An open trial of biofeedback for long COVID.

OBJECTIVE: Biofeedback is a therapeutic treatment model that teaches self-regulation of autonomic functions to alleviate stress-related symptoms. "Long COVID" refers to chronic physical and cognitive sequelae post-SARS-CoV-2 infection. This study examined the efficacy of a six-week intervention, consisting of weekly one-hour sessions combining heart rate variability and temperature biofeedback, for alleviating mood symptoms, somatic symptoms and sleep disturbance of patients diagnosed with long COVID. METHODS: Data were collected from 20 adult participants aged 22-63 (Mage = 44.1, SDage = 12.2) with varying long COVID symptoms. Within this single arm design, 16 of the 20 participants completed all six sessions of biofeedback; 14 completed an assessment at the three-month post-treatment time point. RESULTS: Participants self-reported significant improvements in somatic, anxiety, and depressive symptoms, sleep quality, quality of life, and number of "bad days" immediately after the intervention and three months later (Cohen's d effect size (ES) = 1.09-0.46). Reduced number of medical doctor visits (ES = 0.85) and prescription drug use over the last month (odds ratio = 0.33), as well as improved emotional wellbeing (ES = 0.97) were observed at the three-month time point only. CONCLUSION: Results suggest that this short, readily scalable intervention can be potentially efficacious in alleviating symptoms of long COVID. Despite notable improvements, the major limitation of this study is its lack of control group. While a randomized trial merits study, biofeedback appears to be a brief, effective, non-invasive, and low-cost treatment option for patients with chronic somatic symptoms secondary to SARS-CoV-2 infection. CLINICALTRIALS: govID: NCT05120648.

A Simple Apparatus for Individual C. elegans Culture.

We miniaturized standard, solid-phase C. elegans culture conditions to produce a system in which many isolated, individual C. elegans can be housed throughout their lives. This system, the "worm corral," is compatible with high-resolution brightfield and fluorescent microscopy, allowing imaging of fluorescent transgenes and morphological phenotypes from hatch until death. These culture devices can be constructed on the benchtop with commercially available reagents and standard laboratory equipment, making this an attainable solution for most labs.

A simple culture system for long-term imaging of individual C. elegans.

We have miniaturized standard culture techniques to rear arrays of isolated, individual C. elegans throughout their lives on solid gel media. The resulting apparatus is compatible with brightfield and fluorescence microscopy, enabling longitudinal studies of morphology and fluorescent transgene expression. Our culture system exploits a novel crosslinking reaction between a polyethylene glycol hydrogel and a silicone elastomer to constrain animals to individual "corrals" on the gel surface. These devices are simple to construct on the benchtop with commercially available reagents, and, unlike microfluidic isolation methods, do not rely on micropatterned materials. We demonstrate that this new culture method has negligible effects on the physiology of C. elegans compared to standard culture on agar plates. In addition, RNAi techniques are effective in this system. Finally, the hydrogel-silicone binding chemistry that we developed also allows traditional microfluidic devices to be covalently attached to gel substrates instead of glass.

Extended Twilight among Isogenic C. elegans Causes a Disproportionate Scaling between Lifespan and Health.

Although many genetic factors and lifestyle interventions are known to affect the mean lifespan of animal populations, the physiological variation displayed by individuals across their lifespans remains largely uncharacterized. Here, we use a custom culture apparatus to continuously monitor five aspects of aging physiology across hundreds of isolated Caenorhabditis elegans individuals kept in a constant environment from hatching until death. Aggregating these measurements into an overall estimate of senescence, we find two chief differences between longer- and shorter-lived individuals. First, though long- and short-lived individuals are physiologically equivalent in early adulthood, longer-lived individuals experience a lower rate of physiological decline throughout life. Second, and counter-intuitively, long-lived individuals have a disproportionately extended "twilight" period of low physiological function. While longer-lived individuals experience more overall days of good health, their proportion of good to bad health, and thus their average quality of life, is systematically lower than that of shorter-lived individuals. We conclude that, within a homogeneous population reared under constant conditions, the period of early-life good health is comparatively uniform, and the most plastic period in the aging process is end-of-life senescence.

Case study and lessons learned from the ammonium nitrate explosion at the West Fertilizer facility.

In West, Texas on April 17, 2013, a chemical storage and distribution facility caught fire followed by the explosion of around 30 tons of ammonium nitrate while the emergency responders were trying to extinguish the fire, leading to 15 fatalities and numerous buildings, businesses and homes destroyed or damaged. This incident resulted in devastating consequences for the community around the facility, and shed light on a need to improve the safety management of local small businesses similar to the West facility. As no official report on the findings of the incident has been released yet, this article first investigates the root causes of the incident, and presents a simplified consequence analysis. The article reviews the regulations applicable to this type of facility and recommended emergency response procedures to identify gaps between what happened in West and the current regulations, and discusses how the current regulations could be modified to prevent or minimize future losses. Finally, the federal response that followed the incident until the publication of this paper is summarized.

Lessons to be learned from an analysis of ammonium nitrate disasters in the last 100 years.

Process safety, as well as the safe storage and transportation of hazardous or reactive chemicals, has been a topic of increasing interest in the last few decades. The increased interest in improving the safety of operations has been driven largely by a series of recent catastrophes that have occurred in the United States and the rest of the world. A continuous review of past incidents and disasters to look for common causes and lessons is an essential component to any process safety and loss prevention program. While analyzing the causes of an accident cannot prevent that accident from occurring, learning from it can help to prevent future incidents. The objective of this article is to review a selection of major incidents involving ammonium nitrate in the last century to identify common causes and lessons that can be gleaned from these incidents in the hopes of preventing future disasters. Ammonium nitrate has been involved in dozens of major incidents in the last century, so a subset of major incidents were chosen for discussion for the sake of brevity. Twelve incidents are reviewed and ten lessons from these incidents are discussed.

Numb family proteins are essential for cardiac morphogenesis and progenitor differentiation.

Numb family proteins (NFPs), including Numb and numb-like (Numbl), are cell fate determinants for multiple progenitor cell types. Their functions in cardiac progenitor differentiation and cardiac morphogenesis are unknown. To avoid early embryonic lethality and study NFP function in later cardiac development, Numb and Numbl were deleted specifically in heart to generate myocardial double-knockout (MDKO) mice. MDKOs were embryonic lethal and displayed a variety of defects in cardiac progenitor differentiation, cardiomyocyte proliferation, outflow tract (OFT) and atrioventricular septation, and OFT alignment. By ablating NFPs in different cardiac populations followed by lineage tracing, we determined that NFPs in the second heart field (SHF) are required for OFT and atrioventricular septation and OFT alignment. MDKOs displayed an SHF progenitor cell differentiation defect, as revealed by a variety of methods including mRNA deep sequencing. Numb regulated cardiac progenitor cell differentiation in an endocytosis-dependent manner. Studies including the use of a transgenic Notch reporter line showed that Notch signaling was upregulated in the MDKO. Suppression of Notch1 signaling in MDKOs rescued defects in p57 expression, proliferation and trabecular thickness. Further studies showed that Numb inhibits Notch1 signaling by promoting the degradation of the Notch1 intracellular domain in cardiomyocytes. This study reveals that NFPs regulate trabecular thickness by inhibiting Notch1 signaling, control cardiac morphogenesis in a Notch1-independent manner, and regulate cardiac progenitor cell differentiation in an endocytosis-dependent manner. The function of NFPs in cardiac progenitor differentiation and cardiac morphogenesis suggests that NFPs might be potential therapeutic candidates for cardiac regeneration and congenital heart diseases.

Effect of host lizard anemia on host choice and feeding rate of larval western black-legged ticks (Ixodes pacificus).

Although ticks are known to exhibit preferences among host species, there is little evidence that ticks select hosts within a species based on physiological condition. It may be beneficial for ticks to choose hosts that are easier to feed upon if the ticks can perceive indicative chemical or other signals from the host. For example, if ticks can detect host hematocrit they may choose hosts with high hematocrit, facilitating a faster blood meal. It may similarly be adaptive for ticks to avoid anemic hosts because it may be difficult for them to obtain an adequate meal and feeding duration may be extended. We tested the hypothesis that larval western black-legged ticks (Ixodes pacificus) detect host hematocrit using external cues and choose healthy over anemic hosts, allowing them to feed more quickly. We presented groups of larval ticks with pairs of healthy and anemic male western fence lizards (Sceloporus occidentalis), allowed them to select a host, and measured the feeding duration of the ticks. We found that the ticks did not exhibit a statistically significant preference for healthy over anemic lizards, but that the ticks fed to repletion significantly faster on healthy hosts than on anemic hosts. Larval ticks may not be able to detect external cues indicating the health of the host, at least not in terms of their hematocrit. The extended feeding duration likely reflects the extra time needed for the ticks to concentrate the blood meal of their anemic hosts.