Radiological diagnosis of prevalent osteoporotic vertebral fracture on radiographs: an interim consensus from a group of experts of the ESSR osteoporosis and metabolism subcommittee.

When a low-energy trauma induces an acute vertebral fracture (VF) with clinical symptoms, a definitive diagnosis of osteoporotic vertebral fracture (OVF) can be made. Beyond that, a "gold" radiographic standard to distinguish osteoporotic from non-osteoporotic VFs does not exist. Fracture-shaped vertebral deformity (FSVD) is defined as a deformity radiographically indistinguishable from vertebral fracture according to the best of the reading radiologist's knowledge. FSVD is not uncommon among young populations with normal bone strength. FSVD among an older population is called osteoporotic-like vertebral fracture (OLVF) when the FSVD is likely to be associated with compromised bone strength. In more severe grade deformities or when a vertebra is collapsed, OVF diagnosis can be made with a relatively high degree of certainty by experienced readers. In "milder" cases, OVF is often diagnosed based on a high probability rather than an absolute diagnosis. After excluding known mimickers, singular vertebral wedging in older women is statistically most likely an OLVF. For older women, three non-adjacent minimal grade OLVF (< 20% height loss), one minimal grade OLVF and one mild OLVF (20-25% height loss), or one OLVF with ≥ 25% height loss, meet the diagnosis of osteoporosis. For older men, a single OLVF with < 40% height loss may be insufficient to suggest the subject is osteoporotic. Common OLVF differential diagnoses include X-ray projection artifacts and scoliosis, acquired and developmental short vertebrae, osteoarthritic wedging, oncological deformities, deformity due to high-energy trauma VF, lateral hyperosteogeny of a vertebral body, Cupid's bow, and expansive endplate, among others.

Efficacy of radiofrequency in lumbar facet joint pain: a systematic review and meta-analysis of placebo-controlled randomized controlled trials.

BACKGROUND: Lumbar facet joint pain (LFJP) is one of the main causes of chronic low back pain (LBP) and can be treated using radiofrequency (RF) sensory denervation. The aim of this work is to analyze the efficacy of RF in LFJP through a systematic review and meta-analysis of randomized controlled trials (RCTs) with placebo control. MATERIALS AND METHODS: A systematic search was conducted in the Medline (PubMed), Scopus, Web of Science databases, and the Cochrane Central Register of Controlled Trials (CENTRAL). The variables of interest were pain, functional status, quality of life (QoL), and global perceived effect (GPE) measured at different time intervals: short (< 3 months), medium (> 3 and < 12 months), and long term (> 12 months). RESULTS: Eight RCTs with placebo control were included. RF showed significant benefits over placebo in pain relief in the short (MD - 1.01; 95% CI - 1.98 to -0.04; p = 0.04), medium (MD - 1.42; 95% CI - 2.41 to - 0.43; p = 0.005), and long term (MD - 1.12; 95% CI - 1.57 to - 0.68; p < 0.001), as well as improvement in functional disability in the short (SMD - 0.94; 95% CI - 1.73 to - 0.14; p = 0.02) and long term (SMD - 0.74; 95% CI - 1.09 to - 0.39; p < 0.001). No statistically significant differences were observed in QoL or quantitative GPE, but benefits for RF were observed in dichotomous GPE in the medium (OR 0.19; 95% CI 0.07-0.52; p = 0.001) and long term (OR 0.22; 95% CI 0.06-0.78; p = 0.02). Subgroup analyses showed more benefits for RF in LBP < 1 year in the short term and in RCTs that did not require performing an MRI for patient selection. CONCLUSIONS: RF demonstrated significant improvement in pain and functionality, but the benefits in terms of QoL and GPE are inconclusive. Future clinical trials should investigate the long-term effects of RF, its impact on quality of life, and define appropriate criteria for patient selection.

Long-term comparison between blind and ultrasound-guided corticoid injections in Morton neuroma.

OBJECTIVES: This work compares the effectiveness of blind versus ultrasound (US)-guided injections for Morton neuroma (MN) up to 3 years of follow-up. METHODS: This is an evaluator-blinded randomised trial in which 33 patients with MN were injected by an experienced orthopaedic surgeon based on anatomical landmarks (blind injection, group 1) and 38 patients were injected by an experienced musculoskeletal radiologist under US guidance (group 2). Patients were assessed using the visual analogue scale and the Manchester Foot Pain and Disability index (MFPDI). Injections consisted of 1 ml of 2% mepivacaine and 40 mg triamcinolone acetonide in each web space with MN. Up to 4 injections were allowed during the first 3 months of follow-up. Follow-up was performed by phone calls and/or scheduled consultations at 15 days, 1 month, 45 days, 2 months, 3 months, 6 months and 1, 2 and 3 years. Statistical analysis was performed using unpaired Student's t tests. RESULTS: No differences in age or clinical measures were found at presentation between group 1 (VAS, 8.5 ± 0.2; MFPDI, 40.9 ± 1.1) and group 2 (VAS, 8.4 ± 0.2; MFPDI, 39.8 ± 1.2). Improvement in VAS was superior in group 2 up to 3 years of follow-up (p < 0.05). Improvement in MFPDI was superior in group 2 from 45 days to 2 years of follow-up (p < 0.05). Satisfaction with the treatment was higher in group 2 (87%) versus group 1 (59.1%) at 3 years of follow-up. CONCLUSION: Ultrasound-guided injections lead to a greater percentage of long-term improvement than blind injections in MN. KEY POINTS: • Ultrasound-guided corticosteroid injections in Morton neuroma provide long-term pain relief in more than 75% of patients. • Ultrasound-guided injections in Morton neuroma led to greater long-term pain relief and less disability than blind injections up to 3 years of follow-up. • The presence of an ipsilateral neuroma is associated with worse long-term disability score.

Predicting habitat use by the Argentine hake Merluccius hubbsi in a warmer world: inferences from the Middle Holocene.

Fish skeletal remains recovered from two archaeological sites dated in the Middle Holocene of Tierra del Fuego (Argentina) were analysed to describe habitat use patterns by hake in the past and predict changes in a warmer world. Mitochondrial DNA was successfully extracted and amplified from 42 out of 45 first vertebra from ancient hake and phylogenetic analysis assigned all haplotypes to Argentine hake (Merluccius hubbsi). According to osteometry, the Argentine hake recovered from the archaeological site were likely adults ranging 37.2-58.1 cm in standard length. C and N stable isotope analysis showed that currently Argentine hake use foraging grounds deeper than those of Patagonian blenny and pink cusk-eel. Argentine hake, however, had a much broader isotopic niche during the Middle Holocene, when a large part of the population foraged much shallower than contemporary pink cusk-eel. The overall evidence suggests the presence of large numbers of Argentine hake onshore Tierra del Fuego during the Middle Holocene, which allowed exploitation by hunter-gatherer-fisher groups devoid of fishing technology. Interestingly, average SST off Tierra del Fuego during the Middle Holocene was higher than currently (11 °C vs 7 °C) and matched SST in the current southernmost onshore spawning aggregations, at latitude 47 °S. This indicates that increasing SST resulting from global warming will likely result into an increased abundance of adult Argentine hake onshore Tierra del Fuego, as during the Middle Holocene. Furthermore, stable isotope ratios from mollusc shells confirmed a much higher marine primary productivity during the Middle Holocene off Tierra del Fuego.

Extracellular signal-regulated kinase-1 phosphorylates early growth response-1 at serine 26.

Egr-1, an immediate-early gene product and master regulator was originally described as a phosphoprotein following its discovery in the 1980s. However specific residue(s) phosphorylated in Egr-1 remain elusive. Here we phosphorylated recombinant Egr-1 in vitro with ERK1 prior to mass spectrometry, which identified phosphorylation of Ser12 and Ser26 with the latter ∼12 times more abundant than Ser12. Phosphorylation of wild-type recombinant Egr-1 (as compared with Ser26>Ala26 mutant Egr-1) revealed that Ser26 accounts for the majority of phosphorylation of Egr-1 by ERK1. N-FGSFPH(pS)PTMDNYC-C was used as an antigen to generate mouse monoclonal antibodies (pS26 MAb). pS26 MAb recognised ERK1-phosphorylated Egr-1 but not Egr-1 bearing a point mutation at Ser26. pS26 MAb recognised inducible ∼75 kDa and 100 kDa species in nuclear extracts of cells exposed to FGF-2. Peptide blocking revealed both inducible species were phosphosite-specific. Immunoprecipitation of nuclear extracts of cells exposed to FGF-2 with pS26 MAb followed by SDS-PAGE and mass spectrometry identified Egr-1 sequences corresponding to the ∼75 kDa species but not ∼100 kDa species. This study identifies a specific amino acid phosphorylated in endogenous Egr-1.

Short term comparison between blind and ultrasound guided injection in morton neuroma.

OBJECTIVE: The aim of this work is to compare the effectiveness of blind and ultrasound-guided injection for Morton's neuroma (MN) to determine which is more appropriate as the initial procedure in conservative treatment. METHODS: This is an evaluator-blinded randomised trial. Of the 56 included patients, 27 were assigned to the blind group (A) and 29 to the ultrasound-guided group (B). Injection includes 1 ml of 2% mepivacaine and 40 mg of triamcinolone in each web space with MN. The included patients were assessed clinically by VAS score and the Manchester Foot Pain and Disability Score (MFPDS). The follow-up was performed at 15 days, 1 month, 45 days, 2 months, 3 months and 6 months after the initial injection. RESULTS: No differences in age or clinical measurements were found at presentation between group A and group B. At the follow-up, the ultrasound-guided group showed greater symptomatic relief at several stages of the follow-up: 45 days (VAS 3.0 ± 0.5 versus 5.5 ± 0.5, p = 0.001; MFPDS: 32.2 ± 1.8 versus 38.8 ± 2.0, p = 0.018), 2 months (VAS: 3.1 ± 0.5 versus 5.6 ± 0.5, p = 0.002; MFPDS: 31.5 ± 1.9 versus 38.5 ± 2.1, p = 0.020) and 3 months (VAS: 3.1 ± 0.4 versus 5.2 ± 0.6, p = 0.010; MFPDS: 31.2 ± 1.9 versus 37.7 ± 2.4, p = 0.047). CONCLUSION: Injection of MN under ultrasound guidance provides a statistically significant improvement at some stages of the follow-up (45 days, 2 and 3 months), compared with blind injection. KEY POINTS: • Ultrasound-guided steroid injections in Morton's neuroma provide short-term pain relief to over 60% of the patients. • Ultrasound-guided injections in Morton's neuroma lead to a higher percentage of short-term pain relief than blind injections. • Ultrasound-guided injections in Morton's neuroma lead to a lower percentage of skin side effects than blind injections.

Vertebral metastases from neuroendocrine tumours: How to avoid false positives on 68Ga-DOTA-TOC PET using CT pattern analysis?

OBJECTIVES: To develop criteria to improve discrimination between vertebral metastases from neuroendocrine tumours (NETs) and benign bone lesions on PET combined with CT using DOTA-D-Phe1-Tyr3-octreotide labelled with gallium-68 (68Ga-DOTA-TOC). METHODS: In 535 NET patients, 68Ga-DOTA-TOC PET/CT examinations were reviewed retrospectively for vertebral CT lesions and/or PET foci. For each vertebral PET abnormality, appearance on CT, biological volume (BV), standardized uptake value (SUVmax) and ratios to those of reference organs were determined. All vertebral abnormalities were characterized as a metastasis, a typical vertebral haemangioma (VH) or other benign lesion. RESULTS: In 79 patients (14.8 %), we found 107 metastases, 34 VHs and 31 other benign lesions in the spine. The optimal cut-off values to differentiate metastases from benign lesions were BV ≥0.72 cm3, SUVmax ≥2, SUVmax ratio to a reference vertebra ≥2.1, to liver ≥0.28 and to spleen ≥0.14. They corresponded to lesion-based 68Ga-DOTA-TOC PET/CT sensitivity of 87 %, 98 %, 97 %, 99 % and 94 %, and specificity of 55 %, 100 %, 90 %, 97 %, 100 %, respectively. CONCLUSIONS: The high sensitivity of 68Ga-DOTA-TOC-PET/CT in detecting NET vertebral metastases was confirmed; this study showed that specificity could be improved by combining CT features and quantifying 68Ga-DOTA-TOC uptake. KEY POINTS: • Bone metastases in neuroendocrine tumours correlate with prognosis. • Benign bone lesions may mimic metastases on 68 Ga-DOTA-TOC PET/CT imaging. • The specific polka-dot CT pattern may be missing in some vertebral haemangiomas. • Lesion atypical for haemangiomas can be better characterized by quantifying 68 Ga-DOTA-TOC uptake.

The Co-chaperone BAG2 Mediates Cold-Induced Accumulation of Phosphorylated Tau in SH-SY5Y Cells.

Inclusions of phosphorylated tau (p-tau) are a hallmark of many neurodegenerative disorders classified as "tauopathy," of which Alzheimer's disease is the most prevalent form. Dysregulation of tau phosphorylation disrupts neuron structure and function, and hyperphosphorylated tau aggregates to form neurotoxic inclusions. The abundance of ubiquitin in tau inclusions suggests a defect in ubiquitin-mediated tau protein degradation by the proteasome. Under the temperature of 37 °C, the co-chaperone BAG2 protein targets phosphorylated tau for degradation via by a more-efficient, ubiquitin-independent pathway. In both in vivo and in vitro studies, cold exposure induces the accumulation of phosphorylated tau protein. The SH-SY5Y cell line differentiates into neuron-like cells on treatment with retinoic acid and is an established model for research on the effects of cold on tau phosphorylation. The aim of the present study was to investigate whether BAG2 mediates the cold-induced accumulation of phosphorylated tau protein. Our findings show that cold exposure causes a decrease in BAG2 expression in undifferentiated cells. Conversely, BAG2 expression is increased in differentiated cells exposed to cold. Further, undifferentiated cells exposed to cold had an increased proportion of p-tau to total tau, suggesting an accumulation of p-tau that is consistent with decreased levels of BAG2. Overexpression of BAG2 in cold-exposed undifferentiated cells restored levels of p-tau to those of 37 °C undifferentiated control. Interestingly, although BAG2 expression increased in differentiated cells, this increase was not accompanied by a decrease in the proportion of p-tau to total tau. Further, overexpression of BAG2 in cold exposed differentiated cells showed no significant difference in p-tau levels compared to 37 °C controls. Taken together, these data show that expression of BAG2 is differently regulated in a differentiation-dependent context. Our results suggest that repression of BAG2 expression or BAG2 activity by cold-sensitive pathways, as modeled in undifferentiated and differentiated cells, respectively, may be a causal factor in the accumulation of cytotoxic hyperphosphorylated tau protein via restriction of BAG2-mediated clearance of cellular p-tau.

The Association between t-PA Administration and In-Hospital Mortality following Acute Ischemic Stroke in Puerto Rican Patients.

OBJECTIVE: Despite being the standard of care, thrombolytic therapy with tissue plasminogen activator (t-PA) is currently administered to only 5% of acute ischemic stroke (AIS) patients in the United States. Published scientific information regarding both the use of t-PA for AIS in Hispanic patients and its impact on short-term mortality is scarce. The objectives of this study are to investigate, among Puerto Rican patients hospitalized with AIS, the rate of t-PA administration, and the risk of in-hospital mortality in patients who received t-PA vs. those patients who did not receive t-PA. METHODS: We performed a secondary analysis of data from patients with AIS admitted to acute care facilities throughout Puerto Rico in study years 2007, 2009, and 2011who were participating in the Puerto Rico Cardiovascular Disease Surveillance System. Multivariate logistic regression was used to determine the independent association between treatment with t-PA within 4.5 hours of symptom onset and in-hospital mortality. RESULTS: Of the 1968 study patients hospitalized with AIS, 104 (5%) received t-PA treatment. After adjustments for demographic and clinical confounders, patients receiving t-PA had similar odds of in-hospital mortality as patients not receiving t-PA did (OR = 2.49, 95% CI = 0.81-7.66). The receipt of concomitant anticoagulation medication was independently associated with relatively lower odds of in-hospital mortality (OR = 0.42, 95% CI = 0.20-0.88). Being over 80 years of age (OR = 2.03, 95% CI = 1.13-3.68), being obese (OR = 1.88, 95% CI = 1.01-3.49), and arriving in an ambulance (OR = 3.61, 95% CI = 1.95-6.68) were all independently associated with relatively higher odds of in-hospital mortality. CONCLUSION: Among patients hospitalized in Puerto Rico with acute ischemic stroke, t-PA treatment was not significantly associated with in-hospital mortality.

Impact of Day of the Week and Time of Arrival on Ischemic Stroke Management.

OBJECTIVE: The purpose of this study was to evaluate the association between measures of patient arrival day (weekday or weekend day), day part (nighttime vs. daytime) and hour (regular hours vs. off hours) at the stroke unit of the Emergency Department of the Puerto Rico Medical Center and the following time-to-treatment measures: door-to-CT-scan, door-to-needle, and stroke-onset-to-treatment. METHODS: In this retrospective study, the data of 54 patients was obtained from the stroke unit of the Puerto Rico Medical Center through the Get With The Guidelines- Stroke Registry. Inclusion criteria were as follows: having an ischemic stroke within the period covering from August 2008 through February 2010 and being at least 18 years old. Associations between patient arrival time and timeliness of interventions were assessed using t-tests/Mann-Whitney tests and chi-square tests/Fisher's exact tests, as appropriate. RESULTS: The majority of the patients (74%) were men. The mean and standard deviation of age was 67±14 years. The median of times for door-to-CT-scan and onset to treatment were 15 minutes (interquartile range=15) and 2.7 hours (interquartile range=0.6), respectively. The mean and standard deviation for door-to-needle time was 77±18 minutes. No differences were found for any of the variables in terms of arrival date, day part or hour (p>0.05). The median time for door-to-CT- scan was shorter for patients receiving intravenous tissue plasminogen activator treatment than it was for those not receiving such treatment (12 minutes vs. 20 minutes; p=0.02). CONCLUSION: The timeliness of the stroke management interventions did not differ significantly in terms of arrival day, day part, or hour.

Interventional procedures of the spine.

Different interventional procedures performed under imaging guidance permit the diagnosis and treatment of the many causes of back pain. Sources of pain amenable to be treated include facet joints, vertebral body, intervertebral disk, and paraspinal structures including nerves and ganglion roots. These procedures may be merely diagnostic, therapeutic, or intended for both purposes. We review the main indications, advantages, and complications of these techniques.

Ultrasound guided injections in ankle and foot.

Ultrasound guidance is particularly useful for percutaneous injections in the diagnosis and management of painful conditions of the ankle and foot. The injectates used include steroids and local anesthetics, such as lidocaine, mepivacaine, bupivacaine, ropivacaine, and platelet-rich plasma. Osteoarthritis is the main indication for joint injections. Joints amenable to being injected include the tibiotalar, subtalar, midtarsal, and metatarsophalangeal joints. Tendon injections mainly involve the Achilles, peroneus, extensors, and tibialis tendons, while plantar fascia injections are useful for treating plantar fasciitis and plantar fibromatosis. Forefoot injections include joint arthritis, intermetatarsal bursitis, and Morton neuroma. The standardized approaches and doses reviewed in this paper are based on the authors' experience and can lead to high success in symptomatic relief for various conditions. These injections can be curative or serve as a guide to identify the source of pain when surgery or other therapeutic options are planned.

The Educational Impact of Radiology in Anatomy Teaching: A Field Study Using Cross-Sectional Imaging and 3D Printing for the Study of the Spine.

INTRODUCTION: Cross-sectional imaging and 3D printing represent state-of-the-art approaches to improve anatomy teaching compared to traditional learning, but their use in medical schools remains limited. This study explores the utility of these educational tools for teaching normal and pathological spinal anatomy, aiming to improve undergraduate medical education. MATERIALS AND METHODS: A field study was conducted on a cohort of undergraduate medical students who were exposed to anatomy lessons of the spine considering three learning paradigms: traditional learning, cross-sectional imaging examinations, and 3D printed models. 20 students (intervention group) received the three approaches, and other 20 students (control group) received the conventional (traditional) approach. The students were examined through a multiple-choice test and their results were compared to those of a control group exposed to traditional learning matched by age, sex and anatomy grades. In addition, students in the experimental group were assessed for their satisfaction with each learning method by means of an ad hoc questionnaire. RESULTS: Students exposed to cross-sectional imaging and 3D printing demonstrated better knowledge outcomes compared to the control group. They showed high satisfaction rates and reported that these technologies enhanced spatial understanding and facilitated visualization of specific pathologies. However, limitations such as the representativeness of non-bone conditions in 3D printed models and the need for further knowledge on imaging fundamentals were highlighted. CONCLUSION: Cross-sectional imaging and 3D printing offer valuable tools for enhancing the teaching of spinal anatomy in undergraduate medical education. Radiologists are well positioned to lead the integration of these technologies, and further research should explore their potential in teaching anatomy across different anatomical regions.

Factors influencing vertebral collapse in osteoporotic vertebral fractures: a case-control study of symptomatic patients attended in the emergency department.

This study aimed to identify risk factors for the collapse of osteoporotic vertebral fractures (OVFs). We analyzed data from conventional radiography and computed tomography in patients with OVFs and found that older age and two radiological measurements were predictive for vertebral collapse. These factors can be useful for clinical practice. PURPOSE: To identify risk factors for collapse of osteoporotic vertebral fractures (OVF) on computed tomography (CT) and conventional radiography (CR). METHODS: This is a retrospective case-control study including a series of patients with OVF diagnosed at the emergency department of our institution from January to September 2019. Inclusion criteria were to have standing CR and supine CT within 2 weeks after the diagnosis of OVF and a follow-up CR at 6 months or later. We evaluated different imaging measurements at the initial diagnostic examinations, including vertebral height loss, local kyphosis, vertebral density, and fracture type according to the grading systems of Genant, Sugita, Association of Osteosynthesis (AO) Spine, and the German Society for Orthopaedics and Trauma. Vertebral collapse was defined as loss of ≥ 50% of vertebral area or height. Cases and controls were defined as OVFs which collapse and do not collapse, respectively, on follow-up. RESULTS: Fifty-six patients were included in the study, with a mean age of 72.6 ± 1.2 years, including 48 women. Twenty-five (44.6%) OVFs developed collapse on follow-up. None of the fracture classification systems were found to be predictive of collapse. Multivariate analysis showed that older age, increased density ratio (≥ 2) between the fractured and non-fractured vertebral bodies, and a ≥ 6% difference in posterior vertebral height (PVH) loss between standing CR and supine CT exhibited 88% discriminative power in predicting vertebral collapse. CONCLUSIONS: Age over 72.5 years, a density ratio ≥ 2 between the fractured and non-fractured vertebral bodies, and a difference equal to or higher than 6% in PVH loss between standing CR and supine CT, are risk factors for developing vertebral collapse after OVF.

The microbiome in HLA-B27-associated disease: implications for acute anterior uveitis and recommendations for future studies.

The pathogenesis of human leukocyte antigen (HLA)-B27-associated diseases such as acute anterior uveitis (AAU) and ankylosing spondylitis (AS) remains poorly understood, though Gram-negative bacteria and subclinical bowel inflammation are strongly implicated. Accumulating evidence from animal models and clinical studies supports several hypotheses, including HLA-B27-dependent dysbiosis, altered intestinal permeability, and molecular mimicry. However, the existing literature is hampered by inadequate studies designed to establish causation or uncover the role of viruses and fungi. Moreover, the unique disease model afforded by AAU to study the gut microbiota has been neglected. This review critically evaluates the current literature and prevailing hypotheses on the link between the gut microbiota and HLA-B27-associated disease. We propose a new potential role for HLA-B27-driven altered antibody responses to gut microbiota in disease pathogenesis and outline recommendations for future well-controlled human studies, focusing on AAU.

Persistence of a Frameshifting Deletion in SARS-CoV-2 ORF7a for the Duration of a Major Outbreak.

Australia experienced widespread COVID-19 outbreaks from infection with the SARS-CoV-2 Delta variant between June 2021 and February 2022. A 17-nucleotide frameshift-inducing deletion in ORF7a rapidly became represented at the consensus level (Delta-ORF7aΔ17del) in most Australian outbreak cases. Studies from early in the COVID-19 pandemic suggest that frameshift-inducing deletions in ORF7a do not persist for long in the population; therefore, Delta-ORF7aΔ17del genomes should have disappeared early in the Australian outbreak. In this study, we conducted a retrospective analysis of global Delta genomes to characterise the dynamics of Delta-ORF7aΔ17del over time, determined the frequency of all ORF7a deletions worldwide, and compared global trends with those of the Australian Delta outbreak. We downloaded all GISAID clade GK Delta genomes and scanned them for deletions in ORF7a. For each deletion we identified, we characterised its frequency, the number of countries it was found in, and how long it persisted. Of the 4,018,216 Delta genomes identified globally, 134,751 (~3.35%) possessed an ORF7a deletion, and ORF7aΔ17del was the most common. ORF7aΔ17del was the sole deletion in 28,014 genomes, of which 27,912 (~99.6%) originated from the Australian outbreak. During the outbreak, ~87% of genomes were Delta-ORF7aΔ17del, and genomes with this deletion were sampled until the outbreak's end. These data demonstrate that, contrary to suggestions early in the COVID-19 pandemic, genomes with frameshifting deletions in ORF7a can persist over long time periods. We suggest that the proliferation of Delta-ORF7aΔ17del genomes was likely a chance founder effect. Nonetheless, the frequency of ORF7a deletions in SARS-CoV-2 genomes worldwide suggests they might have some benefit for virus transmission.

Ghost Fat: Altered Female Body Perception After Bariatric Surgery.

Body perception is an individual's ability to recognize their body in attitudinal and/or dimensional aspects. We investigated women's body perceptions before and after bariatric surgery. Participants were 31 women (M age = 36.23, SD = 7.95 years old) with an average pre-operative body mass index of 44.58 (SD = 4.65) kg/m2. We collected anthropometric and body perception measures (attitudinal body image [ABI] and dimensional body image [DBI]) before bariatric surgery and 30, 60, 90, and 120 days after it. There was an average decrease of 21.09% in participants' body weight over the 120 days. Regarding ABI, 51.61% of participants had high body dissatisfaction before surgery, and this proportion of dissatisfied participants decreased to 3.23% 120 days after surgery. We observed no statistically significant differences in DBI perceptions. Fast weight loss caused by bariatric surgery appeared to generate a perception of ghost fat. Somatosensory interventions and/or a longer follow-up are needed to alter this persistent distortion of body dimensions.

Interplay between heme oxygenase-1 and the multifunctional transcription factor yin yang 1 in the inhibition of intimal hyperplasia.

RATIONALE: induction of heme oxygenase (HO)-1 protects against experimental atherosclerotic diseases, and certain pharmacological HO-1 inducers, like probucol, inhibit the proliferation of vascular smooth muscle cells and, at the same time, promote the growth of endothelial cells in vivo and in vitro. OBJECTIVE: because such cell-specific effects are reminiscent of the action of the transcription factor Yin Yang (YY)1, we tested the hypothesis that there is a functional relationship between HO-1 and YY1. METHODS AND RESULTS: we report that probucol increases the number of YY1(+) cells in rat carotid artery following balloon injury at a time coinciding with increased HO-1 expression. The drug also induces the expression of YY1 mRNA and protein in rat aortic smooth muscle cells (RASMCs) in vitro, as do other known HO-1 inducers (tert-butylhydroquinone and hemin) and overexpression of HO-1 using a human HMOX1 cDNA plasmid. Conversely, overexpression of YY1 induces expression of HO-1 in RASMCs. Induction of YY1 expression is dependent on HO-1 enzyme activity and its reaction product CO, because pharmacological inhibition of heme oxygenase activity or CO scavenging block, whereas exposure of RASMCs to a CO-releasing molecule increases, YY1 expression. Furthermore, RNA interference knockdown of YY1 prevents probucol or adeno-HO-1 from inhibiting RASMC proliferation in vitro and neointimal formation in vivo. CONCLUSIONS: our findings show, for the first time, that HO-1 functionally interplays with the multifunctional transcription factor YY1 and that this interplay explains some of the protective activities of HO-1.

Macrophage migration inhibitory factor increases leukocyte-endothelial interactions in human endothelial cells via promotion of expression of adhesion molecules.

Macrophage migration inhibitory factor (MIF) has been shown to promote leukocyte-endothelial cell interactions, although whether this occurs via an effect on endothelial cell function remains unclear. Therefore, the aims of this study were to examine the ability of MIF expressed by endothelial cells to promote leukocyte adhesion and to investigate the effect of exogenous MIF on leukocyte-endothelial interactions. Using small interfering RNA to inhibit HUVEC MIF production, we found that MIF deficiency reduced the ability of TNF-stimulated HUVECs to support leukocyte rolling and adhesion under flow conditions. These reductions were associated with decreased expression of E-selectin, ICAM-1, VCAM-1, IL-8, and MCP-1. Inhibition of p38 MAPK had a similar effect on adhesion molecule expression, and p38 MAPK activation was reduced in MIF-deficient HUVECs, suggesting that MIF mediated these effects via promotion of p38 MAPK activation. In experiments examining the effect of exogenous MIF, application of MIF to resting HUVECs failed to induce leukocyte rolling and adhesion, whereas addition of MIF to TNF-treated HUVECs increased these interactions. This increase was independent of alterations in TNF-induced expression of E-selectin, VCAM-1, and ICAM-1. However, combined treatment with MIF and TNF induced de novo expression of P-selectin, which contributed to leukocyte rolling. In summary, these experiments reveal that endothelial cell-expressed MIF and exogenous MIF promote endothelial adhesive function via different pathways. Endogenous MIF promotes leukocyte recruitment via effects on endothelial expression of several adhesion molecules and chemokines, whereas exogenous MIF facilitates leukocyte recruitment induced by TNF by promoting endothelial P-selectin expression.