Spatial delivery of immune cues to lymph nodes to define therapeutic outcomes in cancer vaccination.

Recently approved cancer immunotherapies - including CAR-T cells and cancer vaccination, - show great promise. However, these technologies are hindered by the complexity and cost of isolating and engineering patient cells . Lymph nodes (LNs) are key tissues that integrate immune signals to coordinate adaptive immunity.

Stroke Caused by Arterial Thoracic Outlet Syndrome in an Adolescent.

Arterial thoracic outlet syndrome is a rare condition characterized by compression of the subclavian artery, often with post-stenotic aneurysm formation. Artery-to-artery embolic strokes related to thoracic outlet syndrome have been reported in the posterior circulation and in the ipsilateral anterior circulation. We present a case in which a thrombus secondary to thoracic outlet syndrome caused a contralateral anterior circulation stroke in an adolescent and postulate mechanisms of this rare occurrence.

When is it safe for the liver donor to be discharged home and prevent unnecessary re-hospitalizations? - A systematic review of the literature and expert panel recommendations.

Background: Few data are available on discharge criteria after living liver donation (LLD).

Objectives: To identify the features for fit for discharge checklist after LLD to prevent unnecessary re-hospitalizations and to provide international expert recommendations.

Data Sources: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central.

Low Salt Delivery Triggers Autocrine Release of Prostaglandin E2 From the Aldosterone-Sensitive Distal Nephron in Familial Hyperkalemic Hypertension Mice.

Aberrant activation of with-no-lysine kinase (WNK)-STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) kinase signaling in the distal convoluted tubule (DCT) causes unbridled activation of the thiazide-sensitive sodium chloride cotransporter (NCC), leading to familial hyperkalemic hypertension (FHHt) in humans. Studies in FHHt mice engineered to constitutively activate SPAK specifically in the DCT (CA-SPAK mice) revealed maladaptive remodeling of the aldosterone sensitive distal nephron (ASDN), characterized by decrease in the potassium excretory channel, renal outer medullary potassium (ROMK), and epithelial sodium channel (ENaC), that contributes to the hyperkalemia. The mechanisms by which NCC activation in DCT promotes remodeling of connecting tubule (CNT) are unknown, but paracrine communication and reduced salt delivery to the ASDN have been suspected.

Assessing risk factors for hypertension in young adults with perinatally acquired HIV infection: A case-control study.

Objectives: Although the risk of AIDS-associated diseases has declined dramatically with combination antiretroviral therapy (cART), the incidence rates of chronic non-AIDS-associated diseases in perinatally HIV-infected adults have risen and have not been well characterized. Both traditional and HIV-associated risk factors have been found to contribute to hypertension in non-perinatally HIV-infected adults; whether these same factors contribute to hypertension in perinatally infected adults is not known. The purpose of this study was to determine the socio-demographic, clinical, virological and immunological factors associated with systemic hypertension among a cohort of perinatally HIV-infected adolescents and young adults.

Biomaterial-enabled induction of pancreatic-specific regulatory T cells through distinct signal transduction pathways.

Autoimmune diseases-where the immune system mistakenly targets self-tissue-remain hindered by non-specific therapies. For example, even molecularly specific monoclonal antibodies fail to distinguish between healthy cells and self-reactive cells. An experimental therapeutic approach involves delivery of self-molecules targeted by autoimmunity, along with immune modulatory signals to produce regulatory T cells (T) that selectively stop attack of host tissue.

The Current and Potential Application of Medicinal Cannabis Products in Dentistry.

Oral and dental diseases are a major global burden, the most common non-communicable diseases (NCDs), and may even affect an individual's general quality of life and health. The most prevalent dental and oral health conditions are tooth decay (otherwise referred to as dental caries/cavities), oral cancers, gingivitis, periodontitis, periodontal (gum) disease, Noma, oro-dental trauma, oral manifestations of HIV, sensitive teeth, cracked teeth, broken teeth, and congenital anomalies such as cleft lip and palate. Herbs have been utilized for hundreds of years in traditional Chinese, African and Indian medicine and even in some Western countries, for the treatment of oral and dental conditions including but not limited to dental caries, gingivitis and toothaches, dental pulpitis, halitosis (bad breath), mucositis, sore throat, oral wound infections, and periodontal abscesses.

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases.

The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development. The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases.

Alpha oscillatory power decreases are associated with better memory for higher valued information.

Items associated with high value are often better remembered. Value may increase attention toward item in context associations. Alpha oscillations (8-13 Hz) are thought to underlie attention and their observation may reveal the role attention plays in value-based memory.

Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) Contributes to Bordetella pertussis Inflammatory Pathology.

Whooping cough (pertussis) is a severe pulmonary infectious disease caused by the bacteria Bordetella pertussis. Pertussis infects an estimated 24 million people annually, resulting in >150,000 deaths. The NIH placed pertussis on the list of emerging pathogens in 2015.

Biophysical Properties of Self-Assembled Immune Signals Impact Signal Processing and the Nature of Regulatory Immune Function.

Outcomes during immunotherapy are impacted not only by the specific therapeutic signals and pharmacodynamics, but also by the biophysical forms in which signals are delivered. This integration is determinative in autoimmunity because the disease is caused by immune dysregulation and inflammation. Unfortunately, the links between nanomaterial design, biophysical properties, and immune regulation are poorly defined.

Exploiting Rational Assembly to Map Distinct Roles of Regulatory Cues during Autoimmune Therapy.

Autoimmune diseases like multiple sclerosis (MS), type 1 diabetes, and lupus occur when the immune system attacks host tissue. Immunotherapies that promote selective tolerance without suppressing normal immune function are of tremendous interest. Here, nanotechnology was used for rational assembly of peptides and modulatory immune cues into immune complexes.

Impact of Excipients on Stability of Polymer Microparticles for Autoimmune Therapy.

Therapies for autoimmune diseases such as multiple sclerosis and diabetes are not curative and cause significant challenges for patients. These include frequent, continued treatments required throughout the lifetime of the patient, as well as increased vulnerability to infection due to the non-specific action of therapies. Biomaterials have enabled progress in antigen-specific immunotherapies as carriers and delivery vehicles for immunomodulatory cargo.

Design of Dissolvable Microneedles for Delivery of a Pfs47-Based Malaria Transmission-Blocking Vaccine.

The development of effective malaria vaccines remains a global health priority. In addition to an effective vaccine, there is urgent demand for effective delivery technologies that can be easily deployed. The need for effective vaccine delivery tools is particularly pertinent in resource-poor settings where access to healthcare is limited.

Impact of Global Health Electives on Neurology Trainees.

We surveyed neurologists who completed a global health experience as residents or fellows to assess the impact of the experience. A total of 100% (n = 72) would recommend the experience to others. Most reported improved clinical (86%) and examination (82%) skills.

Altering Antigen Charge to Control Self-Assembly and Processing of Immune Signals During Cancer Vaccination.

Biomaterial delivery systems offer unique potential to improve cancer vaccines by offering targeted delivery and modularity to address disease heterogeneity. Here, we develop a simple platform using a conserved human melanoma peptide antigen (Trp2) modified with cationic arginine residues that condenses an anionic toll-like receptor agonist (TLRa), CpG, into polyplex-like nanoparticles. We reasoned that these structures could offer several useful features for immunotherapy - such as tunable loading, co-delivery of immune cues, and cargo protection - while eliminating the need for synthetic polymers or other complicating delivery systems.

Integrating Biomaterials and Immunology to Improve Vaccines Against Infectious Diseases.

Despite the success of vaccines in preventing many infectious diseases, effective vaccines against pathogens with ongoing challenges - such as HIV, malaria, and tuberculosis - remain unavailable. The emergence of new pathogen variants, the continued prevalence of existing pathogens, and the resurgence of yet other infectious agents motivate the need for new, interdisciplinary approaches to direct immune responses. Many current and candidate vaccines, for example, are poorly immunogenic, provide only transient protection, or create risks of regaining pathogenicity in certain immune-compromised conditions.

Self-Assembly as a Molecular Strategy to Improve Immunotherapy.

Immunotherapies harness an individual's immune system to battle diseases such as cancer and autoimmunity. During cancer, the immune system often fails to detect and destroy cancerous cells, whereas during autoimmune disease, the immune system mistakenly attacks self-tissue. Immunotherapies can help guide more effective responses in these settings, as evidenced by recent advances with monoclonal antibodies and adoptive cell therapies.

Designing inorganic nanomaterials for vaccines and immunotherapies.

Vaccines and immunotherapies have changed the face of health care. Biomaterials offer the ability to improve upon these medical technologies through increased control of the types and concentrations of immune signals delivered. Further, these carriers enable targeting, stability, and delivery of poorly soluble cargos.

Distribution of Femoral Metastases; Potential Role for Extended FDG PET/CT Scanning.

This study investigates the distribution of femoral metastases in cancer patients, specifically addressing the incidence of distal femoral metastases. PET/CT examinations routinely extend only to mid-thigh level, precluding detection of distal metastases. We found a total of 208 femoral metastases in 112 patients.