The role of PAs in providing mental health care.

The prevalence of psychiatric and substance use disorders in the United States is rising and of growing concern. Because such behavioral conditions are widespread, one approach is to collaborate with various medical professionals to help offset this demand. To address this issue, the frequency and types of mental health conditions encountered by physician assistants (PAs) were assessed. The National Commission on the Certification of Physician Assistants Practice Analysis was examined for the types of mental health conditions encountered across the spectrum of medical and surgical practices. The findings reveal that, in 2015, at least 62% of PAs saw and evaluated mental health conditions and behavioral disorders at least weekly in their settings. These patient diagnoses were seen with variability based on the specialty of the PA. The highest percentage of cases reported by PAs were in psychiatry, followed by general internal medicine, emergency medicine, family medicine, and hospital medicine. With the profession projected to grow, recruiting, retaining, and integrating more PAs into mental health care is a suggested strategy for addressing national provider shortages.

PA practice analysis: Multidisciplinary tasks, knowledge, and skills.

In conducting its practice analysis, the National Commission on Certification of Physician Assistants incorporated new approaches in 2015. Twelve groups of PAs identified knowledge, tasks, and skills required for practice not only in primary care, but also in 11 practice focus areas (specialties). In addition, a list of diseases and disorders likely to be encountered was identified for each specialty. A representative sample of 15,771 certified PAs completed an online algorithm-driven survey and data were analyzed to determine how practice is the same for all PAs and how it differs depending on the practice focus. Larger differences between PAs in different specialties were seen in the frequency ratings of diseases and disorders encountered than for ratings of task, knowledge, and skill statements. Distinctions between PAs in primary care and those in other specialties were more pronounced, as the specialty was more divergent from primary care.

Similarities and differences in the default mode network across rest, retrieval, and future imagining.

The default mode network (DMN) has been identified reliably during rest, as well as during the performance of tasks such as episodic retrieval and future imagining. It remains unclear why this network is engaged across these seemingly distinct conditions, though many hypotheses have been proposed to account for these effects. Prior to generating hypotheses explaining common DMN involvement, the degree of commonality in the DMN across these conditions, within individuals, must be statistically determined to test whether or not the DMN is truly a unitary network, equally engaged across rest, retrieval and future imagining. To provide such a test, we used comparable paradigms (self-directed, uninterrupted thought of equal duration) across the three conditions (rest, retrieval, and future imagining) in a within-participant design. We found lower than expected pattern similarity in DMN functional connectivity across the three conditions. Similarity in connectivity accounted for only 40-50% of the total variance. Partial Least Squares (PLS) analyses revealed the medial temporal regions of the DMN were preferentially coupled with one another during episodic retrieval and future imagining, whereas the non-medial temporal regions of the DMN (e.g., medial prefrontal cortex, lateral temporal cortex, and temporal pole) were preferentially coupled during rest. These results suggest that DMN connectivity may be more flexible than previously considered. Our findings are in line with emerging evidence that the DMN is not a static network engaged commonly across distinct cognitive processes, but is instead a dynamic system, topographically changing in relation to ongoing cognitive demands. Hum Brain Mapp 38:1155-1171, 2017. © 2016 Wiley Periodicals, Inc.

Living Outside the Gender Box in Mexico: Testimony of Transgender Mexican Asylum Seekers.

OBJECTIVES: To explore preimmigration experiences of violence and postimmigration health status in male-to-female transgender individuals (n = 45) from Mexico applying for asylum in the United States. METHODS: We used a document review process to examine asylum declarations and psychological evaluations of transgender Mexican asylum seekers in the United States from 2012. We coded documents in 2013 and 2014 using NVivo, a multidisciplinary team reviewed them, and then we analyzed them for themes. RESULTS: Mexican transgender asylum applicants experienced pervasive verbal, physical, and sexual abuse from multiple sources, including family, school, community, and police. Applicants also experienced discrimination in school and in the workplace. Applicants immigrated to the United States to escape persistent assaults and threats to their life. Applicants suffered health and psychological effects from their experiences in Mexico that affected opportunities in the United States for employment, education, and social inclusion. CONCLUSIONS: Additional social protections for transgender individuals and antidiscrimination measures in Mexican schools and workplaces are warranted as are increased mental health assessment and treatment, job training, and education services for asylum seekers in the United States.

Prolonged constant load cycling exercise is associated with reduced gross efficiency and increased muscle oxygen uptake.

This study investigated the effects of prolonged constant load cycling exercise on cycling efficiency and local muscle oxygen uptake responses. Fourteen well-trained cyclists each completed a 2-h steady-state cycling bout at 60% of their maximal minute power output to assess changes in gross cycling efficiency (GE) and muscle oxygen uptake (mVO2 ) at time points 5, 30, 60, 90, and 120 min. Near-infrared spatially resolved spectroscopy (NIRS) was used to continually monitor tissue oxygenation of the Vastus Lateralis muscle, with arterial occlusions (OCC) applied to assess mVO2 . The half-recovery time of oxygenated hemoglobin (HbO2 ) was also assessed pre and post the 2-h cycling exercise by measuring the hyperemic response following a 5-min OCC. GE significantly declined during the 2-h cycling bout (18.4 ± 1.6 to 17.4 ± 1.4%; P < 0.01). Conversely, mVO2 increased, being significantly higher after 90 and 120 min than at min 5 (+0.04 mlO2 /min/100 g; P = 0.03). The half-recovery time for HbO2 was increased comparing pre and post the 2-h cycling exercise (+7.1 ± 19s), albeit not significantly (d: 0.48; P = 0.27). This study demonstrates that GE decreases during prolonged constant load cycling exercise and provides evidence of an increased mVO2 , suggestive of progressive mitochondrial or contractile inefficiency.

Reported consent processes and demographics: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: Efforts are needed to improve informed consent of participants in research. The Strategic Timing of AntiRetroviral Therapy (START) study provides a unique opportunity to study the effect of length and complexity of informed consent documents on understanding and satisfaction among geographically diverse participants. METHODS: Interested START sites were randomized to use either the standard consent form or the concise consent form for all of the site's participants. RESULTS: A total of 4473 HIV-positive participants at 154 sites world-wide took part in the Informed Consent Substudy, with consent given in 11 primary languages. Most sites sent written information to potential participants in advance of clinic visits, usually including the consent form. At about half the sites, staff reported spending less than an hour per participant in the consent process. The vast majority of sites assessed participant understanding using informal nonspecific questions or clinical judgment. CONCLUSIONS: These data reflect the interest of START research staff in evaluating the consent process and improving informed consent. The START Informed Consent Substudy is by far the largest study of informed consent intervention ever conducted. Its results have the potential to impact how consent forms are written around the world.

Phase IIa randomized, placebo-controlled study of antimicrobial photodynamic therapy in bacterially colonized, chronic leg ulcers and diabetic foot ulcers: a new approach to antimicrobial therapy.

BACKGROUND: With increasing problems of antibiotic resistance, photodynamic therapy (PDT) is being developed as a novel antimicrobial treatment. Following light activation, cationic photosensitizer PPA904 [3,7-bis(N,N-dibutylamino) phenothiazin-5-ium bromide] kills a broad spectrum of bacteria in vitro and this has a variety of potential clinical applications. OBJECTIVES: To determine if PDT in bacterially colonized chronic leg ulcers and chronic diabetic foot ulcers can reduce bacterial load, and potentially lead to accelerated wound healing. METHODS: Sixteen patients with chronic leg ulcers and 16 patients with diabetic foot ulcers (each eight active treatment/eight placebo) were recruited into a blinded, randomized, placebo-controlled, single-treatment, Phase IIa trial. All patients had ulcer duration > 3 months, bacterially colonized with > 10 colony-forming units cm . After quantitatively assessing pretreatment bacterial load via swabbing, PPA904 or placebo was applied topically to wounds for 15 min, followed immediately by 50 J cm of red light and the wound again sampled for quantitative microbiology. The wound area was measured for up to 3 months following treatment. RESULTS: Treatment was well tolerated with no reports of pain or other safety issues. In contrast to placebo, patients on active treatment showed a reduction in bacterial load immediately post-treatment (P < 0·001). After 3 months, 50% (four of eight) of patients with actively treated chronic leg ulcer showed complete healing, compared with 12% (one of eight) of patients on placebo. CONCLUSIONS: This first controlled study of PDT in chronic wounds demonstrated significant reduction in bacterial load. An apparent trend towards wound healing was observed; further study of this aspect with larger patient numbers is indicated.

Inability to demonstrate fish-to-fish transmission of Ichthyophonus from laboratory infected Pacific herring Clupea pallasii to naïve conspecifics.

The parasite Ichthyophonus is enzootic in many marine fish populations of the northern Atlantic and Pacific Oceans. Forage fishes are a likely source of infection for higher trophic level predators; however, the processes that maintain Ichthyophonus in forage fish populations (primarily clupeids) are not well understood. Lack of an identified intermediate host has led to the convenient hypothesis that the parasite can be maintained within populations of schooling fishes by waterborne fish-to-fish transmission. To test this hypothesis we established Ichthyophonus infections in Age-1 and young-of-the-year (YOY) Pacific herring Clupea pallasii (Valenciennes) via intraperitoneal (IP) injection and cohabitated these donors with naïve conspecifics (sentinels) in the laboratory. IP injections established infection in 75 to 84% of donor herring, and this exposure led to clinical disease and mortality in the YOY cohort. However, after cohabitation for 113 d no infections were detected in naïve sentinels. These data do not preclude the possibility of fish-to-fish transmission, but they do suggest that other transmission processes are necessary to maintain Ichthyophonus in wild Pacific herring populations.

Navigating Pandemic Moral Distress at Home and at Work: Frontline Workers' Experiences.

Background: During the COVID-19 pandemic, frontline workers faced a series of challenges balancing family and work responsibilities. These challenges included making decisions about how to reduce COVID-19 exposure to their families while still carrying out their employment duties and caring for their children. We sought to understand how frontline workers made these decisions and how these decisions impacted their experiences.Methods: Between October 2020 and May 2021, we conducted 61 semi-structured interviews in English or Spanish, with individuals who continued to work outside of the home during the pandemic and had children living at home. Interviews were recorded, transcribed verbatim, and analyzed using abductive methods.Results: Frontline workers experienced moral distress, the inability to act in accordance with their values and obligations because of internal or external constraints. Their moral distress was a result of the tensions they felt as workers and parents, which sometimes led them to feel like they had to compromise on either or both responsibilities. Individuals felt morally conflicted because 1) their COVID-19 work exposures presented risk that often jeopardized their family's health; 2) their work hours often conflicted with their increased childcare responsibilities; and 3) they felt a duty to their colleagues, patients/customers, and communities to continue to show-up to work.Conclusions: Our findings point to a need to expand the concept of moral distress to include the perspectives of frontline workers outside of the healthcare professions and the fraught decisions that workers make outside of work that may impact their moral distress. Expanding the concept of moral distress also allows for a justice-based framing that can focus attention on the disparities inherent in much frontline work and can justify programmatic recommendations, like increasing paid childcare opportunities, to alleviate moral distress.

Differentiation of brain and retinal organoids from confluent cultures of pluripotent stem cells connected by nerve-like axonal projections of optic origin.

Advances in the study of neurological conditions have been possible because of pluripotent stem cell technologies and organoids. Studies have described the generation of neural ectoderm-derived retinal and brain structures from pluripotent stem cells. However, the field is still troubled by technical challenges, including high culture costs and variability. Here, we describe a simple and economical protocol that reproducibly gives rise to the neural retina and cortical brain regions from confluent cultures of stem cells. The spontaneously generated cortical organoids are transcriptionally comparable with organoids generated by other methods. Furthermore, these organoids showed spontaneous functional network activity and proteomic analysis confirmed organoids maturity. The generation of retinal and brain organoids in close proximity enabled their mutual isolation. Suspension culture of this complex organoid system demonstrated the formation of nerve-like structures connecting retinal and brain organoids, which might facilitate the investigation of neurological diseases of the eye and brain.

Viral replication in excised fin tissues (VREFT) corresponds with prior exposure of Pacific herring, Clupea pallasii (Valenciennes), to viral haemorrhagic septicaemia virus (VHSV).

Procedures for a viral replication in excised fin tissue (VREFT) assay were adapted to Pacific herring, Clupea pallasii, and optimized both to reduce processing time and to provide the greatest resolution between naïve herring and those previously exposed to viral haemorrhagic septicaemia virus (VHSV), Genogroup IVa. The optimized procedures included removal of the left pectoral fin from a euthanized fish, inoculation of the fin with >10(5) plaque-forming units (PFU) mL(-1) VHSV for 1 h, rinsing the fin in fresh medium six times to remove unadsorbed virions, incubation of the fin in fresh medium for 4 days and enumeration of the viral titre in a sample of the incubation medium by plaque assay. The optimized VREFT assay was effective at identifying the prior exposure history of laboratory-reared Pacific herring to VHSV. The geometric mean VREFT value was significantly greater (P < 0.01) among naïve herring (1.2 × 10(3) PFU mL(-1) ) than among groups that survived exposure to VHSV (1.0-2.9 × 10(2) PFU mL(-1) ); additionally, the proportion of cultures with no detectable virus was significantly greater (P = 0.0002) among fish that survived exposure to VHSV (39-47%) than among naïve fish (3.3%). The optimized VREFT assay demonstrates promise for identifying VHSV exposure history and forecasting disease potential in populations of wild Pacific herring.

Factors controlling the early stages of viral haemorrhagic septicaemia epizootics: low exposure levels, virus amplification and fish-to-fish transmission.

Viral haemorrhagic septicaemia virus, Genogroup IVa (VHSV), was highly infectious to Pacific herring, Clupea pallasii (Valenciennes), even at exposure doses occurring below the threshold of sensitivity for a standard viral plaque assay; however, further progression of the disease to a population-level epizootic required viral amplification and effective fish-to-fish transmission. Among groups of herring injected with VHSV, the prevalence of infection was dose-dependent, ranging from 100%, 75% and 38% after exposure to 19, 0.7 and 0.07 plaque-forming units (PFU)/fish, respectively. Among Pacific herring exposed to waterborne VHSV (140 PFU mL(-1) ), the prevalence of infection, geometric mean viral tissue titre and cumulative mortality were greater among cohabitated herring than among cohorts that were held in individual aquaria, where fish-to-fish transmission was prevented. Fish-to-fish transmission among cohabitated herring probably occurred via exposure to shed virus which peaked at 680 PFU mL(-1) ; shed virus was not detected in the tank water from any isolated individuals. The results provide insights into mechanisms that initiate epizootic cascades in populations of wild herring and have implications for the design of VHSV surveys in wild fish populations.

"It's Just Another Added Benefit": Women's Experiences with Employment-Based Egg Freezing Programs.

BACKGROUND: In 2014, companies began covering the costs of egg freezing for their employees. The adoption of this benefit was highly contentious. Some argued that it offered women more reproductive autonomy, buying time to succeed in their careers and postpone childbearing. Others suggested this benefit might place inappropriate pressure on women, unduly influencing them to freeze their eggs to prioritize their career over reproduction. Although ethical problems with this benefit have been explored, there has not been research analyzing the perspectives of women working for companies that offer employer-based egg freezing. Furthermore, existing empirical studies often focus on the experiences of egg freezers rather than the young women thinking about, but not yet using, this technology. Methods: Through in-depth semi-structured interviews, we explore the perceptions and attitudes of 25 women employees of companies with employer-based egg freezing. Results: These women describe delaying childbearing for a multitude of reasons, including not having a partner, and the desire to achieve social and career goals. Many women did not know that their employers covered egg freezing before the interview (44%; 11/24), suggesting this benefit is not essential to their career and family-building decisions. While women did not describe pressure to use this technology, they did describe how this benefit would not solve the difficulties of becoming a mother while excelling in their careers. Conclusion: Although women may not feel pressure to freeze their eggs and delay childbearing, they still feel constricted in their reproductive options. While employer programs may offer women the ability to delay childbearing, many saw this delay as postponing problems with work-life balance rather than solving them. We suggest that sociocultural shifts, such as workplace daycare, flexible workplace hours, and acceptability of non-biological parenthood, might allow women to feel more empowered about their reproduction choices.

Use, re-use or discard? Quantitatively defined variance in the functional integrity of N95 respirators following vaporized hydrogen peroxide decontamination during the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 has stretched the ability of many institutions to supply needed personal protective equipment, especially N95 respirators. N95 decontamination and re-use programmes provide one potential solution to this problem. Unfortunately, a comprehensive evaluation of the effects of decontamination on the fit of various N95 models using a quantitative fit test (QNFT) approach is lacking. AIMS: To investigate the effects of up to eight rounds of vaporized hydrogen peroxide (VHP) decontamination on the fit of N95 respirators currently in use in a hospital setting, and to examine if N95 respirators worn by one user can adapt to the face shape of a second user with no compromise to fit following VHP decontamination. METHODS: The PortaCount Pro+ Respirator Fit Tester Model 8038 was used to quantitatively define functional integrity, measured by fit, of N95 respirators following decontamination with VHP. FINDINGS: There was an observable downward trend in the functional integrity of Halyard Fluidshield 46727 N95 respirators throughout eight cycles of decontamination with VHP. Functional integrity of 3M 1870 N95 respirators was reduced significantly after the respirator was worn, decontaminated with VHP, and then quantitatively fit tested on a second user. Furthermore, inconsistencies between qualitative fit test and QNFT results were uncovered that may have strong implications on the fit testing method used by institutions. CONCLUSIONS: The data revealed variability in the functional integrity of different N95 models after VHP decontamination, and exposed potential limitations of N95 decontamination and re-use programmes.

Functional MRI for language lateralization in individuals with intellectual and cognitive dysfunction: Two clinical case examples.

OBJECTIVE: Task-based functional MRI (fMRI) is a common non-invasive method of confirming hemispheric language dominance prior to neurosurgery in epilepsy. However, the use of this method is not recommended for individuals with cognitive dysfunction and in those with IQ below 70 due to concerns about accuracy of task performance in the scanner. This manuscript describes successful use of task-based functional MRI to lateralize language dominance in two individuals with cognitive dysfunction and intellectual disability. METHODS: Two patients completed a pre-surgical epilepsy work-up at the QEII Health Sciences Centre in Halifax, Nova Scotia, which included comprehensive neuropsychological assessment. They also completed an fMRI paradigm that involved semantic category fluency, sentence completion, naming to description and passage listening tasks with stimuli delivered both visually and auditorily. RESULTS: In both cases, fMRI maps were successful in lateralizing language dominance in relation to other clinical data, including intraoperative cortical mapping in one of the cases. CONCLUSIONS: This manuscript is the first to demonstrate that task-based fMRI can be used successfully to lateralize language in adult patients with cognitive and intellectual disabilities, and is the first to propose a specific paradigm for this purpose.

Decontaminating N95 respirators during the COVID-19 pandemic: simple and practical approaches to increase decontamination capacity, speed, safety and ease of use.

BACKGROUND: The COVID-19 pandemic has caused a severe shortage of personal protective equipment (PPE), especially N95 respirators. Efficient, effective and economically feasible methods for large-scale PPE decontamination are urgently needed. AIMS: (1) to develop protocols for effectively decontaminating PPE using vaporized hydrogen peroxide (VHP); (2) to develop novel approaches that decrease set-up and take-down time while also increasing decontamination capacity; (3) to test decontamination efficiency for N95 respirators heavily contaminated by make-up or moisturizers. METHODS: We converted a decommissioned Biosafety Level 3 laboratory into a facility that could be used to decontaminate N95 respirators. N95 respirators were hung on metal racks, stacked in piles, placed in paper bags or covered with make-up or moisturizer. A VHP® VICTORY™ unit from STERIS was used to inject VHP into the facility. Biological and chemical indicators were used to validate the decontamination process. FINDINGS: N95 respirators individually hung on metal racks were successfully decontaminated using VHP. N95 respirators were also successfully decontaminated when placed in closed paper bags or if stacked in piles of up to six. Stacking reduced the time needed to arrange N95 respirators for decontamination by approximately two-thirds while almost tripling facility capacity. Make-up and moisturizer creams did not interfere with the decontamination process. CONCLUSIONS: Respirator stacking can reduce the hands-on time and increase decontamination capacity. When personalization is needed, respirators can be decontaminated in labelled paper bags. Make up or moisturizers do not appear to interfere with VHP decontamination.

DNA methylation is required to maintain both DNA replication timing precision and 3D genome organization integrity.

DNA replication timing and three-dimensional (3D) genome organization are associated with distinct epigenome patterns across large domains. However, whether alterations in the epigenome, in particular cancer-related DNA hypomethylation, affects higher-order levels of genome architecture is still unclear. Here, using Repli-Seq, single-cell Repli-Seq, and Hi-C, we show that genome-wide methylation loss is associated with both concordant loss of replication timing precision and deregulation of 3D genome organization. Notably, we find distinct disruption in 3D genome compartmentalization, striking gains in cell-to-cell replication timing heterogeneity and loss of allelic replication timing in cancer hypomethylation models, potentially through the gene deregulation of DNA replication and genome organization pathways. Finally, we identify ectopic H3K4me3-H3K9me3 domains from across large hypomethylated domains, where late replication is maintained, which we purport serves to protect against catastrophic genome reorganization and aberrant gene transcription. Our results highlight a potential role for the methylome in the maintenance of 3D genome regulation.

Chronic and persistent viral hemorrhagic septicemia virus infections in Pacific herring.

Chronic viral hemorrhagic septicemia virus (VHSV) infections were established in a laboratory stock of Pacific herring Clupea pallasii held in a large-volume tank supplied with pathogen-free seawater at temperatures ranging from 6.8 to 11.6 degrees C. The infections were characterized by viral persistence for extended periods and near-background levels of host mortality. Infectious virus was recovered from mortalities occurring up to 167 d post-exposure and was detected in normal-appearing herring for as long as 224 d following initial challenge. Geometric mean viral titers were generally as high as or higher in brain tissues than in pools of kidney and spleen tissues, with overall prevalence of infection being higher in the brain. Upon re-exposure to VHSV in a standard laboratory challenge, negligible mortality occurred among groups of herring that were either chronically infected or fully recovered, indicating that survival from chronic manifestations conferred protection against future disease. However, some survivors of chronic VHS infections were capable of replicating virus upon re-exposure. Demonstration of a chronic manifestation of VHSV infection among Pacific herring maintained at ambient seawater temperatures provides insights into the mechanisms by which the virus is maintained among populations of endemic hosts.

The development of a noisy brain.

Early in life, brain development carries with it a large number of structural changes that impact the functional interactions of distributed neuronal networks. Such changes enhance information processing capacity, moving the brain from a deterministic system to one that is more stochastic. The evidence from empirical studies with EEG and functional MRI suggests that this stochastic property is a result of an increased number of possible functional network configurations for a given situation. This is captured in the variability of endogenous and evoked responses or "brain noise ". In empirical data from infants and children, brain noise increases with maturation and correlates positively with stable behavior and accuracy. The noise increase is best explained through increased noise from network level interactions with a concomitant decrease of local noise. In old adults, brain noise continues to change, although the pattern of changes is not as global as in early development. The relation between high brain noise and stable behavior is maintained, but the relationships differ by region, suggesting changes in local dynamics that then impact potential network configurations. These data, when considered in concert with our extant modeling work, suggest that maturational changes in brain noise represent the enhancement offunctional network potential--the brain's dynamic repertoire.