The prevalence and significance of nonuniform thyroid radio-isotope uptake in patients with Graves' disease.

OBJECTIVE: To evaluate the prevalence and clinical significance of nonuniform technetium (99m Tc) uptake among patients with Graves' disease (GD). DESIGN, PATIENTS AND MEASUREMENTS: Patients with GD, referred between July 2005 and March 2018, had Tc99 - uptake scans and TSH-receptor antibody (TRAb) measured before antithyroid drug (ATD) therapy. Risk of relapse after ATD cessation was monitored until June 2021 and compared between GD patients based on uptake patterns. RESULTS: Of the 276 GD patients (mean age, 49.8 years; 84% female), 25 (9.0%) had nonuniform Tc99 uptake. At diagnosis, individuals with nonuniform uptake were older (mean age of 61.8 vs. 48.5 years, p < .001), had lower mean thyroid hormone levels (free thyroxine: 36.3 vs. 45.4 pmol/L, p = .04 and free triiodothyronine: 10.0 vs. 17.8 pmol/L, p < .001) and median TRAb levels (4.2 vs. 6.6 U/L, p = .04) compared with those with a uniform uptake. Older age was a significant predictor for the presence of nonuniform uptake in GD patients; odds ratio (95% confidence intervals) of 1.07 (1.03 - 1.10). The risk of relapse was similar in both groups after a median (IQR) follow-up of 41 (13-74) months after ATD cessation (56.0% vs. 46.3%, respectively); hazard ratio (95% confidence intervals) of 1.74 (0.96-3.15). CONCLUSIONS: Nonuniform radio-isotope uptake is seen in 1 in 11 patients with GD which could be misdiagnosed as toxic multinodular goitre if TRAb levels are not measured. Treatment of GD patients with nonuniform radio-isotope uptake with ATD therapy as first-line appears to be equally effective as compared with those with uniform uptake. TRAb testing should be the main diagnostic test for patients with suspected GD with radio-labelled uptake scans being reserved for those who are TRAb negative.

Trade-offs between reducing complex terminology and producing accurate interpretations from environmental DNA: Comment on "Environmental DNA: What's behind the term?" by Pawlowski et al., (2020).

In a recent paper, "Environmental DNA: What's behind the term? Clarifying the terminology and recommendations for its future use in biomonitoring," Pawlowski et al. argue that the term eDNA should be used to refer to the pool of DNA isolated from environmental samples, as opposed to only extra-organismal DNA from macro-organisms. We agree with this view. However, we are concerned that their proposed two-level terminology specifying sampling environment and targeted taxa is overly simplistic and might hinder rather than improve clear communication about environmental DNA and its use in biomonitoring. This terminology is based on categories that are often difficult to assign and uninformative, and it overlooks a fundamental distinction within eDNA: the type of DNA (organismal or extra-organismal) from which ecological interpretations are derived.

Leveraging eDNA to expand the study of hybrid zones.

Hybrid zones are important windows into ecological and evolutionary processes. Our understanding of the significance and prevalence of hybridization in nature has expanded with the generation and analysis of genome-spanning data sets. That said, most hybridization research still has restricted temporal and spatial resolution, which limits our ability to draw broad conclusions about evolutionary and conservation related outcomes. Here, we argue that rapidly advancing environmental DNA (eDNA) methodology could be adopted for studies of hybrid zones to increase temporal sampling (contemporary and historical), refine and geographically expand sampling density, and collect data for taxa that are difficult to directly sample. Genomic data in the environment offer the potential for near real-time biological tracking of hybrid zones, and eDNA provides broad, but as yet untapped, potential to address eco-evolutionary questions.

Evaluating monitoring options for conservation: comparing traditional and environmental DNA tools for a critically endangered mammal.

While conservation management has made tremendous strides to date, deciding where, when and how to invest limited monitoring budgets is a central concern for impactful decision-making. New analytical tools, such as environmental DNA (eDNA), are now facilitating broader biodiversity monitoring at unprecedented scales, in part, due to time, and presumably cost, of methodological efficiency. Genetic approaches vary from conventional PCR (cPCR; species presence), to metabarcoding (community structure), and qPCR (relative DNA abundance, detection sensitivity). Knowing when to employ these techniques over traditional protocols could enable practitioners to make more informed choices concerning data collection. Using 12 species-specific primers designed for cPCR, eDNA analysis of the Yangtze finless porpoise (YFP; Neophocaena asiaeorientalis asiaeorientalis), a critically endangered aquatic mammal within the Yangtze River, we validated and optimized these primers for use in qPCR. We tested repeatability and sensitivity to detect YFP eDNA and subsequently compared the cost of traditional (visual and capture) sampling to eDNA tools. Our results suggest cPCR as the least expensive sampling option but the lack of PCR sensitivity suggests it may not be the most robust method for this taxon, predominately useful as a supplementary tool or with large expected populations. Alternatively, qPCR remained less expensive than traditional surveys, representing a highly repeatable and sensitive method for this behaviorally elusive species. Cost comparisons of surveying practices have scarcely been discussed; however, given budgetary constraints particularly for developing countries with limited local oversight but high endemism, we encourage managers to carefully consider the trade-offs among accuracy, cost, coverage, and speed for biodiversity monitoring.

The effect of Aliskiren on exercise capacity in older patients with heart failure and preserved ejection fraction: A randomized, placebo-controlled, double-blind trial.

In older patients (70 ± 7 years) with chronic well-compensated heart failure with preserved ejection and controlled blood pressure, 6 months treatment with aliskiren (direct renin inhibitor) showed non-significant trends for modest improvements in peak exercise oxygen consumption (14.9 ± 0.2 mL kg-1 min-1 versus 14.4 ± 0.2 mL kg-1 min-1; P = .10, trend) and ventilatory anaerobic threshold (888 ± 19 mL/min versus 841 ± 18 mL/min; P = .08).

An examination of the perceived impact of a continuing interprofessional education experience on opiate prescribing practices.

Chronic pain is increasingly recognized as a public health problem. We assessed the effectiveness of a multi-modal, interprofessional educational approach aimed at empowering healthcare professionals to make deliberative changes, especially in opiate prescribing practices. Education activities included enduring webcasts, regional interprofessional roundtable events, and state-level conference presentations within targeted Kentucky and West Virginia regions of the United States. Over 1,000 participants accessed the various activities. For the live events, the largest groups reached included nurses (38.1%), nurse practitioners (31.2%), and physicians (22.1%). In addition to our reach, higher levels of educational effectiveness were measured, specifically, learner's intentions to change practice patterns, confidence in meeting patient's needs, and knowledge of pain management guidelines. The majority of the conference (58%) and roundtable (69%) participants stated they intend to make a practice change in one or more areas of chronic pain patient management in post-event evaluation. Differences in pre- and post-activity responses on the measures of confidence and knowledge, with additional comparison to a control population who were not in attendance, were analyzed using non-parametric tests of significance. While neither activity produced significant changes in confidence from pre-activity, participants were more confident post-activity than their control group peers. There were significant changes in knowledge for both live event and webcast participants. Impactful chronic pain continuing the education that emphasizes collaborative care is greatly needed; these results show that the approaches taken here can impact learner's knowledge and confidence, and hold potential for creating change in how opioid prescribing is managed.

Using environmental DNA to assess population-wide spatiotemporal reserve use.

Scientists increasingly rely on protected areas to assist in biodiversity conservation, yet the efficacy of these areas is rarely systematically assessed, often because of underfunding. Still, adaptive management strategies to maximize conservation success often rely on understanding the temporal and spatial dynamism of populations therein. Examination of environmental DNA (eDNA) is a time and cost-effective way to monitor species' distribution, and quantitative polymerase chain reaction (qPCR) provides information on organismal abundance. To date, however, such techniques remain underused for population assessments in protected areas. We determined eDNA concentration of the critically endangered Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis) to describe its occurrence, range, and use of the Tian e-Zhou National Nature Reserve in Hubei, China, across seasons and hydrological depths. Despite the observation that total eDNA concentrations were highest in surface waters in summer, finless porpoise eDNA concentrations were significantly higher in deeper waters than in surface waters in summer. During the breeding season (spring), eDNA signals were site specific and restricted to the core area of the reserve. However, postbreeding eDNA concentrations were widespread across the reserve, encompassing sites previously thought to be unfrequented by the species. Our results suggest spatiotemporal idiosyncrasies in site, depth, and seasonal use of the reserve and a propensity for postbreeding population dispersal. With eDNA and qPCR we were able to assess an entire population's use of a protected area. Illuminating nuances in habitat use via eDNA could be valuable to set pragmatic conservation goals for this, and other, species.

Real-World Massage Therapy Produces Meaningful Effectiveness Signal for Primary Care Patients with Chronic Low Back Pain: Results of a Repeated Measures Cohort Study.

OBJECTIVE: While efficacy of massage and other nonpharmacological treatments for chronic low back pain is established, stakeholders have called for pragmatic studies of effectiveness in "real-world" primary health care. The Kentucky Pain Research and Outcomes Study evaluated massage impact on pain, disability, and health-related quality of life for primary care patients with chronic low back pain. We report effectiveness and feasibility results, and make comparisons with established minimal clinically important differences. METHODS: Primary care providers referred eligible patients for 10 massage sessions with community practicing licensed massage therapists. Oswestry Disability Index and SF-36v2 measures obtained at baseline and postintervention at 12 and 24 weeks were analyzed with mixed linear models and Tukey's tests. Additional analyses examined clinically significant improvement and predictive patient characteristics. RESULTS: Of 104 enrolled patients, 85 and 76 completed 12 and 24 weeks of data collection, respectively. Group means improved at 12 weeks for all outcomes and at 24 weeks for SF-36v2's Physical Component Summary and Bodily Pain Domain. Of those with clinically improved disability at 12 weeks, 75% were still clinically improved at 24 weeks ( P < 0.01). For SF-36v2 Physical and Mental Component Summaries, 55.4% and 43.4%, respectively, showed clinically meaningful improvement at 12 weeks, 46.1% and 30.3% at 24 weeks. For Bodily Pain Domain, 49.4% were clinically improved at 12 weeks, 40% at 24 weeks. Adults older than age 49 years had better pain and disability outcomes than younger adults. CONCLUSIONS: Results provide a meaningful signal of massage effect for primary care patients with chronic low back pain and call for further research in practice settings using pragmatic designs with control groups.

Association Between 6-Minute Walk Test Distance and Objective Variables of Functional Capacity After Exercise Training in Elderly Heart Failure Patients With Preserved Ejection Fraction: A Randomized Exercise Trial.

OBJECTIVE: To evaluate the change in the 6-minute walk test (6-MWT) distance relative to changes in key functional capacity measures after 16 weeks of exercise training in older patients (≥65y) who have heart failure with preserved ejection fraction (HFpEF). DESIGN: Prospective, randomized, single-blinded (by researchers to patient group) comparison of 2 groups of HFpEF patients. SETTING: Hospital and clinic records; ambulatory outpatients. PARTICIPANTS: Participants (N=47) randomly assigned to an attention control (AC) (n=24) or exercise training (ET) (n=23) group. INTERVENTION: The ET group performed cycling and walking at 50% to 70% of peak oxygen uptake (V˙o2peak) intensity (3d/wk, 60min each session). MAIN OUTCOME MEASURES: V˙o2peak, ventilatory threshold (VT), and 6-MWT distance were measured at baseline and after the 16-week study period. RESULTS: At follow-up, the 6-MWT distance was higher than at the baseline in both the ET (11%, P=.005) and AC (9%, P=.004) groups. In contrast, V˙o2peak and VT values increased in the ET group (19% and 11%, respectively; P=.001), but decreased in the AC group at follow-up (2% and 0%, respectively). The change in V˙o2peak versus 6-MWT distance after training was also not significantly correlated in the AC group (r=.01, P=.95) or in the ET group (r=.13, P=.57). The change in 6-MWT distance and VT (an objective submaximal exercise measure) was also not significantly correlated in the AC group (r=.08, P=.74) or in the ET group (r=.16, P=.50). CONCLUSIONS: The results of this study challenge the validity of using the 6-MWT as a serial measure of exercise tolerance in elderly HFpEF patients and suggest that submaximal and peak exercise should be determined objectively by VT and V˙o2peak in this patient population.

Extensive variation in sperm morphology in a frog with no sperm competition.

BACKGROUND: Recent comparative studies of several taxa have found that within-species variation in sperm size decreases with increasing levels of sperm competition, suggesting that male-male gamete competition selects for an optimal sperm phenotype. Previous studies of intraspecific sperm length variation have all involved internal fertilizers where some other factors-e.g., sperm storage and sperm movement along the walls of the female's reproductive tract-probably also influence and reduce sperm size variation. Thus external fertilizers, where those factors are absent, might be expected to exhibit even more variation when there is little or no sperm competition. To test that idea, we studied the sperm morphology of a North American chorus frog, the spring peeper (Pseudacris crucifer), a species in which males encounter little or no sperm competition. RESULTS: As expected, sperm size was highly variable in the spring peeper, largely due to variation in flagellum length within and among individual males, among populations and between mitochondrial lineages in southwestern Ontario. In addition, a large proportion of spermatozoa in all males was abnormal in such a way that the ability of abnormal spermatozoa to fertilize was probably compromised. There were no differences in the frequencies of abnormalities among populations or mitochondrial lineages. CONCLUSIONS: In the absence of sperm competition, we suggest that genetic drift has probably played a role in the generation of diversity in sperm morphology in this species, potentially resulting in the observed differences among populations. Such interpopulation difference in sperm morphology might be expected to increase the degree of reproductive isolation between populations even before other isolating mechanisms evolve.

The unseen invaders: Tracking phylogeographic dynamics and genetic diversity of cryptic Pomacea canaliculata and P. maculata (Golden apple snails) across Taiwan.

The cryptic invasion of golden apple snails (Pomacea canaliculata and P. maculata) in Taiwan has caused significant ecological and economical damage over the last few decades, however, their management remains difficult due to inadequate taxonomic identification, complex phylogeny, and limited population genetic information. We aim to understand the current distribution, putative population of origin, genetic diversity, and potential path of cryptic invasion of Pomacea canaliculata and P. maculata across Taiwan to aid in improved mitigation approaches. The present investigation conducted a nationwide survey with 254 samples collected from 41 locations in 14 counties or cities across Taiwan. We identified P. canaliculata and P. maculata based on mitochondrial COI and compared their genetic diversity across Taiwan, as well as other introduced and native countries (based on publicly available COI data) to understand the possible paths of invasion to Taiwan. Based on mitochondrial COI barcoding, sympatric and heterogeneous distributions of invasive P. canaliculata and P. maculata were noted. Our haplotype analysis and mismatch distribution results suggested multiple introductions of P. canaliculata in Taiwan was likely originated directly from Argentina, whereas P. maculata was probably introduced from a single, or a few, introduction event(s) from Argentina and Brazil. Our population genetic data further demonstrated a higher haplotype and genetic diversity for P. canaliculata and P. maculata in Taiwan compared to other introduced regions. Based on our current understanding, the establishment of P. canaliculata and P. maculata is alarming and widespread beyond geopolitical borders, requiring a concerted and expedited national and international invasive species mitigation program.

Environmental DNA.

Emilie Didaskalou and colleagues introduce the analysis of DNA form environmental samples.

Nutrient-dependent allometric plasticity in a male-diphenic mite.

Male secondary sexual traits often scale allometrically with body size. These allometries can be variable within species and may shift depending on environmental conditions, such as food quality. Such allometric plasticity has been hypothesized to initiate local adaptation and evolutionary diversification of scaling relationships, but is under-recorded, and its eco-evolutionary effects are not well understood. Here, we tested for allometric plasticity in the bulb mite (Rhizoglyphus robini), in which large males tend to develop as armed adult fighters with thickened third legs, while small males become adult scramblers without thickened legs. We first examined the ontogenetic timing for size- and growth-dependent male morph determination, using experimentally amplified fluctuations in growth rate throughout juvenile development. Having established that somatic growth and body size determine male morph expression immediately before metamorphosis, we examined whether the relationship between adult male morph and size at metamorphosis shifts with food quality. We found that the threshold body size for male morph expression shifts toward lower values with deteriorating food quality, confirming food-dependent allometric plasticity. Such allometric plasticity may allow populations to track prevailing nutritional conditions, potentially facilitating rapid evolution of allometric scaling relationships.

Appendiceal endosalpingiosis: a case report of a rare finding from appendicectomy.

Endosalpingiosis is occasionally incidentally found on histopathologic examination of gynecologic or gastrointestinal specimen, most commonly in the ovary, fallopian tube, omentum and uterus. Recently an association between endosalpingiosis and, ovarian and uterine cancer has been described. Here, we describe a rare case of appendiceal endosalpingiosis mimicking appendicitis. Further prospective studies are required to elucidate the clinical significance of appendiceal endosalpingiosis, the potential association with gynecologic malignancy and implications for management.

Toward an understanding of the chemical ecology of alternative reproductive tactics in the bulb mite (Rhizoglyphus robini).

BACKGROUND: Under strong sexual selection, certain species evolve distinct intrasexual, alternative reproductive tactics (ARTs). In many cases, ARTs can be viewed as environmentally-cued threshold traits, such that ARTs coexist if their relative fitness alternates over the environmental cue gradient. Surprisingly, the chemical ecology of ARTs has been underexplored in this context. To our knowledge, no prior study has directly quantified pheromone production for ARTs in a male-polymorphic species. Here, we used the bulb mite-in which males are either armed fighters that kill conspecifics, or unarmed scramblers (which have occasionally been observed to induce mating behavior in other males)-as a model system to gain insight into the role of pheromones in the evolutionary maintenance of ARTs. Given that scramblers forgo investment into weaponry, we tested whether scramblers produce higher quantities of the putative female sex-pheromone α-acaridial than fighters, which would improve the fitness of the scrambler phenotype through female mimicry by allowing avoidance of aggression from competitors. To this end, we sampled mites from a rich and a poor nutritional environment and quantified their production of α-acaridial through gas chromatography analysis. RESULTS: We found a positive relationship between pheromone production and body size, but males exhibited a steeper slope in pheromone production with increasing size than females. Females exhibited a higher average pheromone production than males. We found no significant difference in slope of pheromone production over body size between fighters and scramblers. However, scramblers reached larger body sizes and higher pheromone production than fighters, providing some evidence for a potential female mimic strategy adopted by large scramblers. Pheromone production was significantly higher in mites from the rich nutritional environment than the poor environment. CONCLUSION: Further elucidation of pheromone functionality in bulb mites, and additional inter- and intrasexual comparisons of pheromone profiles are needed to determine if the observed intersexual and intrasexual differences in pheromone production are adaptive, if they are a by-product of allometric scaling, or diet-mediated pheromone production under weak selection. We argue chemical ecology offers a novel perspective for research on ARTs and other complex life-history traits.

Development of the Leapfrog Group's Bar Code Medication Administration Standard to Address Hospital Inpatient Medication Safety.

ABSTRACT: Medication errors are the most common type of error in hospitals and reflect a leading cause of avoidable harm to patients. Bar code medication administration (BCMA) systems are a technology designed to help intercept medication errors at the point of medication administration. This article describes the process of developing, testing, and refining a standard for BCMA adoption and use in U.S. hospitals, as measured through the Leapfrog Hospital Survey. Building on the published literature and an expert panel's collective experience in studying, implementing, and using BCMA systems, the expert panel recommended a standard with 4 key domains. Leapfrog's BCMA standard provides hospitals with a "how-to guide" on what best practice looks like for using BCMA to ensure safe medication administration at the bedside.

Traumatic brain injury patients with platelet inhibition receiving platelet transfusion demonstrate decreased need for neurosurgical intervention and decreased mortality.

BACKGROUND: Platelet dysfunction is known to occur in patients with traumatic brain injury (TBI), and the correction of platelet dysfunction may prevent hemorrhagic progression in TBI. Thromboelastography with platelet mapping (TEG-PM; Haemonetics) evaluates the degree of platelet function inhibition through the adenosine diphosphate (ADP) and arachidonic acid (AA) pathways. We hypothesized that ADP and AA inhibition would improve with the transfusion of platelets in patients with TBI. METHODS: A retrospective review was conducted at a Level I trauma center of all patients presenting with TBI from December 2019 to December 2020. Per a practice management guideline, a platelet mapping assay was obtained on all patients with TBI upon admission. If ADP or AA was found to be inhibited (>60%), the patient was transfused 1 unit of platelets and a repeat platelet mapping assay was ordered. Demographic data, laboratory values, and outcomes were analyzed. RESULTS: Over the 13-month study period, 453 patients with TBI underwent TEG-PM with a protocol adherence rate of 66.5% resulting in a total of 147 patients who received platelets for ADP and/or AA inhibition; of those, 107 underwent repeat TEG-PM after platelets were administered. With the administration of platelets, ADP (p < 0.0001), AA (p < 0.0001), and MA (p = 0.0002) all significantly improved. Of 330 patients with TBI not taking antiplatelet medications, 50.9% showed inhibition in ADP and/or AA. If AA or ADP inhibition was noted on admission, mortality was increased (p = 0.0108). If ADP improved with platelet administration, the need for neurosurgical intervention was noted to decrease (p = 0.0182). CONCLUSION: Patients with TBI and platelet inhibition may benefit from the administration of platelets to correct platelet dysfunction. Thromboelastography with platelet mapping may be implemented in the initial workup of patients presenting with TBI to assess platelet dysfunction and provide prognostic information, which may guide treatment. LEVEL OF EVIDENCE: Therapeutic / Care Management, level III.

Environmental DNA analysis as an emerging non-destructive method for plant biodiversity monitoring: a review.

Environmental DNA (eDNA) analysis has recently transformed and modernized biodiversity monitoring. The accurate detection, and to some extent quantification, of organisms (individuals/populations/communities) in environmental samples is galvanizing eDNA as a successful cost and time-efficient biomonitoring technique. Currently, eDNA's application to plants remains more limited in implementation and scope compared to animals and microorganisms. This review evaluates the development of eDNA-based methods for (vascular) plants, comparing its performance and power of detection with that of traditional methods, to critically evaluate and advise best-practices needed to innovate plant biomonitoring. Recent advancements, standardization and field applications of eDNA-based methods have provided enough scope to utilize it in conservation biology for numerous organisms. Despite our review demonstrating only 13% of all eDNA studies focus on plant taxa to date, eDNA has considerable environmental DNA has considerable potential for plants, where successful detection of invasive, endangered and rare species, and community-level interpretations have provided proof-of-concept. Monitoring methods using eDNA were found to be equal or more effective than traditional methods; however, species detection increased when both methods were coupled. Additionally, eDNA methods were found to be effective in studying species interactions, community dynamics and even effects of anthropogenic pressure. Currently, elimination of potential obstacles (e.g. lack of relevant DNA reference libraries for plants) and the development of user-friendly protocols would greatly contribute to comprehensive eDNA-based plant monitoring programs. This is particularly needed in the data-depauperate tropics and for some plant groups (e.g., Bryophytes and Pteridophytes). We further advocate to coupling traditional methods with eDNA approaches, as the former is often cheaper and methodologically more straightforward, while the latter offers non-destructive approaches with increased discrimination ability. Furthermore, to make a global platform for eDNA, governmental and academic-industrial collaborations are essential to make eDNA surveys a broadly adopted and implemented, rapid, cost-effective and non-invasive plant monitoring approach.

Preschoolers' knowledge about the appearance of proper names.

Preschoolers' knowledge of the appearance of proper names was tested in three experiments with 25 boys and 22 girls from low-income families. Children from a Head Start program, whose parents signed a permission letter, participated. Their ages ranged from 3 yr. 6 mo. to 5 yr. 6 mo. (M = 52.2 mo., SD = 4.9). When shown consonant-vowel-consonant trigrams such as Rit or baF or dEg with various capitalization patterns, the children showed a tendency to recognize that CVC trigrams with the first letter capitalized or all letters capitalized were the ones most likely to represent a person's name. When their own names were substituted, which typically contained more than three letters, their performance was markedly better. Children also had a strong tendency to consider trigrams of Latin letters as more likely to be a person's name than trigrams of non-Latin characters (e.g., Sanskrit).