Inflammation and olfactory loss are associated with at least 139 medical conditions.

Olfactory loss accompanies at least 139 neurological, somatic, and congenital/hereditary conditions. This observation leads to the question of whether these associations are correlations or whether they are ever causal. Temporal precedence and prospective predictive power suggest that olfactory loss is causally implicated in many medical conditions.

In situ single-cell profiling sheds light on IFI27 localisation during SARS-CoV-2 infection.

The utilization of single-cell resolved spatial transcriptomics to delineate immune responses during SARS-CoV-2 infection was able to identify M1 macrophages to have elevated expression of IFI27 in areas of infection.

Spatial characterization of interface dermatitis in cutaneous lupus reveals novel chemokine ligand-receptor pairs that drive disease.

Chemokines play critical roles in the recruitment and activation of immune cells in both homeostatic and pathologic conditions. Here, we examined chemokine ligand-receptor pairs to better understand the immunopathogenesis of cutaneous lupus erythematosus (CLE), a complex autoimmune connective tissue disorder. We used suction blister biopsies to measure cellular infiltrates with spectral flow cytometry in the interface dermatitis reaction, as well as 184 protein analytes in interstitial skin fluid using Olink targeted proteomics.

Overnight olfactory enrichment using an odorant diffuser improves memory and modifies the uncinate fasciculus in older adults.

Objective: Cognitive loss in older adults is a growing issue in our society, and there is a need to develop inexpensive, simple, effective in-home treatments. This study was conducted to explore the use of olfactory enrichment at night to improve cognitive ability in healthy older adults.

Methods: Male and female older adults ( = 43), age 60-85, were enrolled in the study and randomly assigned to an Olfactory Enriched or Control group.

Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease.

Ulcerative colitis and Crohn's disease are chronic inflammatory intestinal diseases with perplexing heterogeneity in disease manifestation and response to treatment. While the molecular basis for this heterogeneity remains uncharacterized, single-cell technologies allow us to explore the transcriptional states within tissues at an unprecedented resolution which could further understanding of these complex diseases. Here, we apply single-cell RNA-sequencing to human inflamed intestine and show that the largest differences among patients are present within the myeloid compartment including macrophages and neutrophils.

Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment.

Purpose: Cancer drug development is currently limited by a paradigm of preclinical evaluation that does not adequately recapitulate the complexity of the intact human tumor microenvironment (TME). To overcome this, we combined trackable intratumor microdosing (CIVO) with spatial biology readouts to directly assess drug effects in patient tumors in situ.

Experimental Design: In a first-of-its-kind phase 0 clinical trial, we explored the effects of an investigational stage SUMOylation-activating enzyme (SAE) inhibitor, subasumstat (TAK-981) in 12 patients with head and neck carcinoma (HNC).

Strengthening rural surgery in the Philippines: Essential in achieving universal health care.

The Lancet Commission on Global Surgery (LCoGS) launched Global Surgery 2030 to address the surgical services inequities with a bias toward low-income and middle-income countries like the Philippines. The same inequity is observed particularly when it comes to the urban-rural divide. With more than half of the population living in rural areas, access to surgery becomes a major challenge that further impedes the much-needed health of an economically productive workforce.

Olfactory loss is a predisposing factor for depression, while olfactory enrichment is an effective treatment for depression.

The loss of olfactory stimulation correlates well with at least 68 widely differing neurological disorders, including depression, and we raise the possibility that this relationship may be causal. That is, it seems possible that olfactory loss makes the brain vulnerable to expressing the symptoms of these neurological disorders, while daily olfactory enrichment may decrease the risk of expressing these symptoms. This situation resembles the cognitive reserve that is thought to protect people with Alzheimer's neuropathology from expressing the functional deficit in memory through the cumulative effect of intellectual stimulation.

SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice.

A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal tissue samples. The mouse-adapted SARS-CoV-2 strain MA10 produces an acute respiratory distress syndrome in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute to clinical recovery phases.

A model of persistent post SARS-CoV-2 induced lung disease for target identification and testing of therapeutic strategies.

COVID-19 survivors develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal samples. Mouse-adapted SARS-CoV-2 MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute disease through clinical recovery.

An Immunomodulatory Therapeutic Vaccine Targeting Oligomeric Amyloid-β.

Background: Aging is considered the most important risk factor for Alzheimer's disease (AD). Recent research supports the theory that immunotherapy targeting the "oligomeric" forms of amyloid-β (Aβ) may halt the progression of AD. However, previous clinical trial of the vaccine against Aβ, called AN1792, was suspended due to cases of meningoencephalitis in patients.

Treating Eating: A Dynamical Systems Model of Eating Disorders.

Mainstream forms of psychiatric talk therapy and cognitive behavioral therapy (CBT) do not reliably generate lasting recovery for eating disorders. We discuss widespread assumptions regarding the nature of eating disorders as fundamentally psychological disorders and highlight the problems that underlie these notions, as well as related practical problems in the implementation of mainstream treatments. We then offer a theoretical and practical alternative: a dynamical systems model of eating disorders in which behavioral interventions are foregrounded as powerful mediators between psychological and physical states.

Environmental Enrichment and Successful Aging.

The human brain sustains a slow but progressive decline in function as it ages and these changes are particularly profound in cognitive processing. A potential contributor to this deterioration is the gradual decline in the functioning of multiple sensory systems and the effects they have on areas of the brain that mediate cognitive function. In older adults, diminished capacity is typically observed in the visual, auditory, masticatory, olfactory, and motor systems, and these age-related declines are associated with both a decline in cognitive proficiency, and a loss of neurons in regions of the brain.

Therapeutic Cocktail Approach for Treatment of Hyperhomocysteinemia in Alzheimer's Disease.

In the United States, Alzheimer's disease (AD) is the most common cause of dementia, accompanied by substantial economic and emotional costs. During 2015, more than 15 million family members who provided care to AD patients had an estimated total cost of 221 billion dollars. Recent studies have shown that elevated total plasma levels of homocysteine (tHcy), a condition known as hyperhomocysteinemia (HHcy), is a risk factor for AD.

Using the WHO Surgical Safety Checklist to Direct Perioperative Quality Improvement at a Surgical Hospital in Cambodia: The Importance of Objective Confirmation of Process Completion.

Background: The WHO surgical safety checklist (SSC) is known to prevent postoperative complications; however, strategies for effective implementation are unclear. In addition to cultural and organizational barriers faced by high-income countries, resource-constrained settings face scarcity of durable and consumable goods. We used the SSC to better understand barriers to improvement at a trauma hospital in Battambang, Cambodia.

Environmental Enrichment Therapy for Autism: Outcomes with Increased Access.

We have previously shown in two randomized clinical trials that environmental enrichment is capable of ameliorating symptoms of autism spectrum disorder (ASD), and in the present study, we determined whether this therapy could be effective under real-world circumstances. 1,002 children were given daily Sensory Enrichment Therapy, by their parents, using personalized therapy instructions given over the Internet. Parents were asked to assess the symptoms of their child every 2 weeks for up to 7 months.

Control of Body Weight by Eating Behavior in Children.

Diet, exercise, and pharmacological interventions have limited effects in counteracting the worldwide increase in pediatric body weight. Moreover, the promise that individualized drug design will work to induce weight loss appears to be exaggerated. We suggest that the reason for this limited success is that the cause of obesity has been misunderstood.

Environmental enrichment as a therapy for autism: A clinical trial replication and extension.

Based on work done in animal models showing that autism-like symptoms are ameliorated following exposure to an enriched sensorimotor environment, we attempted to develop a comparable therapy for children with autism. In an initial randomized controlled trial, children with autism who received sensorimotor enrichment at home for 6 months had significant improvements in both their cognitive ability and the severity of their autism symptoms (Woo & Leon, 2013). We now report the outcomes of a similar randomized controlled trial in which children with autism, 3 to 6 years old, were randomly assigned to groups that received either daily sensorimotor enrichment, administered by their parents, along with standard care, or they received standard care alone.

Effective treatment of eating disorders: Results at multiple sites.

We report the results of a study based on 1,428 patients with eating disorders treated at 6 clinics. These patients were consecutively referred over 18 years and used inpatient and outpatient treatment. The subjects were diagnosed with anorexia nervosa, bulimia nervosa, or an eating disorder not otherwise specified.

Environmental enrichment as an effective treatment for autism: a randomized controlled trial.

Enriched sensorimotor environments enable rodents to compensate for a wide range of neurological challenges, including those induced in animal models of autism. Given the sensorimotor deficits in most children with autism, we attempted to translate that approach to their treatment. In a randomized controlled trial, 3-12 year-old children with autism were assigned to either a sensorimotor enrichment group, which received daily olfactory/tactile stimulation along with exercises that stimulated other paired sensory modalities, or to a control group.

Children eat their school lunch too quickly: an exploratory study of the effect on food intake.

Background: Speed of eating, an important aspect of eating behaviour, has recently been related to loss of control of food intake and obesity. Very little time is allocated for lunch at school and thus children may consume food more quickly and food intake may therefore be affected. Study 1 measured the time spent eating lunch in a large group of students eating together for school meals.

Cluster analysis of rat olfactory bulb responses to diverse odorants.

In an effort to deepen our understanding of mammalian olfactory coding, we have used an objective method to analyze a large set of odorant-evoked activity maps collected systematically across the rat olfactory bulb to determine whether such an approach could identify specific glomerular regions that are activated by related odorants. To that end, we combined fuzzy c-means clustering methods with a novel validity approach based on cluster stability to evaluate the significance of the fuzzy partitions on a data set of glomerular layer responses to a large diverse group of odorants. Our results confirm the existence of glomerular response clusters to similar odorants.