Introducing the halophyte Salicornia europaea to investigate combined impact of salt and tidal submergence conditions.

Tolerance mechanisms to single abiotic stress events are being investigated in different plant species, but how plants deal with multiple stress factors occurring simultaneously is still poorly understood. Here, we introduce Salicornia europaea as a species with an extraordinary tolerance level to both flooding and high salt concentrations. Plants exposed to 0.5MNaCl (mimicking sea water concentrations) grew larger than plants not exposed to salt. Adding more salt reduced growth, but concentrations up to 2.5MNaCl were not lethal. Regular tidal flooding with salt water (0.5MNaCl) did not affect growth or chlorophyll fluorescence, whereas continuous flooding stopped growth while plants survived. Quantitative polymerase chain reaction (qPCR) analysis of plants exposed to 1% oxygen in air revealed induction of selected hypoxia responsive genes, but these genes were not induced during tidal flooding, suggesting that S. europaea did not experience hypoxic stress. Indeed, plants were able to transport oxygen into waterlogged soil. Interestingly, sequential exposure to salt and hypoxic air changed the expression of several but not all genes as compared to their expression upon hypoxia only, demonstrating the potential to use S . europaea to investigate signalling-crosstalk between tolerance reactions to multiple environmental perturbations.

Fermented biochar has a markedly different effect on fate of pesticides in soil than compost, straw, and a mixed biochar-product.

Current knowledge about how biochars affect the fate of pesticides in soil is based on studies that used pure biochars. After finding that an additional biological post-pyrolysis treatment, such as co-composting or lactic fermentation, is required for biochars for superior performance in temperate arable soils, a knowledge gap formed of how such further processed biochar products would affect the fate of pesticides in soil. This study compared the effects of a novel fermented biochar alone or mixed with biogas residues on the fate of two pesticides, 4-chloro-2-methylphenoxyacetic acid (MCPA) and metalaxyl-M, in a temperate arable soil to the traditional organic amendments wheat straw and compost. The fate of 14C-labeled MCPA was markedly affected in different ways. Fermented biochar effectively reduced the water-extractability and mineralization due to adsorption that was comparable to adsorption strengths reported for pure biochars. However, this effect was weak for the biochar mixed with biogas residues. Straw reduced water-extractable amounts due to increased biodegradation and formation of likely biogenic non-extractable residues of MCPA. In contrast, compost decelerated mineralization and increased the water solubility of the MCPA residues due to released dissolved organic matter. The amendments' effects were minor regarding 14C-metalaxyl-M, except for the fermented biochar which again reduced water-extractability and delayed degradation due to adsorption. Thus, the effects of the organic amendments differed for the two pesticide compounds with only the fermented biochar's effect being similar for both. However, this effect was no longer present in the mixed product containing 20% biochar. Our findings clearly show that biologically treated biochar-containing products can affect the fate of pesticides in soil very differently, also when compared to traditional organic amendments. Such impacts and their desirable and undesirable ecotoxicological implications need to be considered before the large-scale application of biochars to temperate arable soils.

Prevalence of incidental distal biceps signal changes on magnetic resonance imaging.

BACKGROUND: Knowledge of the base rate of signal changes consistent with distal biceps tendinopathy on magnetic resonance imaging (MRI) has the potential to influence strategies for diagnosis and treatment of people that present with elbow pain. The aim of this study is to measure the prevalence of distal biceps tendon signal changes on MRIs of the elbow by indication for imaging. METHODS: MRI data for 1,306 elbows were retrospectively reviewed for mention of signal change in distal biceps tendon. The reports were sorted by indication. RESULTS: Signal changes consistent with distal biceps tendinopathy were noted in 197 of 1,306 (15%) patients, including 34% of patients with biceps pain, 14% of patients with unspecified pain, and 8% of patients with a specific non-biceps indication. Distal biceps tendon changes noted on radiology reports were associated with older age, male sex, and radiologists with musculoskeletal fellowship training. CONCLUSIONS: The finding that distal biceps MRI signal changes consistent with tendinopathy are common even in asymptomatic elbows reduces the probability that symptoms correlate with pathology on imaging. The accumulation of signal changes with age, also independent of symptoms, suggests that tendon pathology persists after symptoms resolve, that some degree of distal biceps tendinopathy is common in a human lifetime, and that tendinopathy may often be accommodated without seeking care. Level of evidence: IV.

Correlation of the I-HaND Scale with Other Musculoskeletal Patient-Reported Outcome Measurement Scores.

Background Experiments can determine if nerve-specific patient-reported outcome measures (PROMs) can outperform regional or condition-specific PROMs. We compared a nerve-specific PROM of the upper extremity, the Impact of Hand Nerve Disorders (I-HaND) scale, to other validated measures quantifying activity intolerance and sought to assess interquestionnaire correlations and factors independently associated with activity intolerance and pain intensity. Methods One hundred and thirty patients with any upper extremity nerve-related condition completed measures of demographics, psychological limitations, quality of life, activity intolerance, and pain intensity. To quantify activity intolerance, we used the I-HaND, Patient-Reported Outcomes Measurement Information System Physical Function Upper Extremity, and Disabilities of the Arm, Shoulder and Hand short form. Results Strong interquestionnaire correlations were found between the activity intolerance measures ( r between 0.70 and 0.91). Multivariable analysis revealed that greater activity intolerance and greater pain intensity correlated most with greater symptoms of depression on all scales, with symptoms of depression accounting for 53 to 84% of the variability in the PROMs. Conclusion There is no clear advantage of the nerve-specific I-HaND over shorter, regional PROMs, perhaps because they are all so closely tied to mental health. Unless an advantage relating to responsiveness to treatment is demonstrated, we support using a brief arm-specific PROM for all upper extremity conditions. Level of Evidence Level II; Prognostic.

The Arabidopsis thaliana onset of leaf death 12 mutation in the lectin receptor kinase P2K2 results in an autoimmune phenotype.

BACKGROUND: Plant immunity relies on the perception of immunogenic signals by cell-surface and intracellular receptors and subsequent activation of defense responses like programmed cell death. Under certain circumstances, the fine-tuned innate immune system of plants results in the activation of autoimmune responses that cause constitutive defense responses and spontaneous cell death in the absence of pathogens. RESULTS: Here, we characterized the onset of leaf death 12 (old12) mutant that was identified in the Arabidopsis accession Landsberg erecta. The old12 mutant is characterized by a growth defect, spontaneous cell death, plant-defense gene activation, and early senescence. In addition, the old12 phenotype is temperature reversible, thereby exhibiting all characteristics of an autoimmune mutant. Mapping the mutated locus revealed that the old12 phenotype is caused by a mutation in the Lectin Receptor Kinase P2-TYPE PURINERGIC RECEPTOR 2 (P2K2) gene. Interestingly, the P2K2 allele from Landsberg erecta is conserved among Brassicaceae. P2K2 has been implicated in pathogen tolerance and sensing extracellular ATP. The constitutive activation of defense responses in old12 results in improved resistance against Pseudomonas syringae pv. tomato DC3000. CONCLUSION: We demonstrate that old12 is an auto-immune mutant and that allelic variation of P2K2 contributes to diversity in Arabidopsis immune responses.

Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial.

INTRODUCTION: Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4-8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy. Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is anticipated to reduce radiation-induced toxicity and enable radiotherapy dose escalation. This trial aims to establish the maximum tolerated dose (MTD) of dose-escalated SCRT using online adaptive MRgRT. METHODS AND ANALYSIS: The preRADAR is a multicentre phase I trial with a 6+3 dose-escalation design. Patients with intermediate-risk rectal cancer (cT3c-d(MRF-)N1M0 or cT1-3(MRF-)N1M0) interested in organ preservation are eligible. Patients are treated with a radiotherapy boost of 2×5 Gy (level 0), 3×5 Gy (level 1), 4×5 Gy (level 2) or 5×5 Gy (level 3) on the gross tumour volume in the week following standard SCRT using online adaptive MRgRT. The trial starts on dose level 1. The primary endpoint is the MTD based on the incidence of dose-limiting toxicity (DLT) per dose level. DLT is a composite of maximum one in nine severe radiation-induced toxicities and maximum one in three severe postoperative complications, in patients treated with TME or local excision within 26 weeks following start of treatment. Secondary endpoints include the organ preservation rate, non-DLT, oncological outcomes, patient-reported QoL and functional outcomes up to 2 years following start of treatment. Imaging and laboratory biomarkers are explored for early response prediction. ETHICS AND DISSEMINATION: The trial protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht. The primary and secondary trial results will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: WHO International Clinical Trials Registry (NL8997; https://trialsearch.who.int).

Risk factors of postoperative intensive care unit admission during the COVID-19 pandemic: A multicentre retrospective cohort study.

Background: During the Coronavirus disease 2019 (COVID-19) pandemic, intensive care unit (ICU) capacity was scarce. Since surgical patients also require ICU admission, determining which factors lead to an increased risk of postoperative ICU admission is essential. This study aims to determine which factors led to an increased risk of unplanned postoperative ICU admission during the COVID-19 pandemic. Methods: This multicentre retrospective cohort study investigated all patients who underwent surgery between 9 March 2020 and 30 June 2020. The primary endpoint was the number of surgical patients requiring postoperative ICU admission. The secondary endpoint was to determine factors leading to an increased risk of unplanned postoperative ICU admission, calculated by multivariate analysis with odds ratios (OR's) and 95% confidence (CI) intervals. Results: One hundred eighty-five (4.6%) of the 4051 included patients required unplanned postoperative ICU admission. COVID-19 positive patients were at an increased risk of being admitted to the ICU compared to COVID-19 negative (OR 3.14; 95% CI 1.06-9.33; p = 0.040) and untested patients (OR 0.48; 95% CI 0.32-0.70; p = 0.001). Other predictors were male gender (OR 1.36; 95% CI 1.02-1.82; p = 0.046), body mass index (BMI) (OR 1.05; 95% CI 1.02-1.08; p = 0.001), surgical urgency and surgical discipline. Conclusion: A confirmed COVID-19 infection, male gender, elevated BMI, surgical urgency, and surgical discipline were independent factors for an increased risk of unplanned postoperative ICU admission. In the event of similar pandemics, postponing surgery in patients with an increased risk of postoperative ICU admission may be considered.

Moderators and Mediators of the Relationship of Shared Decision-Making and Satisfaction.

Background:Evidence suggests that health literacy, perceived availability of information and guidance to adapt to challenges (informational support), and symptoms of depression all have the potential to mediate or moderate the relationship between patient-rated involvement in decisions and satisfaction with care. If so these could be useful targets for improving patient experience. Methods: We prospectively enrolled 130 new adult patients visiting an orthopedic surgeon over a 4-month period. All patients were asked to complete measures of satisfaction with care (21-item Medical Interview Satisfaction Scale), perceived involvement in decisions (9-item Shared Decision-Making Questionnaire), symptoms of depression (the Patient-Reported Outcomes Measurement Information Scale [PROMIS] Depression Computerized Adaptive Test [CAT]), perceived availability of information and guidance to adapt to challenges (PROMIS Informational Support CAT), and the Newest Vital Sign test of health literacy. Results: The strong correlation between satisfaction with care (ρ = 0.60, P < .001) and perceived involvement in decisions was neither mediated nor moderated by health literacy, perceived availability of information and guidance, and symptoms of depression. Conclusions: The observation that patient-rated shared decision-making is strongly related to satisfaction with an office visit, independent of health literacy, perceived support, and symptoms of depression, is consistent with evidence that various measures of patient experience tend to correlate and emphasizes the importance of the patient-clinician relationship. Level of Evidence: Level II, prospective study.

A direct examination of microbial specialized metabolites associated with ocean sediments from Baffin Bay and the Gulf of Maine.

Specialized metabolites produced by microorganisms found in ocean sediments display a wide range of clinically relevant bioactivities, including antimicrobial, anticancer, antiviral, and anti-inflammatory. Due to limitations in our ability to culture many benthic microorganisms under laboratory conditions, their potential to produce bioactive compounds remains underexplored. However, the advent of modern mass spectrometry technologies and data analysis methods for chemical structure prediction has aided in the discovery of such metabolites from complex mixtures. In this study, ocean sediments were collected from Baffin Bay (Canadian Arctic) and the Gulf of Maine for untargeted metabolomics using mass spectrometry. A direct examination of prepared organic extracts identified 1468 spectra, of which ∼45% could be annotated using in silico analysis methods. A comparable number of spectral features were detected in sediments collected from both locations, but 16S rRNA gene sequencing revealed a significantly more diverse bacterial community in samples from Baffin Bay. Based on spectral abundance, 12 specialized metabolites known to be associated with bacteria were selected for discussion. The application of metabolomics directly on marine sediments provides an avenue for culture-independent detection of metabolites produced under natural settings. The strategy can help prioritize samples for novel bioactive metabolite discovery using traditional workflows.

Endoplasmic reticulum-bound ANAC013 factor is cleaved by RHOMBOID-LIKE 2 during the initial response to hypoxia in Arabidopsis thaliana.

Aerobic reactions are essential to sustain plant growth and development. Impaired oxygen availability due to excessive water availability, e.g., during waterlogging or flooding, reduces plant productivity and survival. Consequently, plants monitor oxygen availability to adjust growth and metabolism accordingly. Despite the identification of central components in hypoxia adaptation in recent years, molecular pathways involved in the very early activation of low-oxygen responses are insufficiently understood. Here, we characterized three endoplasmic reticulum (ER)-anchored Arabidopsis ANAC transcription factors, namely ANAC013, ANAC016, and ANAC017, which bind to the promoters of a subset of hypoxia core genes (HCGs) and activate their expression. However, only ANAC013 translocates to the nucleus at the onset of hypoxia, i.e., after 1.5 h of stress. Upon hypoxia, nuclear ANAC013 associates with the promoters of multiple HCGs. Mechanistically, we identified residues in the transmembrane domain of ANAC013 to be essential for transcription factor release from the ER, and provide evidence that RHOMBOID-LIKE 2 (RBL2) protease mediates ANAC013 release under hypoxia. Release of ANAC013 by RBL2 also occurs upon mitochondrial dysfunction. Consistently, like ANAC013 knockdown lines, rbl knockout mutants exhibit impaired low-oxygen tolerance. Taken together, we uncovered an ER-localized ANAC013-RBL2 module, which is active during the initial phase of hypoxia to enable fast transcriptional reprogramming.

Correlation of defect size with fatty infiltration on MRIs of rotator cuff tendinopathy.

Introduction: Sizable rotator cuff defects with limited muscle atrophy and fat replacement may represent acute traumatic ruptures that are less likely to recur after surgery to close the defect, while closure of defects with poor quality muscle are associated with defect recurrence. These distinct lesions are both referred to as tears. We analyzed the relationship between rotator cuff defect size and muscle quality to determine the relative proportion of sizable defects associated with good muscle and factors associated with muscle deterioration. Material and methods: A cohort of 230 consecutive shoulder MRIs in patients with full-thickness rotator cuff tendon defects, limited acromioclavicular arthrosis (to avoid hindrance of defect measurement), and a duration of symptoms in the radiology report from a large urban center in the United States was evaluated for the measured distance between the supraspinatus tendon edge and the greater tuberosity medial to lateral (coronal plane defect size), anterior to posterior (sagittal plane defect width), and fatty infiltration (Goutallier classification), and atrophy (Warner classification) of the supraspinatus. We sought factors independently associated with fatty infiltration and muscle atrophy in multivariable logistic regression analyses. Results: Forty-nine of 109 shoulders (45%) with a coronal plane defect >20 mm had reasonable muscle quality as defined by Goutallier grade less than 2 and Warner grade less than 2. Both greater fatty infiltration of the supraspinatus muscle and greater supraspinatus muscle atrophy were associated with older age and greater coronal plane defect size. Conclusion: The observation that supraspinatus muscle health deteriorates with age and defect size, but nearly half of the largest defects had good muscle, suggests an important distinction between relatively recent traumatic ruptures and old untreated rupture or gradual attrition that may be obfuscated by referring to all lesions as tears. Level of evidence: Level III; Retrospective diagnostic cohort.

Electrodiagnostic test results in people with a working diagnosis of cubital tunnel syndrome.

Background: Electrodiagnostic tests (EDx) can determine when symptoms and signs suggestive of idiopathic ulnar neuropathy at the elbow (cubital tunnel syndrome; CubTS) is due to measurable ulnar neuropathy at the elbow (UNE), cervical radiculopathy, or median neuropathy at the carpal tunnel, and when there is no measurable neuropathology associated with the symptoms. The role of EDx in management of CubTS is debated. Questions: (1) What is the percentage of patients with CubTS (both including and excluding patients with a previous electrodiagnosis of idiopathic UNE) that have EDx results consistent with idiopathic UNE, other neuropathology, and no detectable neuropathology (2) What factors (e.g. age and gender); are independently associated with electrodiagnosis of UNE. Methods: We retrospectively reviewed all medical records of 133 patients with a working diagnosis of CubTS sent for EDx over a 5-year period in one large urban medical center. We recorded data on patient demographics, comorbidities, non-specialist or specialist referring physician, and EDx results. Results: Among 133 patients, 61% (N = 81) of EDx identified idiopathic UNE, 14% (N = 18) identified other neuropathology, and for 26% (N = 34) there was no measurable neuropathology. Among the 14 patients with a previous ipsilateral or contralateral electrodiagnosis of UNE, all 14 had electrodiagnosis of UNE. Older age and men were independently associated with an increased likelihood of UNE. Conclusions: The observation that people diagnosed with CubTS often do not have UNE, particularly if they are relatively young, suggests that the diagnosis of CubTS may benefit from a more stringent clinical prediction rule. Level of Evidence: Diagnostic; Retrospective cohort study; Level III.

There is Little or No Association Between Independently Assessed Communication Strategies and Patient Ratings of Clinician Empathy.

BACKGROUND: Quality of care is increasingly assessed and incentivized using measures of patient-reported outcomes and experience. Little is known about the association between measurement of clinician communication strategies by trained observers and patient-rated clinician empathy (a patient-reported experience measure). An effective independent measure could help identify and promote clinician behaviors associated with good patient experience of care. QUESTIONS/PURPOSES: (1) What is the association between independently assessed clinician communication effectiveness and patient-rated clinician empathy? (2) Which factors are associated with independently assessed communication effectiveness? METHODS: One hundred twenty adult (age > 17 years) new or returning patients seeking musculoskeletal specialty care between September 2019 and January 2020 consented to video recording of their visit followed by completion of questionnaires rating their perceptions of providers' empathy levels in this prospective study. Patients who had operative treatment and those who had nonoperative treatment were included in our sample. We pooled new and returning patients because our prior studies of patient experience found no influence of visit type and because we were interested in the potential influences of familiarity with the clinician on empathy ratings. We did not record the number of patients or baseline data of patients who were approached, but most patients (> 80%) were willing to participate. For 7% (eight of 120 patients), there was a malfunction with the video equipment or files were misplaced, leaving 112 records available for analysis. Patients were seen by one provider among four attending physicians, four residents, or four physician assistants or nurse practitioners. The primary study question addressed the correlation between patient-rated clinician empathy using the Jefferson Scale of Patient Perceptions of Physician Empathy and clinician communication effectiveness, independently rated by two communication scholars using the Liverpool Communication Skills Assessment Scale. Based on a subset of 68 videos (61%), the interrater reliability was considered good for individual items on the Liverpool Communication Skills Assessment Scale (intraclass correlation coefficient [ICC] 0.78 [95% confidence interval (CI) 0.75 to 0.81]) and excellent for the sum of the items (that is, the total score) (ICC = 0.92 [95% CI 0.87 to 0.95]). To account for the potential association of personal factors with empathy ratings, patients completed measures of symptoms of depression (the Patient-Reported Outcome Measurement Information System depression computerized adaptive test), self-efficacy in response to pain (the two-item Pain Self-Efficacy Questionnaire), health anxiety (the five-item Short Health Anxiety Inventory), and basic demographics. RESULTS: Accounting for potentially confounding variables, including specific clinicians, marital status, and work status in the multivariable analysis, we found higher independent ratings of communication effectiveness had a slight association (odds ratio [OR] 1.1 [95% CI 1.0 to 1.3]; p = 0.02) with higher (dichotomized) ratings of patient-rated clinician empathy, while being single was associated with lower ratings (OR 0.40 [95% CI 0.16 to 0.99]; p = 0.05). Independent ratings of communication effectiveness were slightly higher for women (regression coefficient 1.1 [95% CI 0.05 to 2.2]); in addition, two of the four attending physicians were rated notably higher than the other 10 participants after controlling for confounding variables (differences up to 5.8 points on average [95% CI 2.6 to 8.9] on a 36-point scale). CONCLUSION: The observation that ratings of communication effectiveness by trained communication scholars have little or no association with patient-rated clinician empathy suggests that either effective communication is insufficient for good patient experience or that the existing measures are inadequate or inappropriate. This line of investigation might be enhanced by efforts to identify clinician behaviors associated with better patient experience, develop reliable and effective measures of clinician behaviors and patient experience, and use those measures to develop training approaches that improve patient experience. LEVEL OF EVIDENCE: Level I, prognostic study .

Mitochondrial alternative NADH dehydrogenases NDA1 and NDA2 promote survival of reoxygenation stress in Arabidopsis by safeguarding photosynthesis and limiting ROS generation.

Plant submergence stress is a growing problem for global agriculture. During desubmergence, rising O2 concentrations meet a highly reduced mitochondrial electron transport chain (mETC) in the cells. This combination favors the generation of reactive oxygen species (ROS) by the mitochondria, which at excess can cause damage. The cellular mechanisms underpinning the management of reoxygenation stress are not fully understood. We investigated the role of alternative NADH dehydrogenases (NDs), as components of the alternative mETC in Arabidopsis, in anoxia-reoxygenation stress management. Simultaneous loss of the matrix-facing NDs, NDA1 and NDA2, decreased seedling survival after reoxygenation, while overexpression increased survival. The absence of NDAs led to reduced maximum potential quantum efficiency of photosystem II linking the alternative mETC to photosynthetic function in the chloroplast. NDA1 and NDA2 were induced upon reoxygenation, and transcriptional activation of NDA1 was controlled by the transcription factors ANAC016 and ANAC017 that bind to the mitochondrial dysfunction motif (MDM) in the NDA1 promoter. The absence of NDA1 and NDA2 did not alter recovery of cytosolic ATP levels and NADH : NAD+ ratio at reoxygenation. Rather, the absence of NDAs led to elevated ROS production, while their overexpression limited ROS. Our observations indicate that the control of ROS formation by the alternative mETC is important for photosynthetic recovery and for seedling survival of anoxia-reoxygenation stress.

Patient- and physician-reported radiation-induced toxicity of short-course radiotherapy with a prolonged interval to surgery for rectal cancer.

AIM: A prolonged interval (>4 weeks) between short-course radiotherapy (25 Gy in five fractions) (SCRT-delay) and total mesorectal excision for rectal cancer has been associated with a decreased postoperative complication rate and offers the possibility of organ preservation in the case of a complete tumour response. This prospective cohort study systematically evaluated patient-reported bowel dysfunction and physician-reported radiation-induced toxicity for 8 weeks following SCRT-delay. METHOD: Patients who were referred for SCRT-delay for intermediate risk, oligometastatic or locally advanced rectal cancer were included. Repeated measurements were done for patient-reported bowel dysfunction (measured by the low anterior resection syndrome [LARS] questionnaire and categorized as no, minor or major LARS) and physician-reported radiation-induced toxicity (according to Common Terminology Criteria for Adverse Events version 4.0) before start of treatment (baseline), at completion of SCRT and 1, 2, 3, 4, 6 and 8 weeks thereafter. RESULTS: Fifty-one patients were included; 31 (61%) were men and the median age was 67 years (range 44-91). Patient-reported bowel dysfunction and physician-reported radiation-induced toxicity peaked at weeks 1-2 after completion of SCRT and gradually declined thereafter. Major LARS was reported by 44 patients (92%) at some time during SCRT-delay. Grade 3 radiation-induced toxicity was reported in 17 patients (33%) and concerned predominantly diarrhoea. No Grade 4-5 radiation-induced toxicity occurred. CONCLUSION: During SCRT-delay, almost every patient experiences temporary mild-moderate radiation-induced toxicity and major LARS, but life-threatening toxicity is rare. SCRT-delay is a safe alternative to SCRT-direct surgery that should be proposed when counselling rectal cancer patients on neoadjuvant strategies.

Acquisition of hypoxia inducibility by oxygen sensing N-terminal cysteine oxidase in spermatophytes.

N-terminal cysteine oxidases (NCOs) use molecular oxygen to oxidise the amino-terminal cysteine of specific proteins, thereby initiating the proteolytic N-degron pathway. To expand the characterisation of the plant family of NCOs (plant cysteine oxidases [PCOs]), we performed a phylogenetic analysis across different taxa in terms of sequence similarity and transcriptional regulation. Based on this survey, we propose a distinction of PCOs into two main groups. A-type PCOs are conserved across all plant species and are generally unaffected at the messenger RNA level by oxygen availability. Instead, B-type PCOs appeared in spermatophytes to acquire transcriptional regulation in response to hypoxia. The inactivation of two A-type PCOs in Arabidopsis thaliana, PCO4 and PCO5, is sufficient to activate the anaerobic response in young seedlings, whereas the additional removal of B-type PCOs leads to a stronger induction of anaerobic genes and impairs plant growth and development. Our results show that both PCO types are required to regulate the anaerobic response in angiosperms. Therefore, while it is possible to distinguish two clades within the PCO family, we conclude that they all contribute to restrain the anaerobic transcriptional programme in normoxic conditions and together generate a molecular switch to toggle the hypoxic response.

Prevalence of incidental distal biceps signal changes on magnetic resonance imaging

Background@#Knowledge of the base rate of signal changes consistent with distal biceps tendinopathy on magnetic resonance imaging (MRI) has the potential to influence strategies for diagnosis and treatment of people that present with elbow pain. The aim of this study is to measure the prevalence of distal biceps tendon signal changes on MRIs of the elbow by indication for imaging. @*Methods@#MRI data for 1,306 elbows were retrospectively reviewed for mention of signal change in distal biceps tendon. The reports were sorted by indication. @*Results@#Signal changes consistent with distal biceps tendinopathy were noted in 197 of 1,306 (15%) patients, including 34% of patients with biceps pain, 14% of patients with unspecified pain, and 8% of patients with a specific non-biceps indication. Distal biceps tendon changes noted on radiology reports were associated with older age, male sex, and radiologists with musculoskeletal fellowship training. @*Conclusions@#The finding that distal biceps MRI signal changes consistent with tendinopathy are common even in asymptomatic elbows reduces the probability that symptoms correlate with pathology on imaging. The accumulation of signal changes with age, also independent of symptoms, suggests that tendon pathology persists after symptoms resolve, that some degree of distal biceps tendinopathy is common in a human lifetime, and that tendinopathy may often be accommodated without seeking care.Level of evidence: IV.

Distinct epidemiological profiles of porcine circovirus 3 and fox circovirus in Canadian foxes (Vulpes spp.).

Circoviruses (genus Circovirus, family Circoviridae) are ssDNA viruses that infect mammals, and they sometimes can transmit among different species. We investigated the distribution and diversity of porcine circovirus 3 (PCV-3, species Porcine circovirus 3) and fox circovirus (species Canine circovirus 1) in different populations of foxes (Vulpes spp.) inhabiting the Canadian province of Newfoundland and Labrador to compare their epidemiological profiles. Of the 210 samples tested in this study 9 were positive for PCV-3 and 99 were positive for fox circovirus. Eight foxes were PCV-3-positive (8/128, 6.3%) and the virus was only found in the most human-populated areas. The PCV-3 positivity rate was significantly higher in stool (7/180, 8.8%) than in spleen (2/120, 1.7%: p < 0.05). Phylogenetic analyses showed that sequences from different animals were unrelated to each other. Fox circovirus was identified in 66 animals (51.6%) and positivity rates were the highest in the least human-populated areas. There were no significant differences between positivity rates in stool (32/80, 40.0%), spleen (59/120, 49.2%), or lymph nodes (8/10, 80.0%). Among 54 positive animals for which both spleen and stool samples were available, 25 (46.3%) had detectable virus in both samples. All fox circovirus sequences recovered in this study formed a monophyletic clade, and no geographic segregation of study strains was observed. The high prevalence and high genetic diversity observed for fox circovirus implies that the virus has been circulating in this population for a long time. PCV-3 cases were consistent with sporadic infections from multiple sources, possibly related to scavenging behavior and consumption of meat by-products and human waste, while fox circovirus was endemic, indicating that foxes are likely the maintenance host for this virus. To the best of our knowledge this is the first study demonstrating the presence of fox circovirus in North America and to show that PCV-3 can be detected in foxes. Future studies should evaluate the pathogenic potential of these viruses for wildlife.

A novel calicivirus discovered in trumpeter swans (Cygnus buccinator) expands the richness of known avian caliciviruses.

Caliciviruses are ssRNA viruses that can infect a wide range of hosts, including birds. While several avian caliciviruses have been discovered, their taxonomy and host distribution are largely unknown. We molecularly characterized a novel calicivirus (trumpeter swan calicivirus: TruSCV) in trumpeter swans over-wintering in south-west British Columbia, Canada. The positivity rate was 20.3% (14/69) and there were no significant differences in infection rates between males (5/34, 14.7%) and females (9/35, 25.7%) or among considered age groups (juveniles: 4/14, 28.6%; sub-adults: 1/9, 11.1%; adults: 9/46, 19.6%). Twelve infected swans died of lead poisoning, one because of starvation, and one from physical injuries. TruSCV complete genome possessed the typical organization and protein motifs of caliciviruses and a type 2 IRES and its closest relative was a virus circulating in Australian ducks. Phylogenetic analyses showed the existence of 34 different but monophyletic avian caliciviruses. These viruses, while having conserved genomic organization and protein motifs, possess different IRES types and group in several divergent clades, with only two of them corresponding to currently defined genera, highlighting the need for epidemiological investigations and systematic analyses to better define their taxonomy. Follow-up studies are needed to elucidate the diversity, distribution, and pathogenic potential of TruSCV.

Radiographs and Corticosteroid Injections at a New Patient Visit for Care of Carpal Tunnel Syndrome and Ulnar Neuropathy at the Elbow.

Introduction The benefit of radiographs or steroid injection for idiopathic carpal tunnel syndrome (CTS) or ulnar neuropathy at the elbow (UNE) is open to debate. We assessed: (1) Radiographs ordered and injections performed at a new patient visit for patients presenting with either idiopathic CTS or UNE; (2) The estimated payment reduction if we omit these interventions; and (3) Patient age, sex, geographic region, and work status associated with radiographs or injections at a new patient visit for patients presenting with either idiopathic CTS or UNE. Materials and Methods Using a large database of commercial insurance claims, we identified patients with a new visit for either CTS ( N = 9,522), UNE ( N = 2,507), or both ( N = 962; 8.7%). We identified injections and radiographs, and estimated total payments for these interventions. We created three multivariable logistic regression models for each diagnosis to identify factors associated with the interventions. Results Nearly one third of patients had radiographs at a new patient visit (30% and 32% for idiopathic CTS and UNE, respectively). Nearly 10% of patients with CTS and 2.6% with UNE received an injection. Both radiographs and injections representing annual minimum payments of over $345,000 and $294,000, respectively. Among people with CTS, radiographs were independently more common in the South and less common in the West. Injection for CTS was associated with younger age; North, Central, and South regions; and retired employment status. For people with UNE, radiographs were independently associated with younger age; South or West region; and retired or working employment status. Injection for UNE was associated with retired employment status. Conclusion The prevalence of radiographs and injections suggests opportunities for savings, which might benefit clinicians with bundled or capitated payments and patients with large copayments or deductibles. The observed variation may reflect debate about whether these interventions are worthwhile. Level of Evidence Diagnostic; Retrospective Database Level III study.