Background:
The occurrence of physiologic knee hyperextension (HE) in the revision anterior cruciate ligament reconstruction (ACLR) population and its effect on outcomes have yet to be reported.
...Hypothesis/Purpose:
The prevalence of knee HE in revision ACLR and its effect on 2-year outcome were studied with the hypothesis that preoperative physiologic knee HE ≥5° is a risk factor for anterior cruciate ligament (ACL) graft rupture.
Study Design:
Cohort study; Level of evidence, 2.
Methods:
Patients undergoing revision ACLR were identified and prospectively enrolled between 2006 and 2011. Study inclusion criteria were patients undergoing single-bundle graft reconstructions. Patients were followed up at 2 years and asked to complete an identical set of outcome instruments (International Knee Documentation Committee, Knee injury and Osteoarthritis Outcome Score, WOMAC, and Marx Activity Rating Scale) as well as provide information regarding revision ACL graft failure. A regression model with graft failure as the dependent variable included age, sex, graft type at the time of the revision ACL surgery, and physiologic preoperative passive HE ≥5° (yes/no) to assess these as potential risk factors for clinical outcomes 2 years after revision ACLR.
Results:
Analyses included 1145 patients, for whom 2-year follow-up was attained for 91%. The median age was 26 years, with age being a continuous variable. Those below the median were grouped as “younger” and those above as “older” (age: interquartile range = 20, 35 years), and 42% of patients were female. There were 50% autografts, 48% allografts, and 2% that had a combination of autograft plus allograft. Passive knee HE ≥5° was present in 374 (33%) patients in the revision cohort, with 52% being female. Graft rupture at 2-year follow-up occurred in 34 cases in the entire cohort, of which 12 were in the HE ≥5° group (3.2% failure rate) and 22 in the non-HE group (2.9% failure rate). The median age of patients who failed was 19 years, as opposed to 26 years for those with intact grafts. Three variables in the regression model were significant predictors of graft failure: younger age (odds ratio OR = 3.6; 95% CI, 1.6-7.9; P = .002), use of allograft (OR = 3.3; 95% CI, 1.5-7.4; P = .003), and HE ≥5° (OR = 2.12; 95% CI, 1.1-4.7; P = .03).
Conclusion:
This study revealed that preoperative physiologic passive knee HE ≥5° is present in one-third of patients who undergo revision ACLR. HE ≥5° was an independent significant predictor of graft failure after revision ACLR with a >2-fold OR of subsequent graft rupture in revision ACL surgery.
Registration:
NCT00625885 (ClinicalTrials.gov identifier).
Three Ottawa control strains and a current commercial laying stock were reared and housed in the same environment. Eggs were collected at 5 different hen ages throughout the 2 production cycles of ...the flock. The eggs were inoculated with Salmonella Enteritidis (SE), Pseudomonas fluorescens (PF), a combination of the 2, or sterile buffered peptone water and stored up to 5 wk. After storage at room temperature, contamination levels were determined for the exterior surface, air cell, egg contents, and within the shell. Interior, egg contents, and shell contamination levels of SE and PF increased with storage time. There were no apparent increases in the infectivity of SE or PF in the presence of the other organism. PF was a poor survivor on the shell surface under these storage conditions. Throughout the 5-wk storage, eggs from control strain 10 maintained their microbial integrity more effectively. Eggs from control strain 5 and the current commercial stock were more easily contaminated than the other strains. These data suggest that genetic selection has altered microbiological defenses of the eggs produced.
Regulatory T cells (Treg) are immunosuppressive and negatively impact response to cancer immunotherapies. CREB-binding protein (CBP) and p300 are closely related acetyltransferases and ...transcriptional coactivators. Here, we evaluate the mechanisms by which CBP/p300 regulate Treg differentiation and the consequences of
loss-of-function mutations in follicular lymphoma. Transcriptional and epigenetic profiling identified a cascade of transcription factors essential for Treg differentiation. Mass spectrometry analysis showed that CBP/p300 acetylates prostacyclin synthase, which regulates Treg differentiation by altering proinflammatory cytokine secretion by T and B cells. Reduced Treg presence in tissues harboring
loss-of-function mutations was observed in follicular lymphoma. Our findings provide novel insights into the regulation of Treg differentiation by CBP/p300, with potential clinical implications on alteration of the immune landscape. SIGNIFICANCE: This study provides insights into the dynamic role of CBP/p300 in the differentiation of Tregs, with potential clinical implications in the alteration of the immune landscape in follicular lymphoma.
ABSTRACT Discovering transiting exoplanets with relatively long orbital periods (>10 d) is crucial to facilitate the study of cool exoplanet atmospheres (Teq < 700 K) and to understand exoplanet ...formation and inward migration further out than typical transiting exoplanets. In order to discover these longer period transiting exoplanets, long-term photometric, and radial velocity campaigns are required. We report the discovery of TOI-2447 b (=NGTS-29 b), a Saturn-mass transiting exoplanet orbiting a bright (T = 10.0) Solar-type star (Teff = 5730 K). TOI-2447 b was identified as a transiting exoplanet candidate from a single transit event of 1.3 per cent depth and 7.29 h duration in TESS Sector 31 and a prior transit event from 2017 in NGTS data. Four further transit events were observed with NGTS photometry which revealed an orbital period of P = 69.34 d. The transit events establish a radius for TOI-2447 b of $0.865 \pm 0.010\, \rm R_{\rm J}$, while radial velocity measurements give a mass of $0.386 \pm 0.025\, \rm M_{\rm J}$. The equilibrium temperature of the planet is 414 K, making it much cooler than the majority of TESS planet discoveries. We also detect a transit signal in NGTS data not caused by TOI-2447 b, along with transit timing variations and evidence for a ∼150 d signal in radial velocity measurements. It is likely that the system hosts additional planets, but further photometry and radial velocity campaigns will be needed to determine their parameters with confidence. TOI-2447 b/NGTS-29 b joins a small but growing population of cool giants that will provide crucial insights into giant planet composition and formation mechanisms.
Background: The purpose of this study was to retrospectively review the results of patients treated with hallux MTP joint arthrodesis using dome-shaped reamers for joint preparation and a ...precontoured dorsal stainless steel plate for internal fixation. Materials and Methods: A series of 145 patients (155 feet) were identified. Postoperative evaluation included weightbearing radiographs, physical examination, and chart review. Outcomes were assessed with a pain visual analog scale, AOFAS hallux score, as well as a detailed questionnaire and a subjective satisfaction survey. Results: 98 patients (107 feet) met the criteria for the study. The mean followup was 61 weeks. Revision cases accounted for 18.7% (20/107). Rheumatoid arthritis (RA) was present in 32.7% (35/107). The average postoperative AOFAS hallux score was 79.7 and pain VAS was 19. The average pre and postoperative hallux valgus angle was 26.5 and 12.3 degrees, respectively (p < 0.05). Eighty-nine of 107 patients (83.1%) reported good to excellent results at final followup. Discomfort related to prominence of the plate occurred in 14.9% (16/107). The nonunion rate was 12.1% (13/107). The nonunion rate for patients with/without RA was 22.9% (8/35) and 6.9% (5/72), respectively (p < 0.05). Patients with a nonunion noted more hardware related pain than those with a union (p < 0.05). Conclusion: First MTP joint arthrodesis using this technique achieves a high union rate. RA patients have a lower union and higher complication rate.
Level of Evidence: IV, Retrospective Case Series
Long‐term time series of hydrogen chloride (HCl) and chlorine nitrate (ClONO2) total column abundances has been retrieved from high spectral resolution ground‐based solar absorption spectra recorded ...with infrared Fourier transform spectrometers at nine NDSC (Network for the Detection of Stratospheric Change) sites in both Northern and Southern Hemispheres. The data sets span up to 24 years and most extend until the end of 2001. The time series of Cly (defined here as the sum of the HCl and ClONO2 columns) from the three locations with the longest time‐span records show rapid increases until the early 1990s superimposed on marked day‐to‐day, seasonal and inter‐annual variability. Subsequently, the buildup in Cly slows and reaches a broad plateau after 1996, also characterized by variability. A similar time evolution is also found in the total chlorine concentration at 55 km altitude derived from Halogen Occultation Experiment (HALOE) global observations since 1991. The stabilization of inorganic chlorine observed in both the total columns and at 55 km altitude indicates that the near‐global 1993 organic chlorine (CCly) peak at the Earth's surface has now propagated over a broad altitude range in the upper atmosphere, though the time lag is difficult to quantify precisely from the current data sets, due to variability. We compare the three longest measured time series with two‐dimensional model calculations extending from 1977 to 2010, based on a halocarbon scenario that assumes past measured trends and a realistic extrapolation into the future. The model predicts broad Cly maxima consistent with the long‐term observations, followed by a slow Cly decline reaching 12–14% relative to the peak by 2010. The data reported here confirm the effectiveness of the Montreal Protocol and its Amendments and Adjustments in progressively phasing out the major man‐related perturbations of the stratospheric ozone layer, in particular, the anthropogenic chlorine‐bearing source gases.
New variants of SARS-CoV-2 are continuing to emerge and dominate the global sequence landscapes. Several variants have been labeled variants of concern (VOCs) because they may have a transmission ...advantage, increased risk of morbidity and/or mortality, or immune evasion upon a background of prior infection or vaccination. Placing the VOCs in context with the underlying variability of SARS-CoV-2 is essential in understanding virus evolution and selection pressures. Dominant genome sequences and the population genetics of SARS-CoV-2 in nasopharyngeal swabs from hospitalized patients were characterized. Nonsynonymous changes at a minor variant level were identified. These populations were generally preserved when isolates were amplified in cell culture. To place the Alpha, Beta, Delta, and Omicron VOCs in context, their growth was compared to clinical isolates of different lineages from earlier in the pandemic. The data indicated that the growth in cell culture of the Beta variant was more than that of the other variants in Vero E6 cells but not in hACE2-A549 cells. Looking at each time point, Beta grew more than the other VOCs in hACE2-A549 cells at 24 to 48 h postinfection. At 72 h postinfection there was no difference in the growth of any of the variants in either cell line. Overall, this work suggested that exploring the biology of SARS-CoV-2 is complicated by population dynamics and that these need to be considered with new variants. In the context of variation seen in other coronaviruses, the variants currently observed for SARS-CoV-2 are very similar in terms of their clinical spectrum of disease.
SARS-CoV-2 is the causative agent of COVID-19. The virus has spread across the planet, causing a global pandemic. In common with other coronaviruses, SARS-CoV-2 genomes can become quite diverse as a consequence of replicating inside cells. This has given rise to multiple variants from the original virus that infected humans. These variants may have different properties and in the context of a widespread vaccination program may render vaccines less effective. Our research confirms the degree of genetic diversity of SARS-CoV-2 in patients. By comparing the growth of previous variants to the pattern seen with four variants of concern (VOCs) (Alpha, Beta, Delta, and Omicron), we show that, at least in cells, Beta variant growth exceeds that of Alpha, Delta, and Omicron VOCs at 24 to 48 h in both Vero E6 and hACE2-A549 cells, but by 72 h postinfection, the amount of virus is not different from that of the other VOCs.
Background: Tibialis anterior tendon rupture is an uncommon injury that can cause significant functional deficit. Recent series have supported surgical reconstruction in younger, more active ...patients. We investigated our clinical outcomes of patients having undergone surgical management of tibialis anterior tendon ruptures. Materials and Methods: Fifteen tibialis anterior tendon ruptures in 14 patients were retrospectively reviewed after surgical management. Five had primary repair, while 10 had tendon transfers. Average age at time of surgery was 70.6 years with an average followup of 27.2 months. Patients were evaluated with American Orthopaedic Foot and Ankle Society (AOFAS) and SF-36 clinical outcome scores. Strength measurements utilizing a dynamometer and range of motion (ROM) were documented on the operative and non-operative ankles. Patient satisfaction surveys were performed. Results: Average postoperative AOFAS hindfoot score was 88.8 and SF-36 score was 76.4. There was a statistically significant difference in average dorsiflexion strength of 21.8 lbs/in2 on the operative side and 28.8 lbs/in2 on the non-operative limb, and in dorsi-flexion ROM of patients that received a gastrocnemius recession. There was no statistically significant difference between primary tendon repair versus tendon transfer groups nor plan-tarflexion strength or ROM among any group. Patient surveys revealed that seven patients were completely satisfied, six had minor reservations, and one had major reservations. There were no complications. Conclusion: This study supports the surgical repair or reconstruction of the tibialis anterior tendon ruptures to restore functional strength and ROM.
Level of Evidence: IV, Retrospective Case Series
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of ...screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = -0.34 years, s.e. = 0.08), major depression (β = -0.34 years, s.e. = 0.08), schizophrenia (β = -0.39 years, s.e. = 0.08), and educational attainment (β = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
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