Programable Albumin-Hitchhiking Nanobodies Enhance the Delivery of STING Agonists to Potentiate Cancer Immunotherapy.

Stimulator of interferon genes (STING) is a promising target for potentiating antitumor immunity, but multiple pharmacological barriers limit the clinical utility, efficacy, and/or safety of STING agonists. Here we describe a modular platform for systemic administration of STING agonists based on nanobodies engineered for hitchhiking of agonist cargo on serum albumin. Using site-selective bioconjugation chemistries to produce molecularly defined products, we found that covalent conjugation of a STING agonist to anti-albumin nanobodies improved pharmacokinetics and increased cargo accumulation in tumor tissue, stimulating innate immune programs that increased the infiltration of activated natural killer cells and T cells, which potently inhibited tumor growth in multiple mouse tumor models.

STING-Activating Polymer-Drug Conjugates for Cancer Immunotherapy.

The stimulator of interferon genes (STING) pathway links innate and adaptive antitumor immunity and therefore plays an important role in cancer immune surveillance. This has prompted widespread development of STING agonists for cancer immunotherapy, but pharmacological barriers continue to limit the clinical impact of STING agonists and motivate the development of drug delivery systems to improve their efficacy and/or safety. To address this challenge, we developed SAPCon, a STING-activating polymer-drug conjugate platform based on strain-promoted azide-alkyne cycloaddition of dimeric-amidobenzimidazole (diABZI) STING agonists to hydrophilic polymer chains through an enzyme-responsive chemical linker.

Cannabis Retail Market Indicators in Five Legal States in the United States: A Public Health Perspective.

Purpose: Adult-use cannabis markets are operating in multiple US states and abroad. Sales and licensing data for alcohol and tobacco are often used to understand consumption patterns and evaluate policy changes. Cannabis market data may provide similar insights, although these newly legal markets are complex and evolving, and the state data structures can differ.

A Research Agenda to Inform Cannabis Regulation: How Science Can Shape Policy.

In the United States, changes to cannabis policy have outpaced scientific knowledge about cannabis, its effects, and the impacts of different policy approaches. Research barriers stem from key federal policies, including strict drug scheduling of cannabis, which comprehensively hinder the ability to conduct cannabis research, affecting state markets, evidence-based regulation, and scientific gains that could more effectively shape policy moving forward. The Cannabis Regulators Association (CANNRA) is a nonpartisan nonprofit organization that convenes and supports government agencies to facilitate information exchange and learning from existing cannabis regulations across US states and territories and other governmental jurisdictions.

STING-activating nanoparticles normalize the vascular-immune interface to potentiate cancer immunotherapy.

The tumor-associated vasculature imposes major structural and biochemical barriers to the infiltration of effector T cells and effective tumor control. Correlations between stimulator of interferon genes (STING) pathway activation and spontaneous T cell infiltration in human cancers led us to evaluate the effect of STING-activating nanoparticles (STANs), which are a polymersome-based platform for the delivery of a cyclic dinucleotide STING agonist, on the tumor vasculature and attendant effects on T cell infiltration and antitumor function. In multiple mouse tumor models, intravenous administration of STANs promoted vascular normalization, evidenced by improved vascular integrity, reduced tumor hypoxia, and increased endothelial cell expression of T cell adhesion molecules.

Chemical and Biomolecular Strategies for STING Pathway Activation in Cancer Immunotherapy.

The stimulator of interferon genes (STING) cellular signaling pathway is a promising target for cancer immunotherapy. Activation of the intracellular STING protein triggers the production of a multifaceted array of immunostimulatory molecules, which, in the proper context, can drive dendritic cell maturation, antitumor macrophage polarization, T cell priming and activation, natural killer cell activation, vascular reprogramming, and/or cancer cell death, resulting in immune-mediated tumor elimination and generation of antitumor immune memory. Accordingly, there is a significant amount of ongoing preclinical and clinical research toward further understanding the role of the STING pathway in cancer immune surveillance as well as the development of modulators of the pathway as a strategy to stimulate antitumor immunity.

Cannabis sales increases during COVID-19: Findings from Alaska, Colorado, Oregon, and Washington.

Background And Aims: Following emergency declarations related to COVID-19 in the United States, many states issued stay-at-home orders and designated essential business categories. Most states allowed medical and/or non-medical adult-use cannabis retailers to remain open. This study assesses changes in cannabis sales across Alaska, Colorado, Oregon, and Washington before and during the pandemic.

Delirium and abnormal autonomic nervous system response to head-up tilt testing.

Background: Delirium is a common condition with poorly understood pathophysiology. Various theories have been proposed including that delirious patients have reduced cerebral blood flow. We hypothesised that patients with delirium could have abnormal autonomic nervous system function, as assessed by tilt table testing, which would explain the alteration in blood flow.

Mass and the Dangers of Syncope.

Introduction Syncope is defined as a transient, self-limited loss of consciousness with an inability to maintain postural tone that is followed by spontaneous recovery. We revisit situational syncope focusing on one situation, Mass. Methods We interrogated our electronic syncope database for key terms associated with situational syncope.

At the bench: Engineering the next generation of cancer vaccines.

Cancer vaccines hold promise as an immunotherapeutic modality based on their potential to generate tumor antigen-specific T cell responses and long-lived antitumor responses capable of combating metastatic disease and recurrence. However, cancer vaccines have historically failed to deliver significant therapeutic benefit in the clinic, which we maintain is due in part to drug delivery challenges that have limited vaccine immunogenicity and efficacy. In this review, we examine some of the known and putative failure mechanisms of common first-generation clinical cancer vaccines, and describe how the rational design of materials engineered for vaccine delivery and immunomodulation can address these shortcomings.

Trends in energy and nutrient supply in Ethiopia: a perspective from FAO food balance sheets.

Background: Ethiopia is the second-most populous country in Africa. Although most people still live in rural areas, the urban population is increasing. Generally, urbanisation is associated with a nutrition transition and an increase in risk factors for non-communicable diseases (NCDs).

Is vitamin D deficiency a public health concern for low middle income countries? A systematic literature review.

Purpose: Vitamin D deficiency has been receiving increasing attention as a potential public health concern in low and lower-middle income countries (LMICs), of which there are currently 83. We aimed to conduct a comprehensive systematic literature review (SLR) of available data on vitamin D status and prevalence of vitamin D deficiency in all 83 LMICs.

Methods: We followed the general methodology for SLRs in the area of serum 25-hydroxyvitamin D.

Dedicated Orthogeriatric Service Saves the HSE a Million Euro.

Hip fracture is common in older adults and is associated with high morbidity, mortality and significant health care costs. A pilot orthogeriatrics service was established in an acute hospital. We aimed to establish the cost effectiveness of this service.

Changes in Weight Loss, Health Behaviors, and Intentions among 400 Participants Who Dropped out from an Insurance-Sponsored, Community-Based Weight Management Program.

The majority of weight management research is based on data from randomized controlled studies conducted in clinical settings. As these findings are translated into community-based settings, additional research is needed to understand patterns of lifestyle change and dropout. The purpose of this study was to examine reasons for and consequences associated with dropout (or removal) from an insurance-funded weight management program.

Food and Nutrient Intake in African American Children and Adolescents Aged 5 to 16 Years in Baltimore City.

Objective: This study aimed to describe food and nutrient intake for low-income, urban African American children and adolescents, to highlight the need for further nutrition intervention programs and appropriate tools to address overweight and obesity.

Methods: This was a cross-sectional study using interviewer-administered single 24-hour dietary recalls. Participants were low-income African American boys and girls aged 5-16 years or their caregivers in Baltimore City.

Traditional food consumption is associated with better diet quality and adequacy among Inuit adults in Nunavut, Canada.

The Inuit population is undergoing a rapid nutrition transition as a result of reduced consumption of traditional foods. This study aims to describe the differences in dietary adequacy between non-traditional and traditional eaters among Inuit populations in Nunavut, Canada. A cross-sectional survey was conducted using a culturally appropriate quantitative food frequency questionnaire.

Physician organization care management capabilities associated with effective inpatient utilization management: a fuzzy set qualitative comparative analysis.

Background: We studied the relationship between physician organization (PO) care management capabilities and inpatient utilization in order to identify PO characteristics or capabilities associated with low inpatient bed-days per thousand.

Methods: We used fuzzy-set qualitative comparative analysis (fsQCA) to conduct an exploratory comparative case series study. Data about PO capabilities were collected using structured interviews with medical directors at fourteen California POs that are delegated to provide inpatient utilization management (UM) for HMO members of a California health plan.

Changing dietary patterns in the Canadian Arctic: frequency of consumption of foods and beverages by inuit in three Nunavut communities.

Background: Inuit in Arctic regions are experiencing a rapid diet and lifestyle transition. There are limited data on food consumption patterns among this unique population, raising concerns about assessing the risk for the development of diet-related chronic diseases.

Objective: To assess the current frequency of consumption of foods and beverages among Inuit in Nunavut, Arctic Canada.

Traditional food patterns are associated with better diet quality and improved dietary adequacy in Aboriginal peoples in the Northwest Territories, Canada.

Background: Traditionally, the Arctic diet has been derived entirely from locally harvested animal and plant species; however, in recent decades, imported foods purchased from grocery stores have become widely available. The present study aimed to examine Inuvialuit, traditional or nontraditional dietary patterns; nutrient density of the diet; dietary adequacy; and main food sources of energy and selected nutrient intakes.

Methods: This cross-sectional study used a culturally appropriate quantitative food frequency questionnaire to assess diet.

Food expenditure patterns in the Canadian Arctic show cause for concern for obesity and chronic disease.

Background: Little is understood about the economic factors that have influenced the nutrition transition from traditional to store-bought foods that are typically high in fat and sugar amongst people living in the Canadian Arctic. This study aims to determine the pattern of household food expenditure in the Canadian Arctic.

Method: Local food prices were collected over 12 months in six communities in Nunavut and the Northwest Territories.

Assessment of dietary intake among Inuvialuit in Arctic Canada using a locally developed quantitative food frequency questionnaire.

Objective: Inuvialuit in Arctic Canada are experiencing a nutritional and lifestyle transition, characterized by a declining consumption of traditional foods, increased consumption of non-nutrient-dense store-bought foods (NNDF), and reduced levels of physical activity with a concurrent rise in chronic diseases. The aim of the present study was to determine dietary intake of Inuvialuit adults in the Northwest Territories, Canada, using a culturally specific, validated quantitative food frequency questionnaire (QFFQ).

Methods: A cross-sectional dietary survey of 213 randomly selected adults (≥19 years) was conducted in 3 remote communities in the Northwest Territories.

Sources of vegetables, fruits and vitamins A, C and E among five ethnic groups: results from a multiethnic cohort study.

Objectives: Data are limited on how dietary sources of food and nutrients differ among ethnic groups. The objective of this study was to determine the main sources of fruit, vegetables and vitamins A, C and E for five ethnic groups.

Subjects/methods: Dietary data were collected using a validated quantitative food frequency questionnaire from participants in a multiethnic cohort in Hawaii and Los Angeles county between 1993 and 1996.

Dietary adequacy of vitamin D and calcium among Inuit and Inuvialuit women of child-bearing age in Arctic Canada: a growing concern.

Background: Arctic populations are at an increased risk of vitamin D inadequacy due to geographic latitude and a nutrition transition. This study aimed to assess the adequacy of dietary vitamin D and calcium among women of child-bearing age in Arctic Canada.

Methods: This study collected data from 203 randomly selected women of child-bearing age (19-44 years) in Nunavut and the Northwest Territories of Arctic Canada.

Development of a quantitative food frequency questionnaire for use among rural South Africans in KwaZulu-Natal.

Background: South Africa is experiencing a dietary and lifestyle transition as well as increased rates of noncommunicable chronic diseases. Limited information is available on the diets of rural populations. The present study aimed to characterise the diets of men and women from rural KwaZulu-Natal (KZN) and develop a quantitative food-frequency questionnaire (QFFQ) specific for this population.