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This article describes a community collaborative project, "I've got yer back," that utilized the craft of needle felting to raise awareness and develop understanding of the anatomy of the human spine. The project took place in 2023 and engaged with participants from across the United Kingdom and abroad and its completion was timed to coincide with National Back Health Awareness week in October 2023. We describe the process of creating a vertebra using needle felt and examine how the particularities of the process and the use of the sense of touch helped participants notice and understand the complex form of the human vertebra. We consider how the project encompassed creative processes of hands-on learning to enhance knowledge about this aspect of human anatomy. We discuss how the project evolved to include public and academic participation in a shared goal and argue for the effectiveness of seemingly simple and straightforward art or craft workshops in teaching relatively complex science. The article includes detailed feedback from participants who reflect on the process of learning through making and how it went on to affect individuals in very different, and sometimes very personal, ways.

Neuroanatomy is a notoriously challenging subject for medical students to learn. Due to the coronavirus disease-19 (COVID-19) pandemic, anatomical education transitioned to an online format. We assessed student performance in, and attitudes toward, an online neuroanatomy assessment compared to an in-person equivalent, as a marker of the efficacy of remote neuroanatomy education. Participants in the National Undergraduate Neuroanatomy Competition (NUNC) 2021 undertook two online examinations: a neuroanatomically themed multiple-choice question paper and anatomy spotter. Students completed pre- and post-examination questionnaires to gauge their attitudes toward the online competition and prior experience of online anatomical teaching/assessment. To evaluate performance, we compared scores of students who sat the online (2021) and in-person (2017) examinations, using 12 identical neuroradiology questions present in both years. Forty-six percent of NUNC 2021 participants had taken an online anatomy examination in the previous 12 months, but this did not impact examination performance significantly (p > 0.05). There was no significant difference in examination scores between in-person and online examinations using the 12 neuroradiology questions (p = 0.69). Fifty percent of participants found the online format less enjoyable, with 63% citing significantly fewer networking opportunities. The online competition was less stressful for 55% of participants. This study provides some evidence to suggest that student performance is not affected when undertaking online examinations and proposes that online neuroanatomy teaching methods, particularly for neuroradiology, may be equally as effective as in-person approaches within this context. Participants perceived online examinations as less stressful but raised concerns surrounding the networking potential and enjoyment of online events.

CASE SUMMARY: A 10-year-old male castrated domestic shorthair cat was presented for evaluation of a 3-day history of increased inspiratory effort. The cat had received prednisolone 1 mg/kg PO q24h for 1 year due to chronic diarrhea. On physical examination, the patient exhibited severe stridor, intermittent open-mouth breathing and bilateral mucopurulent nasal discharge. Subcutaneous emphysema was palpated over the dorsal cervical region. Mild hypoventilation (PvCO2 55.1 mmHg; approximate reference interval 35-45 mmHg) was identified. Cervicothoracic radiographs showed marked gas tracking within cervical soft tissues with concurrent laryngeal thickening, pulmonary nodules, a bronchial pulmonary pattern, pneumomediastinum and aerophagia. The cat was hospitalized and treated overnight with oxygen and intravenous fluid therapy before anesthesia the next day. On laryngoscopy, a large tracheal mass was observed arising from the right subglottic region and was removed using biopsy forceps. CT revealed an additional mass at the level of the tracheal bifurcation causing marked luminal narrowing of the trachea and proximal main bronchi. The cat made a good initial recovery, although moderate stridor persisted. Five days later, the cat was re-examined due to recurrence of respiratory distress and orthopnea, and the owner elected euthanasia. Histopathology revealed severe nodular obstructive eosinophilic plasmacytic laryngotracheitis with intranuclear inclusion bodies positive for feline herpesvirus-1 on immunohistochemistry. RELEVANCE AND NOVEL INFORMATION: This report describes the presentation and management of a cat with respiratory distress secondary to intratracheal eosinophilic masses caused by feline herpesvirus-1. Although the outcome was ultimately unsatisfactory, to the authors knowledge, this clinical presentation has not been previously reported.

This Meta-Aggregative (MA) Qualitative Evidence Synthesis (QES) identified, investigated, and critically appraised examples of 'quality' Teacher Critical Reflection (TCR) in recent peer-reviewed research. The key question guiding the synthesis of literature was, How is teacher critical reflection evidenced, justified, and communicated in peer-reviewed research? The synthesis detected the importance of TCR in supporting quality teacher practice in early childhood and primary school settings. The MA element guided the choice of articles and the QES identified evidence of the intricacies of teacher critical reflection. The MA QES provides insights into sustainable and purposeful TCR. Thirteen studies conducted between 2013 and 2019 met the requirements of a four-phased MA QES and were critically appraised to inform the synthesis. Recommendations derived from this review include the importance of identifying the objectives of TCR, TCR as part of teacher identity and its impact on TCR, the significant role that social collaboration plays in TCR, and the tools that support successful TCR.

Abstract Introduction Many stroke survivors do not receive optimal levels of personalised therapy to support their recovery. Use of technology for stroke rehabilitation has increased in recent years to help minimise gaps in service provision. Markerless motion capture technology is currently being used for musculoskeletal and occupational health screening and could offer a means to provide personalised guidance to stroke survivors struggling to access rehabilitation. Aims This study considered context, stakeholders, and key uncertainties surrounding the use of markerless motion capture technology in community stroke rehabilitation from the perspectives of stroke survivors and physiotherapists with a view to adapting an existing intervention in a new context. Methods Three focus groups were conducted with eight stroke survivors and five therapists. Data were analysed using reflexive thematic analysis. Results Five themes were identified: limited access to community care; personal motivation; pandemic changed rehabilitation practice; perceptions of technology; and role of markerless technology for providing feedback. Conclusions Participants identified problems associated with the access of community stroke rehabilitation, exacerbated by Covid-19 restrictions. Participants were positive about the potential for the use of markerless motion capture technology to support personalised, effective stroke rehabilitation in the future, providing it is developed to meet stroke survivor specific needs.

Abstract Wheat is an important source of minerals for human nutrition and increasing grain mineral content can contribute to reducing mineral deficiencies. Here, we identify QTLs for mineral micronutrients in grain of wheat by determining the contents of six minerals in a total of eleven sample sets of three biparental populations from crosses between A.E. Watkins landraces and cv. Paragon. Twenty-three of the QTLs are mapped in two or more sample sets, with LOD scores above five in at least one set with the increasing alleles for sixteen of the QTLs being present in the landraces and seven in Paragon. Of these QTLs, the number for each mineral varies between three and five and they are located on 14 of the 21 chromosomes, with clusters on chromosomes 5A (four), 6A (three), and 7A (three). The gene content within 5 megabases of DNA on either side of the marker for the QTL with the highest LOD score is determined and the gene responsible for the strongest QTL (chromosome 5A for Ca) identified as an ATPase transporter gene (TraesCS5A02G543300) using mutagenesis. The identification of these QTLs, together with associated SNP markers and candidate genes, will facilitate the improvement of grain nutritional quality.

Abstract Metabolic reprogramming and energetic rewiring are hallmarks of cancer that fuel disease progression and facilitate therapy evasion. The remodelling of oxidative phosphorylation and enhanced lipogenesis have previously been characterised as key metabolic features of prostate cancer (PCa). Recently, succinate-dependent mitochondrial reprogramming was identified in high-grade prostate tumours, as well as upregulation of the enzymes associated with branched-chain amino acid (BCAA) catabolism. In this study, we hypothesised that the degradation of the BCAAs, particularly valine, may play a critical role in anapleurotic refuelling of the mitochondrial succinate pool, as well as the maintenance of intracellular lipid metabolism. Through the suppression of BCAA availability, we report significantly reduced lipid content, strongly indicating that BCAAs are important lipogenic fuels in PCa. This work also uncovered a novel compensatory mechanism, whereby fatty acid uptake is increased in response to extracellular valine deprivation. Inhibition of valine degradation via suppression of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) resulted in a selective reduction of malignant prostate cell proliferation, decreased intracellular succinate and impaired cellular respiration. In combination with a comprehensive multi-omic investigation that incorporates next-generation sequencing, metabolomics, and high-content quantitative single-cell imaging, our work highlights a novel therapeutic target for selective inhibition of metabolic reprogramming in PCa.

Objectives: To describe member adherence to a mail-based, health insurer-sponsored gap closure program for colorectal cancer (CRC) screening using multi-target stool DNA (mt-sDNA; Cologuard ® ) tests. Methods: Combined patient data from Exact Sciences Laboratories LLC and data from mass-mailed mt-sDNA orders placed by a large Medicare Advantage Insurance Plan were analyzed (03/01/2023-06/30/2023). Adherence and time to test return were the primary and secondary outcomes, respectively. Their association with patient characteristics was evaluated using multivariable regression. Results: Among the 3201 member-patients included (86.6% aged 65-75 years; 58.7% female), adherence rate was 49.4%, and mean time to test return was 25.5 days. After multivariable adjustment, the odds of test return were significantly higher among 65- to 75-year-olds (odds ratio [OR] = 1.59 relative to 45- to 64-year-olds), those living in small towns (OR = 1.43 relative to metropolitan-located individuals), and with digital outreach via both SMS and email (OR = 4.31 relative to no digital outreach). Time to test return was shorter in 65- to 75-year-olds than in 45- to 64-year-olds and was not associated with other patient characteristics. Conclusions: Mass-mailed mt-sDNA tests for CRC screening were associated with an overall adherence rate of about 50% in this Medicare Advantage population, with higher likelihood of test return among patients receiving digital outreach.

The Nix-TB clinical trial evaluated a new 6 month regimen containing three oral drugs; bedaquiline (B), pretomanid (Pa), and linezolid (L) (BPaL regimen) for the treatment of tuberculosis (TB). This regimen achieved remarkable results as almost 90% of the multidrug-resistant or extensively drug-resistant TB participants were cured but many patients also developed severe adverse events (AEs). The AEs were associated with the long-term administration of the protein synthesis inhibitor linezolid. Spectinamide 1599 is also a protein synthesis inhibitor of Mycobacterium tuberculosis with an excellent safety profile, but it lacks oral bioavailability. Here, we propose to replace L in the BPaL regimen with spectinamide (S) administered via inhalation and we demonstrate that inhaled spectinamide 1599, combined with BPa ––BPaS regimen––has similar efficacy to that of the BPaL regimen while simultaneously avoiding the L-associated AEs. The BPaL and BPaS regimens were compared in the BALB/c and C3HeB/FeJ murine chronic TB efficacy models. After 4-weeks of treatment, both regimens promoted equivalent bactericidal effects in both TB murine models. However, treatment with BPaL resulted in significant weight loss and the complete blood count suggested the development of anemia. These effects were not similarly observed in mice treated with BPaS. BPaL and BPa, but not the BPaS treatment, also decreased myeloid to erythroid ratio suggesting the S in the BPaS regimen was able to recover this effect. Moreover, the BPaL also increased concentration of proinflammatory cytokines in bone marrow compared to mice receiving BPaS regimen. These combined data suggest that inhaled spectinamide 1599 combined with BPa is an effective TB regimen without L-associated AEs.

BackgroundThe prevalence of chronic kidney disease (CKD) is high in general populations around the world. Targeted testing and screening for CKD are often conducted to help identify individuals that may benefit from treatment to ameliorate or prevent their disease progression.AimsThis systematic review examines the methods used in economic evaluations of testing and screening in CKD, with a particular focus on whether test accuracy has been considered, and how analysis has incorporated issues that may be important to the patient, such as the impact of testing on quality of life and the costs they incur.MethodsArticles that described model-based economic evaluations of patient testing interventions focused on CKD were identified through the searching of electronic databases and the hand searching of the bibliographies of the included studies.ResultsThe initial electronic searches identified 2,671 papers of which 21 were included in the final review. Eighteen studies focused on proteinuria, three evaluated glomerular filtration rate testing and one included both tests. The full impact of inaccurate test results was frequently not considered in economic evaluations in this setting as a societal perspective was rarely adopted. The impact of false positive tests on patients in terms of the costs incurred in re-attending for repeat testing, and the anxiety associated with a positive test was almost always overlooked. In one study where the impact of a false positive test on patient quality of life was examined in sensitivity analysis, it had a significant impact on the conclusions drawn from the model.ConclusionFuture economic evaluations of kidney function testing should examine testing and monitoring pathways from the perspective of patients, to ensure that issues that are important to patients, such as the possibility of inaccurate test results, are properly considered in the analysis.

Disseminated intravascular coagulation following melarsomine therapy for Dirofilaria immitis (D. immitis) is reported in a 9-year-old female intact pit bull-type dog. The dog had been diagnosed with D. immitis (antigen and microfilaria positive) and treated with imidacloprid, moxidectin, doxycycline and 3 doses of melarsomine over a 92-day period. Seven days after the third melarsomine injection, the patient was presented to her family veterinarian due to right pelvic limb swelling. Prothrombin and activated partial thromboplastin times were prolonged beyond the detectable range. Treatment included vitamin K1 and fresh frozen plasma (FFP) prior to referral to the authors' institution. At this time the patient remained coagulopathic. Further investigations included thoracic radiographs, abdominal ultrasound and an echocardiogram. The patient was administered multiple units of packed red blood cells and FFP, sildenafil, dexamethasone SP, aminocaproic acid and vitamin K1. Repeat CBC approximately 20 h after admission showed persistent anemia and thrombocytopenia. Despite ongoing administration of FFP, a repeat coagulation panel showed worsening of the coagulopathy with prothrombin time of 84.2s [reference interval (RI) 7.0-9.3s], activated partial thromboplastin time >140s (RI 10.4-12.9s) and fibrinogen

Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiation in vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis (Calr+/-), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS.

Abstract In recent decades, the role of tumor biomechanics on cancer cell behavior at the primary site has been increasingly appreciated. However, the effect of primary tumor biomechanics on the latter stages of the metastatic cascade, such as metastatic seeding of secondary sites and outgrowth remains underappreciated. This work sought to address this in the context of triple negative breast cancer (TNBC), a cancer type known to aggressively disseminate at all stages of disease progression. Using mechanically tuneable model systems, mimicking the range of stiffness's typically found within breast tumors, it is found that, contrary to expectations, cancer cells exposed to softer microenvironments are more able to colonize secondary tissues. It is shown that heightened cell survival is driven by enhanced metabolism of fatty acids within TNBC cells exposed to softer microenvironments. It is demonstrated that uncoupling cellular mechanosensing through integrin β1 blocking antibody effectively causes stiff primed TNBC cells to behave like their soft counterparts, both in vitro and in vivo. This work is the first to show that softer tumor microenvironments may be contributing to changes in disease outcome by imprinting on TNBC cells a greater metabolic flexibility and conferring discrete cell survival advantages.

Patients referred by their general practitioner (GP) with a definite diagnosis, for example, recurrent sore throat for consideration of tonsillectomy in adults, may wait for months without receiving any further clinical information from the hospital until their outpatient consultation. Prompt provision of condition-specific information after referral has received little attention despite considerable potential to enhance patients’ understanding, thereby relieving uncertainty and anxiety, and facilitating shared decision-making.This study aimed to report the experience of patients with recurrent tonsillitis who had been sent a booklet outlining the benefits and risks of tonsillectomy immediately after GP referral.Greater Glasgow and Clyde Health Board received 218 referrals of patients aged 16–40 to discuss tonsillectomy between January and August 2022. Every patient was sent a 16-page booklet by post and given the choice to opt in for a consultation.165 (76%) patients opted in, and 53 (24%) did not. Feedback was obtained from 143 patients (66%) from both groups. 99% found the information booklet easy to understand, 97% would recommend it to a friend with recurrent tonsillitis, 93% felt their questions had been answered and 92% believed it helped them to decide whether to proceed with tonsillectomy. Socioeconomic deprivation did not influence the outcome.In conclusion, most patients found provision of clinical information immediately after vetting of the referral to be beneficial, irrespective of whether they opted in for a consultation. This concept has broad applicability across all specialties, and the principles can be readily adopted and adapted by clinicians and managers in local units.

Chickpea (Cicer arietinum L.) is a very important food legume and needs improved drought tolerance for higher seed production in dry environments. The aim of this study was to determine diversity and genetic polymorphism in zinc finger knuckle genes with CCHC domains and their functional analysis for practical improvement of chickpea breeding. Two CaZF-CCHC genes, Ca04468 and Ca07571, were identified as potentially important candidates associated with plant responses to drought and dehydration. To study these genes, various methods were used including Sanger sequencing, DArT (Diversity array technology) and molecular markers for plant genotyping, gene expression analysis using RT-qPCR, and associations with seed-related traits in chickpea plants grown in field trials. These genes were studied for genetic polymorphism among a set of chickpea accessions, and one SNP was selected for further study from four identified SNPs between the promoter regions of each of the two genes. Molecular markers were developed for the SNP and verified using the ASQ and CAPS methods. Genotyping of parents and selected breeding lines from two hybrid populations, and SNP positions on chromosomes with haplotype identification, were confirmed using DArT microarray analysis. Differential expression profiles were identified in the parents and the hybrid populations under gradual drought and rapid dehydration. The SNP-based genotypes were differentially associated with seed weight per plant but not with 100 seed weight. The two developed and verified SNP molecular markers for both genes, Ca04468 and Ca07571, respectively, could be used for marker-assisted selection in novel chickpea cultivars with improved tolerance to drought and dehydration.

Most genes in photosynthetic organisms remain functionally uncharacterized. Here, using a barcoded mutant library of the model eukaryotic alga Chlamydomonas reinhardtii, we determined the phenotypes of more than 58,000 mutants under more than 121 different environmental growth conditions and chemical treatments. A total of 59% of genes are represented by at least one mutant that showed a phenotype, providing clues to the functions of thousands of genes. Mutant phenotypic profiles place uncharacterized genes into functional pathways such as DNA repair, photosynthesis, the CO2-concentrating mechanism and ciliogenesis. We illustrate the value of this resource by validating phenotypes and gene functions, including three new components of an actin cytoskeleton defense pathway. The data also inform phenotype discovery in land plants; mutants in Arabidopsis thaliana genes exhibit phenotypes similar to those we observed in their Chlamydomonas homologs. We anticipate that this resource will guide the functional characterization of genes across the tree of life.

Abstract Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. Lastly, TLR7 mRNA is increased in pre-existing datasets from patients with COPD, while TLR7+ mast cells are increased in COPD lungs and associated with severity of COPD. Our results thus support roles for TLR7 in mediating emphysema and COPD through mast cell activity, and may implicate TLR7 as a potential therapeutic target.

Abstract Background Shoot branching of flowering plants exhibits phenotypic plasticity and variability. This plasticity is determined by the activity of axillary meristems, which in turn is influenced by endogenous and exogenous cues such as nutrients and light. In many species, not all buds on the main shoot develop into branches despite favorable growing conditions. In petunia, basal axillary buds (buds 1–3) typically do not grow out to form branches, while more apical axillary buds (buds 6 and 7) are competent to grow. Results The genetic regulation of buds was explored using transcriptome analyses of petunia axillary buds at different positions on the main stem. To suppress or promote bud outgrowth, we grew the plants in media with differing phosphate (P) levels. Using RNA-seq, we found many (> 5000) differentially expressed genes between bud 6 or 7, and bud 2. In addition, more genes were differentially expressed when we transferred the plants from low P to high P medium, compared with shifting from high P to low P medium. Buds 6 and 7 had increased transcript abundance of cytokinin and auxin-related genes, whereas the basal non-growing buds (bud 2 and to a lesser extent bud 3) had higher expression of strigolactone, abscisic acid, and dormancy-related genes, suggesting the outgrowth of these basal buds was actively suppressed. Consistent with this, the expression of ABA associated genes decreased significantly in apical buds after stimulating growth by switching the medium from low P to high P. Furthermore, comparisons between our data and transcriptome data from other species suggest that the suppression of outgrowth of bud 2 was correlated with a limited supply of carbon to these axillary buds. Candidate genes that might repress bud outgrowth were identified by co-expression analysis. Conclusions Plants need to balance growth of axillary buds into branches to fit with available resources while allowing some buds to remain dormant to grow after the loss of plant parts or in response to a change in environmental conditions. Here we demonstrate that different buds on the same plant with different developmental potentials have quite different transcriptome profiles.