A Longitudinal Cohort Study of Youth Mental Health and Substance use Before and During the COVID-19 Pandemic in Ontario,Canada: An Exploratory Analysis

BackgroundYouth mental health appears to have been negatively impacted by the COVID-19 pandemic. The impact on substance use is less clear, as is the impact on subgroups of youth, including those with pre-existing mental health or substance use challenges.ObjectiveThis hypothesis-generating study examines the longitudinal evolution of youth mental health and substance use from before the COVID-19 pandemic to over one year into the pandemic among youth with pre-existing mental health or substance use challenges.MethodA total of 168 youth aged 14–24 participated. Participants provided sociodemographic data, as well as internalizing disorder, externalizing disorder, and substance use data prior to the pandemic’s onset, then every two months between April 2020–2021. Linear mixed models and Generalized Estimating Equations were used to analyze the effect of time on mental health and substance use. Exploratory analyses were conducted to examine interactions with sociodemographic and clinical characteristics.ResultsThere was no change in internalizing or externalizing disorder scores from prior to the pandemic to any point throughout the first year of the pandemic. Substance use scores during the pandemic declined compared to pre-pandemic scores. Exploratory analyses suggest that students appear to have experienced more mental health repercussions than non-students; other sociodemographic and clinical characteristics did not appear to be associated with mental health or substance use trajectories.ConclusionsWhile mental health remained stable and substance use declined from before the COVID-19 pandemic to during the pandemic among youth with pre-existing mental health challenges, some youth experienced greater challenges than others. Longitudinal monitoring among various population subgroups is crucial to identifying higher risk populations. This information is needed to provide empirical evidence to inform future research directions.     

Trichodermamides A and B,cytotoxic modified dipeptides from the marine-derived fungus Trichoderma virens

Trichodermamides A (1) and B (2), two modified dipeptides, have been isolated from cultures of the marine-derived fungus Trichoderma virens. The trichodermamides possess a rare cyclic O-alkyl-oxime functionality incorporated into a six-membered ring. The structure of trichodermamide B was established by X-ray diffraction analysis, while the structure assignment of trichodermamide A, and determination of the absolute stereochemistry, was accomplished by spectral and chemical methods. Trichodermamide B displayed significant in vitro cytotoxicity against HCT-116 human colon carcinoma with an IC(50) of 0.32 microg/mL.     

Fetal biophysical profile scoring: selective use of the nonstress test

The fetal biophysical profile score was modified by selective use of the nonstress test. In 2712 study patients (7851 tests) the incidence of nonstress test was reduced to 2.7% with no measurable effect or test accuracy. The nonstress test was most useful in evaluation of abnormal ultrasound monitored variables.     

Detection threshold differences to crossed and uncrossed disparities

Using a sample of 85 subjects measurements were made of minimum stimulus durations necessary for detection of crossed and uncrossed disparity stimuli which were presented in five positions in the visual field: centre, lower, upper, right, and left field. The results indicated large detection duration differences between the two disparity conditions, with a marked superiority for crossed disparity detection at all positions. A left-right visual field anisotropy was demonstrated for crossed disparity stimuli.     

Limitations in health care access and utilization among long‐term survivors of adolescent and young adult cancer

BACKGROUND:

Health care outcomes for long‐term survivors of adolescent and young adult (AYA) cancer were compared with young adults without a cancer history, using the 2009 Behavioral Risk Factor Surveillance System data.

METHODS:

Eligible participants were 20 to 39 years of age. There were N = 979 who self‐reported a cancer diagnosis between the ages of 15 to 34 years and were at least 5 years from diagnosis (excluding nonmelanoma skin cancer). The remaining 67,216 participants with no cancer history were used as controls. Using multivariable regressions, relative risks and 95% confidence intervals were generated to examine the relationship of survivor status on indicators of poor health care (uninsured, no personal health care provider, no routine care, and avoiding seeing a doctor due to cost). Adjusted proportions were calculated by demographic groups. Results are weighted by Behavioral Risk Factor Surveillance System survey design.

RESULTS:

Although the proportion uninsured did not differ (21% of survivors vs 23% of controls), AYA survivors reported forgoing care due to cost at higher levels than controls (relative risk = 1.67, 95% CI = 1.44‐1.94). Cost barriers were particularly high for survivors aged 20 to 29 years (44% vs 16% of controls; P < .001) and female survivors (35% vs 18% of controls; P < .001). Survivors reporting poorer health had more cost barriers. Moreover, uninsured survivors tended to report lower use of health care than did controls.

CONCLUSIONS:

AYA cancer survivors may forgo health care due to cost barriers, potentially inhibiting the early detection of late effects. Expanding health insurance coverage for young cancer survivors may be insufficient without adequate strategies to reduce their medical cost burdens. Cancer 2012. © 2012 American Cancer Society.     

Neurodevelopmental changes of fetal pain

Pain in the developing fetus is controversial because of the difficulty in measuring and interpreting pain during gestation. It has received increased attention lately because of recently introduced legislation that would require consideration of fetal pain during intentional termination of pregnancy. During development, sensory fibers are abundant by 20 weeks; a functional spinal reflex is present by 19 weeks; connections to the thalamus are present by 20 weeks; and connections to subplate neurons are present by 17 weeks with intensive differentiation by 25 weeks. These cells are important developmentally, but decline as a result of natural apoptosis. Mature thalamocortical projections are not present until 29 to 30 weeks, which has led many to believe the fetus does not experience emotional "pain" until then. Pain requires both nociception and emotional reaction or interpretation. Nociception causes physiologic stress, which in turn causes increases in catecholamines, cortisol, and other stress hormones. Physiological stress is different from the emotional pain felt by the more mature fetus or infant, and this stress is mitigated by pain medication such as opiates. The plasticity of the developing brain makes it vulnerable to the stressors that cause long-term developmental changes, ultimately leading to adverse neurological outcomes. Whereas evidence for conscious pain perception is indirect, evidence for the subconscious incorporation of pain into neurological development and plasticity is incontrovertible. Scientific data, not religious or political conviction, should guide the desperately needed research in this field. In the meantime, it seems prudent to avoid pain during gestation.     

Hybrid measurement of respiratory aerosol reveals a dominant coarse fraction resulting from speech that remains airborne for minutes

Accurate measurements of the size and quantity of aerosols generated by various human activities in different environments are required for efficacious mitigation strategies and accurate modeling of respiratory disease transmission. Previous studies of speech droplets, using standard aerosol instrumentation, reported very few particles larger than 5 μm. This starkly contrasts with the abundance of such particles seen in both historical slide deposition measurements and more recent light scattering observations. We have reconciled this discrepancy by developing an alternative experimental approach that addresses complications arising from nucleated condensation. Measurements reveal that a large volume fraction of speech-generated aerosol has diameters in the 5- to 20-μm range, making them sufficiently small to remain airborne for minutes, not hours. This coarse aerosol is too large to penetrate the lower respiratory tract directly, and its relevance to disease transmission is consistent with the vast majority of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections initiating in the upper respiratory tract. Our measurements suggest that in the absence of symptoms such as coughing or sneezing, the importance of speech-generated aerosol in the transmission of respiratory diseases is far greater than generally recognized.

Respiratory tract infections are caused by a wide range of pathogenic organisms (1), including a large array of respiratory viruses, such as influenza virus, rhinovirus, measles virus, respiratory syncytial virus, adenovirus, and most recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In all these diseases, person-to-person spread involves respiratory droplets, which originate from the mucus layer that covers the epithelium of the respiratory tract or from oral fluid present in the mouth, mostly as saliva. Thus, characterizing respiratory droplets is essential to understanding respiratory pathogen transmission and will inform effective public health policies to curb infections. Four mechanisms for droplet generation are generally considered: breathing, speaking (singing, laughing, etc.), coughing, and sneezing (2). Considering the well-recognized importance of asymptomatic transmission of SARS-CoV-2 (3), our study focuses on the first two of these mechanisms.As highlighted by Wells (4) and Duguid (2) nearly a century ago, the vast majority of respiratory droplets are smaller than ca. 100-μm diameter and fully dehydrate once entering the atmosphere. These desiccated droplets can remain airborne for minutes to hours before landing on solid surfaces. If generated by a person infected by a respiratory virus, they will contain virions that can remain viable and infectious for many hours (5, 6). Upon inhalation, airborne particles can reach different parts of the respiratory tract depending on their size: coarse aerosols with diameter D ≳ 5 μm (7) deposit in the upper respiratory tract (URT), and fine aerosols with D < 5 μm can penetrate deep into the lower respiratory tract (LRT). Many viral pathogens, including SARS-CoV-2, influenza, rhinovirus, and measles virus, can infect both URT and LRT epithelia (1, 8, 9), with URT infections typically associated with mild initial symptoms and LRT infections possibly resulting in life-threatening pneumonia (1, 10–13). Direct infection of the LRT, before the adaptive immune system has been triggered by vaccination or a preceding URT infection, presents a greater risk.An URT infection also can expand into the LRT through microaspiration of oropharyngeal fluids (14, 15). The extent to which inhalation of self-generated URT cough, speech, or sneeze aerosols may contribute to this migration remains unknown. However, it has been argued that this pathway could be significant because an infected carrier is invariably at the center of their own speech aerosol cloud, which results in strongly elevated exposure (16). The risk of migration from the URT to the LRT rises with the viral load and the viability of the virus, which peak around and just prior to the onset of symptoms, respectively (17, 18). For the original Wuhan strain of the SARS-CoV-2 virus, the onset of symptoms occurs about 5 days after the initial infection (17, 19), but it occurs somewhat earlier for the more infectious delta and omicron variants (20).To evaluate the risk of LRT infection, it is important to know the size distribution of particles generated by various respiratory activities. For talking, coughing, and sneezing, studies historically relied on slide sampling techniques of increasing sophistication, followed by microscope observation (2, 21, 22). Droplets generated by breathing or vowel sounds are numerous but very small (≲2 μm) and thus more difficult to evaluate with those classical methods. Instead, such small droplets are now commonly quantified by aerosol detection equipment, such as optical particle sizers (OPSs), based on light scattering (22, 23); aerodynamic particle sizers (APSs), based on the time-of-flight measurement in an accelerating flow field (24); and scanning mobility particle sizers that derive a particle’s size from its mobility in an electric field and are best suited for very small sizes (≲1 μm) (25, 26). APS instruments are less efficient at detecting medium-sized liquid particles, and undercounts as high as 75% for 10-μm droplets have been reported (27).There is some confusion in the literature about the hydration state of reported sizes of respiratory aerosol particles, which shrink by a factor of γ upon evaporation of their aqueous content, thus by a factor of γ³ in volume. After full dehydration, a particle’s radius is determined by its amount of nonvolatile matter. Estimates for γ vary substantially: Nicas et al. (28) proposed γ = 2 for breath particles, based on data extracted from breath condensate by Effros et al. (29) that indicated a high fraction (ca. 8% wt/vol) of glycoproteins, presumably mucins. Holmgren et al. (30) reported γ = 2.4 for breath particles when the relative humidity (RH) is reduced from 99.5% in the small airways to 75%. Bagheri et al. (26) observed γ = 4.5 for singing particles in a diffusion dryer or γ = 4 for large saliva droplets observed directly by microscope imaging. Some of those measurements were conducted directly at the mouth opening, observing the hydrated state using light scattering or holographic imaging techniques (26, 31). Clearly, the concentration of pathogens in dehydrated particles scales with γ³ relative to the originating airway lining fluid (ALF) or saliva. However, the high uncertainty in the applicable γ value, which is frequently not even reported, prevents accurate estimates of airborne virus concentrations.Recently, we and others demonstrated that speech particles can be readily observed by simple video recordings of light scattering by these particles (32–35). Such recordings not only present a visually compelling warning to the public but also provide opportunities to monitor particles before, during, and after dehydration. Those light scattering measurements focused on particles larger than a few microns due to technical sensitivity issues. The intensity of scattered light scales with the square of a particle’s diameter, causing a dynamic range problem and rendering it more challenging to observe the smallest particles, especially in the presence of larger particles. Inexpensive, fast consumer cameras typically use 10- to 12-bit analog-to-digital converters (ADCs), thereby limiting dynamic range; while detectors with an increased ADC range are available, their speed is often insufficient for high-speed recording.Here, we aim to evaluate the entire range of speech droplet sizes produced during different breathing and speaking protocols. To do so, we combined video-recorded light scattering and an OPS to evaluate droplets from 0.3 to 100 μm. Our data show a continuous spectrum that lacks previously reported gaps in the size distribution (36). Our measurements confirm that the gravitational settling rate for dehydrated particles larger than 5 μm steeply increases with size, but considering the high numbers, volumes, and airborne lifetimes of those particles, they are likely to be a dominant factor in transmission of disease.     

Application of LC/MS to determine specific activity variation in a series of sulfonamide tracers from the [35S]methane sulfonate reagent

The specific activities for a series of S‐35 tracers were found to vary from the decay‐corrected specific activity of the labeled reagent. If not known before the stock solution preparation and binding assay, this variation would have resulted in performing the assay at approximately two to three times over the targeted concentration, thereby leading to considerable error in the calculated binding and related conclusions. Copyright © 2012 John Wiley & Sons, Ltd.     

Flow Imaging: Moving Toward Best Practices for Subvisible Particle Quantitation in Protein Products

The potential impact of subvisible particles (SVPs) in protein therapeutic products has received a great deal of attention recently. As a result, new analytical methods have emerged to characterize and quantify SVPs. Among these, flow imaging (also called flow microscopy) has been widely employed. As we have used both FlowCAM® and Micro-Flow Imaging? in a variety of development projects, we wished to share our experiences and observations, with the intention of fostering a discussion that will lead to best practices for the use of flow imaging to quantify SVP levels in biopharmaceuticals. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1133–1134, 2013