Quantitative X-ray microradiography for high-throughput phenotyping of osteoarthritis in mice

Objective To investigate and validate digital X-ray microradiography as a novel, high-throughput and cost-effective screening approach to identify abnormal joint phenotypes in mice. Method Digital X-ray microradiography was used to quantify the subchondral bone mineral content (BMC) in the medial tibial plateau. Accuracy and reproducibility of the method were determined in 22 samples from C57BL/6(B6Brd;B6Dnk;B6N-Tyrc-Brd) wild-type mice. The method was then validated in wild-type mice that had undergone surgical destabilisation of medial meniscus (DMM) and in a genetically modified mouse strain with an established increase in trabecular bone mass. Results The measurement of subchondral BMC by digital X-ray microradiography had a coefficient of variation of 3.6%. Digital X-ray microradiography was able to demonstrate significantly increased subchondral BMC in the medial tibial plateau of male mice 4 and 8 weeks after DMM surgery and in female mice 8 weeks after surgery. Furthermore, digital X-ray microradiography also detected the increase in subchondral BMC in a genetically modified mouse strain with high trabecular bone mass. Conclusion Quantitation of subchondral BMC by digital X-ray microradiography is a rapid, sensitive and cost-effective method to identify abnormal joint phenotypes in mice of both genders at several ages

Delayed healthcare seeking and prolonged illness in healthcare workers during the COVID-19 pandemic: a single-centre observational study

Objectives: To describe a cohort of self-isolating healthcare workers (HCWs) with presumed COVID-19. / Design: A cross-sectional, single-centre study. / Setting: A large, teaching hospital based in Central London with tertiary infection services. / Participants: 236 HCWs completed a survey distributed by internal staff email bulletin. 167 were women and 65 men. / Measures: Information on symptomatology, exposures and health-seeking behaviour were collected from participants by self-report. / Results: The 236 respondents reported illness compatible with COVID-19 and there was an increase in illness reporting during March 2020 Diagnostic swabs were not routinely performed. Cough (n=179, 75.8%), fever (n=138, 58.5%), breathlessness (n=84, 35.6%) were reported. Anosmia was reported in 42.2%. Fever generally settled within 1 week (n=110/138, 88%). Several respondents remained at home and did not seek formal medical attention despite reporting severe breathlessness and measuring hypoxia (n=5/9, 55.6%). 2 patients required hospital admission but recovered following oxygen therapy. 84 respondents (41.2%) required greater than the obligated 7 days off work and 9 required greater than 3 weeks off. / Conclusion: There was a significant increase in staff reporting illness compatible with possible COVID-19 during March 2020. Subsequent serology studies at the same hospital study site have confirmed sero-positivity for COVID-19 up to 45% by the end of April 2020 in frontline HCWs. The study revealed a concerning lack of healthcare seeking in respondents with significant red flag symptoms (severe breathlessness, hypoxia). This study also highlighted anosmia as a key symptom of COVID-19 early in the pandemic, prior to this symptom being more widely recognised as a feature of COVID-19

Compliance with Australian stroke guideline recommendations for outdoor mobility and transport training by post-inpatient rehabilitation services: an observational cohort study

Background: Community participation is often restricted after stroke, due to reduced confidence and outdoor mobility. Australian clinical guidelines recommend that specific evidence-based interventions be delivered to target these restrictions, such as multiple escorted outdoor journeys. The aim of this study was to describe post-inpatient outdoor mobility and transport training delivered to stroke survivors in New South Wales, Australia and whether therapy differed according to type, sector or location of service provider. Methods: Using an observational retrospective cohort study design, 24 rehabilitation service providers were audited. Provider types included outpatient (n = 8), day therapy (n = 9), home-based rehabilitation (n = 5) and transitional aged care services (TAC, n = 2). Records of 15 stroke survivors who had received post-hospital rehabilitation were audited per service, for wait time, duration, amount of therapy and outdoor-related therapy. Results: A total of 311 records were audited. Median wait time for post-hospital therapy was 13 days (IQR, 5–35). Median duration of therapy was 68 days (IQR, 35–109), consisting of 11 sessions (IQR 4–19). Overall, a median of one session (IQR 0–3) was conducted outdoors per person. Outdoor-related therapy was similar across service providers,except that TAC delivered an average of 5.4 more outdoor-related sessions (95 % CI 4.4 to 6.4), and 3.5 more outings into public streets (95 % CI 2.8 to 4.3) per person, compared to outpatient services. Conclusion: The majority of service providers in the sample delivered little evidence-based outdoor mobility and travel training per stroke participant, as recommended in national stroke guidelines

Arm-in-cage testing of natural human-derived mosquito repellents

BACKGROUND: Individual human subjects are differentially attractive to mosquitoes and other biting insects. Previous investigations have demonstrated that this can be attributed partly to enhanced production of natural repellent chemicals by those individuals that attract few mosquitoes in the laboratory. The most important compounds in this respect include three aldehydes, octanal, nonanal and decanal, and two ketones, 6-methyl-5-hepten-2-one and geranylacetone [(E)-6,10-dimethylundeca-5,9-dien-2-one]. In olfactometer trials, these compounds interfered with attraction of mosquitoes to a host and consequently show promise as novel mosquito repellents. METHODS: To test whether these chemicals could provide protection against mosquitoes, laboratory repellency trials were carried out to test the chemicals individually at different concentrations and in different mixtures and ratios with three major disease vectors: Anopheles gambiae, Culex quinquefasciatus and Aedes aegypti. RESULTS: Up to 100% repellency was achieved depending on the type of repellent compound tested, the concentration and the relative composition of the mixture. The greatest effect was observed by mixing together two compounds, 6-methyl-5-hepten-2-one and geranylacetone in a 1:1 ratio. This mixture exceeded the repellency of DEET when presented at low concentrations. The repellent effect of this mixture was maintained over several hours. Altering the ratio of these compounds significantly affected the behavioural response of the mosquitoes, providing evidence for the ability of mosquitoes to detect and respond to specific mixtures and ratios of natural repellent compounds that are associated with host location. CONCLUSION: The optimum mixture of 6-methyl-5-hepten-2-one and geranylacetone was a 1:1 ratio and this provided the most effective protection against all species of mosquito tested. With further improvements in formulation, selected blends of these compounds have the potential to be exploited and developed as human-derived novel repellents for personal protection

Authors' Responses to Peer Review of “Telerehabilitation for People With Physical Disabilities and Movement Impairment: A Survey of United Kingdom Practitioners”

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Telerehabilitation for People With Physical Disabilities and Movement Impairment: A Survey of United Kingdom Practitioners

Background Telerehabilitation is a feasible and potentially effective alternative to face-to-face rehabilitation. However, specific guidance, training, and support for practitioners who undertake remote assessments in people with physical disabilities and movement impairment are limited. Objective The aims of this survey of United Kingdom–based health and social care practitioners were to explore experiences, assess training needs, and collate ideas on best practices in telerehabilitation for physical disabilities and movement impairment. The aim will be to use the findings to inform a practical tool kit and training package for telerehabilitation use. Methods UK rehabilitation practitioners were invited to complete an online questionnaire from November to December 2020. Opportunity and snowball sampling were used to recruit participants from professional and educational networks, special interest groups, and via social media. Closed questionnaire items were analyzed using descriptive statistics. Qualitative inductive analysis using NVivo was used for open responses. Results There were 247 respondents, of which 177 (72%) were physiotherapists and occupational therapists. Most (n=207, 84%) had used video-based consultations (typically supported by telephone and email), and the use of this method had increased in frequency since the COVID-19 pandemic. Practitioners perceived telerehabilitation positively overall and recognized benefits for patients including a reduced infection risk, convenience and flexibility, and reduced travel and fatigue. Common obstacles were technology related (eg, internet connection), practical (eg, difficulty positioning the camera), patient related (eg, health status), practitioner related (eg, lack of technical skills), and organizational (eg, lack of access to technology). Support from family members or carers was a major facilitator for successful remote consultations. Of the 207 respondents who had used video-based consultations, 103 (50%) had assessed physical impairments using this method, 107 (52%) had assessed physical function, and 121 (59%) had used patient-reported outcome measures. Although practitioners generally felt confident in delivering video-based consultations, they felt less proficient in undertaking remote physical assessments, expressing concerns about validity, reliability, and safety. Only 46 of the 247 (19%) respondents had received any training in telerehabilitation or video consultations, and some felt they were “feeling their way in the dark.” Practitioners desired training and guidance on physical assessment tools suitable for remote use, when to use video-based consultations or alternative methods, governance issues, digital platforms, and signposting to digital skills training for themselves and their patients. Conclusions In response to the COVID-19 pandemic, practitioners rapidly adopted telerehabilitation for people with physical disabilities and movement impairment. However, there are technical, practical, and organizational obstacles to overcome, and a clear need for improved guidance and training in remote physical assessments. The findings of this survey will inform the development of a tool kit of resources and a training package for the current and future workforce in telerehabilitation. </jats:sec

Cooperative learning in the first year of undergraduate medical education

<p>Abstract</p> <p>Background</p> <p>Despite extensive research data indicating that cooperative learning promotes higher achievement, the creation of positive relationships, and greater psychological health for students at all levels in their education, cooperative learning as a teaching strategy is still underutilized in undergraduate medical education.</p> <p>Methods</p> <p>A cooperative learning task was introduced as part of the mandatory first Year undergraduate Pathology course. The task was to create an 8.5" × 11" poster summary of pre-assigned content in self-chosen groups of four or five students. On the designated "Poster Day," the posters were displayed and evaluated by the students using a group product evaluation. Students also completed an individual group process reflection survey. An objective evaluation of their understanding was gauged at the midterm examination by specific content-related questions.</p> <p>Results</p> <p>Majority (91–96%) of students judged the group products to be relevant, effective, easy-to-understand, and clearly communicated. The majority of the students (90–100%) agreed that their group process skills of time management, task collaboration, decision-making and task execution were effective in completing this exercise. This activity created a dynamic learning environment as was reflected in the students' positive, professional discussion, and evaluation of their posters. The content-related questions on the midterm examination were answered correctly by 70–92% of the students. This was a mutually enriching experience for the instructor and students.</p> <p>Conclusion</p> <p>These findings demonstrate that cooperative learning as a teaching strategy can be effectively incorporated to address both content <it>and </it>interpersonal skill development in the early years of undergraduate medical education.</p

Cd(II) and Pb(II) complexes of the polyether ionophorous antibiotic salinomycin

<p>Abstract</p> <p>Background</p> <p>The natural polyether ionophorous antibiotics are used for the treatment of coccidiosis in poultry and ruminants. They are effective agents against infections caused by Gram-positive microorganisms. On the other hand, it was found that some of these compounds selectively bind lead(II) ions in <it>in vivo </it>experiments, despite so far no Pb(II)-containing compounds of defined composition have been isolated and characterized. To assess the potential of polyether ionophores as possible antidotes in the agriculture, a detailed study on their <it>in vitro </it>complexation with toxic metal ions is required. In the present paper we report for the first time the preparation and the structure elucidation of salinomycin complexes with ions of cadmium(II) and lead(II).</p> <p>Results</p> <p>New metal(II) complexes of the polyether ionophorous antibiotic salinomycin with Cd(II) and Pb(II) ions were prepared and structurally characterized by IR, FAB-MS and NMR techniques. The spectroscopic information and elemental analysis data reveal that sodium salinomycin (SalNa) undergoes a reaction with heavy metal(II) ions to form [Cd(Sal)₂(H₂O)₂] (<b>1</b>) and [Pb(Sal)(NO₃)] (<b>2</b>), respectively. Abstraction of sodium ions from the cavity of the antibiotic is occurring during the complexation reaction. Salinomycin coordinates with cadmium(II) ions as a bidentate monoanionic ligand through the deprotonated carboxylic moiety and one of the hydroxyl groups to yield <b>1</b>. Two salinomycin anions occupy the equatorial plane of the Cd(II) center, while two water molecules take the axial positions of the inner coordination sphere of the metal(II) cation. Complex <b>2 </b>consists of monoanionic salinomycin acting in polydentate coordination mode in a molar ratio of 1: 1 to the metal ion with one nitrate ion for charge compensation.</p> <p>Conclusion</p> <p>The formation of the salinomycin heavy metal(II) complexes indicates a possible antidote activity of the ligand in case of chronic/acute intoxications likely to occur in the stock farming.</p

Arabidopsis thaliana MIRO1 and MIRO2 GTPases Are Unequally Redundant in Pollen Tube Growth and Fusion of Polar Nuclei during Female Gametogenesis

MIRO GTPases have evolved to regulate mitochondrial trafficking and morphology in eukaryotic organisms. A previous study showed that T-DNA insertion in the Arabidopsis MIRO1 gene is lethal during embryogenesis and affects pollen tube growth and mitochondrial morphology in pollen, whereas T-DNA insertion in MIRO2 does not affect plant development visibly. Phylogenetic analysis of MIRO from plants revealed that MIRO 1 and 2 orthologs in dicots cluster in two separate groups due to a gene/genome duplication event, suggesting that functional redundancy may exists between the two MIRO genes. To investigate this possibility, we generated miro1(+/−)/miro2-2(−/−) plants. Compared to miro1(+/−) plants, the miro1(+/−)/miro2-2(−/−) plants showed increased segregation distortion. miro1(+/−)/miro2-2(−/−) siliques contained less aborted seeds, but more than 3 times the number of undeveloped ovules. In addition, reciprocal crosses showed that co-transmission through the male gametes was nearly absent, whereas co-transmission through the female gametes was severely reduced in miro1(+/−)/miro2-2(−/−) plants. Further investigations revealed that loss of MIRO2 (miro2(−/−)) function in the miro1(+/−) background enhanced pollen tube growth defects. In developing miro1(+/−)/miro2(−/−) embryo sacs, fusion of polar nuclei was further delayed or impaired compared to miro1 plants. This phenotype has not been reported previously for miro1 plants and coincides with studies showing that defects in some mitochondria-targeted genes results in the same phenotype. Our observations show that loss of function in MIRO2 in a miro1(+/−) background enhances the miro1(+/−) phenotype significantly, even though miro2(−/−) plants alone does not display any phenotypes. Based on these findings, we conclude that MIRO1 and MIRO2 are unequally redundant and that a proportion of the miro1(+/−)/miro2(−/−) plants haploid gametes displays the complete null phenotype of MIRO GTPase function at key developmental stages