The Use of Tranexamic Acid for Primary Prophylaxis of Heterotopic Ossification Following Total Hip Arthroplasty.

INTRODUCTION: Heterotopic ossification (HO) is a relatively common complication after total hip arthroplasty (THA) and can range from a radiographic observation only to severely disabling and requiring revision surgery. Prophylaxis is recommended for high-risk patients, though the ideal method and targeted population are open to debate. Tranexamic acid (TXA) is a medication increasingly being used to reduce blood loss associated with orthopaedic surgeries, including THA. METHODS: A retrospective review of 357 patients undergoing THA from November 2020 through December 2023 was conducted. The patients were grouped based on whether they received intravenous TXA perioperatively or not, and their propensity score matched 2:1 TXA to no TXA on age, body mass index, sex, the Charlson Comorbidity Index, and perioperative celecoxib use. Univariate and multivariate analyses were performed. RESULTS: After propensity score matching, the only significant differences between groups were American Society of Anesthesiologists scores and preoperative celecoxib use between groups, as the TXA group had fewer patients who had an ASA of 3 or more (38.9 versus 58.5%, P < 0.001) and more patients who had taken celecoxib preoperatively (16.3 versus 5.9%, P = 0.010). Perioperatively, patients were more likely to undergo THA using the anterior approach (74.5 versus 57.6%, P = 0.002) and were more likely to receive postoperative celecoxib prescriptions (44.8 versus 31.4%, P = 0.021), but there was no difference in other nonsteroidal anti-inflammatory drug usage postoperatively. Postoperatively, patients who received TXA had a lower rate of heterotopic ossification on the last postoperative x-ray (20.1 versus 33.9%, P = 0.007). Multivariable logistic regression, to assess predictors of HO, found that patients who had TXA were 42% less likely to have visible HO (OR [odds ratio] = 0.58, P = 0.047) while holding surgical approach, ASA score, preoperative and postoperative celecoxib use, and postoperative other NSAID use constant. CONCLUSION: The use of tranexamic acid in patients undergoing primary total hip arthroplasty results in a decreased likelihood of heterotopic ossification formation on postoperative x-rays.

Scoping review of the role of social support in women veterans' psychosocial and health outcomes.

Women veterans are a steadily growing population and have unique military experiences (e.g., report high rates of sexual harassment and assault) that are impactful across the lifespan. High levels of positive social support have been linked to a range of positive outcomes in both civilian and military populations. However, research has not consistently explored social support and interpersonal functioning in women veterans, or as potential mechanisms of change within interventions for women veterans. This is a scoping review of peer-reviewed articles that evaluated social support. Articles with at least 10% women or formally evaluated sex or gender in reference to social support were included. A total of 69 studies evaluated social support in relation to women veterans' health outcomes. From a biopsychosocial perspective, social support is an important construct to examine relative to health care engagement and response. Limited research considered aging women veterans needs or focused on the intersectional identities of women veterans. Positive social support can have major physical and mental health benefits, yet limited research and disparate methodological approaches minimize the ability to draw conclusions on how social support can best be leveraged to support women veterans. Women veterans' roles and military experiences (e.g., increased likelihood of combat exposure) are changing and this population is aging. Research is needed to inform best practices for this growing segment of the veteran population.

Women veterans are a growing population with unique military experiences and post-service health needs. Positive social support can have major physical and mental health benefits, however unique effects of women veterans' social support have been understudied particularly with regards to the impact over the lifespan. This review summarizes the state of literature on social support in women veterans, describes relationships among social support and mental and physical health outcomes, and highlights implications for future research, intervention, and prevention work.

Trends in Patient-Reported Physical Function After Hip Fracture Surgery.

Background Hip fractures carry significant morbidity and mortality, yet studies assessing post-surgical functional recovery from the patient's perspective are scarce, lacking benchmarks against age-matched populations. This study aimed to identify factors influencing postoperative functional outcomes, compared to the lower 25th percentile of normal age-matched populations, and to compare postoperative physical function with one-year mortality following hip fracture surgery. Methodology A retrospective review of 214 hip fracture patients reporting to the emergency department (ED) from July 2020 to June 2023 was conducted, with all completing a three-month postoperative Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) survey. Primary outcomes included three-month PROMIS-PF scores, with secondary outcomes focusing on one-year mortality. Factors such as demographics, comorbidities, procedures, time to surgery, length of stay, and postoperative outcomes were analyzed for correlation. Multivariate logistic regression assessed predictors of achieving a PROMIS-PF T-score of at least 32.5, representing the bottom 25th percentile for age-matched populations, and the relationship between three-month PROMIS PF T-scores and one-year mortality. Results Surgery was performed within 24 hours of ED arrival in 118 (55.1%) patients, the average length of stay was 5.2 days, and 64 (29.9%) were discharged home. Total hip arthroplasty and home discharge correlated with higher physical function scores. In contrast, older age, higher American Society of Anesthesiologists scores, certain comorbidities, specific surgical procedures, and longer hospital stays were associated with lower scores. Fewer than half (102 [47.7%]) achieved functional levels comparable to the 25th percentile of age-matched populations. Multivariate analysis indicated chronic obstructive pulmonary disease and home discharge as predictors of achieving this threshold, while higher PROMIS-PF T-scores were associated with reduced one-year mortality. Conclusions Patients undergoing hip fracture surgery are unlikely to achieve high levels of physical function within the three-month postoperative period. Fewer than half of these patients will reach functional levels, and decreased early function is associated with an increased risk of one-year mortality.

Current physiotherapy practice for adults with bronchiectasis: Data from the Australian bronchiectasis registry.

BACKGROUND: Although airway clearance techniques (ACTs) and physical exercise are recommended for adults with bronchiectasis, there is little data on current practice and limited guidance predicting clinical approach. OBJECTIVE: This study aimed to describe current ACT and exercise practice recorded by patients, and identify predictors of regular ACTs, ACT modalities and exercise. METHODS: Physiotherapy-specific interventions, quality of life (Quality-of-Life Bronchiectasis questionnaire, QOL-B), demographics and disease severity were extracted from the Australian Bronchiectasis Registry. Multivariate analyses were undertaken to identify predictors of undertaking ACTs or exercise. RESULTS: We included 461 patients; median age of 72 years (interquartile range 64-78 years). Regular ACT use was recorded by 266 (58 %) patients; the active cycle of breathing technique (n = 175, 74 %) was the most common technique. Regular exercise use was recorded by 213 (46 %) patients, with walking the most common form of exercise. A pulmonary rehabilitation referral was made for 90 (19.5 %) of patients. Regular ACT use was associated with a higher treatment burden on QOL-B (Odds ratio (OR) = 0.97, 95 % confidence interval (CI) 0.96 to 0.99). Regular exercise was more likely amongst patients with severe bronchiectasis compared to those with mild disease (OR = 9.46, 95 % CI 1.94 to 67.83) and in those with greater physical function on the QOL-B (OR = 1.02, 95 % CI 1.01 to 1.04). CONCLUSION: Approximately half the adults in the registry report regular ACT or exercise; QOL and disease severity predict this engagement. This knowledge may guide the tailoring of ACTs and exercise prescription to optimise physiotherapy management in adults with bronchiectasis.

Peripheral-derived regulatory T cells contribute to tumor-mediated immune suppression in a nonredundant manner.

Identifying tumor-mediated mechanisms that impair immunity is instrumental for the design of new cancer therapies. Regulatory T cells (Tregs) are a key component of cancer-derived immune suppression; however, these lymphocytes are necessary to prevent systemic autoimmunity in mice and humans, and thus, direct targeting of Tregs is not a clinical option for cancer patients. We have previously demonstrated that excising transcription factor Kruppel-like factor 2 (Klf2) within the T cell lineage blocks the generation of peripheral-derived Tregs (pTregs) without impairing production of thymic-derived Tregs. Using this mouse model, we have now demonstrated that eliminating pTregs is sufficient to delay/prevent tumor malignancy without causing autoimmunity. Cancer-bearing mice that expressed KLF2 converted tumor-specific CD4+ T cells into pTregs, which accumulated in secondary lymphoid organs and impaired further T cell effector activity. In contrast, pTreg-deficient mice retained cancer-specific immunity, including improved T cell infiltration into "cold" tumors, reduced T cell exhaustion in tumor beds, restricted generation of tumor-associated myeloid-derived suppressor cells, and the continued production of circulating effector T cells that arose in a cancer-dependent manner. Results indicate that tumor-specific pTregs are critical for early stages of cancer progression and blocking the generation of these inhibitory lymphocytes safely delays/prevents malignancy in preclinical models of melanoma and prostate cancer.

Microscale Thermophoresis (MST) as a Tool to Study Binding Interactions of Oxygen-Sensitive Biohybrids.

Microscale thermophoresis (MST) is a technique used to measure the strength of molecular interactions. MST is a thermophoretic-based technique that monitors the change in fluorescence associated with the movement of fluorescent-labeled molecules in response to a temperature gradient triggered by an IR LASER. MST has advantages over other approaches for examining molecular interactions, such as isothermal titration calorimetry, nuclear magnetic resonance, biolayer interferometry, and surface plasmon resonance, requiring a small sample size that does not need to be immobilized and a high-sensitivity fluorescence detection. In addition, since the approach involves the loading of samples into capillaries that can be easily sealed, it can be adapted to analyze oxygen-sensitive samples. In this Bio-protocol, we describe the troubleshooting and optimization we have done to enable the use of MST to examine protein-protein interactions, protein-ligand interactions, and protein-nanocrystal interactions. The salient elements in the developed procedures include 1) loading and sealing capabilities in an anaerobic chamber for analysis using a NanoTemper MST located on the benchtop in air, 2) identification of the optimal reducing agents compatible with data acquisition with effective protection against trace oxygen, and 3) the optimization of data acquisition and analysis procedures. The procedures lay the groundwork to define the determinants of molecular interactions in these technically demanding systems. Key features • Established procedures for loading and sealing tubes in an anaerobic chamber for subsequent analysis. • Sodium dithionite (NaDT) could easily be substituted with one electron-reduced 1,1'-bis(3-sulfonatopropyl)-4,4'-bipyridinium [(SPr)2V•] to perform sensitive biophysical assays on oxygen-sensitive proteins like the MoFe protein. • Established MST as an experimental tool to quantify binding affinities in novel enzyme-quantum dot biohybrid complexes that are extremely oxygen-sensitive.

Relationships among age, motivation, and exercise among women Veterans.

Physical activity (PA) and exercise are central to maintaining health, however research has shown steep declines in PA and exercise among women Veterans as they age. Though motivation may be an important contributor to initiating and sustaining exercise that may change across the lifespan, little is known about exercise motivation and its relation to age and exercise behavior among women Veterans. This cross-sectional study sought to describe exercise motivations, examine relationships among exercise motivations and age, and explore the degree to which age and motivation predict self-reported exercise behavior among women Veterans. We conducted a secondary data analysis from a regional mail survey of 197 women Veterans (mean age = 51; SD = 10.5) enrolled in Veterans Health Administration primary care in a northeastern region (N = 180 in analysis). Measures included demographics (age, body mass index), self-reported exercise motivation, and an estimate of average weekly exercise. Participants endorsed multiple motivators for exercise, most prominently fitness and health management. Age was significantly negatively related to amount of exercise and with socializing as an exercise motivation. After accounting for body mass index, age was a significant predictor of exercise behavior, and exercise motivations accounted for an additional 7.3% of variance in self-reported weekly exercise. Our results suggest that although motivation is a potentially important predictor of exercise, factors beyond motivation may better predict exercise in women Veterans. Further research is needed on personal and practical facilitators and barriers to exercise in this population.

Same-Day Discharge Does Not Increase Resource Utilization Within One Year of Total Joint Arthroplasty.

BACKGROUND: While the safety of rapid recovery total joint arthroplasty is well established, less is known about its impact on postoperative care utilization patterns. We wished to examine whether same-day discharge-and its associated presumed reduction in hospital-based postoperative care and education-translates to the need for more postoperative support during the 1-year recovery period. METHODS: A retrospective review of 1,237 total hip arthroplasty (THA) and 1,710 total knee arthroplasty (TKA) patients who had 0- or 1-day length of stay (LOS) from January 2020 to October 2023 was conducted. The primary outcome was the number of follow-up visits with total joint arthroplasty providers at our institution during the 1-year postoperative period. Secondary outcomes included 30-day emergency department returns, readmissions, 1-year physical therapy utilization, and improvement in Patient-Reported Outcomes Measurement Information System Physical Function scores at 6 to 12 months postoperatively. Bivariate and multivariable analyses were performed to compare outcomes between 0-day and 1-day LOS THA and TKA patients. RESULTS: In both the THA and TKA populations, 0-day LOS patients were younger, had a lower average body mass index, were more likely to be White, men, and had an American Society of Anesthesiologists score < 3 than 1-day LOS patients. After controlling for differences between groups, no significant differences in the number of one-year follow-up visits, physical therapy visits, emergency department returns, or readmissions were seen between 0 and 1-day THA or TKA patients. In TKA patients, 1-day LOS was associated with lower improvements in Patient-Reported Outcomes Measurement Information System Physical Function scores. CONCLUSIONS: After risk adjustment, same-day discharge of THA and TKA patients did not result in increased resource utilization during the one-year postoperative period. In the setting of a coordinated joint arthroplasty program with nurse navigator support, same-day discharge can be safely performed without increasing the need for postoperative care in appropriately selected patients undergoing both THA and TKA.

Rapid Osteoarthritis and Femoral Head Collapse: A Case Series.

Introduction: Rapidly progressive hip osteoarthritis (OA) leading to femoral head collapse (FHC) following intra-articular (IA) corticosteroid injections is a perplexing variant of OA. We explored eight cases of chronic joint pain treated with IA corticosteroid injections. Subsequently, they experienced swift deterioration of the femoral head integrity within as little as 10 weeks. These cases underscore the need for a comprehensive assessment of risk factors versus benefits in this patient population. Case Report: The study reveals a complex interplay between comorbidities, treatments, and outcomes. Patients exhibited various health factors, including obesity, smoking history, cancer treatment, and deficiencies in Vitamin D levels, which have been found to increase the risk of FHC. Furthermore, the study explores the chondrotoxicity of corticosteroids and local anesthetics used in IA injections. In vitro studies show complete loss of chondrocyte viability after a single dose of corticosteroids, potentially leading to cartilage degradation. In addition, local anesthetics may induce cellular demise and structural alterations in the articular cartilage. These factors highlight various influences affecting treatment outcomes in patients with OA. Conclusion: In conclusion, this case series highlights the rare adverse outcome of rapidly progressive hip OA and FHC following IA corticosteroid injections and possible risk factors. While a definitive etiology remains unclear, the study provides valuable conclusions to aid in future treatment decision-making.

Comparison of Postoperative Outcomes of Patients Undergoing Total Hip and Total Knee Arthroplasty Following a Diagnosis of Dementia: A TriNetX Database Study.

Background: As life expectancy improves for patients with dementia, the demand for mobility-improving surgeries such as total joint arthroplasty (TJA) will increase. There is little research on patients with dementia undergoing TJA, although dementia has been shown to be a risk factor for complications. The purpose of this study is to compare postoperative outcomes of patients with dementia undergoing TJA at 90 days, 2 years, and 5 years. Methods: The TriNetX database was retrospectively queried for all patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). Patients were divided into cohorts by preoperative diagnosis of dementia and propensity score matched. The following outcomes were evaluated between groups at 90 days, 2 years, and 5 years postoperatively: revision, resection arthroplasty, closed reduction (THA only), femur fracture plating, and prosthetic joint infection. Readmission and manipulation under anesthesia (TKA only) were evaluated at 90 days postoperatively. Univariate and multivariate analyses were performed. Results: After matching, there were no differences in demographics or comorbidities between groups. TKA (odds ratio [OR] = 1.75, 95% confidence interval [CI] 1.42-2.15, P < .001) and THA (OR = 2.17, 95% CI 1.92-2.45, P < .001) patients with dementia were more likely to be readmitted than patients without dementia. At 2 years (OR = 2.07, 95% CI 1.14-3.77, P = .015) and 5 years (OR = 2.14, 95% CI 1.32-3.48, P = .002) postoperatively, THA patients with dementia were more likely to have proximal femur fracture plating than patients without dementia. Conclusions: Patients undergoing THA with dementia had worse outcomes than patients undergoing THA without dementia and TKA with dementia. The overall rate of complications was low, and a diagnosis of dementia should not be an absolute contraindication to proceeding with TJA.

Managing an epidemic within a pandemic: orthopedic opioid prescribing trends during COVID-19.

INTRODUCTION: In response to the opioid epidemic, a multitude of policy and clinical-guideline based interventions were launched to combat physician overprescribing. However, the sudden rise of the Covid-19 pandemic disrupted all aspects of healthcare delivery. The purpose of this study was to evaluate how opioid prescribing patterns changed during the Covid-19 pandemic within a large multispecialty orthopedic practice. MATERIALS AND METHODS: A retrospective review of 1,048,559 patient encounters from January 1, 2015 to December 31, 2022 at a single orthopedic practice was performed. Primary outcomes were the percent of encounters with opioids prescribed and total morphine milligram equivalents (MMEs) per opioid prescription. Differences in outcomes were assessed by calendar year. Encounters were then divided into two groups: pre-Covid (1/1/2019-2/29/2020) and Covid (3/1/2020-12/31/2022). Univariate analyses were used to evaluate differences in diagnoses and outcomes between periods. Multivariate analysis was performed to assess changes in outcomes during Covid after controlling for differences in diagnoses. Statistical significance was assessed at p < 0.05. RESULTS: The percentage of encounters with opioids prescribed decreased from a high of 4.0% in 2015 to a low of 1.6% in 2021 and 2022 (p < 0.001). MMEs per prescription decreased from 283.6 ± 213.2 in 2015 to a low of 138.6 ± 100.4 in 2019 (p < 0.001). After adjusting for diagnoses, no significant differences in either opioid prescribing rates (post-COVID OR = 0.997, p = 0.893) or MMEs (post-COVID ß = 2.726, p = 0.206) were observed between the pre- and post-COVID periods. CONCLUSION: During the Covid-19 pandemic opioid prescribing levels remained below historical averages. While continued efforts are needed to minimize opioid overprescribing, it appears that the significant progress made toward this goal was not lost during the pandemic era.

A Randomized Controlled Pilot Trial of Primary Care Treatment Integrating Motivation and Exposure Treatment (PC-TIME) in Veterans With PTSD and Harmful Alcohol Use.

Individuals with posttraumatic stress disorder (PTSD) often engage in harmful alcohol use. These co-occurring conditions are associated with negative health consequences and disability. PTSD and harmful drinking are typically experienced as closely related-thus treatments that target both simultaneously are preferred by patients. Many individuals with PTSD and harmful alcohol use receive primary care services but encounter treatment barriers in engaging in specialty mental health and substance use services. A pilot randomized controlled trial of a brief integrated treatment for PTSD and harmful drinking versus primary care treatment as usual (PC-TAU) took place in three U.S. Department of Veterans Affairs (VA) primary care clinics. The intervention (primary care treatment integrating motivation and exposure [PC-TIME]) combines motivational interviewing to reduce alcohol use and brief prolonged exposure for PTSD delivered over five brief sessions. Participants (N = 63) were veterans with PTSD and harmful drinking. Multilevel growth curve modeling examined changes in drinking (average number of drinks per drinking day and percentage of heavy drinking days) and self-reported PTSD severity at baseline, 8, 14, and 20 weeks. Participants reported high satisfaction with PC-TIME and 70% (n = 23) completed treatment. As hypothesized, a significantly steeper decrease in self-reported PTSD severity and heavy drinking was evident for participants randomized to PC-TIME compared with PC-TAU. Contrary to expectations, no significant posttreatment differences in PTSD diagnoses were observed. PC-TIME participants were less likely to exceed National Institute for Alcoholism and Alcohol Abuse (NIAAA) guidelines for harmful alcohol use posttreatment compared with PC-TAU participants. PC-TIME is a promising brief, primary care-based treatment for individuals with co-occurring PTSD and harmful alcohol use. A full-scale randomized clinical trial is needed to fully test its effectiveness.

Neutrophil Extracellular Traps and Respiratory Disease.

Extracellular traps made by neutrophils (NETs) and other leukocytes such as macrophages and eosinophils have a key role in the initial immune response to infection but are highly inflammatory and may contribute to tissue damage. They are particularly relevant to lung disease, with the pulmonary anatomy facilitating their ability to fully extend into the airways/alveolar space. There has been a rapid expansion in the number of published studies demonstrating their role in a variety of important respiratory diseases including chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis, asthma, pneumonia, COVID-19, rhinosinusitis, interstitial lung disease and lung cancer. The expression of NETs and other traps is a specific process, and diagnostic tests need to differentiate them from other inflammatory pathways/causes of cell death that are also characterised by the presence of extracellular DNA. The specific targeting of this pathway by relevant therapeutics may have significant clinical benefit; however, current clinical trials/evidence are at a very early stage. This review will provide a broad overview of the role of NETs and their possible treatment in respiratory disease.

Properties of the iron-sulfur cluster electron transfer relay in an [FeFe]-hydrogenase that is tuned for H2 oxidation catalysis.

[FeFe]-hydrogenases catalyze the reversible oxidation of H2 from electrons and protons at an organometallic active site cofactor named the H-cluster. In addition to the H-cluster, most [FeFe]-hydrogenases possess accessory FeS cluster (F-cluster) relays that function in mediating electron transfer with catalysis. There is significant variation in the structural properties of F-cluster relays among the [FeFe]-hydrogenases; however, it is unknown how this variation relates to the electronic and thermodynamic properties, and thus the electron transfer properties, of enzymes. Clostridium pasteurianum [FeFe]-hydrogenase II (CpII) exhibits a large catalytic bias for H2 oxidation (compared to H2 production), making it a notable system for examining if F-cluster properties contribute to the overall function and efficiency of the enzyme. By applying a combination of multifrequency and potentiometric electron paramagnetic resonance, we resolved two electron paramagnetic resonance signals with distinct power- and temperature-dependent properties at g = 2.058 1.931 1.891 (F2.058) and g = 2.061 1.920 1.887 (F2.061), with assigned midpoint potentials of -140 ± 18 mV and -406 ± 12 mV versus normal hydrogen electrode, respectively. Spectral analysis revealed features consistent with spin-spin coupling between the two [4Fe-4S] F-clusters, and possible functional models are discussed that account for the contribution of coupling to the electron transfer landscape. The results signify the interplay of electronic coupling and free energy properties and parameters of the FeS clusters to the electron transfer mechanism through the relay and provide new insight as to how relays functionally complement the catalytic directionality of active sites to achieve highly efficient catalysis.

The association between losartan potassium prescription and postoperative outcomes following total knee arthroplasty: A TriNetX analysis.

BACKGROUND: Total knee arthroplasty (TKA) is a common surgical procedure performed to alleviate pain and improve functional outcomes in patients with knee osteoarthritis and rheumatoid arthritis who have failed conservative treatments. Arthrofibrosis has been extensively studied due to its negative impact on TKA outcomes. Losartan, an angiotensin receptor blocker (ARB), has the potential to improve TKA outcomes by inhibiting TGF-ß and decreasing fibrosis. This study aims to analyze a large-scale, real-world healthcare database to investigate the association between losartan potassium prescription and postoperative outcomes such as readmissions, ED visits, and the need for MUA or revision TKA. HYPOTHESIS: Based on previous literature and the nature of ARBs, it is expected that the addition of losartan will aid in better outcomes for patients following a primary TKA. PATIENTS AND METHODS: In this retrospective observational study, the TriNetX Research Network (TriNetX) database was queried as of June 21, 2023. All patients who underwent a primary total knee arthroplasty (TKA) prior to June 21, 2022 were included. Patients were then divided into two cohorts by whether they had an active losartan potassium prescription within the year prior to their surgery to within 90days postoperatively. Patients were then propensity-matched to eliminate differences in demographics and comorbidities. RESULTS: Losartan TKA patients were 1.18 [OR: 0.85 (95% CI: 0.79-0.90), p<0.001] times less likely to be readmitted within 90days and were 1.15 (OR: 0.87 (95% CI: 0.79-0.96); p=0.009) times less likely to undergo a manipulation under anesthesia (MUA) within the 1-year postoperative period. There were no statistically significant differences in rates of emergency department (ED) visits at 90days postoperatively or revision TKAs at 1year postoperatively. DISCUSSION: In conclusion, patients with an active losartan prescription prior to TKA had a significantly lower likelihood of readmission within 90days and a lower likelihood of undergoing MUA within the 1-year postoperative period compared to patients not taking losartan. This presents an opportunity for further clinical investigation to explore the value of losartan in TKA. LEVEL OF EVIDENCE: III; an observational cohort study.

The Inhibition of Serine Proteases by Serpins Is Augmented by Negatively Charged Heparin: A Concise Review of Some Clinically Relevant Interactions.

Serine proteases are members of a large family of hydrolytic enzymes in which a particular serine residue in the active site performs an essential role as a nucleophile, which is required for their proteolytic cleavage function. The array of functions performed by serine proteases is vast and includes, among others, the following: (i) the ability to fight infections; (ii) the activation of blood coagulation or blood clot lysis systems; (iii) the activation of digestive enzymes; and (iv) reproduction. Serine protease activity is highly regulated by multiple families of protease inhibitors, known collectively as the SERine Protease INhibitor (SERPIN). The serpins use a conformational change mechanism to inhibit proteases in an irreversible way. The unusual conformational change required for serpin function provides an elegant opportunity for allosteric regulation by the binding of cofactors, of which the most well-studied is heparin. The goal of this review is to discuss some of the clinically relevant serine protease-serpin interactions that may be enhanced by heparin or other negatively charged polysaccharides. The paired serine protease-serpin in the framework of heparin that we review includes the following: thrombin-antithrombin III, plasmin-anti-plasmin, C1 esterase/kallikrein-C1 esterase inhibitor, and furin/TMPRSS2 (serine protease Transmembrane Protease 2)-alpha-1-antitrypsin, with the latter in the context of COVID-19 and prostate cancer.

Hole-scavenging in photo-driven N2 reduction catalyzed by a CdS-nitrogenase MoFe protein biohybrid system.

The light-driven reduction of dinitrogen (N2) to ammonia (NH3) catalyzed by a cadmium sulfide (CdS) nanocrystal­nitrogenase MoFe protein biohybrid is dependent on a range of different factors, including an appropriate hole-scavenging sacrificial electron donor (SED). Here, the impact of different SEDs on the overall rate of N2 reduction catalyzed by a CdS quantum dot (QD)-MoFe protein system was determined. The selection of SED was guided by several goals: (i) molecules with standard reduction potentials sufficient to reduce the oxidized CdS QD, (ii) molecules that do not absorb the excitation wavelength of the CdS QD, and (iii) molecules that could be readily reduced by sustainable processes. Earlier studies utilized buffer molecules or ascorbic acid as the SED. The effectiveness of ascorbic acid as SED was compared to dithionite (DT), triethanolamine (TEOA), and hydroquinone (HQ) across a range of concentrations in supporting N2 reduction to NH3 in a CdS QD-MoFe protein photocatalytic system. It was found that TEOA supported N2 reduction rates comparable to those observed for dithionite and ascorbic acid. HQ was found to support significantly higher rates of N2 reduction compared to the other SEDs at a concentration of 50 mM. A comparison of the rates of N2 reduction by the biohybrid complex to the standard reduction potential (Eo) of the SEDs reveals that Eo is not the only factor impacting the efficiency of hole-scavenging. These findings reveal the importance of the SED properties for improving the efficiency of hole-scavenging in the light-driven N2 reduction reaction catalyzed by a CdS QD-MoFe protein hybrid.

Social vulnerability adversely affects emergency-department utilization but not patient-reported outcomes after total joint arthroplasty.

INTRODUCTION: Multiple studies demonstrate social deprivation is associated with inferior outcomes after total hip (THA) and total knee (TKA) arthroplasty; its effect on patient-reported outcomes is debated. The primary objective of this study evaluated the relationship between social vulnerability and the PROMIS-PF measure in patients undergoing THA and TKA. A secondary aim compared social vulnerability between patients who required increased resource utilization or experienced complications and those who didn't. MATERIALS AND METHODS: A retrospective review of 537 patients from March 2020 to February 2022 was performed. The Centers for Disease Control Social Vulnerability Index (SVI) were used to quantify socioeconomic disadvantage. The cohort was split into THA and TKA populations; univariate and multivariate analyses were performed to evaluate primary and secondary outcomes. Statistical significance was assessed at p < 0.05. RESULTS: 48.6% of patients achieved PROMIS-PF MCID at 1-year postoperatively. Higher levels of overall social vulnerability (0.40 vs. 0.28, p = 0.03) were observed in TKA patients returning to the ED within 90-days of discharge. Increased overall SVI (OR = 9.18, p = 0.027) and household characteristics SVI (OR = 9.57, p = 0.015) were independent risk factors for 90-day ED returns after TKA. In THA patients, increased vulnerability in the household type and transportation dimension was observed in patients requiring 90-day ED returns (0.51 vs. 0.37, p = 0.04). CONCLUSION: Despite an increased risk for 90-day ED returns, patients with increased social vulnerability still obtain good 1-year functional outcomes. Initiatives seeking to mitigate the effect of social deprivation on TJA outcomes should aim to provide safe alternatives to ED care during early recovery.

Non-White Race and Concomitant Orthopedic Conditions Are Risk Factors for Failure to Achieve Clinically Relevant Improvement After Total Knee Arthroplasty.

BACKGROUND: Data from the American Joint Replacement Registry demonstrate that 1-year minimal clinically important difference (MCID) achievement rates after total knee arthroplasty (TKA) are substantially lower when using general patient reported outcome measures, such as Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF), than joint specific measures. The purpose of this study was to evaluate patient characteristics and outcomes associated with MCID achievement after TKA using the PROMIS-PF measure. METHODS: A retrospective review of 263 patients undergoing TKA with preoperative and 1-year postoperative PROMIS-PF scores from March 12, 2020 to February 8, 2022 was performed. Three multivariate models were built to evaluate predictors of MCID achievement. Preoperative predictors evaluated included demographics, comorbidities, history of spine and knee surgery, and baseline PROMIS-PF. Postoperative clinical outcomes evaluated included lengths of stay, discharge statuses, complications, and utilizations of other orthopaedic services. RESULTS: There were 109 patients (41%) who achieved an MCID at 1-year postoperatively. Non-white patients had 2.17 times lower odds of achieving MCID. No clinical outcomes assessed were independently predictive of MCID achievement. During the 1-year postoperative period, 63% of patients sought care for another orthopaedic condition. Patients requiring postoperative injections on another joint had a 2.27 times lower odds of achieving MCID. Those seen for spine conditions postoperatively had a 2.44 lower odds of achieving MCID. CONCLUSIONS: Race, postoperative injections, and treatment for spine conditions after TKA were independent predictors of failure to achieve MCID. These results may guide preoperative patient consultation and risk-adjustment in future studies using PROMIS-PF as an endpoint for evaluation of TKA outcomes.

Structural and biophysical properties of a [4Fe4S] ferredoxin-like protein from Synechocystis sp. PCC 6803 with a unique two domain structure.

Electron carrier proteins (ECPs), binding iron-sulfur clusters, are vital components within the intricate network of metabolic and photosynthetic reactions. They play a crucial role in the distribution of reducing equivalents. In Synechocystis sp. PCC 6803, the ECP network includes at least nine ferredoxins. Previous research, including global expression analyses and protein binding studies, has offered initial insights into the functional roles of individual ferredoxins within this network. This study primarily focuses on Ferredoxin 9 (slr2059). Through sequence analysis and computational modeling, Ferredoxin 9 emerges as a unique ECP with a distinctive two-domain architecture. It consists of a C-terminal iron­sulfur binding domain and an N-terminal domain with homology to Nil-domain proteins, connected by a structurally rigid 4-amino acid linker. Notably, in contrast to canonical [2Fe2S] ferredoxins exemplified by PetF (ssl0020), which feature highly acidic surfaces facilitating electron transfer with photosystem I reaction centers, models of Ferredoxin 9 reveal a more neutral to basic protein surface. Using a combination of electron paramagnetic resonance spectroscopy and square-wave voltammetry on heterologously produced Ferredoxin 9, this study demonstrates that the protein coordinates 2×[4Fe4S]2+/1+ redox-active and magnetically interacting clusters, with measured redox potentials of -420 ± 9 mV and - 516 ± 10 mV vs SHE. A more in-depth analysis of Fdx9's unique structure and protein sequence suggests that this type of Nil-2[4Fe4S] multi-domain ferredoxin is well conserved in cyanobacteria, bearing structural similarities to proteins involved in homocysteine synthesis in methanogens.