The energetics of rapid cellular mechanotransduction.

Cells throughout the human body detect mechanical forces. While it is known that the rapid (millisecond) detection of mechanical forces is mediated by force-gated ion channels, a detailed quantitative understanding of cells as sensors of mechanical energy is still lacking. Here, we combine atomic force microscopy with patch-clamp electrophysiology to determine the physical limits of cells expressing the force-gated ion channels (FGICs) Piezo1, Piezo2, TREK1, and TRAAK. We find that, depending on the ion channel expressed, cells can function either as proportional or nonlinear transducers of mechanical energy and detect mechanical energies as little as ~100 fJ, with a resolution of up to ~1 fJ. These specific energetic values depend on cell size, channel density, and cytoskeletal architecture. We also make the surprising discovery that cells can transduce forces either nearly instantaneously (<1 ms) or with a substantial time delay (~10 ms). Using a chimeric experimental approach and simulations, we show how such delays can emerge from channel-intrinsic properties and the slow diffusion of tension in the membrane. Overall, our experiments reveal the capabilities and limits of cellular mechanosensing and provide insights into molecular mechanisms that different cell types may employ to specialize for their distinct physiological roles.

Distinct ultrastructural phenotypes of glial and neuronal alpha-synuclein inclusions in multiple system atrophy.

Multiple System Atrophy is characterized pathologically by the accumulation of alpha-synuclein (aSyn) into glial cytoplasmic inclusions (GCIs). The mechanism underlying the formation of GCIs is not well understood. In this study, correlative light and electron microscopy was employed to investigate aSyn pathology in the substantia nigra and putamen of post-mortem multiple system atrophy brain donors. Three distinct types of aSyn immuno-positive inclusions were identified in oligodendrocytes, neurons and dark cells presumed to be dark microglia. Oligodendrocytes contained fibrillar GCIs that were consistently enriched with lysosomes and peroxisomes, supporting the involvement of the autophagy pathway in aSyn aggregation in multiple system atrophy. Neuronal cytoplasmic inclusions exhibited ultrastructural heterogeneity resembling both fibrillar and membranous inclusions, linking multiple systems atrophy and Parkinson's disease. The novel aSyn pathology identified in the dark cells, displayed GCI-like fibrils or non-GCI-like ultrastructures suggesting various stages of aSyn accumulation in these cells. The observation of GCI-like fibrils within dark cells suggests these cells may be an important contributor to the origin or spread of pathological aSyn in multiple system atrophy. Our results suggest a complex interplay between multiple cell types that may underlie the formation of aSyn pathology in multiple system atrophy brain and highlight the need for further investigation into cell-specific disease pathologies in multiple system atrophy.

The Psychosocial Impact of the COVID-19 Pandemic on Families of Youth of Color: A Prospective Cohort Study.

OBJECTIVE: Prospectively examine racial and ethnic disparities in exposure to COVID-19-related stressors and their impact on families. METHODS: A racially, ethnically, and socioeconomically diverse cohort of caregivers of youth (n = 1,581) representative of the population served by a pediatric healthcare system completed the COVID-19 Exposure and Family Impact Scales in Oct/Nov 2020 and March/April 2021. Linear mixed-effects models were used to examine exposure to COVID-19-related events (Exposure), impact of the pandemic on family functioning and well-being (Impact), and child and parent distress (Distress) across time and as a function of race and ethnicity, adjusting for other sociodemographic variables. RESULTS: Exposure and Distress increased over time for all participants. After adjusting for sociodemographic factors, caregivers of Black and Hispanic youth reported greater Exposure than caregivers of White youth and caregivers of Black youth had a greater increase in Exposure over time than caregivers of White youth. Caregivers of White youth reported greater Impact than caregivers of Black and Other race youth. CONCLUSIONS: Exposure to and impact of the COVID-19 pandemic on family psychosocial functioning varied by race and ethnicity. Although exposure to COVID-19-related events was greater among Hispanic and non-Hispanic Black families, those of marginalized races reported less family impact than non-Hispanic White families, suggesting resiliency to the pandemic. Research should examine such responses to public health crises in communities of color, with a focus on understanding protective factors. These findings suggest the importance of culturally tailored interventions and policies that support universal psychosocial screenings during times of public health crises.

The RELIEF feasibility trial: topical lidocaine patches in older adults with rib fractures.

BACKGROUND: Lidocaine patches, applied over rib fractures, may reduce pulmonary complications in older patients. Known barriers to recruiting older patients in emergency settings necessitate a feasibility trial. We aimed to establish whether a definitive randomised controlled trial (RCT) evaluating lidocaine patches in older patients with rib fracture(s) was feasible. METHODS: This was a multicentre, parallel-group, open-label, feasibility RCT in seven hospitals in England and Scotland. Patients aged ≥65 years, presenting to ED with traumatic rib fracture(s) requiring hospital admission were randomised to receive up to 3×700 mg lidocaine patches (Ralvo), first applied in ED and then once daily for 72 hours in addition to standard care, or standard care alone. Feasibility outcomes were recruitment, retention and adherence. Clinical end points (pulmonary complications, pain and frailty-specific outcomes) and patient questionnaires were collected to determine feasibility of data collection and inform health economic scoping. Interviews and focus groups with trial participants and clinicians/research staff explored the understanding and acceptability of trial processes. RESULTS: Between October 23, 2021 and October 7, 2022, 206 patients were eligible, of whom 100 (median age 83 years; IQR 74-88) were randomised; 48 to lidocaine patches and 52 to standard care. Pulmonary complications at 30 days were determined in 86% of participants and 83% of expected 30-day questionnaires were returned. Pulmonary complications occurred in 48% of the lidocaine group and 59% in standard care. Pain and some frailty-specific outcomes were not feasible to collect. Staff reported challenges in patient compliance, unfamiliarity with research measures and overwhelming the patients with research procedures. CONCLUSION: Recruitment of older patients with rib fracture(s) in an emergency setting for the evaluation of lidocaine patches is feasible. Refinement of data collection, with a focus on the collection of pain, frailty-specific outcomes and intervention delivery are needed before progression to a definitive trial. TRIAL REGISTRATION NUMBER: ISRCTN14813929.

Gardnerella Vaginolysin Potentiates Glycan Molecular Mimicry by Neisseria gonorrhoeae.

Bacterial vaginosis (BV) is a dysbiotic condition of the vaginal microbiome associated with higher risk of infection by Neisseria gonorrhoeae-the cause of gonorrhea. Here we test if one known facet of BV-the presence of bacterial cytolysins-leads to mobilization of intracellular contents that enhance gonococcal virulence. We cloned and expressed recombinant vaginolysin (VLY), a cytolysin produced by the BV-associated bacterium Gardnerella, verifying that it liberates contents of cervical epithelial (HeLa) cells, while vector control preparations did not. We tested if VLY mediates a well-known gonococcal virulence mechanism-the molecular mimicry of host glycans. To evade host immunity, N. gonorrhoeae caps its lipooligosaccharide (LOS) with α2-3-linked sialic acid. For this, gonococci must scavenge a metabolite made inside host cells. Flow cytometry-based lectin-binding assays showed that gonococci exposed to vaginolysin-liberated contents of HeLa cells displayed greater sialic acid capping of their LOS. This higher level of bacterial sialylation was accompanied by increased binding of the complement regulatory protein factor H, and greater resistance to complement attack. Together these results suggest that cytolytic activities present during BV may enhance the ability of N. gonorrhoeae to capture intracellular metabolites and evade host immunity via glycan molecular mimicry.

Cataloging natural sialic acids and other nonulosonic acids (NulOs), and their representation using the Symbol Nomenclature for Glycans.

Nonulosonic acids or non-2-ulosonic acids (NulOs) are an ancient family of 2-ketoaldonic acids (α-ketoaldonic acids) with a 9-carbon backbone. In nature, these monosaccharides occur either in a 3-deoxy form (referred to as "sialic acids") or in a 3,9-dideoxy "sialic-acid-like" form. The former sialic acids are most common in the deuterostome lineage, including vertebrates, and mimicked by some of their pathogens. The latter sialic-acid-like molecules are found in bacteria and archaea. NulOs are often prominently positioned at the outermost tips of cell surface glycans, and have many key roles in evolution, biology and disease. The diversity of stereochemistry and structural modifications among the NulOs contributes to more than 90 sialic acid forms and 50 sialic-acid-like variants described thus far in nature. This paper reports the curation of these diverse naturally occurring NulOs at the NCBI sialic acid page (https://www.ncbi.nlm.nih.gov/glycans/sialic.html) as part of the NCBI-Glycans initiative. This includes external links to relevant Carbohydrate Structure Databases. As the amino and hydroxyl groups of these monosaccharides are extensively derivatized by various substituents in nature, the Symbol Nomenclature For Glycans (SNFG) rules have been expanded to represent this natural diversity. These developments help illustrate the natural diversity of sialic acids and related NulOs, and enable their systematic representation in publications and online resources.

Glycan cross-feeding supports mutualism between Fusobacterium and the vaginal microbiota.

Women with bacterial vaginosis (BV), an imbalance of the vaginal microbiome, are more likely to be colonized by potential pathogens such as Fusobacterium nucleatum, a bacterium linked with intrauterine infection and preterm birth. However, the conditions and mechanisms supporting pathogen colonization during vaginal dysbiosis remain obscure. We demonstrate that sialidase activity, a diagnostic feature of BV, promoted F. nucleatum foraging and growth on mammalian sialoglycans, a nutrient resource that was otherwise inaccessible because of the lack of endogenous F. nucleatum sialidase. In mice with sialidase-producing vaginal microbiotas, mutant F. nucleatum unable to consume sialic acids was impaired in vaginal colonization. These experiments in mice also led to the discovery that F. nucleatum may also "give back" to the community by reinforcing sialidase activity, a biochemical feature of human dysbiosis. Using human vaginal bacterial communities, we show that F. nucleatum supported robust outgrowth of Gardnerella vaginalis, a major sialidase producer and one of the most abundant organisms in BV. These results illustrate that mutually beneficial relationships between vaginal bacteria support pathogen colonization and may help maintain features of dysbiosis. These findings challenge the simplistic dogma that the mere absence of "healthy" lactobacilli is the sole mechanism that creates a permissive environment for pathogens during vaginal dysbiosis. Given the ubiquity of F. nucleatum in the human mouth, these studies also suggest a possible mechanism underlying links between vaginal dysbiosis and oral sex.

FTLD-TDP assemblies seed neoaggregates with subtype-specific features via a prion-like cascade.

Morphologically distinct TDP-43 aggregates occur in clinically different FTLD-TDP subtypes, yet the mechanism of their emergence and contribution to clinical heterogeneity are poorly understood. Several lines of evidence suggest that pathological TDP-43 follows a prion-like cascade, but the molecular determinants of this process remain unknown. We use advanced microscopy techniques to compare the seeding properties of pathological FTLD-TDP-A and FTLD-TDP-C aggregates. Upon inoculation of patient-derived aggregates in cells, FTLD-TDP-A seeds amplify in a template-dependent fashion, triggering neoaggregation more efficiently than those extracted from FTLD-TDP-C patients, correlating with the respective disease progression rates. Neoaggregates are sequentially phosphorylated with N-to-C directionality and with subtype-specific timelines. The resulting FTLD-TDP-A neoaggregates are large and contain densely packed fibrils, reminiscent of the pure compacted fibrils present within cytoplasmic inclusions in postmortem brains. In contrast, FTLD-TDP-C dystrophic neurites show less dense fibrils mixed with cellular components, and their respective neoaggregates are small, amorphous protein accumulations. These cellular seeding models replicate aspects of the patient pathological diversity and will be a useful tool in the quest for subtype-specific therapeutics.

Acceptability and Feasibility of eSCCIP: Results From a Pilot Study of the Electronic Surviving Cancer Competently Intervention Program.

BACKGROUND: Providing high-quality psychosocial care to parents and other primary caregivers of children with cancer (henceforth referred to as caregivers) is important, given the numerous challenges associated with a pediatric cancer diagnosis and the increased risk for negative psychosocial sequelae among caregivers. The Electronic Surviving Cancer Competently Intervention Program (eSCCIP) is a psychosocial eHealth intervention for caregivers, developed using an iterative, user-centered process. METHOD: eSCCIP was tested in a single-arm pilot trial at Nemours Children's Hospital, Delaware (NCT05333601). The primary outcomes were intervention acceptability and feasibility, assessed via enrollment and retention targets, and item-level acceptability ratings. Enrollment and retention targets of 45% were set based on previous work, and an item-level acceptability threshold of 80% was set. A secondary exploratory analysis was conducted examining acute distress, anxiety, symptoms of post-traumatic stress, and family functioning. RESULTS: 44 caregivers enrolled in the study and 31 completed. The intervention was rated favorably by completers, with over 80% of the sample selecting "mostly true" or "very true" for all items of the eSCCIP Evaluation Questionnaire, which was used to assess acceptability and feasibility. Enrollment and retention rates were 54% and 70%, respectively. Exploratory psychosocial outcomes showed statistically significant decreases from pre-intervention to post-intervention for overall symptoms of post-traumatic stress disorder (PTSD), cluster D symptoms of PTSD (negative mood and cognitions), and anxiety. Small-moderate effect sizes were observed for all psychosocial outcomes of interest. CONCLUSIONS: eSCCIP is an acceptable and feasible intervention for caregivers. Results are promising regarding reductions in symptoms of post-traumatic stress and anxiety.

Validation of the Psychosocial Assessment Tool Sibling Module Follow-Up Version.

OBJECTIVE: Psychosocial screening is recommended to connect siblings of youth with cancer to psychosocial services, but the lack of validated sibling-specific screening tools is a barrier to routine screening. The current study aimed to validate and establish a clinical cutoff for the recently developed Psychosocial Assessment Tool (PAT) Sibling Module follow-up version to address this barrier. METHODS: Parents (N = 246) completed the PAT Sibling Module follow-up version for all siblings within their families ages 0-17 years (N = 458) at three time points between 6- and 24-month post-cancer diagnosis. For one target sibling within each family aged 8-17 years, parents also completed the Strengths and Difficulties Questionnaire, and the target sibling completed the Child PTSD Symptom Scale. Cross-sectional and longitudinal analyses examined internal consistency and convergent and predictive validity. Receiver operator characteristic analyses were used to establish a maximally sensitive and specific clinical cutoff. RESULTS: Internal consistency was acceptable for all age versions (Kuder-Richardson 20s ≥ 0.79), except for the ages 0-2 version, which had low internal consistency at 18 months post-diagnosis (Kuder-Richardson 20 = 0.57). Convergent (r values >0.7, p values <.001) and predictive (r values >0.6, p values <.001) validity were strong at each time point. An optimal clinical cutoff of 0.32 was identified (range: 0.00-1.00). CONCLUSIONS: The PAT Sibling Module follow-up version is a reliable and valid screener for sibling psychosocial risk following cancer diagnosis. Validation of a sibling-specific screener and establishment of a clinical cutoff are necessary first steps to addressing siblings' unmet psychosocial needs and improving trajectories of sibling functioning.

Trajectories of Traumatic Stress Symptoms Among Siblings of Children With Cancer: The First Two Years Post-Diagnosis.

OBJECTIVE: Identify and describe trajectories of cancer-related posttraumatic stress symptoms (PTSS) among siblings of children with cancer within two years of diagnosis. METHOD: Siblings (aged 8-18; M = 11.2 years) across the United States, and for each, one caregiver, were recruited for a cohort sequential longitudinal study with three data collection points six months apart beginning at 6- or 12-months after cancer diagnosis. Siblings (N = 229; 42% of eligible/approached; 53% identifying as female; 68% identifying as non-Hispanic White) completed the Child Posttraumatic Stress Disorder Symptom Scale. Caregivers completed the Strengths and Difficulties Questionnaire (SDQ). Latent class growth analysis (LCGA) and growth mixture modeling (GMM) identified PTSS patterns across time. RESULTS: Fit statistics supported models with three to five PTSS trajectories. The three-class LCGA model included a large mild PTSS group (61%), a moderate PTSS group (35%), and a small (4%) stable severe PTSS group. The four-class LCGA and three- and four-class GMM included groups improving from moderate to mild PTSS (7-21%) and worsening to moderate PTSS across time (12-17%). Across models, siblings with mild PTSS had fewer caregiver-reported emotional and behavioral difficulties on the SDQ. CONCLUSIONS: A large group of siblings of children with cancer demonstrate resiliency, however, substantial subsets experience patterns of PTSS that include levels in the moderate-to-severe range during the first two years post-diagnosis. Future research should examine these patterns in more diverse/representative samples and identify factors associated with increasing and sustained severe PTSS to inform intervention targets and reduce cancer-related burden on families.

Psychosocial Staffing and Implementation of the International Society for Pediatric and Adolescent Diabetes Psychological Care Guidelines in U.S. Pediatric Diabetes Clinics.

Background: Few studies have examined the implementation of the International Society for Pediatric and Adolescent Diabetes (ISPAD) Clinical Practice Consensus Guidelines for the Psychological Care of Children and Adolescents with Type 1 Diabetes. Objective: To collect benchmark data on psychosocial staffing and implementation of the ISPAD guidelines across U.S. pediatric diabetes clinics. Methods: Medical (n = 95; 77 endocrinologists and 18 advance practice providers) and psychosocial (n = 86; 43 social workers and 43 psychologists) providers from 98 of 115 contacted clinics completed an online survey (85% response rate). Providers reported the number of psychosocial staff and rated the adequacy of psychosocial staffing, quality of psychosocial care, and adherence to the ISPAD guidelines in their clinics. χ2 Tests and ANOVA were used to examine differences across clinic size and across medical and psychosocial providers. Results: Clinics averaged a total of ∼4 hours per week of psychosocial provider time per 100 patients with type 1 diabetes. Only 27% of providers agreed that psychosocial staffing was adequate, and 35% described their psychosocial care as comprehensive. Implementation of the ISPAD guidelines varied across clinics, with minimal differences across clinic size. Medical providers reported that evidence-based psychological assessment and interventions were delivered consistently by <55% of clinics. Psychosocial, compared with medical, providers were more likely to report frequent implementation of psychosocial assessment and intervention guidelines. Conclusion: Psychological care in U.S. pediatric type 1 diabetes clinics does not consistently meet the ISPAD guidelines, and many clinics lack adequate psychosocial staff. These benchmark data are a foundational step to improve psychosocial care for pediatric patients with type 1 diabetes.

A community-based trial of a psychosocial eHealth intervention for parents of children with cancer.

BACKGROUND: The Electronic Surviving Cancer Competently Intervention Program (eSCCIP), a psychosocial eHealth intervention for parents and caregivers of children with cancer (parents), was delivered in a community-based psychosocial oncology center. Primary endpoints were intervention acceptability, feasibility, and accessibility, with a secondary exploratory focus on psychosocial outcomes. PROCEDURE: Oncology therapists in a psychosocial oncology center were trained in eSCCIP delivery. Participants were eligible for participation if they were the primary caregiver of a child with cancer between the ages 0 and 17, could read and write in English, and had reliable internet access to complete eSCCIP. Surveys were administered electronically at baseline and post intervention to evaluate study endpoints. Effect sizes (Cohen's d) were computed for exploratory psychosocial outcomes. Nineteen parents completed the intervention. RESULTS: Parents rated eSCCIP as highly acceptable, feasible, and accessible. A large clinical effect was detected for acute distress (d = 0.79). Moderate clinical effects were reported for overall posttraumatic stress disorder (PTSD) symptoms (d = 0.37), negative mood/cognitions (d = 0.59), and symptoms of anxiety (d = 0.48). CONCLUSIONS: Results indicate that eSCCIP is an acceptable, feasible, and accessible psychosocial intervention for parents. Exploratory analyses suggest that participation in eSCCIP may contribute to decreases in acute distress, symptoms of anxiety, and symptoms of PTSD.

Attitudes and Practices of Pediatric Oncologists Regarding Palliative Care Consultation for Pediatric Oncology Patients.

OBJECTIVE: We sought to describe palliative care services available to children with cancer along with pediatric oncologists' current and ideal practices of palliative care involvement in children with cancer. DESIGN: A novel survey tool was administered via REDCap to attending pediatric oncologists in the United States. The survey remained open from June to September 2020. RESULTS: A total of 265 survey responses were evaluated. Most respondents endorsed that palliative care should "always" be consulted for the following scenarios: new diagnosis of advanced/metastatic disease (53%), uncontrolled symptoms (65%), bone marrow transplant (55%), and relapsed/refractory disease (73%). For those same scenarios, the majority noted the current practice was to "sometimes" or "usually" consult. Most respondents (92.6%) felt that palliative care should be consulted more frequently than they were currently being consulted. CONCLUSIONS: Compared with the current practice for various pediatric oncology departments, palliative care was not consulted as often as oncologists desired. While barriers to palliative care consultation are outlined in the literature, exploration of how to address them as well as identification of barriers specific to oncologists who are in favor of palliative care consultation are not well-described. Further research exploring these specific barriers is necessary to understand the disconnect between oncologists' attitudes and palliative care consultation.

Validating the Factor Structure of the Psychosocial Assessment Tool Using Internet-Based Data.

OBJECTIVE: The Psychosocial Assessment Tool (PAT) is a well-validated, brief screener of family psychosocial risk. Since 2014 a web-based version of the PAT (WebPAT) has been available for use by clinicians and researchers, but the psychometric properties have not been examined. The objective of this article was to examine the factor structure and internal consistency of the WebPAT, which was administered to caregivers of youth with cancer. METHODS: The WebPAT was administered to 1,252 caregivers of youth with cancer across 29 institutions. Confirmatory factor analysis (CFA) was used to examine the factor structure of the WebPAT. Internal consistencies of the total and subscale scores were examined via the Kuder-Richardson 20 coefficient. The distribution of total PAT score across the three risk categories of the Pediatric Psychosocial Preventative Health Model (PPPHM) was also examined. RESULTS: The CFA supported the original seven-factor structure of the PAT (Family Structure, Social Support, Child Problems, Sibling Problems, Family Problems, Stress Reactions, and Family Beliefs). Internal consistencies were strong for the total PAT score and four subscales (Social Support, Child Problems, Sibling Problems, and Family Problems). The distribution of total PAT scores across PPPHM risk categories was consistent with prior research. CONCLUSIONS: The WebPAT is a psychometrically sound screener of psychosocial risk in families of youth with cancer. Healthcare providers can use the WebPAT to assess families' psychosocial risk and guide the provision of psychosocial care. Future research should evaluate the implementation of the PAT and identify barriers and facilitators to implementation.

Validation of the COVID-19 Exposure and Family Impact Scales.

OBJECTIVE: The COVID-19 Exposure and Family Impact Scales (CEFIS) were developed in Spring 2020 to assess effects of the COVID-19 pandemic on families and caregivers. Initial psychometric properties were promising. The current study examined the factor structure and evaluated convergent and criterion validity of the CEFIS in a new sample. METHODS: In October and November 2020, caregivers (N = 2,531) of youth (0-21 years) scheduled for an ambulatory care visit at Nemours Children's Hospital, Delaware completed the CEFIS and measures of convergent (PROMIS Global Mental Health Scale, Family Assessment Device) and criterion validity (PTSD Checklist-Civilian). Confirmatory factor analysis was used to examine the factor structure of the CEFIS. Bivariate correlations and logistic regression were used to examine convergent and criterion validity. RESULTS: Factor analysis supported the original six- and three-factor structures for the Exposure and Impact scales, respectively. Second-order factor analyses supported the use of Exposure, Impact, and Distress total scores. Higher scores on the CEFIS Exposure, Impact, and Distress scales were associated with increased mental health concerns and poorer family functioning. Higher scores on all CEFIS scales were also associated with greater odds of having clinically significant posttraumatic stress symptoms. CONCLUSIONS: The CEFIS is a psychometrically sound measure of the impact of the COVID-19 pandemic on family and caregiver functioning and may also be useful in identifying families who would benefit from psychological supports.

COVID-19 Exposure and Family Impact Scales for Adolescents and Young Adults.

OBJECTIVE: To understand the impact of the coronavirus disease 2019 (COVID-19) pandemic on adolescents and young adults (AYAs), we adapted the COVID-19 Exposure and Family Impact Scales (CEFIS; Kazak et al., 2021) for AYAs. Here, we report on the development, structure, and psychometric properties of the CEFIS-AYA. METHODS: The CEFIS-AYA was developed by a multidisciplinary, multi-institutional team using a rapid iterative process. Data from 3,912 AYAs from 21 programs at 16 institutions across the United States were collected from May 2020 to April 2021. We examined the underlying structure of the CEFIS-AYA using principal component analysis (PCA), calculated internal consistencies, and explored differences in scores by gender and age. RESULTS: Participants reported exposure to a range of COVID-19-related events (M = 9.08 events, of 28). On the bidirectional 4-point Impact scale, mean item scores were mostly above the midpoint, indicating a slightly negative impact. Kuder-Richardson 20/Cronbach's Alpha was good for Exposure (α = .76) and excellent for Impact (α = .93). PCA identified seven factors for Exposure (Severe COVID-19, Loss of Income, Limited Access to Essentials, COVID-19 Exposure, Disruptions to Activities, Disruptions to Living Conditions, and Designation as an Essential Worker) and five for Impact (Self and Family Relationships, Physical Well-Being, Emotional Well-Being, Social Well-Being, and Distress). Gender and age differences in CEFIS-AYA scores were identified. DISCUSSION: Initial reliability data are strong and support use of the CEFIS-AYA for measuring the effect of the COVID-19 pandemic on AYAs in research and clinical care.

Touch, Tension, and Transduction - The Function and Regulation of Piezo Ion Channels.

In 2010, two proteins, Piezo1 and Piezo2, were identified as the long-sought molecular carriers of an excitatory mechanically activated current found in many cells. This discovery has opened the floodgates for studying a vast number of mechanotransduction processes. Over the past 6 years, groundbreaking research has identified Piezos as ion channels that sense light touch, proprioception, and vascular blood flow, ruled out roles for Piezos in several other mechanotransduction processes, and revealed the basic structural and functional properties of the channel. Here, we review these findings and discuss the many aspects of Piezo function that remain mysterious, including how Piezos convert a variety of mechanical stimuli into channel activation and subsequent inactivation, and what molecules and mechanisms modulate Piezo function.

Vaginal sialoglycan foraging by Gardnerella vaginalis: mucus barriers as a meal for unwelcome guests?

Bacterial vaginosis (BV) is a condition of the vaginal microbiome in which there are few lactobacilli and abundant anaerobic bacteria. Members of the genus Gardnerella are often one of the most abundant bacteria in BV. BV is associated with a wide variety of poor health outcomes for women. It has been recognized since the 1980s that women with BV have detectable and sometimes markedly elevated levels of sialidase activity in vaginal fluids and that bacteria associated with this condition produce this activity in culture. Mounting evidence collected using diverse methodologies points to the conclusion that BV is associated with a reduction in intact sialoglycans in cervicovaginal secretions. Here we review evidence for the contributions of vaginal bacteria, especially Gardnerella, in the processes of mucosal sialoglycan degradation, uptake, metabolism and depletion. Our understanding of the impacts of vaginal sialoglycan degradation is still limited. However, the potential implications of sialic acid depletion are discussed in light of our current understanding of the roles played by sialoglycans in vaginal physiology.

Tropicalization of temperate ecosystems in North America: The northward range expansion of tropical organisms in response to warming winter temperatures.

Tropicalization is a term used to describe the transformation of temperate ecosystems by poleward-moving tropical organisms in response to warming temperatures. In North America, decreases in the frequency and intensity of extreme winter cold events are expected to allow the poleward range expansion of many cold-sensitive tropical organisms, sometimes at the expense of temperate organisms. Although ecologists have long noted the critical ecological role of winter cold temperature extremes in tropical-temperate transition zones, the ecological effects of extreme cold events have been understudied, and the influence of warming winter temperatures has too often been left out of climate change vulnerability assessments. Here, we examine the influence of extreme cold events on the northward range limits of a diverse group of tropical organisms, including terrestrial plants, coastal wetland plants, coastal fishes, sea turtles, terrestrial reptiles, amphibians, manatees, and insects. For these organisms, extreme cold events can lead to major physiological damage or landscape-scale mass mortality. Conversely, the absence of extreme cold events can foster population growth, range expansion, and ecological regime shifts. We discuss the effects of warming winters on species and ecosystems in tropical-temperate transition zones. In the 21st century, climate change-induced decreases in the frequency and intensity of extreme cold events are expected to facilitate the poleward range expansion of many tropical species. Our review highlights critical knowledge gaps for advancing understanding of the ecological implications of the tropicalization of temperate ecosystems in North America.