BDSM in North America, Europe, and Oceania: A Large-Scale International Survey Gauging BDSM Interests and Activities.

BDSM bondage and discipline, dominance and submission, and sadism and masochism is a widespread and highly prevalent yet stigmatized practice of intimacy and sexuality. In recent years, international interest in BDSM research has grown, mainly resulting in prevalence studies in various countries. To date, however, no research has investigated international and intercontinental differences in the nature of BDSM interests and fantasies, BDSM roles and practicing contexts among BDSM practitioners. In order to explore international discrepancies in BDSM identity, fantasies, and activities among self-identified BDSM practitioners, a group of FetLife (a social network website for BDSM and kink interested individuals) members (N = 1,112) originating from North America (n = 458), Europe (n = 566), Oceania (n = 46), and Other (n = 42) completed the survey. Europeans reported an earlier age of onset of fantasizing about BDSM than did North Americans. More North Americans indicated practicing BDSM in a public context than did Europeans and Oceanians. These differences could in part be explained by different cultural backgrounds, higher levels of religiosity, and current stigmas toward non-traditional sexual interests. Future research should focus on clarifying whether cultural mechanisms underlie these dissimilarities.

Vimentin is required for tumor progression and metastasis in a mouse model of non-small cell lung cancer.

Vimentin is highly expressed in metastatic cancers, and its expression correlates with poor patient prognoses. However, no causal in vivo studies linking vimentin and non-small cell lung cancer (NSCLC) progression existed until now. We use three complementary in vivo models to show that vimentin is required for the progression of NSCLC. First, we crossed LSL-KrasG12D; Tp53fl/fl mice (KPV+/+) with vimentin knockout mice (KPV-/-) to demonstrate that KPV-/- mice have attenuated tumor growth and improved survival compared with KPV+/+ mice. Next, we therapeutically treated KPV+/+ mice with withaferin A (WFA), an agent that disrupts vimentin intermediate filaments (IFs). We show that WFA suppresses tumor growth and reduces tumor burden in the lung. Finally, luciferase-expressing KPV+/+, KPV-/-, or KPVY117L cells were implanted into the flanks of athymic mice to track cancer metastasis to the lung. In KPVY117L cells, vimentin forms oligomers called unit-length filaments but cannot assemble into mature vimentin IFs. KPV-/- and KPVY117L cells fail to metastasize, suggesting that cell-autonomous metastasis requires mature vimentin IFs. Integrative metabolomic and transcriptomic analysis reveals that KPV-/- cells upregulate genes associated with ferroptosis, an iron-dependent form of regulated cell death. KPV-/- cells have reduced glutathione peroxidase 4 (GPX4) levels, resulting in the accumulation of toxic lipid peroxides and increased ferroptosis. Together, our results demonstrate that vimentin is required for rapid tumor growth, metastasis, and protection from ferroptosis in NSCLC.

MBNL1 regulates programmed postnatal switching between regenerative and differentiated cardiac states.

Discovering determinants of cardiomyocyte maturity and the maintenance of differentiated states is critical to both understanding development and potentially reawakening endogenous regenerative programs in adult mammalian hearts as a therapeutic strategy. Here, the RNA binding protein Muscleblind-like 1 (MBNL1) was identified as a critical regulator of cardiomyocyte differentiated states and their regenerative potential through transcriptome-wide control of RNA stability. Targeted MBNL1 overexpression early in development prematurely transitioned cardiomyocytes to hypertrophic growth, hypoplasia, and dysfunction, whereas loss of MBNL1 function increased cardiomyocyte cell cycle entry and proliferation through altered cell cycle inhibitor transcript stability. Moreover, MBNL1-dependent stabilization of the estrogen-related receptor signaling axis was essential for maintaining cardiomyocyte maturity. In accordance with these data, modulating MBNL1 dose tuned the temporal window of cardiac regeneration, where enhanced MBNL1 activity arrested myocyte proliferation, and MBNL1 deletion promoted regenerative states with prolonged myocyte proliferation. Collectively these data suggest MBNL1 acts as a transcriptome-wide switch between regenerative and mature myocyte states postnatally and throughout adulthood.

Intracranial complications of hypercoagulability and superinfection in the setting of COVID-19: illustrative cases.

BACKGROUND: Hypercoagulability with thrombosis and associated inflammation has been well-documented in COVID-19, and catastrophic cerebral venous sinus thromboses (CVSTs) have been described. Another COVID-19-related complication is bacterial superinfection, including sinusitis. Here, the authors reported three cases of COVID-19-associated sinusitis, meningitis, and CVST and summarized the literature about septic intracranial thrombotic events as a cause of headache and fever in COVID-19. OBSERVATIONS: The authors described three adolescent patients with no pertinent past medical history and no prior COVID-19 vaccinations who presented with subacute headaches, photosensitivity, nausea, and vomiting after testing positive for COVID-19. Imaging showed subdural collections, CVST, cerebral edema, and severe sinus disease. Two patients had decline in mental status and progression of neurological symptoms. In all three, emergency cranial and sinonasal washouts uncovered pus that grew polymicrobial cultures. After receiving broad-spectrum antimicrobials and various additional treatments, including two of three patients receiving anticoagulation, all patients eventually became neurologically intact with varying ongoing sequelae. LESSONS: These cases demonstrated similar original presentations among previously healthy adolescents with COVID-19 infections, concurrent sinusitis precipitating CVST, and subdural empyemas. Better recognition and understanding of the multisystem results of severe acute respiratory syndrome coronavirus 2 and the complicated sequelae allows for proper treatment.

The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging.

Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie the differential severity of pneumonia in older patients. We performed an integrated analysis of single-cell RNA-Seq data that revealed homogenous age-related changes in the alveolar macrophage transcriptome in humans and mice. Using genetic lineage tracing with sequential injury, heterochronic adoptive transfer, and parabiosis, we found that the lung microenvironment drove an age-related resistance of alveolar macrophages to proliferation that persisted during influenza A viral infection. Ligand-receptor pair analysis localized these changes to the extracellular matrix, where hyaluronan was increased in aged animals and altered the proliferative response of bone marrow-derived macrophages to granulocyte macrophage colony-stimulating factor (GM-CSF). Our findings suggest that strategies targeting the aging lung microenvironment will be necessary to restore alveolar macrophage function in aging.

Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: a comparison of patients with and without COVID-19.

BACKGROUND: Emerging data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have largely been presented as case series. Few studies have compared these clinical features and outcomes of COVID-19 to other acute respiratory illnesses. METHODS: We examined all patients presenting to an emergency department in San Francisco, California between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared demographics, comorbidities, symptoms, vital signs, and laboratory results including viral diagnostics using PCR and mNGS. Among those hospitalized, we determined differences in treatment (antibiotics, antivirals, respiratory support) and outcomes (ICU admission, ICU interventions, acute respiratory distress syndrome, cardiac injury). FINDINGS: In a cohort of 316 patients, 33 (10%) tested positive for SARS-CoV-2; 31 patients, all without COVID-19, tested positive for another respiratory virus (16%). Among patients with additional viral testing, no co-infections with SARS-CoV-2 were identified by PCR or mNGS. Patients with COVID-19 reported longer symptoms duration (median 7 vs. 3 days), and were more likely to report fever (82% vs. 44%), fatigue (85% vs. 50%), and myalgias (61% vs 27%); p<0.001 for all comparisons. Lymphopenia (55% vs 34%, p=0.018) and bilateral opacities on initial chest radiograph (55% vs. 24%, p=0.001) were more common in patients with COVID-19. Patients with COVID-19 were more often hospitalized (79% vs. 56%, p=0.014). Of 186 hospitalized patients, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p<0.001) and were more likely to develop ARDS (23% vs. 3%, p<0.001). Most comorbidities, home medications, signs and symptoms, vital signs, laboratory results, treatment, and outcomes did not differ by COVID-19 status. INTERPRETATION: While we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. These findings enhance understanding of the clinical characteristics of COVID-19 in comparison to other acute respiratory illnesses. .

Improved Perinatal and Postpartum Human Immunodeficiency Virus Outcomes After Use of a Perinatal Care Coordination Team.

In a high-volume clinic in the Southeastern United States, pregnant women living with human immunodeficiency virus (HIV) had improved HIV outcomes up to 6 months after delivery following the introduction of a multidisciplinary perinatal care coordination team.

Inhibition of the NOD-Like Receptor Protein 3 Inflammasome Is Protective in Juvenile Influenza A Virus Infection.

Influenza A virus (IAV) is a significant cause of life-threatening lower respiratory tract infections in children. Antiviral therapy is the mainstay of treatment, but its effectiveness in this age group has been questioned. In addition, damage inflicted on the lungs by the immune response to the virus may be as important to the development of severe lung injury during IAV infection as the cytotoxic effects of the virus itself. A crucial step in the immune response to IAV is activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and the subsequent secretion of the inflammatory cytokines, interleukin-1ß (IL-1ß), and interleukin-18 (IL-18). The IAV matrix 2 proton channel (M2) has been shown to be an important activator of the NLRP3 inflammasome during IAV infection. We sought to interrupt this ion channel-mediated activation of the NLRP3 inflammasome through inhibition of NLRP3 or the cytokine downstream from its activation, IL-1ß. Using our juvenile mouse model of IAV infection, we show that inhibition of the NLRP3 inflammasome with the small molecule inhibitor, MCC950, beginning 3 days after infection with IAV, improves survival in juvenile mice. Treatment with MCC950 reduces NLRP3 levels in lung homogenates, decreases IL-18 secretion into the alveolar space, and inhibits NLRP3 inflammasome activation in alveolar macrophages. Importantly, inhibition of the NLRP3 inflammasome with MCC950 does not impair viral clearance. In contrast, inhibition of IL-1ß signaling with the IL-1 receptor antagonist, anakinra, is insufficient to protect juvenile mice from IAV. Our findings suggest that targeting the NLRP3 inflammasome in juvenile IAV infection may improve disease outcomes in this age group.

Effects of a Least-to-Most Prompting Procedure on Multisymbol Message Production in Children With Autism Spectrum Disorder Who Use Augmentative and Alternative Communication.

PURPOSE: In this study, we investigated the efficacy of a least-to-most (LTM) prompting procedure (Ault & Griffen, 2013; MacDuff, Krantz, & McClannahan, 2001; Neitzel & Wolery, 2009) for increasing use of multisymbol messages in school-age children with autism spectrum disorder (ASD) who use augmentative and alternative communication (AAC) during a storybook reading activity. METHOD: In the study, we used a single-subject, multiple-probe research design across participants (Kazdin, 1982) with 6 children (ages 8-12) with ASD and who used AAC systems for communication. There were 4 phases in this investigation: (a) baseline, (b) intervention, (c) generalization, and (d) maintenance. RESULTS: All participants exhibited a positive increase in multisymbol message production almost immediately upon introduction of the LTM prompting procedure. CONCLUSIONS: The results of the investigation contribute important information on the efficacy of the LTM prompting procedure for teaching use of multisymbol messages to school-age children with ASD who use AAC.

Service Delivery Experiences and Intervention Needs of Military Families with Children with ASD.

The purpose of this study was to describe the experiences of military families with children with autism spectrum disorder (ASD) specifically as it relates to relocation. Online survey methodology was used to gather information from military spouses with children with ASD. The finalized dataset included 189 cases. Descriptive statistics and frequency analyses were used to examine participant demographics and service delivery questions. Results indicated the larger sample of military spouses largely confirmed the experiences reported qualitatively in previous studies and contributed information that was previously unknown about variables associated with the access, availability, quality, and frequency of intervention services for military families with children with ASD.

Vimentin regulates activation of the NLRP3 inflammasome.

Activation of the NLRP3 inflammasome and subsequent maturation of IL-1ß have been implicated in acute lung injury (ALI), resulting in inflammation and fibrosis. We investigated the role of vimentin, a type III intermediate filament, in this process using three well-characterized murine models of ALI known to require NLRP3 inflammasome activation. We demonstrate that central pathophysiologic events in ALI (inflammation, IL-1ß levels, endothelial and alveolar epithelial barrier permeability, remodelling and fibrosis) are attenuated in the lungs of Vim(-/-) mice challenged with LPS, bleomycin and asbestos. Bone marrow chimeric mice lacking vimentin have reduced IL-1ß levels and attenuated lung injury and fibrosis following bleomycin exposure. Furthermore, decreased active caspase-1 and IL-1ß levels are observed in vitro in Vim(-/-) and vimentin-knockdown macrophages. Importantly, we show direct protein-protein interaction between NLRP3 and vimentin. This study provides insights into lung inflammation and fibrosis and suggests that vimentin may be a key regulator of the NLRP3 inflammasome.

The Experience of Military Families with Children with Autism Spectrum Disorders During Relocation and Separation.

Military families with a child with autism spectrum disorder (ASD) are underrepresented in the literature. In order to provide appropriate services, research must be done to determine the needs of these families. A qualitative methodology was used to interview military spouses with children with ASD about their experiences with therapeutic services. Overall, results indicate military families with a child with ASD experience challenges associated with both the military lifestyle and having a child with special needs. Due to their membership in two groups prone to support limitations and therapeutic service accessibility issues, military families with a child with ASD may be at additional risk for high levels of stress and difficulty obtaining and maintaining ASD related services.

Lymphatic endothelial differentiation in pulmonary lymphangioleiomyomatosis cells.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare, low-grade neoplasm affecting almost exclusively women of childbearing age. LAM belongs to the family of perivascular epithelioid cell tumors, characterized by spindle and epithelioid cells with smooth muscle and melanocytic differentiation. LAM cells infiltrate the lungs, producing multiple, bilateral lesions rich in lymphatic channels and forming cysts, leading to respiratory insufficiency. Here we used antibodies against four lymphatic endothelial markers-podoplanin (detected by D2-40), prospero homeobox 1 (PROX1), vascular endothelial growth factor receptor 3 (VEGFR-3), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1)-to determine whether LAM cells show lymphatic differentiation. Twelve of 12 diagnostic biopsy specimens (early-stage LAM) and 19 of 19 explants (late-stage LAM) showed immunopositivity for D2-40 in most neoplastic cells. PROX1, VEGFR-3, and LYVE1 immunoreactivity varied from scarce in the early stage to abundant in the late stage. Lymphatic endothelial, smooth muscle, and melanocytic markers were partially co-localized. These findings indicate that lymphatic endothelial differentiation is a feature of LAM and provide evidence of a previously unidentified third lineage of differentiation in this neoplasm. This study has implications for the histological diagnosis of LAM, the origin of the neoplastic cells, and potential future treatment with drugs targeting lymphangiogenesis.

Learned helplessness among families and surrogate decision-makers of patients admitted to medical, surgical, and trauma ICUs.

BACKGROUND: We sought to determine the prevalence of and clinical variables associated with learned helplessness, a psychologic state characterized by reduced motivation, difficulty in determining causality, and depression, in family members of patients admitted to ICUs. METHODS: We conducted an observational survey study of a prospectively defined cohort of family members, spouses, and partners of patients admitted to surgical, medical, and trauma ICUs at a large academic medical center. Two validated instruments, the Learned Helplessness Scale and the Perceived Stress Scale, were used, and self-report of patient clinical characteristics and subject demographics were collected. RESULTS: Four hundred ninety-nine family members were assessed. Of these, 238 of 460 (51.7%) had responses consistent with a significant degree of learned helplessness. Among surrogate decision-makers, this proportion was 50% (92 of 184). Characteristics associated with significant learned helplessness included grade or high school education (OR, 3.27; 95% CI, 1.29-8.27; P = .01) and Perceived Stress Scale score > 18 (OR, 4.15; 95% CI, 2.65-6.50; P < .001). The presence of a patient advance directive or do not resuscitate (DNR) order was associated with reduced odds of significant learned helplessness (OR, 0.56; 95% CI, 0.32-0.98; P = .05). CONCLUSIONS: The majority of family members of patients in the ICU experience significant learned helplessness. Risk factors for learned helplessness include lower educational levels, absence of an advance directive or DNR order, and higher stress levels among family members. Significant learned helplessness in family members may have negative implications in the collaborative decision-making process.

Exploring nursing students' level of preparedness for disaster response.

This descriptive study explores students' perceptions of personal and program preparedness for disasters. Participants in this online survey included 1,348 nursing students from every state plus Guam, Puerto Rico, and theVirgin Islands. The study explored three questions: a) the level of preparedness, including learning about different types of disasters, preparing disaster plans, creating disaster kits, and participating in community disaster response efforts; b) the impact of disasters on nursing students; and c) strategies to assist nursing students during disasters. Results indicated that nursing students throughout the country are generally not well prepared for disasters. Nurse educators need to develop strategies to prepare their students for disasters. The American Red Cross provides templates for organizations, including colleges and universities, to prepare their campuses for emergencies. Faculty need to collaborate with staff and students to develop and implement plans appropriate for their programs.

Mucoid nitrate-negative Moraxella nonliquefaciens from three patients with chronic lung disease.

Mucoid strains of Moraxella nonliquefaciens were recovered from the sputa of three indigenous Australians with chronic lung disease. These atypical strains failed to reduce nitrate, and one strain produced beta-lactamase. While the mucoid phenotype of M. nonliquefaciens has rarely been reported, the mucoid nitrate-negative biovar has never been previously reported.

Characterization of a novicida-like subspecies of Francisella tularensis isolated in Australia.

Francisella tularensis is found throughout the Northern Hemisphere, where it is associated with the disease of tularaemia in animals and humans. The isolation and identification is reported of a novicida-like subspecies of F. tularensis from a foot wound sustained in brackish water in the Northern Territory of Australia.