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BackgroundChronic low back pain (cLBP) is a complex with a heterogenous clinical presentation. A better understanding of the factors that contribute to cLBP is needed for accurate diagnosis, optimal treatment, and identification of mechanistic targets for new therapies. The Back Pain Consortium (BACPAC) Research Program provides a unique opportunity in this regard, as it will generate large clinical datasets, including a diverse set of harmonized measurements. The Theoretical Model Working Group was established to guide BACPAC research and to organize new knowledge within a mechanistic framework. This article summarizes the initial work of the Theoretical Model Working Group. It includes a three-stage integration of expert opinion and an umbrella literature review of factors that affect cLBP severity and chronicity.MethodsDuring Stage 1, experts from across BACPAC established a taxonomy for risk and prognostic factors (RPFs) and preliminary graphical depictions. During Stage 2, a separate team conducted a literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to establish working definitions, associated data elements, and overall strength of evidence for identified RPFs. These were subsequently integrated with expert opinion during Stage 3.ResultsThe majority (∼80%) of RPFs had little strength-of-evidence confidence, whereas seven factors had substantial confidence for either a positive association with cLBP (pain-related anxiety, serum C-reactive protein, diabetes, and anticipatory/compensatory postural adjustments) or no association with cLBP (serum interleukin 1-beta / interleukin 6, transversus muscle morphology/activity, and quantitative sensory testing).ConclusionThis theoretical perspective will evolve over time as BACPAC investigators link empirical results to theory, challenge current ideas of the biopsychosocial model, and use a systems approach to develop tools and algorithms that disentangle the dynamic interactions among cLBP factors.

OBJECTIVES: Venous thrombosis has been widely described in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, arterial thrombosis has rarely been reported. This study aims to assess the incidence, risk factors, interventions, and outcomes of acute aortoiliac arterial thrombosis in patients with active SARS-CoV-2 infections. METHODS: We present seven SARS-CoV-2-positive patients from our institution who acutely developed thrombi in the aortoiliac arterial system (7/2020-1/2021). A systematic review of the literature on aortoiliac arterial thrombosis in patients with SARS-CoV-2 infections in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was also performed. The available data from all reported cases in the literature and at our institution were analyzed. RESULTS: Thirty published articles and journal correspondences, including 52 patients, were reviewed and analyzed in addition to our institutions 7 cases. In total, 59 SARS-CoV-2-positive patients were found to have acute aortoiliac thrombosis. The abdominal aorta was the most frequent location for the development of a thrombus. Baseline demographics and medical comorbidities were not significantly different between the symptomatic and asymptomatic cohorts. Seventy-one percent of patients were symptomatic (lower limb ischemia: 75.0%, renal infarction: 20.0%, stroke: 12.5%, mesenteric ischemia: 10.0%). All patients with thrombus involving the ascending aorta, aortic bifurcation, or iliac artery developed thromboembolic or ischemic complications. All patients received systemic anticoagulation. Fifty-three percent of all patients were managed medically. Ninety-four percent of the asymptomatic patients were managed medically. One asymptomatic patient underwent endovascular aspiration of a mobile thrombus. Three (23.1%) deaths occurred in the asymptomatic cohort from hypoxic respiratory failure. Fourteen (36.8%) deaths occurred in the symptomatic cohort. The in-hospital mortality rate was 33.3% overall and 43.8% for patients with thrombi involving more than one aortoiliac segment. CONCLUSIONS: The presence of thrombi in the aortoiliac arterial system appears to be a poor prognostic indicator for patients with active SARS-CoV-2 infections. Medical management of patients with asymptomatic aortoiliac thrombi may be considered. The presence of thrombi involving the ascending aorta, aortic bifurcation, or iliac artery may warrant consideration for operative intervention due to the risk for thromboembolic or ischemic complications. Further study is needed to fully delineate the risk factors, optimal treatment, and outcomes of arterial thrombosis in the setting of SARS-CoV-2 infection.

We analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8,476 finger stick blood specimens were collected before and after an aggressive mRNA vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing 10 SARS-CoV-2 antigens, 4 SARS, 3 MERS, 12 Common CoV, and 8 Influenza antigens. Twenty-six percent of 3,347 specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive. The Ab response was predominantly against nucleocapsid (NP), full length spike and the spike S2 domain. Anti-receptor binding domain (RBD) reactivity was low and there was no cross-reactivity against SARS S1 or SARS RBD. An aggressive mRNA vaccination campaign at the UCI Medical Center started on December 16, 2020 and 6,724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% in December to 79% in January, 93% in February and 99% in March. mRNA vaccination induced much higher Ab levels especially against the RBD domain and significant cross-reactivity against SARS RBD and S1 was also observed. Nucleocapsid protein Abs can be used to distinguish individuals in a population of vaccinees to classify those who have been previously infected and those who have not, because nucleocapsid is not in the vaccine. Previously infected individuals developed higher Ab titers to the vaccine than those who have not been previously exposed. These results indicate that mRNA vaccination rapidly induces a much stronger and broader Ab response than SARS-CoV-2 infection.

We analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8476 finger stick blood specimens were collected before and after a vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing antigens from SARS-CoV-2, SARS, MERS, Common CoV, and Influenza. Twenty-six percent of specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive; out of 852 seropositive individuals 77 had symptoms and 9 sought medical care. The antibody response was predominantly against nucleocapsid (NP), full length, and S2 domain of spike. Anti-receptor binding domain (RBD) reactivity was low and not cross-reactive against SARS S1 or SARS RBD. A vaccination campaign at the University of California Irvine Medical Center (UCIMC) started on December, 2020 and 6724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% pre-vaccination to 79% post-vaccination in January, 93% in February, and 99% in March. mRNA vaccination induced higher antibody levels than natural exposure, especially against the RBD domain and cross-reactivity against SARS RBD and S1 was observed. Nucleocapsid protein antibodies can be used to distinguish vaccinees to classify pre-exposure to SARS-CoV-2 Previously infected individuals developed higher antibody titers to the vaccine than non pre-exposed individuals. Hospitalized patients in intensive care with severe disease reach significantly higher antibody levels than mild cases, but lower antibody levels compared to the vaccine. These results indicate that mRNA vaccination rapidly induces a much stronger and broader antibody response than SARS-CoV-2 infection.

Nuclear compartments have diverse roles in regulating gene expression, yet the molecular forces and components that drive compartment formation remain largely unclear1. The long non-coding RNA Xist establishes an intra-chromosomal compartment by localizing at a high concentration in a territory spatially close to its transcription locus2 and binding diverse proteins3-5 to achieve X-chromosome inactivation (XCI)6,7. The XCI process therefore serves as a paradigm for understanding how RNA-mediated recruitment of various proteins induces a functional compartment. The properties of the inactive X (Xi)-compartment are known to change over time, because after initial Xist spreading and transcriptional shutoff a state is reached in which gene silencing remains stable even if Xist is turned off8. Here we show that the Xist RNA-binding proteins PTBP19, MATR310, TDP-4311 and CELF112 assemble on the multivalent E-repeat element of Xist7 and, via self-aggregation and heterotypic protein-protein interactions, form a condensate1 in the Xi. This condensate is required for gene silencing and for the anchoring of Xist to the Xi territory, and can be sustained in the absence of Xist. Notably, these E-repeat-binding proteins become essential coincident with transition to the Xist-independent XCI phase8, indicating that the condensate seeded by the E-repeat underlies the developmental switch from Xist-dependence to Xist-independence. Taken together, our data show that Xist forms the Xi compartment by seeding a heteromeric condensate that consists of ubiquitous RNA-binding proteins, revealing an unanticipated mechanism for heritable gene silencing.

A retrospective cohort study was conducted to determine the duration of motor block regression following neuraxial anesthesia for caesarean delivery. The study found that using a time threshold of 4 hours for straight leg raise against gravity, a large number of patients required review, leading to a labor-intensive process. The study also hypothesized that the median time to motor block regression after spinal or epidural anesthesia is greater than 4 hours. The results showed that more than 50% of patients still had significant motor block at 4 hours following spinal anesthesia, prompting the extension of the time trigger to 6 hours. The study suggests the need for further research on obstetric neuraxial regression times and the impact of different time triggers for neurological monitoring protocols. [Extracted from the article]

Although major genetic networks controlling early liver specification and morphogenesis are known, the mechanisms responsible for postnatal hepatic maturation are poorly understood. Here we employ global analyses of the mouse liver transcriptome to demonstrate that postnatal remodelling of the liver is accompanied by large-scale transcriptional and post-transcriptional transitions that are cell-type-specific and temporally coordinated. Combining detailed expression analyses with gain- and loss-of-function studies, we identify epithelial splicing regulatory protein 2 (ESRP2) as a conserved regulatory factor that controls the neonatal-to-adult switch of ∼20% of splice isoforms in mouse and human hepatocytes. The normal shift in splicing coincides tightly with dramatic postnatal induction of ESRP2 in hepatocytes. We further demonstrate that forced expression of ESRP2 in immature mouse and human hepatocytes is sufficient to drive a reciprocal shift in splicing and causes various physiological abnormalities. These findings define a direct role for ESRP2 in the generation of conserved repertoires of adult splice isoforms that facilitate terminal differentiation and maturation of hepatocytes.

Background: Unlike tachyarrhythmias, which are common in pregnancy, there is a paucity of data regarding maternal bradycardias. Our objective was to describe the characteristics, associated conditions, and prognosis of women who develop bradycardia post-partum. Method: We conducted a retrospective chart review of patients referred to the Obstetrical Medicine service at British Columbia Women's Hospital from January 2012 to May 2020 for post-partum maternal bradycardia. Results: Twenty-four patients with post-partum bradycardia were included (age 34.2 ± 4.8 years; heart rate 40.4 ± 8.1 beats per minute; blood pressure 131/72 mm Hg). Sinus bradycardia (79.2%) was the most common rhythm. Dyspnea (29.4%) and chest pain (23.5%) were common symptoms. Mean time to resolution of bradycardia was 3.6 ± 3.8 days. Associated conditions potentially explaining the bradycardia were preeclampsia (54.1%), underlying (16.7%), medications (8.3%), and neuraxial anesthesia (8.3%). Conclusions: Maternal bradycardia is an uncommon condition complicating the post-partum period, that is generally self-limiting, with the majority only require clinical observation. [ABSTRACT FROM AUTHOR]

Controversy remains with the use of post-operative subfascial drains for anterior cervical discectomy and fusion, with limited guidelines and a paucity of conclusive evidence. Thus, the aim of this meta-analysis was to analyse and collate an evidence summary to determine the efficacy of such drains. A systematic search of Medline (2002–2022.11), PubMed (2003-2022.11), Scopus (2002-2022.11), Cochrane Library (2015-2022.11) databases and reference lists of articles was conducted as per Cochrane systematic reviews standards. All relevant RCTs and NRCTs were included in this study. Data was extracted in a standardised form and analysed with RevMan version 5.4.1. Bias was assessed with RoB2 tool for RCTs and ROBINS-E tool for NRCTs. Two RCTs (136 patients) and five NRCTs (7563 patients) were included. These had a moderate to high risk of bias, except for one very high-risk article. Meta-analysis results showed no significant differences for post-operative haematoma (P = 0.31), surgical site infection (P = 0.84), take back to theatre (P = 0.27), length of stay (P = 0.34), and estimated blood loss (P = 0.09). Dysphagia (P = 0.002) and median operative time (P = 0.02) were significantly increased in the drain cohort. The low quality of available data in the included studies is insufficient to estimate the effect of post-operative drains for elective spondylotic ACDF. The findings suggest that if the decision to leave a drain in is left to the surgeon, then there is no difference in the rates of POH, SSI, LOS, or take back to the theatre. The significant association of dysphagia and increased operative time with drains, and the non-significant trend towards increased EBL with drains, must be considered in the context in which procedures may influence the decision to place drains. The results could not be stratified by various confounders that affect the decision-making process, including the number of levels operated. Due to the decreased quality and amount of evidence available, large-scale RCTs that adequately account for confounders should be performed. [ABSTRACT FROM AUTHOR]