A 50-state survey study of thoughts of suicide and social isolation among older adults in the United States.

BACKGROUND: We aimed to characterize the prevalence of social disconnection and thoughts of suicide among older adults in the United States, and examine the association between them in a large naturalistic study. METHODS: We analyzed data from 6 waves of a fifty-state non-probability survey among US adults conducted between February and December 2021. The internet-based survey collected the PHQ-9, as well as multiple measures of social connectedness. We applied multiple logistic regression to analyze the association between presence of thoughts of suicide and social disconnection. Exploratory analysis, using generalized random forests, examined heterogeneity of effects across sociodemographic groups. RESULTS: Of 16,164 survey respondents age 65 and older, mean age was 70.9 (SD 5.0); the cohort was 61.4 % female and 29.6 % male; 2.0 % Asian, 6.7 % Black, 2.2 % Hispanic, and 86.8 % White. A total of 1144 (7.1 %) reported thoughts of suicide at least several days in the prior 2 week period. In models adjusted for sociodemographic features, households with 3 or more additional members (adjusted OR 1.73, 95 % CI 1.28-2.33) and lack of social supports, particularly emotional supports (adjusted OR 2.60, 95 % CI 2.09-3.23), were independently associated with greater likelihood of reporting such thoughts, as was greater reported loneliness (adjusted OR 1.75, 95 % CI 1.64-1.87). The effects of emotional support varied significantly across sociodemographic groups. CONCLUSIONS: Thoughts of suicide are common among older adults in the US, and associated with lack of social support, but not with living alone. TRIAL REGISTRATION: NA.

Cholesterol-Amino-Phosphate (CAP) Derived Lipid Nanoparticles for Delivery of Self-Amplifying RNA and Restoration of Spermatogenesis in Infertile Mice.

Male infertility caused by genetic mutations is an important type of infertility. Currently, there is no reliable method in the clinic to address this medical need. The emergence of mRNA therapy provides a possible strategy for restoring mutant genes in the reproductive system. However, effective delivery of mRNA to spermatocytes remains a formidable challenge. Here a series of cholesterol-amino-phosphate (CAP) lipids are reported by integrating three bioactive moieties into a geometric structure, which is favorable for mRNA delivery. The results demonstrate that CAP-derived lipid nanoparticles (CAP LNPs) can deliver RNA including traditional mRNA and self-amplifying RNA (saRNA) encoding DNA Meiotic Recombinase 1 (Dmc1) protein in spermatocytes and treat male infertility caused by the Dmc1 gene mutation. Notably, the delivery efficiency of CAP LNPs is significantly higher than that of the MC3 and ALC-0315 LNPs, which is consistent with the design of CAP molecules. More importantly, a single injection of CAP LNPs-saRNA can produce Dmc1 protein for an extended period, which restores the spermatogenesis in the Dmc1 gene knockout mouse model. Overall, this study proves the concept of LNPs for the delivery of mRNA to spermatocytes, which provides a unique method to probe male infertility caused by the genetic mutation.

Using General Messages to Persuade on a Politicized Scientific Issue

Politics and science have become increasingly intertwined. Salient scientific issues, such as climate change, evolution, and stem-cell research, become politicized, pitting partisans against one another. This creates a challenge of how to effectively communicate on such issues. Recent work emphasizes the need for tailored messages to specific groups. Here, we focus on whether generalized messages also can matter. We do so in the context of a highly polarized issue: extreme COVID-19 vaccine resistance. The results show that science-based, moral frame, and social norm messages move behavioral intentions, and do so by the same amount across the population (that is, homogeneous effects). Counter to common portrayals, the politicization of science does not preclude using broad messages that resonate with the entire population.

Using General Messages to Persuade on a Politicized Scientific Issue

Politics and science have become increasingly intertwined. Salient scientific issues, such as climate change, evolution, and stem-cell research, become politicized, pitting partisans against one another. This creates a challenge of how to effectively communicate on such issues. Recent work emphasizes the need for tailored messages to specific groups. Here, we focus on whether generalized messages also can matter. We do so in the context of a highly polarized issue: extreme COVID-19 vaccine resistance. The results show that science-based, moral frame, and social norm messages move behavioral intentions, and do so by the same amount across the population (that is, homogeneous effects). Counter to common portrayals, the politicization of science does not preclude using broad messages that resonate with the entire population.

Upregulating Human Cathelicidin Antimicrobial Peptide LL-37 Expression May Prevent Severe COVID-19 Inflammatory Responses and Reduce Microthrombosis.

COVID-19 is characterized by hyperactivation by inflammatory cytokines and recruitment of macrophages, neutrophils, and other immune cells, all hallmarks of a strong inflammatory response that can lead to severe complications and multi-organ damage. Mortality in COVID-19 patients is associated with a high prevalence of neutrophil extracellular trap (NET) formation and microthrombosis that are exacerbated by hyperglycemia, diabetes, and old age. SARS-CoV-2 infection in humans and non-human primates have revealed long-term neurological consequences of COVID-19, possibly concomitant with the formation of Lewy bodies in the brain and invasion of the nervous system via the olfactory bulb. In this paper, we review the relevance of the human cathelicidin LL-37 in SARS-CoV-2 infections. LL-37 is an immunomodulatory, host defense peptide with direct anti-SARS-CoV-2 activity, and pleiotropic effects on the inflammatory response, neovascularization, Lewy body formation, and pancreatic islet cell function. The bioactive form of vitamin D and a number of other compounds induce LL-37 expression and one might predict its upregulation, could reduce the prevalence of severe COVID-19. We hypothesize upregulation of LL-37 will act therapeutically, facilitating efficient NET clearance by macrophages, speeding endothelial repair after inflammatory tissue damage, preventing α-synuclein aggregation, and supporting blood-glucose level stabilization by facilitating insulin release and islet ß-cell neogenesis. In addition, it has been postulated that LL-37 can directly bind the S1 domain of SARS-CoV-2, mask angiotensin converting enzyme 2 (ACE2) receptors, and limit SARS-CoV-2 infection. Purposeful upregulation of LL-37 could also serve as a preventative and therapeutic strategy for SARS-CoV-2 infections.

Prevalence of Firearm Ownership Among Individuals With Major Depressive Symptoms.

Importance: Both major depression and firearm ownership are associated with an increased risk for death by suicide in the United States, but the extent of overlap among these major risk factors is not well characterized. Objective: To assess the prevalence of current and planned firearm ownership among individuals with depression. Design, Setting, and Participants: Cross-sectional survey study using data pooled from 2 waves of a 50-state nonprobability internet survey conducted between May and July 7, 2021. Internet survey respondents were 18 years of age or older and were sampled from all 50 US states and the District of Columbia. Main Outcomes and Measures: Self-reported firearm ownership; depressive symptoms as measured by the 9-item Patient Health Questionnaire. Results: Of 24 770 survey respondents (64.6% women and 35.4% men; 5.0% Asian, 10.8% Black, 7.5% Hispanic, and 74.0% White; mean [SD] age 45.8 [17.5]), 6929 (28.0%) reported moderate or greater depressive symptoms; this group had mean (SD) age of 38.18 (15.19) years, 4587 were female (66.2%), and 406 were Asian (5.9%), 725 were Black (10.5%), 652 were Hispanic (6.8%), and 4902 were White (70.7%). Of those with depression, 31.3% reported firearm ownership (n = 2167), of whom 35.9% (n = 777) reported purchasing a firearm within the past year. In regression models, the presence of moderate or greater depressive symptoms was not significantly associated with firearm ownership (adjusted odds ratio [OR], 1.07; 95% CI, 0.98-1.17) but was associated with greater likelihood of a first-time firearm purchase during the COVID-19 pandemic (adjusted OR, 1.77; 95% CI, 1.56-2.02) and greater likelihood of considering a future firearm purchase (adjusted OR, 1.53; 95% CI, 1.23-1.90). Conclusions and Relevance: In this study, current and planned firearm ownership was common among individuals with major depressive symptoms, suggesting a public health opportunity to address this conjunction of suicide risk factors.

Association of Major Depressive Symptoms With Endorsement of COVID-19 Vaccine Misinformation Among US Adults.

Importance: Misinformation about COVID-19 vaccination may contribute substantially to vaccine hesitancy and resistance. Objective: To determine if depressive symptoms are associated with greater likelihood of believing vaccine-related misinformation. Design, Setting, and Participants: This survey study analyzed responses from 2 waves of a 50-state nonprobability internet survey conducted between May and July 2021, in which depressive symptoms were measured using the Patient Health Questionnaire 9-item (PHQ-9). Survey respondents were aged 18 and older. Population-reweighted multiple logistic regression was used to examine the association between moderate or greater depressive symptoms and endorsement of at least 1 item of vaccine misinformation, adjusted for sociodemographic features. The association between depressive symptoms in May and June, and new support for misinformation in the following wave was also examined. Exposures: Depressive symptoms. Main Outcomes and Measures: The main outcome was endorsing any of 4 common vaccine-related statements of misinformation. Results: Among 15 464 survey respondents (9834 [63.6%] women and 5630 [36.4%] men; 722 Asian respondents [4.7%], 1494 Black respondents [9.7%], 1015 Hispanic respondents [6.6%], and 11 863 White respondents [76.7%]; mean [SD] age, 47.9 [17.5] years), 4164 respondents (26.9%) identified moderate or greater depressive symptoms on the PHQ-9, and 2964 respondents (19.2%) endorsed at least 1 vaccine-related statement of misinformation. Presence of depression was associated with increased likelihood of endorsing misinformation (crude odds ratio [OR], 2.33; 95% CI, 2.09-2.61; adjusted OR, 2.15; 95% CI, 1.91-2.43). Respondents endorsing at least 1 misinformation item were significantly less likely to be vaccinated (crude OR, 0.40; 95% CI, 0.36-0.45; adjusted OR, 0.45; 95% CI, 0.40-0.51) and more likely to report vaccine resistance (crude OR, 2.54; 95% CI, 2.21-2.91; adjusted OR, 2.68; 95% CI, 2.89-3.13). Among 2809 respondents who answered a subsequent survey in July, presence of depression in the first survey was associated with greater likelihood of endorsing more misinformation compared with the prior survey (crude OR, 1.98; 95% CI, 1.42-2.75; adjusted OR, 1.63; 95% CI, 1.14-2.33). Conclusions and Relevance: This survey study found that individuals with moderate or greater depressive symptoms were more likely to endorse vaccine-related misinformation, cross-sectionally and at a subsequent survey wave. While this study design cannot address causation, the association between depression and spread and impact of misinformation merits further investigation.

Association Between Social Media Use and Self-reported Symptoms of Depression in US Adults.

Importance: Some studies suggest that social media use is associated with risk for depression, particularly among children and young adults. Objective: To characterize the association between self-reported use of individual social media platforms and worsening of depressive symptoms among adults. Design, Setting, and Participants: This survey study included data from 13 waves of a nonprobability internet survey conducted approximately monthly between May 2020 and May 2021 among individuals aged 18 years and older in the US. Data were analyzed in July and August 2021. Main Outcomes and Measures: Logistic regression was applied without reweighting, with a 5 point or greater increase in 9-item Patient Health Questionnaire (PHQ-9) score as outcome and participant sociodemographic features, baseline PHQ-9, and use of each social media platform as independent variables. Results: In total, 5395 of 8045 individuals (67.1%) with a PHQ-9 score below 5 on initial survey completed a second PHQ-9. These respondents had a mean (SD) age of 55.8 (15.2) years; 3546 respondents (65.7%) identified as female; 329 respondents (6.1%) were Asian, 570 (10.6%) Black, 256 (4.7%) Hispanic, 4118 (76.3%) White, and 122 (2.3%) American Indian or Alaska Native, Pacific Islander or Native Hawaiian, or other. Among eligible respondents, 482 (8.9%) reported 5 points or greater worsening of PHQ-9 score at second survey. In fully adjusted models for increase in symptoms, the largest adjusted odds ratio (aOR) associated with social media use was observed for Snapchat (aOR, 1.53; 95% CI, 1.19-1.96), Facebook (aOR, 1.42; 95% CI, 1.10-1.81), and TikTok (aOR, 1.39; 95% CI, 1.03-1.87). Conclusions and Relevance: Among survey respondents who did not report depressive symptoms initially, social media use was associated with greater likelihood of subsequent increase in depressive symptoms after adjustment for sociodemographic features and news sources. These data cannot elucidate the nature of this association, but suggest the need for further study to understand how social media use may factor into depression among adults.

International Microsurgery Club Webinar Series-Bridging the Knowledge Gap during the COVID-19 Pandemic.

BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) outbreak shut down most conferences. To minimalize the influence, virtual meetings sprang up subsequently. International Microsurgery Club (IMC), as one of the largest professionals-only online microsurgery education groups worldwide, began to host regular weekend webinars during the pandemic to fill the knowledge gap. This study aims to discuss how webinars have fundamentally changed the way knowledge is delivered and exchanged. METHODS: From February 29, 2020 to March 14, 2021, 103 IMC webinars were reviewed and analyzed in detail to determine the use, benefit, and effect. A comparison between webinars hosted by the different societies was made as well. A questionnaire survey focusing on attendees' behavior, attitude, and using habit about webinars was also made. RESULTS: As for the 103 IMC webinar events, the peak participants were 112.3 people in average. The members requesting to join IMC abruptly increased during the pandemic, and the group activity increased dramatically. From the questionnaire (n = 68), the satisfaction level was high (8.88 ± 1.18/10). The respondents were most satisfied with the good quality of the speakers (73.5%). Not only hosts our webinar series but IMC also serves as the platform that welcomes webinars from other societies to share their information. In September 2020, International Microsurgery Webinar League was established via the significant webinar hosts, with more than 300 recorded webinar talks connected successfully. CONCLUSION: As the knowledge revolution driven by COVID-19 will continue, IMC will keep playing an essential role in exploring new and emerging opportunities to improve knowledge dissemination worldwide beyond the space-time boundary.

Gender-specificity of resilience in major depressive disorder.

INTRODUCTION: The major stressors associated with the COVID-19 pandemic provide an opportunity to understand the extent to which protective factors against depression may exhibit gender-specificity. METHOD: This study examined responses from multiple waves of a 50 states non-probability internet survey conducted between May 2020 and January 2021. Participants completed the PHQ-9 as a measure of depression, as well as items characterizing social supports. We used logistic regression models with population reweighting to examine association between absence of even mild depressive symptoms and sociodemographic features and social supports, with interaction terms and stratification used to investigate sex-specificity. RESULTS: Among 73,917 survey respondents, 31,199 (42.2%) reported absence of mild or greater depression-11,011/23,682 males (46.5%) and 20,188/50,235 (40.2%) females. In a regression model, features associated with greater likelihood of depression-resistance included at least weekly attendance of religious services (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.04-1.16) and greater trust in others (OR: 1.04 for a 2-unit increase, 95% CI: 1.02-1.06), along with level of social support measured as number of social ties available who could provide care (OR: 1.05, 95% CI: 1.02-1.07), talk to them (OR: 1.10, 95% CI: 1.07-1.12), and help with employment (OR: 1.06, 95% CI: 1.04-1.08). The first two features showed significant interaction with gender (p < .0001), with markedly greater protective effects among women. CONCLUSION: Aspects of social support are associated with diminished risk of major depressive symptoms, with greater effects of religious service attendance and trust in others observed among women than men.

Potent Antiviral Activity against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids.

Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent that addresses that target. Antimicrobial peptides (AMPs) represent a novel source of potential antiviral drugs. AMPs have been shown to inactivate numerous different enveloped viruses through the disruption of their viral envelopes. However, the clinical development of AMPs as antimicrobial therapeutics has been hampered by a number of factors, especially their enzymatically labile structure as peptides. We have examined the antiviral potential of peptoid mimics of AMPs (sequence-specific N-substituted glycine oligomers). These peptoids have the distinct advantage of being insensitive to proteases, and also exhibit increased bioavailability and stability. Our results demonstrate that several peptoids exhibit potent in vitro antiviral activity against both HSV-1 and SARS-CoV-2 when incubated prior to infection. In other words, they have a direct effect on the viral structure, which appears to render the viral particles non-infective. Visualization by cryo-EM shows viral envelope disruption similar to what has been observed with AMP activity against other viruses. Furthermore, we observed no cytotoxicity against primary cultures of oral epithelial cells. These results suggest a common or biomimetic mechanism, possibly due to the differences between the phospholipid head group makeup of viral envelopes and host cell membranes, thus underscoring the potential of this class of molecules as safe and effective broad-spectrum antiviral agents. We discuss how and why differing molecular features between 10 peptoid candidates may affect both antiviral activity and selectivity.