Life space limitations in visually impaired older adults.

SIGNIFICANCE: Future work should develop and evaluate interventional strategies to help overcome visual and health-related barriers to travel in visually impaired seniors and mitigate adverse impacts of loneliness for those who do not leave town. PURPOSE: Life space refers to the area in which a person travels within a given time period. We explored whether demographics, vision, and/or health characteristics were related to restrictions in self-reported life space for visually impaired seniors. METHODS: Visually impaired (n = 114) clinical trial participants aged ≥55 years learned visual assistive iPhone apps and completed the following baseline questionnaires: Life Space, 36-Item Short-Form Health Survey, University of California, Los Angeles Loneliness Scale, and New-General Self-efficacy Scale. Multiple logistic regressions evaluated associations between life space and patient factors after accounting for their distance to the next county or state. RESULTS: During 2021 to 2023, 17%, 43%, and 70% of participants had not left their town, county, or state, respectively, in the past 3 months, or planned to in the next 3 months. Those with reduced distance best-corrected visual acuity had greater odds of not leaving the county in these time frames (odds ratio [OR] = 3.5; p=0.04). Minority race was associated with greater odds of not leaving town or the county in the past 2 weeks or future 3 months (OR = 4.3 to 6.4; p=0.009 to 0.049). Increased self-efficacy was associated with reduced odds of not leaving the state in the past 3 months, next 3 months, or past and/or future 3 months (OR = 0.54 to 0.55; p=0.02 to 0.03). Better physical function was associated with reduced odds of not leaving the state in the past 2 weeks or 3 months (OR = 0.96 to 0.98; p=0.01 to 0.04). Increased loneliness was related to greater odds of not leaving town in the past and/or future 3 months (OR = 1.8 to 2.0; p=0.007 to 0.009). CONCLUSIONS: Minority race, reduced vision, self-efficacy, and physical health were related to life space restrictions in this cohort of visually impaired seniors, whereas loneliness was greater among those who were not leaving town.

Impact of neighborhood disadvantage on posttrauma outcomes after sexual assault.

In the United States, 8,000,000 people seek emergency care for traumatic injury annually. Motor vehicle collisions (MVCs) and sexual assault are two common sources of trauma, with evidence that reduced neighborhood-level socioeconomic characteristics increase posttraumatic pain and stress after an MVC. We evaluated whether neighborhood disadvantage was also associated with physical and mental posttrauma outcomes after sexual assault in a sample of adult women (N = 656) who presented for emergency care at facilities in the United States following sexual assault and were followed for 1 year. Neighborhood characteristics were assessed via the Area Deprivation Index, and self-reported pain, anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms were collected at 6 weeks posttrauma. Adjusted log-binomial regression models examined the association between each clinical outcome and neighborhood disadvantage. Women in more disadvantaged neighborhoods were more likely to be non-White and have lower annual incomes. At 6 weeks posttrauma, the prevalence of clinically significant pain, anxiety, and depressive symptoms more than doubled from baseline (41.7% vs. 18.8%, 62.4% vs. 23.9%, and 55.2% vs. 22.7%, respectively); 40.7% of women also reported PTSD symptoms. Black, Hispanic, and lower-income participants were more likely to report pre- and postassault pain, anxiety, and depression. After adjusting for race, ethnicity, and income, no significant association existed between neighborhood disadvantage and any outcome, ps = .197 - .859. Although neighborhood disadvantage was not associated with posttrauma outcomes, these findings highlight the need for continued research in diverse populations at high risk of adverse physical and mental health symptoms following sexual assault.

Conducted Electrical Weapon Fire Risk in the Presence of Supplemental Oxygen.

BACKGROUND: Conducted electrical weapons (CEWs) are nonlethal weapons used in tactical environments. Tactical EMS (TEMS) operators provide patient care in environments where CEWs are present. CEWs may produce a spark that can be a source of ignition. When supplemental oxygen is in use by a TEMS operator, the flammability risk from the CEW is unknown. METHODS: We measured oxygen levels over 20 minutes in an enclosed space with a supplemental oxygen source maximally flowing. Measurements were taken at various distances from the oxygen source to establish baseline concentrations. These concentrations were replicated within a plexiglass box where a CEW was activated to create a sparking arc between probes embedded in a fresh swine shoulder (with skin intact). Various flammable materials, typically found in a patient care setting were used as potential fuel sources. RESULTS: The highest oxygen levels were achieved directly at the source. At 15cm from the source, the maximum oxygen concentration was 31.5%. Within the box, ignition was only achieved at oxygen concentrations greater than 45% and only when human hair was present as fuel. No ignition was achieved at oxygen levels below this regardless of the tested fuel present. CONCLUSION: Ignition from a CEW is possible at supplemental oxygen levels greater than 45% when human hair is present. In an enclosed space, oxygen concentration levels of 45% are only present within 15cm of a flush rate oxygen source. The likelihood of CEW-caused ignition in such settings with supplemental oxygen in use is extremely low.

Factors related to training time and achieving proficiency with visual-assistive mobile applications in visually impaired older adults.

SIGNIFICANCE: A majority of visually impaired older adults were able to learn to proficiently use visual-assistive iPhone applications (apps) following a median 1 hour and/or multiple training sessions, which should be considered when planning vision rehabilitation service delivery, including the option for remote telerehabilitation for those who prefer that modality. PURPOSE: Older adults with low vision are increasingly using technology to improve their visual functioning. We examined whether age-related comorbidities were potential barriers to success in learning to use visual-assistive apps on a smartphone. METHODS: A clinical trial assessed visual-assistive apps in 116 older adults aged 55+ years (mean [standard deviation], 72 [10] years). Subjects were randomized to use an app (SuperVision+, Seeing AI, or Aira) preloaded to a loaner iPhone and completed one-on-one training. App proficiency was measured by the participant's ability to use the iPhone/app without cueing at the end of training sessions. Training time was recorded for the initial session and totaled after subsequent sessions. Multiple regression models explored significant factors associated with training time and proficiency. RESULTS: Median initial and total training times were 45 and 60 minutes, respectively. Increased initial and total training times were both significantly related to increased age (p<0.001), legal blindness (p<0.007), Seeing AI versus SuperVision+ app (p<0.03), and participants from New England versus California (p<0.001). Most (71%) achieved proficiency after the initial training session; those odds were significantly greater among younger participants (p=0.04), those who opted for telerehabilitation (p=0.03), those who had higher cognitive scores (p=0.04), or those who were from New England (p=0.04). The majority (90%) was ultimately proficient with the app; those odds were significantly greater among participants who already had an optical magnifier (p=0.008), but were unrelated to other factors including study site. CONCLUSIONS: Following multiple, extensive training sessions, age, mild cognitive loss, or level of visual impairment did not preclude gaining proficiency with visual-assistive apps by visually impaired seniors, but those factors were associated with longer training times. Telerehabilitation can be a viable option to provide app training remotely for visually impaired seniors who choose that modality.

Development of a brief bedside tool to screen women sexual assault survivors for risk of persistent posttraumatic stress six months after sexual assault.

This study aims to develop and validate a brief bedside tool to screen women survivors presenting for emergency care following sexual assault for risk of persistent elevated posttraumatic stress symptoms (PTSS) six months after assault. Participants were 547 cisgender women sexual assault survivors who presented to one of 13 sexual assault nurse examiner (SANE) programs for medical care within 72 h of a sexual assault and completed surveys one week and six months after the assault. Data on 222 potential predictors from the SANE visit and the week one survey spanning seven broadly-defined risk factor domains were candidates for inclusion in the screening tool. Elevated PTSS six months after assault were defined as PCL-5 > 38. LASSO logistic regression was applied to 20 randomly selected bootstrapped samples to evaluate variable importance. Logistic regression models comprised of the top 10, 20, and 30 candidate predictors were tested in 10 cross-validation samples drawn from 80% of the sample. The resulting instrument was validated in the remaining 20% of the sample. AUC of the finalized eight-item prediction tool was 0.77 and the Brier Score was 0.19. A raw score of 41 on the screener corresponds to a 70% risk of elevated PTSS at 6 months. Similar performance was observed for elevated PTSS at one year. This brief, eight-item risk stratification tool consists of easy-to-collect information and, if validated, may be useful for clinical trial enrichment and/or patient screening.

A landscape of response to drug combinations in non-small cell lung cancer.

Combination of anti-cancer drugs is broadly seen as way to overcome the often-limited efficacy of single agents. The design and testing of combinations are however very challenging. Here we present a uniquely large dataset screening over 5000 targeted agent combinations across 81 non-small cell lung cancer cell lines. Our analysis reveals a profound heterogeneity of response across the tumor models. Notably, combinations very rarely result in a strong gain in efficacy over the range of response observable with single agents. Importantly, gain of activity over single agents is more often seen when co-targeting functionally proximal genes, offering a strategy for designing more efficient combinations. Because combinatorial effect is strongly context specific, tumor specificity should be achievable. The resource provided, together with an additional validation screen sheds light on major challenges and opportunities in building efficacious combinations against cancer and provides an opportunity for training computational models for synergy prediction.

Measuring the Impact of Bedroom Privacy on Social Networks in a Long-Term Care Facility for Hong Kong Older Adults: A Spatio-Social Network Analysis Approach.

This study aims to measure the impact of bedroom privacy on residents' social networks in a long-term care (LTC) facility for older adults. Little is known about how the architectural design of bedrooms affects residents' social networks in compact LTC facilities. Five design factors affecting privacy were examined: bedroom occupancy, visual privacy, visibility, bedroom adjacency, and transitional space. We present a spatio-social network analysis approach to analyse the social network structures of 48 residents. Results show that residents with the highest bedroom privacy had comparatively smaller yet stronger groups of network partners in their own bedrooms. Further, residents who lived along short corridors interacted frequently with non-roommates in one another's bedrooms. In contrast, residents who had the least privacy had relatively diverse network partners, however, with weak social ties. Clustering analyses also identified five distinct social clusters among residents of different bedrooms, ranging from diverse to restricted. Multiple regressions showed that these architectural factors are significantly associated with residents' network structures. The findings have methodological implications for the study of physical environment and social networks which are useful for LTC service providers. We argue that our findings could inform current policies to develop LTC facilities aimed at improving residents' well-being.

SULT1A1-dependent sulfonation of alkylators is a lineage-dependent vulnerability of liver cancers.

Adult liver malignancies, including intrahepatic cholangiocarcinoma and hepatocellular carcinoma, are the second leading cause of cancer-related deaths worldwide. Most individuals are treated with either combination chemotherapy or immunotherapy, respectively, without specific biomarkers for selection. Here using high-throughput screens, proteomics and in vitro resistance models, we identify the small molecule YC-1 as selectively active against a defined subset of cell lines derived from both liver cancer types. We demonstrate that selectivity is determined by expression of the liver-resident cytosolic sulfotransferase enzyme SULT1A1, which sulfonates YC-1. Sulfonation stimulates covalent binding of YC-1 to lysine residues in protein targets, enriching for RNA-binding factors. Computational analysis defined a wider group of structurally related SULT1A1-activated small molecules with distinct target profiles, which together constitute an untapped small-molecule class. These studies provide a foundation for preclinical development of these agents and point to the broader potential of exploiting SULT1A1 activity for selective targeting strategies.

A tRNA-derived fragment present in E. coli OMVs regulates host cell gene expression and proliferation.

RNA-sequencing has led to a spectacular increase in the repertoire of bacterial sRNAs and improved our understanding of their biological functions. Bacterial sRNAs have also been found in outer membrane vesicles (OMVs), raising questions about their potential involvement in bacteria-host relationship, but few studies have documented this issue. Recent RNA-Sequencing analyses of bacterial RNA unveiled the existence of abundant very small RNAs (vsRNAs) shorter than 16 nt. These especially include tRNA fragments (tRFs) that are selectively loaded in OMVs and are predicted to target host mRNAs. Here, in Escherichia coli (E. coli), we report the existence of an abundant vsRNA, Ile-tRF-5X, which is selectively modulated by environmental stress, while remaining unaffected by inhibition of transcription or translation. Ile-tRF-5X is released through OMVs and can be transferred to human HCT116 cells, where it promoted MAP3K4 expression. Our findings provide a novel perspective and paradigm on the existing symbiosis between bacteria and human cells.

An Expanded Landscape of Unusually Short RNAs in 11 Samples from Six Eukaryotic Organisms.

Small RNA sequencing (sRNA-Seq) approaches unveiled sequences derived from longer non-coding RNAs, such as transfer RNA (tRNA) and ribosomal RNA (rRNA) fragments, known as tRFs and rRFs, respectively. However, rRNAs and RNAs shorter than 16 nt are often depleted from library preparations/sequencing analyses, although they may be functional. Here, we sought to obtain a complete repertoire of small RNAs by sequencing the total RNA from 11 samples of 6 different eukaryotic organisms, from yeasts to human, in an extended 8- to 30-nt window of RNA length. The 8- to 15-nt window essentially contained fragments of longer non-coding RNAs, such as microRNAs, PIWI-associated RNAs (piRNAs), small nucleolar RNAs (snoRNAs), tRNAs and rRNAs. Notably, unusually short RNAs < 16 nt were more abundant than those >16 nt in bilaterian organisms. A new RT-qPCR method confirmed that two unusually short rRFs of 12 and 13 nt were more overly abundant (~3-log difference) than two microRNAs. We propose to not deplete rRNA and to reduce the lower threshold of RNA length to include unusually short RNAs in sRNA-Seq analyses and datasets, as their abundance and diversity support their potential role and importance as biomarkers of disease and/or mediators of cellular function.

RNA Sequencing Unveils Very Small RNAs With Potential Regulatory Functions in Bacteria.

RNA sequencing (RNA-seq) is the gold standard for the discovery of small non-coding RNAs. Following a long-standing approach, reads shorter than 16 nucleotides (nt) are removed from the small RNA sequencing libraries or datasets. The serendipitous discovery of an eukaryotic 12 nt-long RNA species capable of modulating the microRNA from which they derive prompted us to challenge this dogma and, by expanding the window of RNA sizes down to 8 nt, to confirm the existence of functional very small RNAs (vsRNAs <16 nt). Here we report the detailed profiling of vsRNAs in Escherichia coli, E. coli-derived outer membrane vesicles (OMVs) and five other bacterial strains (Pseudomonas aeruginosa PA7, P. aeruginosa PAO1, Salmonella enterica serovar Typhimurium 14028S, Legionella pneumophila JR32 Philadelphia-1 and Staphylococcus aureus HG001). vsRNAs of 8-15 nt in length [RNAs (8-15 nt)] were found to be more abundant than RNAs of 16-30 nt in length [RNAs (16-30 nt)]. vsRNA biotypes were distinct and varied within and across bacterial species and accounted for one third of reads identified in the 8-30 nt window. The tRNA-derived fragments (tRFs) have appeared as a major biotype among the vsRNAs, notably Ile-tRF and Ala-tRF, and were selectively loaded in OMVs. tRF-derived vsRNAs appear to be thermodynamically stable with at least 2 G-C basepairs and stem-loop structure. The analyzed tRF-derived vsRNAs are predicted to target several human host mRNAs with diverse functions. Bacterial vsRNAs and OMV-derived vsRNAs could be novel players likely modulating the intricate relationship between pathogens and their hosts.

Ebola Virus Encodes Two microRNAs in Huh7-Infected Cells.

MicroRNAs (miRNAs) are important gene regulatory molecules involved in a broad range of cellular activities. Although the existence and functions of miRNAs are clearly defined and well established in eukaryotes, this is not always the case for those of viral origin. Indeed, the existence of viral miRNAs is the subject of intense controversy, especially those of RNA viruses. Here, we characterized the miRNA transcriptome of cultured human liver cells infected or not with either of the two Ebola virus (EBOV) variants: Mayinga or Makona; or with Reston virus (RESTV). Bioinformatic analyses revealed the presence of two EBOV-encoded miRNAs, miR-MAY-251 and miR-MAK-403, originating from the EBOV Mayinga and Makona variants, respectively. From the miRDB database, miR-MAY-251 and miR-MAK-403 displayed on average more than 700 potential human host target candidates, 25% of which had a confidence score higher than 80%. By RT-qPCR and dual luciferase assays, we assessed the potential regulatory effect of these two EBOV miRNAs on selected host mRNA targets. Further analysis of Panther pathways unveiled that these two EBOV miRNAs, in addition to general regulatory functions, can potentially target genes involved in the hemorrhagic phenotype, regulation of viral replication and modulation of host immune defense.

Prehospital Surgical Airway Management: An NAEMSP Position Statement and Resource Document.

Bag-valve-mask ventilation and endotracheal intubation have been the mainstay of prehospital airway management for over four decades. Recently, supraglottic device use has risen due to various factors. The combination of bag-valve-mask ventilation, endotracheal intubation, and supraglottic devices allows for successful airway management in a majority of patients. However, there exists a small portion of patients who are unable to be intubated and cannot be adequately ventilated with either a facemask or a supraglottic airway. These patients require an emergent surgical airway. A surgical airway is an important component of all airway algorithms, and in some cases may be the only viable approach; therefore, it is imperative that EMS agencies that are credentialed to manage airways have the capability to perform surgical airways when appropriate. The National Association of Emergency Medical Services Physicians (NAEMSP) recommends the following for emergency medical services (EMS) agencies that provide advanced airway management.A surgical airway is reasonable in the prehospital setting when the airway cannot be secured by less invasive means.When indicated, a surgical airway should be performed without delay.A surgical airway is not a substitute for other airway management tools and techniques. It should not be the only rescue option available.Success of an open surgical approach using a scalpel is higher than that of percutaneous Seldinger techniques or needle-jet ventilation in the emergency setting.

Pain is common after sexual assault and posttraumatic arousal/reactivity symptoms mediate the development of new or worsening persistent pain.

ABSTRACT: Clinically significant new or worsening pain (CSNWP) is a common, yet often overlooked, sequelae of sexual assault. Little is known regarding factors influencing the development of CSNWP in sexual assault survivors. The current study used data from a recently completed prospective study to evaluate whether posttraumatic alterations in arousal and reactivity in the early aftermath of sexual assault influence the transition from acute to clinically significant new or worsening persistent pain. Women ≥ 18 years of age (n = 706) presenting for emergency care after sexual assault to 13 emergency care sites were enrolled in the study. Women completed assessments at the time of presentation as well as at 1 week (n = 706, 100%) and 6 weeks (n = 630, 91%). Nearly 70% of women reported CSNWP at the time of emergency care (n = 475, 69%), which persisted to 6 weeks in approximately 2 in 5 survivors (n = 248, 41%). A structural equation model adjusted for age, race, past trauma exposure, and preassault pain levels suggested that posttraumatic alterations in arousal/reactivity symptoms 1 week after assault partially mediated the transition from acute to persistent CSNWP. A significant portion (41%) of women sexual assault survivors develop CSNWP 6 weeks postassault. Posttraumatic arousal/reactivity symptoms in the early aftermath of assault contribute to CSNWP development; such symptoms are potential targets for secondary preventive interventions to reduce chronic postassault pain.

Three subtypes of lung cancer fibroblasts define distinct therapeutic paradigms.

Cancer-associated fibroblasts (CAFs) are highly heterogeneous. With the lack of a comprehensive understanding of CAFs' functional distinctions, it remains unclear how cancer treatments could be personalized based on CAFs in a patient's tumor. We have established a living biobank of CAFs derived from biopsies of patients' non-small lung cancer (NSCLC) that encompasses a broad molecular spectrum of CAFs in clinical NSCLC. By functionally interrogating CAF heterogeneity using the same therapeutics received by patients, we identify three functional subtypes: (1) robustly protective of cancers and highly expressing HGF and FGF7; (2) moderately protective of cancers and highly expressing FGF7; and (3) those providing minimal protection. These functional differences among CAFs are governed by their intrinsic TGF-ß signaling, which suppresses HGF and FGF7 expression. This CAF functional classification correlates with patients' clinical response to targeted therapies and also associates with the tumor immune microenvironment, therefore providing an avenue to guide personalized treatment.

"I still feel so lost": experiences of women receiving SANE care during the year after sexual assault.

OBJECTIVE: Emergency caregivers provide initial care to women sexual assault (SA) survivors. An improved understanding of the issues facing this population can aide emergency care practitioners in providing high quality care. The goal of this study was to share the experiences of women SA survivors with the emergency care practitioners that care for them. METHODS: English-speaking adult women (n = 706) who received SA Nurse Examiner (SANE) evaluation within 72 hours of SA at 1 of 13 geographically distributed sites were enrolled in a prospective, longitudinal multi-site observational study. We qualitatively analyzed responses to the open-ended question: "What do you think is most important for researchers to understand about your experience since the assault?" asked 1 week, 6 weeks, 6 months, and 1 year after enrollment. RESULTS: Themes from responses (n = 1434) from 590 women (84% of study sample) fell into 12 broad categories: daily life, justice, medical, and social services, mental health, physical health, prior trauma, recovery, romantic relationships, safety, self, shame, and social interactions. Responses demonstrated that the assault permeates many aspects of assault survivors' daily lives. CONCLUSIONS: Qualitative analyses of open-ended responses from a large cohort of women SA survivors receiving SANE care highlight the challenges for survivors and can increase understanding among the emergency care practitioners who care for them. The authors propose a brief acronym to help emergency care practitioners recall important messages for SA survivors.

Altered microRNA Transcriptome in Cultured Human Liver Cells upon Infection with Ebola Virus.

Ebola virus (EBOV) is a virulent pathogen, notorious for inducing life-threatening hemorrhagic fever, that has been responsible for several outbreaks in Africa and remains a public health threat. Yet, its pathogenesis is still not completely understood. Although there have been numerous studies on host transcriptional response to EBOV, with an emphasis on the clinical features, the impact of EBOV infection on post-transcriptional regulatory elements, such as microRNAs (miRNAs), remains largely unexplored. MiRNAs are involved in inflammation and immunity and are believed to be important modulators of the host response to viral infection. Here, we have used small RNA sequencing (sRNA-Seq), qPCR and functional analyses to obtain the first comparative miRNA transcriptome (miRNome) of a human liver cell line (Huh7) infected with one of the following three EBOV strains: Mayinga (responsible for the first Zaire outbreak in 1976), Makona (responsible for the West Africa outbreak in 2013-2016) and the epizootic Reston (presumably innocuous to humans). Our results highlight specific miRNA-based immunity pathways and substantial differences between the strains beyond their clinical manifestation and pathogenicity. These analyses shed new light into the molecular signature of liver cells upon EBOV infection and reveal new insights into miRNA-based virus attack and host defense strategy.

Perceived Care Quality Among Women Receiving Sexual Assault Nurse Examiner Care: Results From a 1-Week Postexamination Survey in a Large Multisite Prospective Study.

INTRODUCTION: This study examined the perspectives of female patients who had been sexually assaulted regarding the quality of care provided by sexual assault nurse examiners, including whether the patients' perspectives varied by their demographic characteristics and health status before the assault. METHODS: A total of 695 female patients who received care from sexual assault nurse examiners at 13 United States emergency care centers and community-based programs completed standardized surveys 1 week after receiving sexual assault nurse examiners' care for sexual assault. RESULTS: Most patients strongly agreed that the sexual assault nurse examiners provided high-quality care, including taking patients' needs/concerns seriously, not acting as though the assault was the patient's fault, showing care/compassion, explaining the sexual assault examination, and providing follow-up information. The perceptions did not vary by the patients' demographic characteristics or preassault health status. DISCUSSION: Female patients who had been sexually assaulted and who were evaluated at 13 widely geographically distributed sexual assault nurse examiners' programs consistently reported that the sexual assault nurse examiners provided high-quality, compassionate care.

Health care utilization by women sexual assault survivors after emergency care: Results of a multisite prospective study.

BACKGROUND: Approximately, 100,000 US women receive emergency care after sexual assault each year, but no large-scale study has examined the incidence of posttraumatic sequelae, receipt of health care, and frequency of assault disclosure to providers. The current study evaluated health outcomes and service utilization among women in the 6 weeks after sexual assault. METHODS: Women ≥18 years of age presenting for emergency care after sexual assault to twelve sites were approached. Among those willing to be contacted for the study (n = 1080), 706 were enrolled. Health outcomes, health care utilization, and assault disclosure were assessed via 6 week survey. RESULTS: Three quarters (76%) of women had posttraumatic stress, depression, or anxiety, and 65% had pain. Less than two in five reported seeing health care provider; receipt of care was not related to substantive differences in symptoms and was less likely among Hispanic women and women with a high school education or less. Nearly one in four who saw a primary care provider did not disclose their assault, often due to shame, embarrassment, or fear of being judged. CONCLUSION: Most women receiving emergency care after sexual assault experience substantial posttraumatic sequelae, but health care in the 6 weeks after assault is uncommon, unrelated to substantive differences in need, and limited in socially disadvantaged groups. Lack of disclosure to primary care providers was common among women who did receive care.