Understanding clinical implementation coordinators' experiences in deploying evidence-based interventions.

PURPOSE: The fluoroquinolone restriction for the prevention of Clostridioides difficile infection (FIRST) trial is a multisite clinical study in which sites carry out a preauthorization process via electronic health record-based best-practice alert (BPA) to optimize the use of fluoroquinolone antibiotics in acute care settings. Our research team worked closely with clinical implementation coordinators to facilitate the dissemination and implementation of this evidence-based intervention. Clinical implementation coordinators within the antibiotic stewardship team (AST) played a pivotal role in the implementation process; however, considerable research is needed to further understand their role. In this study, we aimed to (1) describe the roles and responsibilities of clinical implementation coordinators within ASTs and (2) identify facilitators and barriers coordinators experienced within the implementation process. METHODS: We conducted a directed content analysis of semistructured interviews, implementation diaries, and check-in meetings utilizing the conceptual framework of middle managers' roles in innovation implementation in healthcare from Urquhart et al. RESULTS: Clinical implementation coordinators performed a variety of roles vital to the implementation's success, including gathering and compiling information for BPA design, preparing staff, organizing meetings, connecting relevant stakeholders, evaluating clinical efficacy, and participating in the innovation as clinicians. Coordinators identified organizational staffing models and COVID-19 interruptions as the main barriers. Facilitators included AST empowerment, positive relationships with staff and oversight/governance committees, and using diverse implementation strategies. CONCLUSION: When implementing healthcare innovations, clinical implementation coordinators facilitated the implementation process through their roles and responsibilities and acted as strategic partners in improving the adoption and sustainability of a fluoroquinolone preauthorization protocol.

A cost-of-illness analysis of the economic burden of obsessive-compulsive disorder in the United Kingdom.

OBJECTIVES: Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric condition, with diagnosed patients typically experiencing moderate or severe symptoms. This study evaluated the cost-of-illness (CoI) of OCD in the UK, capturing the annual costs accrued to the National Health Service (NHS) and Personal Social Services (PSS), people with OCD, caregivers and society. METHODS: The UK OCD population was estimated and stratified by age group (children, adults, elderly), symptom severity (mild, moderate, severe) and treatment received (including no treatment). Costs for each subpopulation were estimated through a prevalence-based approach. Cost inputs were sourced from national databases, while additional inputs were informed by literature searches or expert clinician opinion. Scenario analyses explored other factors including comorbid depression treatment and presenteeism. RESULTS: The base-case analysis estimated a total annual CoI of £378,356,004 to the NHS, rising to £5,095,759,464 when a societal perspective was considered. The annual cost of care per person with OCD increased with severity (mild: £174; moderate: £365; severe: £902) due to increasing healthcare resource utilisation. The largest contributor to healthcare costs was cognitive behavioural therapy, while societal costs were driven by lost productivity through absenteeism. The base-case results likely underestimated the true economic burden of OCD; including comorbid depression led to a 132% increase in treatment costs, while presenteeism in people with OCD and lost productivity in caregivers amplified indirect costs. CONCLUSIONS: The economic burden of OCD in the UK is substantial and extends beyond direct treatment costs, highlighting a need for research into alternative treatments with greater efficacy.

Long-term marine protection enhances kelp forest ecosystem stability.

Trophic downgrading destabilizes ecosystems and can drive large-scale shifts in ecosystem state. While restoring predatory interactions in marine reserves can reverse anthropogenic-driven shifts, empirical evidence of increased ecosystem stability and persistence in the presence of predators is scant. We compared temporal variation in rocky reef ecosystem state in New Zealand's oldest marine reserve to nearby fished reefs to examine whether protection of predators led to more persistent and stable reef ecosystem states in the marine reserve. Contrasting ecosystem states were found between reserve and fished sites, and this persisted over the 22-year study period. Fished sites were predominantly urchin barrens but occasionally fluctuated to short-lived turfs and mixed algal forests, while reserve sites displayed unidirectional successional trajectories toward stable kelp forests (Ecklonia radiata) taking up to three decades following protection. This provides empirical evidence that long-term protection of predators facilitates kelp forest recovery, resists shifts to denuded alternate states, and enhances kelp forest stability.

A New V361A Mutation in Amaranthus palmeri PPX2 Associated with PPO-Inhibiting Herbicide Resistance.

Weeds resistant to PPO-inhibiting herbicides threaten the profitability of crop producers relying on this chemistry. In Amaranthus palmeri, mutations at G210 (∆G210) and R128 (R128G/M) of the PPX2 gene were reported to confer PPO-inhibitor resistance. Here, A. palmeri samples from nine states in America, having survived a field application of a PPO-inhibitor, were genotyped to determine the prevalence of these mutations. Less than 5% of the 1828 A. palmeri plants screened contained the ∆G210 mutation. Of the plants lacking ∆G210, a R128 substitution was only found in a single plant. An A. palmeri population from Alabama without mutations at G210 or R128 had a resistance ratio of 3.1 to 3.5 for fomesafen. Of the candidate PPX2 mutations identified in this population, only V361A conferred resistance to lactofen and fomesafen in a transformed bacterial strain. This is the first report of the V361A substitution of PPX2 conferred PPO-inhibiting herbicide resistance in any plant species. Future molecular screens of PPO-inhibitor resistance in A. palmeri and other species should encompass the V361A mutation of PPX2 to avoid false-negative results.

Cold Weather Injury in a Special Operations Aviation Crew Member: A Case Report.

As arctic warfare becomes a center focus within Special Operations, cold weather injury looms as both a medical and operational threat. While cold weather injury can range from pernio to hemodynamically unstable systemic hypothermia, the more minor injuries are far more common. However, these present a challenge in austere medical care and can drastically impact mission capability. We present a case of a Special Operations crew chief with cold weather digital injury while at the Arctic Isolation Course in Alaska and his subsequent clinical course. Prevention remains the key for mitigating these injuries, while the decision to rewarm must be made with both medical and tactical factors in mind as refreezing incurs significant morbidity. Other components of prehospital treatment include active rewarming, ibuprofen, aloe vera, and pain control.

Marine heat waves drive bleaching and necrosis of temperate sponges.

Marine heat waves (MHWs) are extended periods of excessively warm water1 that are increasing in frequency, duration, intensity, and impact, and they likely represent a greater threat to marine ecosystems than the more gradual increases in sea surface temperature.2,3,4 Sponges are major and important components of global benthic marine communities,5,6,7 with earlier studies identifying tropical sponges as potential climate change "winners."8,9,10,11 In contrast, cold-water sponges may be less tolerant to predicted ocean warming and concurrent MHWs. Here, we report how a series of unprecedented MHWs in New Zealand have impacted millions of sponges at a spatial scale far greater than previously reported anywhere in the world. We reported sponge tissue necrosis12 and bleaching (symbiont loss/dysfunction),13 which have been previously associated with temperature stress,6,12,14 for three common sponge species across multiple biogeographical regions, with the severity of impact being correlated with MHW intensity. Given the ecological importance of sponges,15 their loss from these rocky temperate reefs will likely have important ecosystem-level consequences.

Genome analysis of Erwinia persicina reveals implications for soft rot pathogenicity in plants.

Soft rot disease causes devastating losses to crop plants all over the world, with up to 90% loss in tropical climates. To better understand this economically important disease, we isolated four soft rot-causing Erwinia persicina strains from rotted vegetables. Notably, E. persicina has only recently been identified as a soft rot pathogen and a comprehensive genomic analysis and comparison has yet to be conducted. Here, we provide the first genomic analysis of E. persicina, compared to Pectobacterium carotovorum, P. carotovorum, and associated Erwinia plant pathogens. We found that E. persicina shares common genomic features with other Erwinia species and P. carotovorum, while having its own unique characteristics as well. The E. persicina strains examined here lack Type II and Type III secretion systems, commonly used to secrete pectolytic enzymes and evade the host immune response, respectively. E. persicina contains fewer putative pectolytic enzymes than P. carotovorum and lacks the Out cluster of the Type II secretion system while harboring a siderophore that causes a unique pink pigmentation during soft rot infections. Interestingly, a putative phenolic acid decarboxylase is present in the E. persicina strains and some soft rot pathogens, but absent in other Erwinia species, thus potentially providing an important factor for soft rot. All four E. persicina isolates obtained here and many other E. persicina genomes contain plasmids larger than 100 kbp that encode proteins likely important for adaptation to plant hosts. This research provides new insights into the possible mechanisms of soft rot disease by E. persicina and potential targets for diagnostic tools and control measures.

Genome Sequences of Soft Rot-Causing Pseudomonas Isolates from Spinach.

Two Pseudomonas strains (SR17 and SR18) were isolated from soft rot-diseased spinach leaves. Here, we report their genome sequences and characteristics.

Genome Sequences of Soft Rot-Causing Pectobacterium Isolates from Different Vegetables.

Eleven Pectobacterium strains were isolated from soft rot-diseased vegetables. Here, we report their genome sequences and characteristics. Five isolates were found to be Pectobacterium versatile, while the other six were determined to be Pectobacterium brasiliense.

A New Virtual Reality: Benefits and Barriers to Providing Pediatric Gender-Affirming Health Care Through Telehealth.

Purpose: Access to early, multidisciplinary, gender-affirming health care significantly improves the psychosocial well-being of transgender and gender diverse youth. The Doernbecher Gender Clinic (DGC) is an interdisciplinary pediatric gender clinic consisting of endocrinology, psychology, and social work. Following the initiation of modified operations in March 2020 due to the COVID-19 pandemic, the DGC converted all interdisciplinary new patient appointments to telehealth. The purpose of this article is to (1) describe the model of care implemented during modified operations, (2) compare the number of new patients seen before and after modified operations, and (3) to contextualize this information with data from a patient satisfaction survey. Method: Retrospective chart review was used to determine how many interdisciplinary new patient appointments occurred before and during modified operations. Additional variables included age, gender, visit modality (phone or video), geographic location, and number of caregivers who participated. In addition, patients and families who attended appointments since modified operations were invited to complete a prospective survey regarding their experience and satisfaction with these appointments, and the narrative responses to questions about advantages and disadvantages were analyzed thematically. Results: Chart review revealed a similar number and make up of new patient appointments before and after the initiation of modified operations. The percentage of patients residing in other urban areas outside of the Portland metro increased over the course of the three time periods, but not to a significant degree. Survey results suggest that both telehealth and in-person visits have advantages and disadvantages with regard to (1) access and (2) comfort. Families appear to differ with regard to their priorities in each area. Conclusion: Telehealth has the potential to provide quality pediatric gender-affirming health care without sacrificing the benefits of an interdisciplinary team-based approach.

The perceptions of professional nurses regarding factors affecting the provision of quality health care services at selected rural public clinics in the Capricorn district, Limpopo Province.

BACKGROUND: Despite many initiatives made by the National Department of Health through the Minister of Health, the provision of quality health care services remains a serious challenge in South Africa, especially in public rural clinics. AIM: The study aims to determine the perceptions of professional nurses on the factors affecting the provision of quality health care services at selected public primary health care clinics in rural areas of the Capricorn District, Limpopo Province. SETTING: The study was conducted at selected public primary health care clinics in rural areas of the Capricorn District, Limpopo Province. METHODS: This study utilised a quantitative method, descriptive and a cross-sectional study conducted for three months at the selected public primary health care clinics. A structured self-administered questionnaire was used to collect data from 155 professional nurses who met the selection criteria. Data were analysed using Statistical Package for Social Sciences programme version 26.0. RESULTS: The results of 155 professional nurses were only 116 (74%) and reported that the use of modern technology such as electronic blood pressure, sonar machines and pulse reading computers improves the quality of health care services. Also 129 (84%), 124 (77%) and 118 (76%) reported that they were overwhelmed by the workload, the staff attitude and cleanliness of the clinic, respectively, which all affect the quality of health care services rendered. Moreover, only about 29 (19%) were satisfied with the salary they earned. CONCLUSION: Despite the effort and interventions put in place by the Department of Health with regard to the Ideal Clinic Realisation and Maintenance in response to the current deficiencies in the quality of primary health care services and to lay a strong foundation for the implementation of National Health Insurance. The quality of health care services is still hindered by several factors such as an overwhelming workload, the attitude of the staff and cleanliness in the work environment, poor infrastructure and the professional nurses perceive the environment as lacking equipment.

Coastal darkening substantially limits the contribution of kelp to coastal carbon cycles.

Macroalgal-dominated habitats are rapidly gaining recognition as important contributors to marine carbon cycles and sequestration. Despite this recognition, relatively little is known about the production and fate of carbon originating from these highly productive ecosystems, or how anthropogenic- and climate-related stressors affect the role of macroalgae in marine carbon cycles. Here, we examine the impact of increasing turbidity on carbon storage, fixation and loss in southern hemisphere kelp forests. We quantified net primary production (NPP) and biomass accumulation (BA), and estimated carbon release via detritus and dissolved organic carbon (DOC) across a large-scale turbidity gradient. We show that increased turbidity, resulting in a 63% reduction in light, can result in a 95% reduction in kelp productivity. When averaged annually, estimates of NPP and BA per plant at high-light sites were nearly six and two times greater than those at low-light sites, respectively. Furthermore, the quantity of carbon fixed annually by kelp forests was up to 4.7 times greater than that stored as average annual standing stock. At low-light sites, the majority of C goes directly into tissue growth and is subsequently eroded. In contrast, excess production at high-light sites accounts for up to 39% of the total carbon fixed and is likely released as DOC. Turbidity is expected to increase in response to climate change and our results suggest this will have significant impacts on the capacity of kelp forests to contribute to carbon sequestration pathways. In addition to demonstrating that turbidity significantly reduces the quantity of carbon fixed by kelp forests, and subsequently released as detritus, our results highlight the negative impacts of turbidity on a large source of previously unaccounted for carbon.

Grazer behaviour can regulate large-scale patterning of community states.

Ecosystem patterning can arise from environmental heterogeneity, biological feedbacks that produce multiple persistent ecological states, or their interaction. One source of feedbacks is density-dependent changes in behaviour that regulate species interactions. By fitting state-space models to large-scale (~500 km) surveys on temperate rocky reefs, we find that behavioural feedbacks best explain why kelp and urchin barrens form either reef-wide patches or local mosaics. Best-supported models in California include feedbacks where starvation intensifies grazing across entire reefs create reef-scale, alternatively stable kelp- and urchin-dominated states (32% of reefs). Best-fitting models in New Zealand include the feedback of urchins avoiding dense kelp stands that can increase abrasion and predation risk, which drives a transition from shallower urchin-dominated to deeper kelp-dominated zones, with patchiness at 3-8 m depths with intermediate wave stress. Connecting locally studied processes with region-wide data, we highlight how behaviour can explain community patterning and why some systems exhibit community-wide alternative stable states.

CDK4/6 inhibition synergizes with inhibition of P21-Activated Kinases (PAKs) in lung cancer cell lines.

Theoretically, small molecule CDK4/6 inhibitors (CDK4/6is) represent a logical therapeutic option in non-small cell lung cancers since most of these malignancies have wildtype RB, the key target of CDKs and master regulator of the cell cycle. Unfortunately, CDK4/6is are found to have limited clinical activity as single agents in non-small cell lung cancer. To address this problem and to identify effective CDK4/6i combinations, we screened a library of targeted agents for efficacy in four non-small cell lung cancer lines treated with CDK4/6 inhibitors Palbociclib or Abemaciclib. The pan-PAK (p21-activated kinase) inhibitor PF03758309 emerged as a promising candidate with viability ratios indicating synergy in all 4 cell lines and for both CDK4/6is. It is noteworthy that the PAKs are downstream effectors of small GTPases Rac1 and Cdc42 and are overexpressed in a wide variety of cancers. Individually the compounds primarily induced cell cycle arrest; however, the synergistic combination induced apoptosis, accounting for the synergy. Surprisingly, while the pan-PAK inhibitor PF03758309 synergizes with CDK4/6is, no synergy occurs with group I PAK inhibitors FRAX486 or FRAX597. Cell lines treated only with Ribociclib, FRAX486 or FRAX597 underwent G1/G0 arrest, whereas combination treatment with these compounds predominantly resulted in autophagy. Combining high concentrations of FRAX486, which weakly inhibits PAK4, and Ribociclib, mimics the autophagy and apoptotic effect of PF03758309 combined with Ribociclib. FRAX597, a PAKi that does not inhibit PAK4 did not reduce autophagy in combination with Ribociclib. Our results suggest that a unique combination of PAKs plays a crucial role in the synergy of PAK inhibitors with CDK4/6i. Targeting this unique PAK combination, could greatly improve the efficacy of CDK4/6i and broaden the spectrum of cancer treatment.

Periostin: contributor to abnormal airway epithelial function in asthma?

Periostin (POSTN) may serve as a biomarker for Type-2 mediated eosinophilic airway inflammation in asthma. We hypothesised that a Type-2 cytokine, interleukin (IL)-13, induces airway epithelial expression of POSTN, which in turn contributes to epithelial changes observed in asthma.We studied the effect of IL-13 on POSTN expression in BEAS-2B and air-liquid interface differentiated primary bronchial epithelial cells (PBECs). Additionally, the effects of recombinant human POSTN on epithelial-to-mesenchymal transition (EMT) markers and mucin genes were assessed. POSTN single cell gene expression and protein levels were analysed in bronchial biopsies and induced sputum from asthma patients and healthy controls.IL-13 increased POSTN expression in both cell types and this was accompanied by EMT-related features in BEAS-2B. In air-liquid interface differentiated PBECs, IL-13 increased POSTN basolateral and apical release. Apical administration of POSTN increased the expression of MMP-9, MUC5B and MUC5AC In bronchial biopsies, POSTN expression was mainly confined to basal epithelial cells, ionocytes, endothelial cells and fibroblasts, showing higher expression in basal epithelial cells from asthma patients versus those from controls. A higher level of POSTN protein expression in epithelial and subepithelial layers was confirmed in bronchial biopsies from asthma patients when compared to healthy controls. Although sputum POSTN levels were not higher in asthma, levels correlated with eosinophil numbers and with the coughing-up of mucus.POSTN expression is increased by IL-13 in bronchial epithelial cells and is higher in bronchial biopsies from asthma patients. This may have important consequences, as administration of POSTN increases epithelial expression of mucin genes, supporting the relationship of POSTN with Type-2 mediated asthma and mucus secretion.

A short digital eye-tracking assessment predicts cognitive status among adults.

Current cognitive assessments suffer from limited scalability and high user burden. This study aimed to (1) examine the relationship between a brief eye-tracking-based visual paired-comparison (VPC) and gold standard cognitive assessments, (2) examine longitudinal stability of the VPC task, (3) determine the ability of the VPC task to differentiate between cognitively normal (CN) individuals and individuals with mild cognitive impairment (MCI). Fifty-five adults (n = 44 CN, n = 11 MCI; 56.4 ± 26.7 years) were tested on two occasions, separated by at least 14 days. Visit 1 included VPC, Montreal Cognitive Assessment (MoCA), Digit Symbol Coding test (DSC), and NIH Toolbox Cognitive Battery (NIHTB-CB). Visit 2 included VPC, DSC, NIHTB-CB, and dual-task (DT). Significant differences existed between baseline VPC scores for CN and MCI groups (p < .001). VPC scores remained stable over time in both groups (p < .05). Significant associations existed between VPC and MoCA (p < .01), DSC (p < .001), and various NIHTB-CB subtests at both time points. The VPC test significantly predicts cognitive outcomes (p < .05), with age and VPC being the only significant predictors. Additionally, area under the curve (receiver operator characteristic = 0.80) for VPC scores demonstrated good classification accuracy. VPC reliably predicted cognitive status while remaining stable over time and displayed significant associations with gold standard cognitive assessments. VPC is a less burdensome and more scalable assessment than traditional tests, enabling longitudinal monitoring of cognitive status in resource-limited environments.

Cognitive decline negatively impacts physical function.

Many older adults report difficulty performing one or more activities of daily living. These difficulties may be attributed to cognitive decline and as a result, measuring cognitive status among aging adults may help provide an understanding of current functional status. The purpose of the present investigation was to determine the association between cognitive status and measures of physical functioning. Seventy-six older adults participated in this study; 41 were categorized as normal memory function (NM) and 35 were poor memory function (PM). NM participants had significantly higher physical function as measured by Short Physical Performance Battery (SPPB; 9.4 ± 2.2 vs. 8.4 ± 2.0; p = .03) and peak velocity (0.67 ± 0.16 vs. 0.56 ± 0.19; p = .04) during a quick sit-to-stand task. Dual-task walking velocities were 22% and 126% slower between cognitive groups for the fast and habitual trials, respectively when compared to the single-task walking condition. Significant correlations existed between measures of memory and physical function. The largest correlations with memory were for peak (r = 0.42) and average (r = 0.38) velocity. The results suggest a positive relationship between physical function and cognitive status. However, further research is needed to determine the mechanism of the underlying relationships between physical and cognitive function.

Targeted Activation of Hippocampal Place Cells Drives Memory-Guided Spatial Behavior.

The hippocampus is crucial for spatial navigation and episodic memory formation. Hippocampal place cells exhibit spatially selective activity within an environment and have been proposed to form the neural basis of a cognitive map of space that supports these mnemonic functions. However, the direct influence of place cell activity on spatial navigation behavior has not yet been demonstrated. Using an 'all-optical' combination of simultaneous two-photon calcium imaging and two-photon optogenetics, we identified and selectively activated place cells that encoded behaviorally relevant locations in a virtual reality environment. Targeted stimulation of a small number of place cells was sufficient to bias the behavior of animals during a spatial memory task, providing causal evidence that hippocampal place cells actively support spatial navigation and memory.

Corrigendum: Radiological Mapping of Post-Disaster Nuclear Environments Using Fixed-Wing Unmanned Aerial Systems: A Study From Chornobyl.

[This corrects the article DOI: 10.3389/frobt.2019.00149.].