortality (13.9% vs 2.1%, P = .04).Conclusion: Transfusions are common after starting TAC in trauma patients. Requiring transfusion after starting TAC was associated with shorter time from injury to starting TAC, higher mortality, and fewer ICU and hospital-free days. [ABSTRACT FROM AUTHOR]

HIV-1 integrase-LEDGF allosteric inhibitors (INLAIs) share the binding site on the viral protein with the host factor LEDGF/p75. These small molecules act as molecular glues promoting hyper-multimerization of HIV-1 IN protein to severely perturb maturation of viral particles. Herein, we describe a new series of INLAIs based on a benzene scaffold that display antiviral activity in the single digit nanomolar range. Akin to other compounds of this class, the INLAIs predominantly inhibit the late stages of HIV-1 replication. A series of high-resolution crystal structures revealed how these small molecules engage the catalytic core and the C-terminal domains of HIV-1 IN. No antagonism was observed between our lead INLAI compound BDM-2 and a panel of 16 clinical antiretrovirals. Moreover, we show that compounds retained high antiviral activity against HIV-1 variants resistant to IN strand transfer inhibitors and other classes of antiretroviral drugs. The virologic profile of BDM-2 and the recently completed single ascending dose phase I trial (ClinicalTrials.gov identifier: NCT03634085) warrant further clinical investigation for use in combination with other antiretroviral drugs. Moreover, our results suggest routes for further improvement of this emerging drug class.

Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are an emerging class of small molecules that disrupt viral maturation by inducing the aberrant multimerization of IN. Here, we present cocrystal structures of HIV-1 IN with two potent ALLINIs, namely, BI-D and the drug candidate Pirmitegravir. The structures reveal atomistic details of the ALLINI-induced interface between the HIV-1 IN catalytic core and carboxyl-terminal domains (CCD and CTD). Projecting from their principal binding pocket on the IN CCD dimer, the compounds act as molecular glue by engaging a triad of invariant HIV-1 IN CTD residues, namely, Tyr226, Trp235, and Lys266, to nucleate the CTD-CCD interaction. The drug-induced interface involves the CTD SH3-like fold and extends to the beginning of the IN carboxyl-terminal tail region. We show that mutations of HIV-1 IN CTD residues that participate in the interface with the CCD greatly reduce the IN-aggregation properties of Pirmitegravir. Our results explain the mechanism of the ALLINI-induced condensation of HIV-1 IN and provide a reliable template for the rational development of this series of antiretrovirals through the optimization of their key contacts with the viral target. IMPORTANCE Despite the remarkable success of combination antiretroviral therapy, HIV-1 remains among the major causes of human suffering and loss of life in poor and developing nations. To prevail in this drawn-out battle with the pandemic, it is essential to continue developing advanced antiviral agents to fight drug resistant HIV-1 variants. Allosteric integrase inhibitors (ALLINIs) are an emerging class of HIV-1 antagonists that are orthogonal to the current antiretroviral drugs. These small molecules act as highly specific molecular glue, which triggers the aggregation of HIV-1 integrase. In this work, we present high-resolution crystal structures that reveal the crucial interactions made by two potent ALLINIs, namely, BI-D and Pirmitegravir, with HIV-1 integrase. Our results explain the mechanism of drug action and will inform the development of this promising class of small molecules for future use in antiretroviral regimens.