The feasibility of using ecological momentary assessment to understand urinary and fecal incontinence experiences in adults with spina bifida: A 30-day study.

In this paper, we evaluate the feasibility of using ecological momentary assessment (EMA) to understand urinary (UI) and fecal (FI) incontinence in adults with spina bifida (SB). As part of a larger 30-day prospective study to understand the incontinence in adults with SB (N = 89), participants completed end-of-day EMA diaries assessing the frequency and context of UI and FI. We used these data to assess the method feasibility across six dimensions: (a) compliance, or data entry which is consistent with study protocol and substantially complete; (b) reactivity, or behavior change attributed to study participation; (c) participant acceptability, or convenience and ease of method beneficial to compliance; (d) data capture, or the volume of incontinence behaviors collected; (e) the accuracy of incontinence reports; and f) participant-provided feedback for future studies. Participants were highly compliant with diary entry protocol and schedule: submitting 95.7% (2576/2700) of the expected total daily entries. The average completion time was two minutes. Neither the total number of submissions nor the completion time varied by demographic characteristics or health history. A sufficient volume of incontinence and affective outcomes were captured, with small downtrends in reporting of UI and affect over time. Exit survey recall was highly correlated with diary reports. Participants found the methodology to be acceptable, reported their experiences honestly, enjoyed and felt comfortable participating in the study and would engage in similar study in the future. Accurate information about the daily context of UI and FI is a key factor in the success of intervention or education programs relying on this information. Our findings demonstrate that EMA is a feasible way to describe UI and FI in adults with SB.

Emergence, Tropism, Disease, and Treatment of Australian Bat Lyssavirus Infections in Humans.

Australian bat lyssavirus (ABLV) is a negative-sense, single-stranded RNA rhabdovirus capable of causing fatal acute encephalitis in humans with similar pathogenesis to its closest serologic relative, rabies virus (RABV). In this review, we describe emergence and classification of ABLV, its known virology, reservoirs, and hosts, as well as both the pathogenesis and treatment approaches currently employed for presumed infections. ABLV was first identified in New South Wales, Australia in 1996 and emerged in humans months later in Queensland, Australia. Only five known bat reservoirs, all of which fall within the Pteropus and Saccolaimus genera, have been identified to date. Although ABLV antigens have been identified in bats located outside of Australia, the three known human ABLV infections to date have occurred within Australia. As such, there remains a potential for ABLV to expand its presence within and beyond Australia. ABLV infections are currently treated as if they were RABV infections by administering neutralizing antibodies against RABV at the site of the wound and employing the rabies vaccine upon possible exposures. Due to its recent emergence, there is still much left unknown about ABLV, posing concerns with how to safely and effectively address current and future ABLV infections.

Epigenetic differences in stress response gene FKBP5 among children with abusive vs accidental injuries.

BACKGROUND: Survivors of child abuse experience high rates of adverse physical and mental health outcomes. Epigenetic alterations in the stress response system, the FKBP5 gene specifically, have been implicated as one mechanism that may link abuse to lifelong health issues. Prior studies primarily included older individuals with a remote history of maltreatment; our objective was to test for differential methylation of FKBP5 in children with abusive vs accidental injuries at the time of diagnosis. METHODS: We conducted a cross-sectional pilot study of acutely injured children <4 years old at two children's hospitals (n = 82). Research personnel collected injury histories, buccal swabs (n = 65), and blood samples (n = 25) to measure DNA methylation. An expert panel classified the injuries as abusive, accidental, or indeterminate. RESULTS: Children with abusive as compared to accidental injuries had lower methylation of the FKBP5 promoter in buccal and blood cells, even after controlling for injury severity, socioeconomic status, and psychosocial risk factors. CONCLUSION: These findings suggest that epigenetic variation in FKBP5 may occur at the earliest indication of abuse and may be associated with delayed resolution of the HPA axis stress response. Additional testing for epigenetic differences in larger sample sizes is needed to further verify these findings. IMPACT: Children (<4 years old) with abusive compared to accidental injuries showed lower methylation of the FKBP5 promoter in buccal and blood cells at the time of initial diagnosis even after controlling for injury severity, socioeconomic status, and psychosocial risk factors. Early childhood physical abuse may impact the epigenetic regulation of the stress response system, including demethylation within promoters and enhancers of the FKBP5 gene, even at the earliest indication of abuse. The findings are important because unmitigated stress is associated with adverse health outcomes throughout the life-course.

An RSV Live-Attenuated Vaccine Candidate Lacking G Protein Mucin Domains Is Attenuated, Immunogenic, and Effective in Preventing RSV in BALB/c Mice.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading viral respiratory pathogen in infants. The objective of this study was to generate RSV live-attenuated vaccine (LAV) candidates by removing the G-protein mucin domains to attenuate viral replication while retaining immunogenicity through deshielding of surface epitopes. METHODS: Two LAV candidates were generated from recombinant RSV A2-line19F by deletion of the G-protein mucin domains (A2-line19F-G155) or deletion of the G-protein mucin and transmembrane domains (A2-line19F-G155S). Vaccine attenuation was measured in BALB/c mouse lungs by fluorescent focus unit (FFU) assays and real-time polymerase chain reaction (RT-PCR). Immunogenicity was determined by measuring serum binding and neutralizing antibodies in mice following prime/boost on days 28 and 59. Efficacy was determined by measuring RSV lung viral loads on day 4 postchallenge. RESULTS: Both LAVs were undetectable in mouse lungs by FFU assay and elicited similar neutralizing antibody titers compared to A2-line19F on days 28 and 59. Following RSV challenge, vaccinated mice showed no detectable RSV in the lungs by FFU assay and a significant reduction in RSV RNA in the lungs by RT-PCR of 560-fold for A2-line19F-G155 and 604-fold for A2-line19F-G155S compared to RSV-challenged, unvaccinated mice. CONCLUSIONS: Removal of the G-protein mucin domains produced RSV LAV candidates that were highly attenuated with retained immunogenicity.

Targeting novel structural and functional features of coronavirus protease nsp5 (3CLpro, Mpro) in the age of COVID-19.

Coronavirus protease nsp5 (Mpro, 3CLpro) remains a primary target for coronavirus therapeutics due to its indispensable and conserved role in the proteolytic processing of the viral replicase polyproteins. In this review, we discuss the diversity of known coronaviruses, the role of nsp5 in coronavirus biology, and the structure and function of this protease across the diversity of known coronaviruses, and evaluate past and present efforts to develop inhibitors to the nsp5 protease with a particular emphasis on new and mostly unexplored potential targets of inhibition. With the recent emergence of pandemic SARS-CoV-2, this review provides novel and potentially innovative strategies and directions to develop effective therapeutics against the coronavirus protease nsp5.

Who's Watching the Children? Caregiver Features Associated with Physical Child Abuse versus Accidental Injury.

OBJECTIVE: To compare caregiver features and caregiving arrangements of children with physical abuse vs accidental injuries. STUDY DESIGN: Data came from a prospective, observational, multicenter study investigating bruising and psychosocial characteristics of children younger than 4 years of age. Using logistic regression, we examined how abuse vs accidental injury and severity of injury were associated with caregiver sex, relation to the child, whether caregiving arrangements were different than usual at the time of injury, and length of the main caregiver's relationship with his/her partner. RESULTS: Of 1615 patients, 24% were determined to have been physically abused. Abuse was more likely when a male caregiver was present (OR 3.31, 95% CI 2.38-4.62). When the male was the boyfriend of the mother (or another female caregiver), the odds of abuse were very high (OR 169.2, 95% CI 61.3-614.0). Severe or fatal injuries also were more likely when a male caregiver was present. In contrast, abuse was substantially less likely when a female caregiver was present (OR 0.25, 95% CI 0.17-0.37) with the exception of a female babysitter (OR 3.87, 95% CI 2.15-7.01). Caregiving arrangements that were different than usual and caregiver relationships <1 year were also associated with an increased risk of abuse. CONCLUSIONS: We identified caregiver features associated with physical abuse. In clinical practice, questions regarding caregiver features may improve recognition of the abused child. This information may also inform future abuse prevention strategies.

Are negative/unrealistic parent descriptors of infant attributes associated with physical abuse?

Parents' perceptions of child behavior influence their responses to the child and may be important predictors of physical abuse. We examined whether infants 12 months of age or younger who were described with negative or developmentally unrealistic words were more likely than other infants to have been physically abused. As part of a prospective observational multicenter study investigating bruising and familial psychosocial characteristics, parents were asked to (1) describe their child's personality, and (2) list three words to describe their child. Four independent raters coded parent responses using a qualitative content analysis, identifying descriptors of infants and classifying each as positive, neutral, or negative/unrealistic. A medical expert panel, blinded to the psychosocial data, separately categorized each case as abuse or accident. We then analyzed the potential association between negative/unrealistic descriptors and abusive injury. Of 185 children enrolled, 147 cases (79%) were categorized as accident and 38 (21%) as abuse. Parents used at least one negative/unrealistic descriptor in 35/185 cases (19%), while the remaining 150 cases (81%) included only positive or neutral descriptors. Of the infants described with negative/unrealistic words, 60% were abused, compared to 11% of those described with positive or neutral words (p < .0001; age group-adjusted OR = 9.95; 95% confidence interval [3.98, 24.90]). Though limited by sample-size, this pilot study informs future work to create a screening tool utilizing negative/unrealistic descriptors in combination with other predictive factors to identify infants at high risk for physical child abuse.

Dataset on psychosocial risk factors in cases of fatal and near-fatal physical child abuse.

This article presents the psychosocial risk factors identified in the cases of 20 children less than four years of age who were victims of fatal or near-fatal physical abuse during a 12 month period in the Commonwealth of Kentucky. These data are related to the article "History, injury, and psychosocial risk factor commonalities among cases of fatal and near-fatal physical child abuse" (Pierce et al., 2017) [1].

The effects of early institutionalization on emotional face processing: evidence for sparing via an experience-dependent mechanism.

Early psychosocial deprivation has profound adverse effects on children's brain and behavioural development, including abnormalities in physical growth, intellectual function, social cognition, and emotional development. Nevertheless, the domain of emotional face processing has appeared in previous research to be relatively spared; here, we test for possible sleeper effects emerging in early adolescence. This study employed event-related potentials (ERPs) to examine the neural correlates of facial emotion processing in 12-year-old children who took part in a randomized controlled trial of foster care as an intervention for early institutionalization. Results revealed no significant group differences in two face and emotion-sensitive ERP components (P1 and N170), nor any association with age at placement or per cent of lifetime spent in an institution. These results converged with previous evidence from this population supporting relative sparing of facial emotion processing. We hypothesize that this sparing is due to an experience-dependent mechanism in which the amount of exposure to faces and facial expressions of emotion children received was sufficient to meet the low threshold required for cortical specialization of structures critical to emotion processing. Statement of contribution What is already known on this subject? Early psychosocial deprivation leads to profoundly detrimental effects on children's brain and behavioural development. With respect to children's emotional face processing abilities, few adverse effects of institutionalized rearing have previously been reported. Recent studies suggest that 'sleeper effects' may emerge many years later, especially in the domain of face processing. What does this study add? Examining a cumulative 12 years of data, we found only minimal group differences and no evidence of a sleeper effect in this particular domain. These findings identify emotional face processing as a unique ability in which relative sparing can be found. We propose an experience-dependent mechanism in which the amount of social interaction children received met the low threshold required for cortical specialization.

History, injury, and psychosocial risk factor commonalities among cases of fatal and near-fatal physical child abuse.

Failure to recognize child maltreatment results in chronic exposure to high-risk environments where re-injury or death may occur. We analyzed a series (n=20) of fatal (n=10) and near-fatal (n=10) physical child abuse cases from the Commonwealth of Kentucky to identify commonalities and determine whether indicators of maltreatment were present prior to the child's fatal or near-fatal event. We conducted retrospective state record reviews involving children <4years of age classified as physical child abuse by the Cabinet for Health and Family Services during a 12 month period. Cases were distributed across 17 counties. IRB approvals were obtained. Three reviewers concurrently abstracted case data from medical, social, and legal documents, and descriptive statistics were analyzed. Median age of subjects was 7.5 months (range 1-32 months); 55% were male. Psychosocial risk factors (PRFs) were present in 100% of cases. Traumatic brain injury (95%) and bruising (90%) were the most common injuries. Of the 14 children with available prior medical records, 9 (64%) had sentinel injuries in the form of prior unexplained bruising; all nine suffered subsequent traumatic brain injury resulting in four deaths. A male was caring for the child at the time of the final event in 70% of cases. Our study identified key commonalities across cases of fatal and near-fatal abuse, highlighting the prevalence of psychosocial risk factors and the significance of prior unexplained bruising as a herald of escalating abuse. Further study is warranted to ascertain the predictive value of our findings in the larger population.

A Qualitative Examination of Exergame Motivations in Geocaching.

INTRODUCTION: Exergames are an innovative type of physical activity that engages participants through interactive gameplay. One exergame growing in popularity is geocaching. Geocaching is a high-tech treasure hunt that uses GPS-enabled technology to locate hidden caches. Caches are hidden all over the world, and their coordinates are listed in an online forum ( Geocaching.com ). Exergames like geocaching are widely endorsed; however, there is a lot of information that still needs to be learned about why people participate in these activities. MATERIALS AND METHODS: Thirty-four current geocachers were recruited from a larger geocaching study to learn about their motivations for engaging in the game. Individuals were asked to respond to a 30-minute phone interview, and 12 both consented and participated the interviews. Interviews assessed how individuals became involved in geocaching, how frequently they participated, who they went geocaching with, and their motivations behind geocaching. Interviews were recorded and then thematically coded. RESULTS: The majority of participants had geocached for more than 5 years and had learned about the activity through media. All 12 participants geocached at least once a week. The primary motivations behind geocaching were being outdoors, social interaction, physical activity, and relaxation. Individuals described geocaching as being part of a community. They typically made friends while geocaching or when they were on Geocaching.com and felt connected to other geocachers through their mutual interest. CONCLUSIONS: Geocaching and other exergames that use game-like properties to engage users, specifically though technology, have the potential to impact individual health through nontraditional methods of activity and socialization.

A SAFE DC: a conceptual framework for care of the homeless inpatient.

Homeless patients suffer disproportionately from medical disease and from barriers to healthcare, affecting their likelihood of presentation, severity of disease, long-term outcomes, and mortality. In the hospital, homeless patients are frequently cared for by hospitalists. Homeless patients' unstable social situation may challenge usual systems of inpatient care and discharge. To provide more effective care for this group, it is important to recognize the demographics of the hospitalized homeless patient. We suggest a structured approach to the inpatient care of the unstably housed patient, represented by a simple mnemonic checklist "A SAFE DC," describing evidence-based adaptations of care, where available, and discussing systems-based approaches to discharge.

The public hospital mission at Seattle's Harborview Medical Center: high-quality care for the underserved and excellence in medical education.

United States public hospitals and medical schools commonly enter into partnerships that serve the patient care, education, and research missions of both institutions. Harborview Medical Center, the county hospital in Seattle, Washington, and the University of Washington School of Medicine (UWSOM) have enjoyed a long affiliation that began at the medical school's founding 60 years ago. A formal agreement in 1967 turned over responsibility for all Harborview operations to UWSOM at a time when Harborview's facilities had fallen into serious disrepair and public hospitals were closing across the United States. All faculty and staff based at Harborview are employed by the University of Washington. By the mid-1970s a revitalization was underway at Harborview. The Medic One paramedic program drew national acclaim for pioneering prehospital emergency cardiac care, and the trauma and burn centers grew rapidly to meet specialized intensive care needs of the Pacific Northwest. Today, the success of the trauma, specialty surgery, and rehabilitation services have allowed Harborview to consistently maintain a positive operating margin while caring for the county's uninsured and indigent patients ($98 million in charity care in 2005). The hospital also offers nationally recognized residency programs and supports nationally and internationally acclaimed research. Harborview faces significant challenges for the future, including rapid growth of the indigent patient load, continually changing expectations for physician training, and growing cost pressures.