Concept mapping: An aid to teaching and learning: AMEE Guide No. 157.

Concept maps are graphic representations that learners draw to depict their understanding of the meaning of a set of concepts. Concept maps can be a useful learning strategy in medical education. The purpose of this guide is to provide an understanding of the theoretical basis and instructional use of concept mapping in health professions education. The guide describes the key elements of a concept map and underscores the critical components of the implementation process, from the introduction of the activity to the use of different mapping techniques, based on purpose and context. This guide also examines the learning opportunities offered by collaborative concept mapping, including co-construction of knowledge, and provides suggestions for the use of concept mapping as an assessment for learning. Implications for the use of concept mapping as a tool for remediation are mentioned. Finally, the guide describes some of the challenges related to the implementation of this strategy.

Dietary intake and socio-economic predictors of inadequate energy and nutrient intake among women of childbearing age in Karamoja sub-region of Uganda.

BACKGROUND: Karamoja sub-region is the most food insecure part of Eastern Africa. The poor status of food security in the sub-region is reflected in the high rate of undernutrition among women of childbearing age (WCBA) and children under 5 years (CUFY). The sub-region is unique in Uganda in terms of cultural diversity, agro-ecology and rainfall pattern and agricultural practices. However, the influence of these unique characteristics on dietary intake of WCBA in the sub-region is less understood. Therefore, this study examined dietary intake and socio-economic predictors of inadequate energy and nutrient intake among WCBA in Karamoja sub-region. METHODS: A longitudinal study design was used involving 755 WCBA in the harvesting season where 635 were followed-up in the planting season. Data were collected using 24-h recall, dietary diversity and socio-economic and demographic questionnaires. RESULTS: Intake of energy and nutrients were generally significantly higher (p < 0.05) during the planting season than in the harvesting season. Irrespective of the district, physiological status and season, household consumption of plant-based foods was far higher than intake of animal-based foods dominated by starchy stables (76-100%), dark green leafy vegetables (70-100%) and legumes, nuts and seeds (22-97%) depending on the district. Majority of the respondents had two meals (breakfast: 65-100%; supper: 90-100%) with up to 45% of WCBA who consumed alcohol across meal times. .Overall on average, 57.7, 66.6, 78.5, 60.3, 67.7 and 93.7% of WCBA did not meet the recommended daily allowance (RDA) for energy, protein, calcium, iron, zinc and folic acid, respectively. Binary logistic regression revealed that inadequate intake of energy and nutrients significantly increased (p < 0.05) with the status of being lactating/breastfeeding and was influenced by age of WCBA, number of women married, education level and occupation of the household head depending on season. CONCLUSIONS: This study demonstrated that dietary intake of WCBA in Karamoja sub-region was inadequate. Age of WCBA, number of women married, education level and occupation of the household head and spouse and being a lactating/breastfeeding mother were the key socio-economic and demographic factors that influenced inadequate intake of energy and nutrients among WCBA.

Bioengineering of Soybean Oil and Its Impact on Agronomic Traits.

Soybean is a major oil crop and is also a dominant source of nutritional protein. The 20% seed oil content (SOC) of soybean is much lower than that in most oil crops and the fatty acid composition of its native oil cannot meet the specifications for some applications in the food and industrial sectors. Considerable effort has been expended on soybean bioengineering to tailor fatty acid profiles and improve SOC. Although significant advancements have been made, such as the creation of high-oleic acid soybean oil and high-SOC soybean, those genetic modifications have some negative impacts on soybean production, for instance, impaired germination or low protein content. In this review, we focus on recent advances in the bioengineering of soybean oil and its effects on agronomic traits.

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.

Structural snapshots of R-loop formation by a type I-C CRISPR Cascade.

Type I CRISPR-Cas systems employ multi-subunit Cascade effector complexes to target foreign nucleic acids for destruction. Here, we present structures of D. vulgaris type I-C Cascade at various stages of double-stranded (ds)DNA target capture, revealing mechanisms that underpin PAM recognition and Cascade allosteric activation. We uncover an interesting mechanism of non-target strand (NTS) DNA stabilization via stacking interactions with the "belly" subunits, securing the NTS in place. This "molecular seatbelt" mechanism facilitates efficient R-loop formation and prevents dsDNA reannealing. Additionally, we provide structural insights into how two anti-CRISPR (Acr) proteins utilize distinct strategies to achieve a shared mechanism of type I-C Cascade inhibition by blocking PAM scanning. These observations form a structural basis for directional R-loop formation and reveal how different Acr proteins have converged upon common molecular mechanisms to efficiently shut down CRISPR immunity.

Faecal metabolite deficit, gut inflammation and diet in Parkinson's disease: Integrative analysis indicates inflammatory response syndrome.

BACKGROUND: Gut-brain axis is widely implicated in the pathophysiology of Parkinson's disease (PD). We take an integrated approach to considering the gut as a target for disease-modifying intervention, using continuous measurements of disease facets irrespective of diagnostic divide. METHODS: We characterised 77 participants with diagnosed-PD, 113 without, by dietary/exogenous substance intake, faecal metabolome, intestinal inflammation, serum cytokines/chemokines, clinical phenotype including colonic transit time. Complete-linkage hierarchical cluster analysis of metabolites discriminant for PD-status was performed. RESULTS: Longer colonic transit was linked to deficits in faecal short-chain-fatty acids outside PD, to a 'tryptophan-containing metabolite cluster' overall. Phenotypic cluster analysis aggregated colonic transit with brady/hypokinesia, tremor, sleep disorder and dysosmia, each individually associated with tryptophan-cluster deficit. Overall, a faster pulse was associated with deficits in a metabolite cluster including benzoic acid and an imidazole-ring compound (anti-fungals) and vitamin B3 (anti-inflammatory) and with higher serum CCL20 (chemotactic for lymphocytes/dendritic cells towards mucosal epithelium). The faster pulse in PD was irrespective of postural hypotension. The benzoic acid-cluster deficit was linked to (well-recognised) lower caffeine and alcohol intakes, tryptophan-cluster deficit to higher maltose intake. Free-sugar intake was increased in PD, maltose intake being 63% higher (p = .001). Faecal calprotectin was 44% (95% CI 5%, 98%) greater in PD [p = .001, adjusted for proton-pump inhibitors (p = .001)], with 16% of PD-probands exceeding a cut-point for clinically significant inflammation compatible with inflammatory bowel disease. Higher maltose intake was associated with exceeding this calprotectin cut-point. CONCLUSIONS: Emerging picture is of (i) clinical phenotype being described by deficits in microbial metabolites essential to gut health; (ii) intestinal inflammation; (iii) a systemic inflammatory response syndrome.

Tracking cadmium pollution from source to receptor: A health-risk focused transfer continuum approach.

Cadmium (Cd) exposure poses a substantial risk to human health. Despite this, the multi-stage process through which Cd is released to the environment before being taken up and impacting human receptors has rarely been investigated. Here we utilized an integrated model involving Cd emissions, atmospheric transport, deposition, uptake by rice, receptor ingestion and metabolic processing in quantifying the critical emission sources and human health risks of Cd. Atmospheric Cd emissions in the study area in southeastern China were estimated at 147 kg (2016), with >53 % of emissions from non-ferrous metals (NFM) smelting activities. Atmospheric Cd depositions caused elevated Cd content in soil and rice, accounting for 3-79 % and 50-85 % of, respectively, soil and rice Cd. Cumulative frequency analysis showed that an estimated 1.3 % of predicted urine Cd through the consumption of Cd-contaminated rice and exceeded existing safety standards (1 µg g-1), thus highlighting the risks posed to health from high levels of Cd pollution. Applying stricter industrial emission standards to the NFM sector in particular and effective soil management practices could substantially reduce exposure to Cd pollution. The results contribute to understanding of the Cd transfer process and draw attention to the relative health benefits of interventions aimed at mitigating Cd levels and exposure risks at different stages along the Cd transfer continuum from source to receptor.

RNA targeting unleashes indiscriminate nuclease activity of CRISPR-Cas12a2.

Cas12a2 is a CRISPR-associated nuclease that performs RNA-guided, sequence-nonspecific degradation of single-stranded RNA, single-stranded DNA and double-stranded DNA following recognition of a complementary RNA target, culminating in abortive infection1. Here we report structures of Cas12a2 in binary, ternary and quaternary complexes to reveal a complete activation pathway. Our structures reveal that Cas12a2 is autoinhibited until binding a cognate RNA target, which exposes the RuvC active site within a large, positively charged cleft. Double-stranded DNA substrates are captured through duplex distortion and local melting, stabilized by pairs of 'aromatic clamp' residues that are crucial for double-stranded DNA degradation and in vivo immune system function. Our work provides a structural basis for this mechanism of abortive infection to achieve population-level immunity, which can be leveraged to create rational mutants that degrade a spectrum of collateral substrates.

An investigation into chiropractic intern adherence to radiographic guidelines in clinical decisions with a descriptive comparison to clinical practitioners.

OBJECTIVE: The purpose of this study was to assess chiropractic interns' knowledge and adherence to radiographic clinical practice guidelines (CPGs) and compare their clinical decisions to previous surveys of established practitioners in Canada and Australia. METHODS: A clinical decision-making survey was administered to 88 interns. The survey contained clinical scenarios and vignettes with inquiries regarding indications for radiographic referral, the likelihood of referral, and the application of CPGs. RESULTS: Forty-four percent (43.75%) of the interns were aware of CPGs, 38.75% were unsure, and 17.5% were not aware. When asked specific questions about the appropriateness of diagnostic imaging, the interns' responses were similar to those of practitioners in Canada and Australia. When interns evaluated a clinical vignette, there was lower compliance with CPGs. CONCLUSION: The interns' clinical decisions regarding the use of diagnostic radiography did not significantly differ from those of practitioners who were surveyed in other related studies. Interns were inconsistent in applying their decision making in clinical cases. Notwithstanding the similarities with practitioners, some deviation from the guidelines indicates the need for further intern education to improve the implementation of CPGs for optimal cost-effective and clinically appropriate care.

A case-control study of antipsychotic use and pneumonia-related mortality in the United Kingdom.

BACKGROUND AND AIM: There is increasing evidence linking antipsychotic use with pneumonia, but limited evidence of an effect on pneumonia-related outcomes such as mortality. In this study, we aimed to examine the association of pneumonia-related death with specific antipsychotic exposure. METHOD: Deaths analysed were those reported to a UK-based drug-related deaths database, the National Programme on Substance Abuse Deaths (NPSAD), between 1997 and September 2020. We conducted a case-control study with cases defined as pneumonia-related deaths and controls as cases with alternative causes of death. Cases were analysed by considering drugs detected at post-mortem (PM) and by drugs prescribed to the deceased at the time of their death with calculated odds ratios (ORs) adjusted to account for confounders. RESULTS: There were 2467 PM cases and 40,128 controls; 1818 prescribed cases and 28,018 controls. Second generation antipsychotics (SGAs) were robustly associated with an increased risk of pneumonia-related death compared with those not prescribed or taking antipsychotics (PM detection adjusted OR [AOR] 1·34 [95% CI 1·15-1·55]; prescribed AOR 1·28 [95% CI 1·11-1·49]). First generation antipsychotics had no clear association with death from pneumonia (PM detection AOR 1·06 [95% CI 0·77-1·47]; prescribed AOR 0·91 [95% CI 0·71-1·17]). Amongst SGAs, olanzapine was associated with an increased risk of death due to pneumonia (PM detection AOR 1·49 [95% CI 1·22-1·82]; prescribed AOR 1·44 [95% CI 1·18-1·76]) as was quetiapine (PM detection AOR 1·34 [95% CI 1·07-1·66]; prescribed AOR 1·28 [95% CI 1·01-1·64]). CONCLUSION: Olanzapine and quetiapine were found to increase the risk of pneumonia-related death in this NPSAD sample to a clinically important extent.

A single 2'-O-methylation of ribosomal RNA gates assembly of a functional ribosome.

RNA modifications are widespread in biology and abundant in ribosomal RNA. However, the importance of these modifications is not well understood. We show that methylation of a single nucleotide, in the catalytic center of the large subunit, gates ribosome assembly. Massively parallel mutational scanning of the essential nuclear GTPase Nog2 identified important interactions with rRNA, particularly with the 2'-O-methylated A-site base Gm2922. We found that methylation of G2922 is needed for assembly and efficient nuclear export of the large subunit. Critically, we identified single amino acid changes in Nog2 that completely bypass dependence on G2922 methylation and used cryoelectron microscopy to directly visualize how methylation flips Gm2922 into the active site channel of Nog2. This work demonstrates that a single RNA modification is a critical checkpoint in ribosome biogenesis, suggesting that such modifications can play an important role in regulation and assembly of macromolecular machines.

Estimating Risk of Antidepressant Withdrawal from a Review of Published Data.

Adaptation of the brain to the presence of a drug predicts withdrawal on cessation. The outcome of adaptation is often referred to as 'physical dependence' in pharmacology, as distinct from addiction, although these terms have unfortunately become conflated in some diagnostic guides. Physical dependence to antidepressants may occur in some patients, consistent with the fact that some patients experience withdrawal effects from these medications. It is thought that longer duration of use, higher dose and specific antidepressants affect the risk of antidepressant withdrawal effects as they might cause greater adaptation of the brain. We searched PubMed for relevant systematic reviews and other relevant analyses to summarise existing data on determinants of antidepressant withdrawal incidence, severity and duration. Overall, data were limited. From survey data, increased duration of use was associated with an increased incidence and severity of withdrawal effects, consistent with some evidence from data provided by drug manufacturers. Duration of use may be related to duration of withdrawal effects but data are heterogenous and sparse. Serotonin and noradrenaline reuptake inhibitors and paroxetine are associated with higher risks than other antidepressants, though data for some antidepressants are lacking. Higher doses of antidepressant has some weak association with an increased risk of withdrawal, with some ceiling effects, perhaps reflecting receptor occupancy relationships. Past experience of withdrawal effects is known to predict future risk. Based on these data, we outline a preliminary rubric for determining the risk of withdrawal symptoms for a particular patient, which may have relevance for determining tapering rates. Given the limited scope of the current research, future research should aim to clarify prediction of antidepressant withdrawal risk, especially by examining the risk of withdrawal in long-term users of medication, as well as the severity and duration of effects, to improve the preliminary tool for predictive purposes. Further research into the precise adaptations in long-term antidepressant use may improve the ability to predict withdrawal effects for a particular patient.

Beginning With the End in Mind: Implementing Backward Design to Improve Sports Injury Rehabilitation Practices.

SYNOPSIS: Current injury-specific return-to-performance rehabilitation programs are not comprehensive, lack intensity, and need better tailoring to the demands of sport. The vast number of rehabilitation and return to sport protocols also reflects a lack of consensus about what the best program looks like, which hinders beginning practitioners from implementing best practices across the spectrum of injuries and sports. Backward design, which has underpinnings in educational research, can facilitate implementation by encouraging practitioners to begin with the end in mind before logically and intentionally working backwards to design transferable and context-specific rehabilitation plans that improve sports injury rehabilitation practices. We discuss and illustrate using case examples how clinicians can apply backward design in best practice sports injury rehabilitation. J Orthop Sports Phys Ther 2022;52(12):770-776. Epub: 7 October 2022. doi:10.2519/jospt.2022.11440.

The Development of an Infrastructure to Facilitate the Use of Whole Genome Sequencing for Population Health.

The clinical use of genomic analysis has expanded rapidly resulting in an increased availability and utility of genomic information in clinical care. We have developed an infrastructure utilizing informatics tools and clinical processes to facilitate the use of whole genome sequencing data for population health management across the healthcare system. Our resulting framework scaled well to multiple clinical domains in both pediatric and adult care, although there were domain specific challenges that arose. Our infrastructure was complementary to existing clinical processes and well-received by care providers and patients. Informatics solutions were critical to the successful deployment and scaling of this program. Implementation of genomics at the scale of population health utilizes complicated technologies and processes that for many health systems are not supported by current information systems or in existing clinical workflows. To scale such a system requires a substantial clinical framework backed by informatics tools to facilitate the flow and management of data. Our work represents an early model that has been successful in scaling to 29 different genes with associated genetic conditions in four clinical domains. Work is ongoing to optimize informatics tools; and to identify best practices for translation to smaller healthcare systems.

Reasons for admission to a general medical hospital for patients taking clozapine.

Background: Clozapine is associated with a diverse range of side effects. In addition, patients prescribed clozapine commonly suffer with medical comorbidities. Objectives: This study aimed to characterise patients prescribed clozapine who required medical admission, understand reasons for admission, identify areas for interventions to prevent future admission and describe clozapine management during the inpatient stay. Design: We conducted a retrospective analysis of patients prescribed clozapine who were admitted to a general medical hospital in a 12-month period. Method: Data were collected using electronic drug charts and notes. Results: In total, 114 clozapine patients were hospitalised. Twenty-eight patients (25%) were admitted because of infection, 12 (11%) were elective admissions and 12 (11%) had gastrointestinal problems. Most patients admitted were Black (54%) and half were female. Few changes were made to clozapine dosing on admission or during the inpatient stay. Most patients had been taking clozapine for many years at the point of admission, the majority were able to continue taking it for the duration of their medical treatment and were discharged on the same dose they were taking prior to admission. Clozapine plasma concentrations were not consistently measured with only 18 (16%) patients having one or more plasma concentrations determined during their admission. The median clozapine plasma concentration on admission was 0.48 mg/L (nor-clozapine 0.21 mg/L), with a range of 0.09 to 3.9 mg/L. Three patients were admitted to the intensive care unit during their admission; all were discharged on clozapine. Four patients died; one from lung adenocarcinoma, one bowel obstruction, one cardiac arrest and one chest sepsis. In total, 27 patients (23%) had their clozapine stopped on admission, 6 (22% of this group) unintentionally. Conclusions: Our study found that the most common reason for admission for patients taking clozapine was infection. Plasma concentrations were not measured routinely despite clozapine having a narrow therapeutic index and enhanced potential for toxicity in the medically unwell patient.

Dopamine partial agonists: a discrete class of antipsychotics.

Worldwide, there are now three marketed dopamine D2 partial agonists: aripiprazole, brexpiprazole and cariprazine. These three drugs share a number of properties other than their action at D2 receptors. Pharmacologically, they are 5HT2 antagonists and D3 and 5HT1A partial agonists but with little or no alpha-adrenergic, anticholinergic or antihistaminic activity. They also share a long duration of action. Clinically, D2 partial agonists are effective antipsychotics and generally have useful antimanic and antidepressant activity. They are usually well tolerated, causing akathisia and insomnia only at the start of treatment, and are non-sedating. These drugs also share a very low risk of increased prolactin and of weight gain and accompanying metabolic effects. They may also have a relatively low risk of tardive dyskinesia. There is some evidence that they are preferred by patients to dopamine antagonists. Individual dopamineD2 partial agonists have much in common and as a group they differ importantly from dopamine D2 antagonists. Dopamine D2 partial agonists should be considered a distinct class of antipsychotics.Key pointsD2 partial agonists share many pharmacological and clinical propertiesD2 partial agonists differ in several important respects from D2 antagonistsD2 partial agonists should be considered a discrete class of antipsychotics.

Instructional review of key factors to achieve successful outcomes when using low-intensity pulsed ultrasound in fracture repair.

Low-intensity pulsed ultrasound (LIPUS) treatment of fractures has been available to the orthopaedic community for nearly three decades; however, it is still considered an experimental treatment by some clinicians, even though there is a wealth of clinical data. Based on the evaluation of clinical trial data, we have established key criteria which can lead to LIPUS success and avoid failure. These are fracture gap size and stability, accurate transducer placement and minimum treatment number. However, from a clinician's view, the correct attitude to treatment must be observed, and this has also been discussed. It is hoped, armed with this new evaluation of the clinical data, that clinicians can treat patients with LIPUS more effectively, resulting in fewer failures of treatment.

Comparison of three rebound tonometers in normal and glaucomatous dogs.

OBJECTIVE: The objectives of the study were to compare intraocular pressure (IOP) readings across a wide range and obtained via three rebound tonometers in ADAMTS10-mutant Beagle-derived dogs with different stages of open-angle glaucoma (OAG) and normal control dogs and to investigate the effect of central corneal thickness (CCT). ANIMALS STUDIED: Measurements were performed on 99 eyes from 50 Beagle-derived dogs with variable genetics-16 non-glaucomatous and 34 with ADAMTS10-OAG. Seventeen OAG eyes were measured twice-with and without the use of IOP-lowering medications. PROCEDURES: IOP was measured in each eye using three tonometers with their "dog" setting-ICare® Tonovet (TV), ICare® Tonovet Plus® (TVP), and the novel Reichert® Tono-Vera® Vet (TVA)-in randomized order. CCT was measured with the Accutome® PachPen. Statistical analyses included one-way ANOVA, Tukey pairwise comparisons, and regression analyses of tonometer readings and pairwise IOP-CCT Pearson correlations (MiniTab®). RESULTS: A total of 116 IOP measurements were taken with each of the three tonometers. When comparing readings over a range of ~7-77 mmHg, mean IOPs from the TV were significantly lower compared with TVP (-4.6 mmHg, p < .001) and TVA (-3.7 mmHg, p = .001). We found no significant differences between TVA and TVP measurements (p = .695). There was a moderate positive correlation between CCT and IOP for TVA (r = 0.53, p < .001), TVP (r = 0.48, p < .001), and TV (r = 0.47, p < .001). CONCLUSIONS: Our data demonstrate strong agreement between TVP and TVA, suggesting that the TVA may similarly reflect true IOP values in canines. CCT influenced IOP measurements of all three tonometers.