Energy expenditure estimation during activities of daily living in middle-aged and older adults using an accelerometer integrated into a hearing aid.

Background: Accelerometers were traditionally worn on the hip to estimate energy expenditure (EE) during physical activity but are increasingly replaced by products worn on the wrist to enhance wear compliance, despite potential compromises in EE estimation accuracy. In the older population, where the prevalence of hearing loss is higher, a new, integrated option may arise. Thus, this study aimed to investigate the accuracy and precision of EE estimates using an accelerometer integrated into a hearing aid and compare its performance with sensors simultaneously worn on the wrist and hip. Methods: Sixty middle-aged to older adults (average age 64.0 ± 8.0 years, 48% female) participated. They performed a 20-min resting energy expenditure measurement (after overnight fast) followed by a standardized breakfast and 13 different activities of daily living, 12 of them were individually selected from a set of 35 activities, ranging from sedentary and low intensity to more dynamic and physically demanding activities. Using indirect calorimetry as a reference for the metabolic equivalent of task (MET), we compared the EE estimations made using a hearing aid integrated device (Audéo) against those of a research device worn on the hip (ZurichMove) and consumer devices positioned on the wrist (Garmin and Fitbit). Class-estimated and class-known models were used to evaluate the accuracy and precision of EE estimates via Bland-Altman analyses. Results: The findings reveal a mean bias and 95% limit of agreement for Audéo (class-estimated model) of -0.23 ± 3.33 METs, indicating a slight advantage over wrist-worn consumer devices (Garmin: -0.64 ± 3.53 METs and Fitbit: -0.67 ± 3.40 METs). Class-know models reveal a comparable performance between Audéo (-0.21 ± 2.51 METs) and ZurichMove (-0.13 ± 2.49 METs). Sub-analyses show substantial variability in accuracy for different activities and good accuracy when activities are averaged over a typical day's usage of 10 h (+61 ± 302 kcal). Discussion: This study shows the potential of hearing aid-integrated accelerometers in accurately estimating EE across a wide range of activities in the target demographic, while also highlighting the necessity for ongoing optimization efforts considering precision limitations observed across both consumer and research devices.

Restoring South African subtropical succulent thicket using Portulacaria afra: root growth of cuttings differs depending on the harvest site during a drought.

The restoration of succulent thicket (the semi-arid components of the Albany Subtropical Thicket biome endemic to South Africa) has largely focused on the reintroduction of Portulacaria afra L. Jacq-a leaf- and stem-succulent shrub-through the planting of unrooted cuttings directly into field sites. However, there has been inconsistent establishment and survival rates, with low rates potentially due to a range of factors (e.g., post-planting drought, frost or herbivory), including the poor condition of source material used. Here we test the effect of parent-plant and harvesting site on the root development of P. afra cuttings in a common garden experiment. Ten sites were selected along a ∼110 km transect, with cuttings harvested from five parent-plants per site. Leaf moisture content was determined for each parent-plant at the time of harvesting as a proxy for plant condition. Root development-percentage of rooted cuttings and mean root dry weight-was recorded for a subset of cuttings from each parent-plant after 35, 42, 48, 56, and 103 days after planting in a common garden setting. We found evidence for cutting root development (rooting percentage and root dry mass) to be strongly associated with harvesting site across all sampling days (p < 0.005 for all tests). These differences are likely a consequence of underlying physiological factors; this was supported by the significant but weak correlation (r 2 = 0.10-0.26) between the leaf moisture content of the parent-plant (at the time of harvesting) and dry root mass of the cuttings (at each of the sampling days). Our findings demonstrate that varying plant condition across sites can significantly influence root development during dry phases (i.e., intra- and inter-annual droughts) and that this may be a critical component that needs to be understood as part of any restoration programme. Further work is required to identify the environmental conditions that promote or impede root development in P. afra cuttings.

Transdural retrieval of retropulsed transforaminal lumbar interbody fusion cages.

Transforaminal lumbar interbody fusions (TLIFs) are performed for various lumbar spine pathologies. Posterior migration of an interbody cage is a complication that may result in neurologic injury and require reoperation. Sparse information exists regarding the safety and efficacy of a transdural approach for cage retrieval. We describe a surgical technique, in which centrally retropulsed cages were safely retrieved transdurally. A patient with prior L3-S1 posterior lumbar fusion and L4-S1 TLIFs presented with radiculopathy and weakness in dorsiflexion. Imaging revealed posterior central migration of TLIF cages causing compression of the traversing L5 nerve root. Cages were removed transdurally; the correction was performed with an all-posterior T10-pelvis fusion. Aside from temporary weakness in right-sided dorsiflexion, the patient experienced complete resolution in their radiculopathy and strength returned to its presurgical state by 3 months. The transdural approach for interbody removal can be safely performed and should be a tool in the spine surgeon's armamentarium.

Osteoporotic Fractures: Diagnosis, Evaluation, and Significance From the International Working Group on DXA Best Practices.

Osteoporotic fractures, also known as fragility fractures, are reflective of compromised bone strength and are associated with significant morbidity and mortality. Such fractures may be clinically silent, and others may present clinically with pain and deformity at the time of the injury. Unfortunately, and even at the time of detection, most individuals sustaining fragility fractures are not identified as having underlying metabolic bone disease and are not evaluated or treated to reduce the incidence of future fractures. A multidisciplinary international working group with representation from international societies dedicated to advancing the care of patients with metabolic bone disease has developed best practice recommendations for the diagnosis and evaluation of individuals with fragility fractures. A comprehensive narrative review was conducted to identify key articles on fragility fractures and their impact on the incidence of further fractures, morbidity, and mortality. This document represents consensus among the supporting societies and harmonizes best practice recommendations consistent with advances in research. A fragility fracture in an adult is an important predictor of future fractures and requires further evaluation and treatment of the underlying osteoporosis. It is important to recognize that most fragility fractures occur in patients with bone mineral density T scores higher than -2.5, and these fractures confirm the presence of skeletal fragility even in the presence of a well-maintained bone mineral density. Fragility fractures require further evaluation with exclusion of contributing factors for osteoporosis and assessment of clinical risk factors for fracture followed by appropriate pharmacological intervention designed to reduce the risk of future fracture. Because most low-trauma vertebral fractures do not present with pain, dedicated vertebral imaging and review of past imaging is useful in identifying fractures in patients at high risk for vertebral fractures. Given the importance of fractures in confirming skeletal fragility and predicting future events, it is recommended that an established classification system be used for fracture identification and reporting.

Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Physical fitness profile of a large urban fire department: Exploring age and rank dynamics.

BACKGROUND: Firefighter physical fitness (PF) plays a crucial role in mitigating health issues and supporting occupational performance. The influence of rank on firefighter PF remains understudied and previous research is often limited by small sample sizes of firefighters volunteering for research studies, potentially biasing results towards fitter firefighters not representative of entire departments. OBJECTIVE: To examine the PF profile of firefighters in a large urban fire department and the influence of age and rank on PF. METHODS: Data, including muscular fitness, estimated aerobic capacity (VO2max), and body fat percentage (BF%) measures from 1361 firefighters (90% male; age: 37.4±10.1yrs; 60 recruits, 973 firefighters, 290 lieutenants/captains, 38 chiefs) were analyzed. Correlation and ANCOVAs were conducted to examine the impact of rank on PF while controlling for age. Score distributions were scrutinized to profile the PF of the department. RESULTS: Age was negatively associated with pull-ups (r = - 0.39), sit-ups (r = - 0.39), and push-ups (r = - 0.32), but positively associated with relative VO2max (r = 0.17) and BF% (r = 0.39). Rank had a statistically significant, but trivial effect size, on pull-ups (p = 0.028, η2 = 0.007) and sit-ups (p = 0.034, η2 = 0.005). Firefighters with lower PF levels were older, had higher BF%, lower fat-free mass, and were a greater proportion of females. CONCLUSIONS: Firefighters exhibited diverse levels of PF. Age, not rank, appeared to influence firefighters' PF. The findings that firefighters who were older, female, with poorer body composition are more likely to have lower PF levels highlights the need for individualized PF training to enhance occupational performance and health across the fire department.

Transition Metal Complexes with Appended Benzimidazole Groups for Sensing Dihydrogenphosphate.

Four new complexes [Ru(bpy)2(bbib)](PF6)2, [Ru(phen)2(bbib)](PF6)2, [Re(CO)3(bbib)(py)](PF6) and [Ir(ppy)2(bbib)](PF6) [where bbib = 4,4'-bis(benzimidazol-2-yl)-2,2'-bipyridine] have been prepared and their photophysical properties determined. Their behaviour has been studied with a variety of anions in acetonitrile, DMSO and 10% aquated DMSO. Acetate and dihydrogenphosphate demonstrate a redshift in the bbib ligand associated absorptions suggesting that the ligand is strongly interacting with these anions. The 3MLCT emissive state is sensitive to the introduction of small quantities of anion (sub-stoichiometric quantities) and significant quenching is typically observed with acetate, although this is less pronounced in the presence of water. The emissive behaviour with dihydrogenphosphate is variable, showing systematic changes as anion concentration increases with several distinct interactions evident . 1H NMR and 31P NMR titrations in a 10% D2O - D6-DMSO mixture suggest that with dihydrogenphosphate, the imidazole group able to act as both a proton acceptor and donor. It appears that all four complexes can form a {[complex]2-H2PO4} "dimer", a one-to-one species (which the X-ray crystallography study suggests is dimeric in the solid-state), and a complex with a combined bis(dihydrogenphosphate) complex anion. The speciation relies on complex equilibria dependent on several factors including the complex charge, the hydrophobicity of the associated ligands, and the solvent.

The history of diapers and their environmental impact.

IMPACT: This article examines diaper practices around the world throughout history. This article reviews the innovation of the modern diaper and the environmental effects of disposable diapers.

Cognitive Disengagement Syndrome-Clinical Interview (CDS-CI): Psychometric support for caregiver and youth versions.

Cognitive disengagement syndrome (CDS), formerly termed sluggish cognitive tempo, is a set of symptoms characterized by excessive daydreaming, mental confusion, and slowed behavior/thinking. CDS is distinct from symptoms of attention-deficit/hyperactivity disorder (ADHD) and other psychopathologies and uniquely associated with functional impairment. However, despite significant progress in developing and evaluating rating scale measures of CDS, no clinical interview of CDS exists with established psychometric properties that can facilitate a multimethod approach assessing CDS. Accordingly, the present study evaluated the psychometric properties of the semistructured Cognitive Disengagement Syndrome-Clinical Interview (CDS-CI). The CDS-CI and the ADHD inattention (ADHD-IN) and hyperactive-impulsivity (ADHD-HI) modules from the Kiddie Schedule of Affective Disorders and Schizophrenia for School-Age Children (K-SADS) were administered to a sample of early adolescents (N = 341, ages 10-12 years) and their caregivers. Adolescents and caregivers also completed rating scale measures of CDS and ADHD symptoms. The CDS-CI demonstrated high internal consistency and interrater reliability. CDS-CI scores showed excellent same-source discriminant validity from K-SADS, ADHD-IN, and ADHD-HI scores and encouraging convergent and discriminant validity with rating scale measures, especially for caregivers. Above and beyond K-SADS, ADHD-IN, and ADHD-HI scores, higher parent and adolescent CDS-CI scores were both significantly associated with greater functional impairment. A threshold of ≥ 6 out of 15 symptoms was selected as an initial threshold for determining clinically elevated CDS using the CDS-CI. Findings provide psychometric support for the CDS-CI as a tool in the multimethod assessment of CDS. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A dynamic subpopulation of CRISPR-Cas overexpressers allows Streptococcus pyogenes to rapidly respond to phage.

Many CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated protein) systems, which provide bacteria with adaptive immunity against phages, are transcriptionally repressed in their native hosts. How CRISPR-Cas expression is induced as needed, for example, during a bacteriophage infection, remains poorly understood. In Streptococcus pyogenes, a non-canonical guide RNA tracr-L directs Cas9 to autorepress its own promoter. Here we describe a dynamic subpopulation of cells harbouring single mutations that disrupt Cas9 binding and cause CRISPR-Cas overexpression. Cas9 actively expands this population by elevating mutation rates at the tracr-L target site. Overexpressers show higher rates of memory formation, stronger potency of old memories and a larger memory storage capacity relative to wild-type cells, which are surprisingly vulnerable to phage infection. However, in the absence of phage, CRISPR-Cas overexpression reduces fitness. We propose that CRISPR-Cas overexpressers are critical players in phage defence, enabling bacterial populations to mount rapid transcriptional responses to phage without requiring transient changes in any one cell.

The impact of population ageing on the burden of chronic kidney disease.

The burden of chronic kidney disease (CKD) and its risk factors are projected to rise in parallel with the rapidly ageing global population. By 2050, the prevalence of CKD category G3-G5 may exceed 10% in some regions, resulting in substantial health and economic burdens that will disproportionately affect lower-income countries. The extent to which the CKD epidemic can be mitigated depends largely on the uptake of prevention efforts to address modifiable risk factors, the implementation of cost-effective screening programmes for early detection of CKD in high-risk individuals and widespread access and affordability of new-generation kidney-protective drugs to prevent the development and delay the progression of CKD. Older patients require a multidisciplinary integrated approach to manage their multimorbidity, polypharmacy, high rates of adverse outcomes, mental health, fatigue and other age-related symptoms. In those who progress to kidney failure, comprehensive conservative management should be offered as a viable option during the shared decision-making process to collaboratively determine a treatment approach that respects the values and wishes of the patient. Interventions that maintain or improve quality of life, including pain management and palliative care services when appropriate, should also be made available.

Chronic Deltoid Insufficiency in Stage IV Adult Acquired Flatfoot Deformity: Do We Have a Good Answer?

Stage IV adult acquired flatfoot deformity (AAFD) with secondary chronic deltoid ligament insufficiency is a challenging deformity to treat, with minimal consensus in the literature concerning its surgical management. Many surgical treatment options have been described, including joint-sparing techniques, fusions, osteotomies, and even arthroplasties. However, questions remain as to what, if any, treatment is optimal. This contribution reviews studies on surgical treatments for stage IV AAFD with deltoid ligament failure and provides a critical analysis regarding the quality of outcomes reported for those different treatment options. PubMed and Google Scholar databases were searched between June 1, 2022, and August 15, 2022, for studies published between 1990 and 2022 that describe the treatment of stage IV AAFD with deltoid ligament insufficiency. Articles included in the study focused on subjects with stage IV AAFD and associated deltoid ligament insufficiency undergoing surgical correction. Exclusion criteria included stage I, II, and III AAFD, as well as deltoid ligament repair following acute injury/rupture. Nine studies covering five different treatment options for patients with stage IV AAFD and chronic deltoid insufficiency were included, with minimal overlap in outcome measures used to assess the efficacy of the procedure. Triple arthrodesis with deltoid ligament reconstruction resulted in a 62.5% (5/8) success rate with a residual tibiotalar (TT) angulation of 2° (success defined as <3°). Tibiotalar arthrodesis of four patients resulted in an average post-operative tibiotalar angulation of 4.8° with all patients showing progressive destabilization of the hindfoot complex at 12-18 year follow-ups. Deltoid arthroscopic laminoplasty (Brostrom) resulted in an increased American Orthopaedic Foot and Ankle Society (AOFAS) score from 49.7 pre-op to 91.9 post-op. There was no long-term follow-up of these patients. Deltoid ligament reconstruction using autografts of the peroneus longus resulted in a post-operative valgus of 2.1° in one study and <5° in another. Deltoid ligament reconstruction using an anterior tibial tendon autograft resulted in a gain of 126.4 + 40.2% in stiffness compared to an intact ligament. Twinfix suture anchors resulted in a post-operative hindfoot angle averaging 5.3°. Combined deltoid and spring ligament reconstruction resulted in a 5.1° valgus angulation. There is currently no standard of care or clinical consensus regarding surgical treatment for stage IV AAFD with deltoid insufficiency. Several studies imply that mild valgus malalignment around the tibiotalar joint can result in satisfactory outcomes. A few studies even deemed <5° of valgus tilt post-operatively successful. However, it has been described that any imbalance in tibiotalar tilt is a significant risk factor for progressive arthritis and future ligamentous failure. No treatment option was able to correct valgus tilt to an anatomical standard (i.e., to normal anatomy). These varied findings, along with the lack of consensus on post-surgical measures to assess efficacy, are worrisome and emphasize the need for better surgical options. Moreover, there is a critical need for additional research on the long-term outcomes following stage IV AAFD and deltoid insufficiency repair, particularly, as over five million people in the United States and 10% of the geriatric population are affected by AAFD with a risk of progressing to stage IV.

Association between CKD-MBD biomarkers and symptom burden in older patients with advanced CKD: Results from the EQUAL study.

BACKGROUND: Patients with advanced chronic kidney disease (CKD) develop numerous symptoms, with a multifactorial origin. Evidence linking mineral disorders (CKD-MBD) and uremic symptoms is scant and mostly limited to dialysis patients. Here we aim to assess the association between CKD-MBD and symptom burden in non-dialysis CKD patients. METHODS: We used data from the European Quality study, which includes patients aged ≥65 with eGFR ≤20 ml/min/1.73m2 from six European countries, followed up to five years. We used generalized linear mixed-effect models to determine the association between repeated measurements of parathyroid hormone (PTH), phosphate and calcium with the overall symptom number (0-33), the overall symptom severity (0-165), and the presence of 33 CKD-related symptoms. We also analyzed subgroups by sex, age, and diabetes mellitus, and assessed effect mediation and joint effects between mineral biomarkers. RESULTS: The 1396 patients included in the study had a mean of 13±6 symptoms at baseline, with a median overall severity score of 32 (IQR 19-50). The association between PTH levels and symptom burden appeared U-shaped with a lower symptom burden found for mild-to-moderately increased PTH levels. Phosphate and calcium were not independently associated with overall symptom burden. The highest symptom burden was found in patients with a combination of both severe hyperparathyroidism and severe hyperphosphatemia (+2.44 symptoms (0.50, 4.38), P=0.01). The association of both hypocalcemia and hyperphosphatemia with symptom burden seemed to differ by sex and age. CONCLUSIONS: In older patients with advanced CKD not on dialysis, mild-to-moderately increased PTH was associated with a lower symptom burden, although the effect size was relatively small (less than one symptom). Neither phosphate nor calcium were associated with the overall symptom burden, except for the combination of severe hyperphosphatemia and severe hyperparathyroidism which was associated with an increased number of symptoms.

Selecting PedsQL items to derive the PedsUtil health state classification system to measure health utilities in children.

BACKGROUND: There is a lack of preference-based health-related quality of life (HRQoL) measures that consistently value health across a full range of child age groups. The PedsQL is a generic HRQoL instrument validated for children 2-18 years, but it is not preference-based. The objective of this study was to derive the PedsUtil health state classification system from the PedsQL as a basis for a preference-based HRQoL measure for children. METHODS: A two-step process was used to select PedsQL items to include in the health state classification system: 1) exclude poorly functioning items according to Rasch analysis in each of the previously established seven dimensions of the PedsUtil health state classification system and 2) select a single item to represent each dimension based on Rasch and psychometric analyses, as well as input from child health experts and parents. All secondary analyses were conducted using data from the Longitudinal Study of Australian Children (LSAC). Analyses were stratified by age group (i.e., 2-5 years, 6-13 years, and 14-17 years) to represent the different developmental stages of children and to reflect the study design of the LSAC. Rasch analyses were also performed on five random subsamples for each age group to enhance robustness of results. RESULTS: Twelve items were excluded from the PedsUtil health state classification system after the first step of the item selection process. An additional four items were excluded in the second step, resulting in seven items that were selected to represent the seven dimensions of the PedsUtil health state classification system: Physical Functioning ("participating in sports activity or exercise"), Pain ("having hurts or aches"), Fatigue ("low energy level"), Emotional Functioning ("worrying about what will happen to them"), Social Functioning ("other kids not wanting to be their friend"), School Functioning ("keeping up with schoolwork"), and School Absence ("missing school because of not feeling well"). CONCLUSIONS: The PedsUtil health state classification system was derived from the PedsQL based on several criteria and was constructed to be applicable to children two years and older. Research is ongoing to elicit preferences for the PedsUtil health state classification system to construct the PedsUtil scoring system.

Seasonal influenza A virus lineages exhibit divergent abilities to antagonize interferon induction and signaling.

The circulation of seasonal influenza A viruses (IAVs) in humans relies on effective evasion and subversion of the host immune response. While the evolution of seasonal H1N1 and H3N2 viruses to avoid humoral immunity is well characterized, relatively little is known about the evolution of innate immune antagonism phenotypes in these viruses. Numerous studies have established that only a small subset of infected cells is responsible for initiating the type I and type III interferon (IFN) response during IAV infection, emphasizing the importance of single cell studies to accurately characterize the IFN response during infection. We developed a flow cytometry-based method to examine transcriptional changes in IFN and interferon stimulated gene (ISG) expression at the single cell level. We observed that NS segments derived from seasonal H3N2 viruses are more efficient at antagonizing IFN signaling but less effective at suppressing IFN induction, compared to the pdm2009 H1N1 lineage. We compared a collection of NS segments spanning the natural history of the current seasonal IAV lineages and demonstrate long periods of stability in IFN antagonism potential, punctuated by occasional phenotypic shifts. Altogether, our data reveal significant differences in how seasonal and pandemic H1N1 and H3N2 viruses antagonize the human IFN response at the single cell level.

Postsurgical Pain Risk Stratification to Enhance Pain Management Workflow in Adult Patients: Design, Implementation, and Pilot Evaluation.

BACKGROUND: Exposure to opioids after surgery is the initial contact for some people who develop chronic opioid use disorder. Hence, effective postoperative pain management, with less reliance on opioids, is critical. The Perioperative Opioid Quality Improvement (POQI) program developed (1) a digital health platform leveraging patient-survey-reported risk factors and (2) a postsurgical pain risk stratification algorithm to personalize perioperative care by integrating several commercially available digital health solutions into a combined platform. Development was reduced in scope by the COVID-19 pandemic. OBJECTIVE: This pilot study aims to assess the screening performance of the risk algorithm, quantify the use of the POQI platform, and evaluate clinicians' and patients' perceptions of its utility and benefit. METHODS: A POQI platform prototype was implemented in a quality improvement initiative at a Canadian tertiary care center and evaluated from January to September 2022. After surgical booking, a preliminary risk stratification algorithm was applied to health history questionnaire responses. The estimated risk guided the patient assignment to a care pathway based on low or high risk for persistent pain and opioid use. Demographic, procedural, and medication administration data were extracted retrospectively from the electronic medical record. Postoperative inpatient opioid use of >90 morphine milligram equivalents per day was the outcome used to assess algorithm performance. Data were summarized and compared between the low- and high-risk groups. POQI use was assessed by completed surveys on postoperative days 7, 14, 30, 60, 90, and 120. Semistructured patient and clinician interviews provided qualitative feedback on the platform. RESULTS: Overall, 276 eligible patients were admitted for colorectal procedures. The risk algorithm stratified 203 (73.6%) as the low-risk group and 73 (26.4%) as the high-risk group. Among the 214 (77.5%) patients with available data, high-risk patients were younger than low-risk patients (age: median 53, IQR 40-65 years, vs median 59, IQR 49-69 years, median difference five years, 95% CI 1-9; P=.02) and were more often female patients (45/73, 62% vs 80/203, 39.4%; odds ratio 2.5, 95% CI 1.4-4.5; P=.002). The risk stratification was reasonably specific (true negative rate=144/200, 72%) but not sensitive (true positive rate=10/31, 32%). Only 39.7% (85/214) patients completed any postoperative quality of recovery questionnaires (only 14, 6.5% patients beyond 60 days after surgery), and 22.9% (49/214) completed a postdischarge medication survey. Interviewed participants welcomed the initiative but noted usability issues and poor platform education. CONCLUSIONS: An initial POQI platform prototype was deployed operationally; the risk algorithm had reasonable specificity but poor sensitivity. There was a significant loss to follow-up in postdischarge survey completion. Clinicians and patients appreciated the potential impact of preemptively addressing opioid exposure but expressed shortcomings in the platform's design and implementation. Iterative platform redesign with additional features and reevaluation are required before broader implementation.

The West Nile virus genome harbors essential riboregulatory elements with conserved and host-specific functional roles.

West Nile virus (WNV) is an arthropod-borne, positive-sense RNA virus that poses an increasing global threat due to warming climates and lack of effective therapeutics. Like other enzootic viruses, little is known about how host context affects the structure of the full-length RNA genome. Here, we report a complete secondary structure of the entire WNV genome within infected mammalian and arthropod cell lines. Our analysis affords structural insights into multiple, conserved aspects of flaviviral biology. We show that the WNV genome folds with minimal host dependence, and we prioritize well-folded regions for functional validation using structural homology between hosts as a guide. Using structure-disrupting, antisense locked nucleic acids, we then demonstrate that the WNV genome contains riboregulatory structures with conserved and host-specific functional roles. These results reveal promising RNA drug targets within flaviviral genomes, and they highlight the therapeutic potential of ASO-LNAs as both WNV-specific and pan-flaviviral therapeutic agents.

Discovery of GS-7682, a Novel 4'-Cyano-Modified C-Nucleoside Prodrug with Broad Activity against Pneumo- and Picornaviruses and Efficacy in RSV-Infected African Green Monkeys.

Acute respiratory viral infections, such as pneumovirus and respiratory picornavirus infections, exacerbate disease in COPD and asthma patients. A research program targeting respiratory syncytial virus (RSV) led to the discovery of GS-7682 (1), a novel phosphoramidate prodrug of a 4'-CN-4-aza-7,9-dideazaadenosine C-nucleoside GS-646089 (2) with broad antiviral activity against RSV (EC50 = 3-46 nM), human metapneumovirus (EC50 = 210 nM), human rhinovirus (EC50 = 54-61 nM), and enterovirus (EC50 = 83-90 nM). Prodrug optimization for cellular potency and lung cell metabolism identified 5'-methyl [(S)-hydroxy(phenoxy)phosphoryl]-l-alaninate in combination with 2',3'-diisobutyrate promoieties as being optimal for high levels of intracellular triphosphate formation in vitro and in vivo. 1 demonstrated significant reductions of viral loads in the lower respiratory tract of RSV-infected African green monkeys when administered once daily via intratracheal nebulized aerosol. Together, these findings support additional evaluation of 1 and its analogues as potential therapeutics for pneumo- and picornaviruses.

Spatial decoupling of taxon richness, phylogenetic diversity and threat status in the megagenus Erica (Ericaceae).

Estimates of the number of vascular plant species currently under threat of extinction are shockingly high, with the highest extinction rates reported for narrow-range, woody plants, especially in biodiversity hotspots with Mediterranean and tropical climates. The large genus Erica is a prime example, as a large proportion of its 851 species, all shrubs or small trees, are endemic to the Cape Floristic Region (CFR) of South Africa. Almost two hundred are known to be threatened and a further hundred are 'Data Deficient'. We need to target conservation efforts and research to fill the most problematic knowledge gaps. This can be especially challenging in large genera, such as Erica, with numerous threatened species that are closely related. One approach involves combining knowledge of phylogenetic diversity with that of IUCN threat status to identify the most Evolutionarily Distinct and Globally Endangered (EDGE) species. We present an expanded and improved phylogenetic hypothesis for Erica (representing 65% of described species diversity) and combine this with available threat and distribution data to identify species and geographic areas that could be targeted for conservation effort to maximise preservation of phylogenetic diversity (PD). The resulting 39 EDGE taxa include 35 from the CFR. A further 32 high PD, data deficient taxa are mostly from outside the CFR, reflecting the low proportion of assessed taxa outside South Africa. The most taxon-rich areas are found in the south-western CFR. They are not the most phylogenetically diverse, but do include the most threatened PD. These results can be cross-referenced to existing living and seed-banked ex situ collections and used to target new and updated threat assessments and conservation action.