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Background: Every degree of change in pelvic tilt (PT) leads to a 0.7° change in anteversion and a 0.3° change in inclination. This study aimed to determine the significance of contralateral hip arthritis on changes in PT using preoperative and postoperative anteroposterior radiographs. Methods: There were 193 primary total hip arthroplasties done by 2 surgeons at a single academic tertiary referral center reviewed between September 2021 and January 2023. PT was calculated as Tilt = -(ln[(B/A) × (1/0.483)]) / 0.051. Value A is the distance from the base of the SI joint to the superior margin of the obturator foramen; value B is the height of the obturator foramen. After exclusions, contralateral hips were identified as being normal (n = 75), arthritic (n = 39) (Tönnis grade 3/4), replaced (n = 34), or having undergone simultaneous bilateral total hip arthroplasty (n = 5) on postoperative films. Difference in PT was measured between preoperative and postoperative films taken 1-3 months after surgery. Analyses for statistical significance were calculated using t-tests and one-way analysis of variance. Results: Average change in PT in patients with normal contralateral hips was -5.2° with an absolute mean difference of 7.6°, -1.5° for arthritic contralateral hips with an absolute mean difference of 5.0°, -1.6° for replaced contralateral hips with a mean absolute difference of 4.3°, and 2.2° for bilateral hips with a mean absolute difference of 2.6° (P < .01). Conclusions: Differences in postoperative PT changes between healthy, arthritic, and replaced contralateral hip study groups were significant. Changes in preoperative to postoperative tilt may have implications for optimal cup placement.
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BACKGROUND: Trochanteric bursitis (TB) is a prevalent complication following total hip arthroplasty (THA), with increased offset hypothesized as a potential risk factor. This study investigated potential TB predictors in THA patients, including radiographic measurements of offset and leg length, comorbidities, and patient characteristics. METHODS: In this retrospective cohort study, all THA patients from a single academic tertiary care center between 2005 and 2021 were reviewed. Exclusion criteria included less than one-year follow-up, osteonecrosis, or fracture. Manual radiographic measurements of offset (acetabular, femoral, and total) and leg length from preoperative and postoperative antero-posterior pelvis X-rays were taken, with scaling using femoral cortical diameter. Univariable and multivariable Cox proportional hazard models were employed to estimate TB risk. RESULTS: Of 1,094 patients, 103 (9.4%) developed TB, with a median (Q1, Q3) time to presentation of 41.8 weeks (25.5, 66.9). In univariable models, only sex was associated with increased TB risk, with women exhibiting a 1.79 times increased risk (hazard ratio: 1.79 (1.16, 2.76), P = .009). Changes in acetabular offset, femoral offset, total offset, and leg length between preoperative and postoperative radiographs were not associated with an increased risk of developing TB in the univariate or multivariate models. Furthermore, various offset thresholds were evaluated, with no amount of increased offset showing increased TB risk. CONCLUSIONS: This study found no relationship between femoral, acetabular, or total offset and TB following THA. These findings suggest that surgeons may consider adding offset for increased prosthetic stability in high-risk cases. However, given that this is a retrospective study, the authors are not advocating for the routine use of increased offset. The study identified women as a risk factor with a 1.79 times higher TB risk, highlighting the importance of counseling women patients on this heightened risk.
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Tap dance generates forces and joint motions that can lead to injury; however, little is known about the magnitude of load across different tap steps. The purpose of this study was to calculate peak vertical forces, average vertical foot velocities, and maximum/minimum ankle angles produced by tap dancers with different levels of experience performing the toe cannon, heel cannon, flap, and cramp roll. This prospective cross-sectional study included 14 female tap dancers aged ≥18 years with varying tap experience. Participants were recorded by three cameras while performing a choreographed tap combination containing four steps of interest on a force platform. Adjusting for experience and dancer-level clustering, we identified the steps-cramp roll and toe cannon-that had the highest peak vertical ground reaction force, angles, and velocities compared to flap and heel cannon. There was no effect of experience. The results supported our hypothesis and provide new insights into step production. Over time, the larger forces associated with these steps could pose an increased risk of injury to bones and joints when compared to smaller forces, which may suggest the importance of adjusting routines to reduce or avoid injury.
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Articulação do Tornozelo , Dança , Humanos , Feminino , Dança/fisiologia , Adulto , Estudos Transversais , Articulação do Tornozelo/fisiologia , Estudos Prospectivos , Adulto Jovem , Fenômenos Biomecânicos , Suporte de Carga/fisiologia , Tornozelo/fisiologia , AdolescenteRESUMO
Candida auris is an opportunistic fungal pathogen with high mortality rates which presents a clear threat to public health. The risk of C. auris infection is high because it can colonize the body, resist antifungal treatment, and evade the immune system. The genetic mechanisms for these traits are not well known. Identifying them could lead to new targets for new treatments. To this end, we present an analysis of the genetics and gene expression patterns of C. auris carbon metabolism, drug resistance, and macrophage interaction. We chose to study two C. auris isolates simultaneously, one drug sensitive (B11220 from Clade II) and one drug resistant (B11221 from Clade III). Comparing the genomes, we confirm the previously reported finding that B11220 was missing a 12.8 kb region on chromosome VI. This region contains a gene cluster encoding proteins related to alternative sugar utilization. We show that B11221, which has the gene cluster, readily assimilates and utilizes D-galactose and L-rhamnose as compared to B11220, which harbors the deletion. B11221 exhibits increased adherence and drug resistance compared to B11220 when grown in these sugars. Transcriptomic analysis of both isolates grown on glucose or galactose showed that the gene cluster was upregulated when grown on D-galactose. These findings reinforce growing evidence of a link between metabolism and drug tolerance. B11221 resists phagocytosis by macrophages and exhibits decreased ß-1,3-glucan exposure, a key determinant that allows Candida to evade the host immune system, as compared to B11220. In a transcriptomic analysis of both isolates co-cultured with macrophages, we find upregulation of genes associated with transport and transcription factors in B11221. Our studies show a positive correlation between membrane composition and immune evasion, alternate sugar utilization, and drug tolerance in C. auris.
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Antifúngicos , Candida auris , Virulência/genética , Candida auris/genética , Candida auris/efeitos dos fármacos , Antifúngicos/farmacologia , Candidíase/microbiologia , Candidíase/imunologia , Farmacorresistência Fúngica/genética , Genoma Fúngico , Humanos , Macrófagos/microbiologia , Macrófagos/imunologia , Regulação Fúngica da Expressão Gênica , Perfilação da Expressão Gênica , AnimaisRESUMO
BACKGROUND: The optimal anesthetic mode in total joint arthroplasty (TJA) has yet to be clearly identified. Patients undergoing TJA may recieve spinal anesthesia (SA) or general anesthesia (GA). While arthroplasty literature indicates differences in postoperative morbidity, hip fracture literature does not show clear superiority of SA or GA. The purpose of this study was to further investigate this relationship and determine if there is a significant difference in morbidity and mortality between GA and SA in patients undergoing primary total joint arthroplasty. METHODS: Patients undergoing primary THA or TKA from February 2007 to February 2021 were retrospectively reviewed, creating four cohorts: THA/GA (n = 1,266), THA/SA (n = 1,084), TKA/GA (n = 882), and THA/SA (n = 2,067). Readmission within 90 days, mortality within 365 days, and thromboembolic events within 30 days postoperatively were compared using logistic regression, controlling for age, body mass index, and Charlson Comorbidity Index. RESULTS: The odds of experiencing a deep venous thrombosis within 30 days postoperatively were elevated in the analysis of both the THA/GA (odds ratio (OR) = 3.1; 95% confidence interval (CI): 1.5 to 7.0; P = .004) and the TKA/GA (OR = 1.9; 95% CI: 1.2 to 3.0; P = .005) groups. Similarly, the risk of pulmonary embolism as higher in the THA/GA cohort (OR = 3.9; 95% CI: 1.2 to 17.3; P = .04). There were also higher odds of mortality within 365 days postoperatively in THA/GA patients (OR = 4.3; 95% CI: 1.7 to 13.0; P = .004). No other differences existed among TKA patients. CONCLUSIONS: Based upon these data, both SA and GA are reasonable options for primary TKA with similar risk profiles. However, GA may be associated with higher rates of deep venous thrombosis in TJA and pulmonary embolism in THA. General anesthesia (GA) was also loosely associated with increased mortality within 1 year of THA, but this result should be considered with caution.
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Background: Anterior approach surgeons who utilize intraoperative fluoroscopy often try to match a preoperative radiograph as a reference for intraoperative cup position. Every degree of inaccuracy in tilt leads to a roughly 0.7° change in anteversion. This study aimed to determine how closely pelvic tilt (PT) is approximated intraoperatively when compared to preoperative anteroposterior (AP) radiographs. Methods: This was a retrospective review of 193 primary THA's done by 2 surgeons at an academic tertiary referral center between September 2021-January 2023. There were 24 patients excluded for distorted anatomy, post-traumatic arthritis, insufficient x-rays, or a sacroiliac joint that could not be visualized on film. Data collected included age and BMI. PT was calculated using the formula, Tilt = -(ln((B/A) x (1/0.483)))/0.051. Value A is the distance from the base of the SI joint to the superior margin of the obturator foramen; value B is the height of the obturator foramen. Results: Mean preoperative PT was 0.2° versus intraoperative PT was 3.4° (p < 0.001). Mean absolute difference was 6.5°. 48% of patients (n = 81) had an absolute difference less than 5°, 31% (n = 52) between 5° and 10°, 14% (n = 24) between 10° and 15°, and 7% (n = 12) greater than 15°. There was no correlation between BMI or age and PT discrepancy. Conclusion: Of the patients, 21% had a discrepancy of 10° or greater between their preoperative radiographs and intraoperative fluoroscopic images. Surgeons should be aware of potential errors in cup positioning and be particularly diligent in high-risk cases.
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Time series biomechanical data inform our understanding of normal gait mechanics and pathomechanics. This study examines the utility of different quantitative methods to distinguish vertical ground reaction forces (VGRFs) from experimentally distinct gait strategies. The goals of this study are to compare measures of VGRF data-using the shape factor method and a Fourier series-based analysis-to (1) describe how these methods reflect and distinguish gait patterns and (2) determine which Fourier series coefficients discriminate normal walking, with a relatively stiff-legged gait, from compliant walking, using deep knee flexion and limited vertical oscillation. This study includes a reanalysis of previously presented VGRF data. We applied the shape factor method and fit 3- to 8-term Fourier series to zero-padded VGRF data. We compared VGRF renderings using Euclidean L2 distances and correlations stratified by gait strategy. Euclidean L2 distances improved with additional harmonics, with limited improvement after the seventh term. Euclidean L2 distances were greater in shape factor versus Fourier series renderings. In the 8 harmonic model, amplitudes of 9 Fourier coefficients-which contribute to VGRF features including peak and local minimum amplitudes and limb loading rates-were different between normal and compliant walking. The results suggest that Fourier series-based methods distinguish between gait strategies.
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Análise de Fourier , Marcha , Caminhada , Humanos , Marcha/fisiologia , Caminhada/fisiologia , Fenômenos Biomecânicos , Análise da Marcha/métodos , MasculinoRESUMO
Metallosis is a known yet rare late complication of unicompartmental and total knee arthroplasty (TKA), usually secondary to either metal-backed patellar component failure, mobile-bearing polyethylene dislocation, or catastrophic polyethylene failure and wear through. The majority of literature surrounding metallosis has been published in relation to total hip arthroplasty (THA) metal on metal bearing wear or mechanically assisted crevice corrosion.This case report describes the development of metallosis in a 77-year-old male patient with advanced (Kellgren-Lawrence Grade 4) osteoarthritis with associated valgus deformity, who underwent index TKA with a semiconstrained revision knee system due to intraoperative medial collateral ligament laxity. The taper junction between the titanium alloy stem and cobalt chromium femoral component was the source of diffuse intra-articular metallosis.
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Artroplastia do Joelho , Prótese do Joelho , Falha de Prótese , Reoperação , Humanos , Masculino , Idoso , Prótese do Joelho/efeitos adversos , Corrosão , Osteoartrite do Joelho/cirurgia , Desenho de Prótese , TitânioRESUMO
Total ankle arthroplasty (TAA) is a common surgical solution for patients with debilitating arthritis of the ankle. Prior to surgery patients experience high levels of pain and fatigue and low mechanical energy recovery. It is not known if TAA restores healthy levels of mechanical energy recovery in this patient population. This study was designed to determine whether mechanical energy recovery was restored following TAA. Ground reaction forces during self-selected speed walking were collected from patients with symptomatic, unilateral ankle arthritis (N = 29) before and one and two years after primary, unilateral TAA. The exchange of potential (PE) and kinetic (KE) energy was examined, and direction of change (%congruity) and energy exchange (%recovery) between the two curves was calculated, with those subjects with low congruity experiencing high energy recovery. Linear regressions were used to examine the impact of walking speed, congruity, and amplitude of the center of mass (COM) displacement on %recovery, while ANOVA and ANCOVA models were used to compare energy recovery and congruity across the three time points. Gender, BMI, and age at surgery had no effect in this study. TAA improved walking speed (p = 0.001), increased energy recovery (p = 0.020), and decreased congruity (p = 0.002), and these levels were maintained over at least two years. Differences in congruity were independent of walking speed. In some patients, especially those who are severely debilitated by ankle arthritis, TAA is effective in restoring mechanical energy recovery to levels similar to an asymptomatic population of a similar age recorded by other studies.
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Artrite , Artroplastia de Substituição do Tornozelo , Humanos , Marcha , Tornozelo , Caminhada , Articulação do Tornozelo/cirurgia , Artrite/cirurgia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
BACKGROUND: Prior studies suggest that distressed patients or those who have poor mental health have inferior postoperative outcomes when compared to nondistressed patients. However, these studies typically do not account for substance use or other comorbidities often found in this population, which can independently contribute to postoperative complications. This study sought to control for these factors and assess if a diagnosis of a mental health condition is directly associated with worse outcomes after total joint arthroplasty. METHODS: A retrospective chart review was performed for 3,182 patients who underwent a total hip arthroplasty and 4,430 patients who underwent a total knee arthroplasty. Diagnosis of the mental health disorders included depression, anxiety disorder, adjustment disorder, bipolar disorder, trauma, stressor-related disorder, and schizophrenia or schizoaffective disorder. Multivariable analyses were performed to control for alcohol use, drug use, tobacco use, body mass index, and a comorbidity index. RESULTS: When controlling for body mass index and Charlson comorbidity index, no statistically significant associations were found between a diagnosis of any mental health condition or a specific diagnosis of depression or anxiety, and 90-day readmission, reoperation, or 1 year mortality for patients undergoing total knee arthroplasty or total hip arthroplasty. CONCLUSIONS: When accounting for confounding factors, there does not appear to be a direct association between diagnosis of any of the psychiatric conditions we studied and outcomes after primary total joint arthroplasty. While prior studies suggest addressing the mental health condition may improve outcomes, this study suggests that preoperative medical optimization and potentially addressing substance use may be more effective strategies.
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Artroplastia de Quadril , Transtorno Bipolar , Transtornos Relacionados ao Uso de Substâncias , Humanos , Saúde Mental , Estudos Retrospectivos , Transtorno Bipolar/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Fatores de RiscoRESUMO
Advances in genetic engineering, synthetic biology, and DNA sequencing have transformed the re-emergent therapeutic bacteriophage field. The increasing rate of multidrug resistant (MDR) infections and the speed at which new bacteriophages can be isolated, sequenced, characterized, and engineered has reinvigorated phage therapy and unlocked new applications of phages for modulating bacteria. The methods used to genetically engineer bacteriophages are undergoing significant development, but identification of heterologous gene payloads with desirable activity and determination of their impact on bacteria or human cells in translationally relevant applications remain underexplored areas. Here, we discuss and categorize recombinant gene payloads for their potential outcome on phage-bacteria interactions when genetically engineered into phage genomes for expression in their bacterial hosts.
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Bacteriófagos , Humanos , Bacteriófagos/genética , Engenharia Genética , Bactérias/genética , Genoma ViralRESUMO
Highly substituted aminotetrahydropyrans were synthesized via sequential C-H functionalizations. The process was initiated with a Pd(II)-catalyzed stereoselective γ-methylene C-H arylation of aminotetrahydropyran, followed by α-alkylation or arylation of the corresponding primary amine. The initial γ-C-H (hetero)arylation was compatible with a range of aryl iodides containing various substituents and provided the corresponding products in moderate to good yields. The subsequent α-alkylation or arylation of the isolated arylated products proceeded with high diastereoselectivity to afford value-added disubstituted aminotetrahydropyrans.
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Tranexamic acid has been shown to significantly reduce blood loss in patients undergoing total knee arthroplasty and total hip arthroplasty. However, there is a paucity of data regarding its safety and efficacy in total ankle arthroplasty. The purpose of this study was to determine whether tranexamic acid use in patients with total ankle arthroplasty affects blood loss or overall complication rate. A retrospective chart review was conducted for 64 patients who underwent total ankle arthroplasty with (n = 32) and without (n = 32) intraoperative tranexamic acid from 2014 to 2023 at a single academic medical center. Recorded blood loss, pre-to-postoperative hemoglobin changes, hidden blood loss, and complication rates were recorded and compared. There was no statistically significant difference in recorded blood loss, total calculated blood loss, pre-to-postoperative hemoglobin difference, hidden blood loss, or overall complications between the groups (all, P > .05). A lower rate of wound complications was observed in the tranexamic acid group, but the difference between each group was not statistically significant (P > .05). Tranexamic acid did not decrease blood loss during total ankle arthroplasty, as measured in our study. Tranexamic acid was not associated with any increase in overall complications. Based on our findings, tranexamic acid may be a safe intervention in total ankle arthroplasty, but further studies are needed to better elucidate its clinical impact.Level of Evidence: Level 3.
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Aims: The diagnosis of periprosthetic joint infection (PJI) can be challenging as the symptoms are similar to other conditions, and the markers used for diagnosis have limited sensitivity and specificity. Recent research has suggested using blood cell ratios, such as platelet-to-volume ratio (PVR) and platelet-to-lymphocyte ratio (PLR), to improve diagnostic accuracy. The aim of the study was to further validate the effectiveness of PVR and PLR in diagnosing PJI. Methods: A retrospective review was conducted to assess the accuracy of different marker combinations for diagnosing chronic PJI. A total of 573 patients were included in the study, of which 124 knees and 122 hips had a diagnosis of chronic PJI. Complete blood count and synovial fluid analysis were collected. Recently published blood cell ratio cut-off points were applied to receiver operating characteristic curves for all markers and combinations. The area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values were calculated. Results: The results of the analysis showed that the combination of ESR, CRP, synovial white blood cell count (Syn. WBC), and polymorphonuclear neutrophil percentage (PMN%) with PVR had the highest AUC of 0.99 for knees, with sensitivity of 97.73% and specificity of 100%. Similarly, for hips, this combination had an AUC of 0.98, sensitivity of 96.15%, and specificity of 100.00%. Conclusion: This study supports the use of PVR calculated from readily available complete blood counts, combined with established markers, to improve the accuracy in diagnosing chronic PJI in both total hip and knee arthroplasties.
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Background: Ostomy surgery is associated with a high rate of postoperative complications and poses several theoretical concerns for subsequent total joint arthroplasty (TJA). There is concern that ostomy may negatively impact nutrition or increase risk of known gastrointestinal (GI) complications such as obstruction, constipation, or diarrhea, particularly with the use of postoperative opioids. There is also concern that the open nature of the ostomy may increase the risk of infection. This case series reports outcomes and assesses the risk associated with TJA in patients with previous surgical history of intestinal ostomy. Methods: This is an institutional review board-approved retrospective case series of patients with surgical history of ostomy who underwent total hip or total knee arthroplasty. Cohort consisted of 14 cases in 10 patients and was examined to report individual TJA and ostomy procedural details and outcomes. Results: Of the 14 cases, none required GI clearance or prophylaxis outside of standard perioperative antibiotics prior to TJA surgeries, and all TJAs resulted in good outcomes. Four cases (29%) had a complication, although only 2 of these were GI complications and none were life-threatening or required further surgery. The first of the 2 experienced increased ostomy output, and symptoms were resolved promptly with rehydration. The second experienced decreased ostomy output, and symptoms were resolved promptly with changes in prn pain medications. Other complications were postoperative urinary tract infection and syncopal episode. Conclusions: TJA can be performed safely in the setting of ostomy with major consideration being risk of diarrhea or constipation during postoperative period.
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Introduction: Native knee septic arthritis is a rare condition with a potential for high morbidity if not promptly treated. Treatment involves surgical decompression of the affected joint along with systemic antibiotic therapy. The purpose of this study is to compare arthroscopic versus open irrigation and debridement for treatment of native knee septic arthritis. Methods: A retrospective review was conducted at a single academic institution of all patients treated for native knee septic arthritis from January 2007 until August 2018 utilizing ICD and CPT codes. Patient demographics, type of surgical procedure, need for reoperation, laboratory values, length of stay, and comorbidities were compared. Results: A cohort of sixty-six patients who underwent 85 surgeries were included. Among these surgeries, 52 (61%) were arthroscopic while 33 (39%) were open arthrotomies, and 21% required more than one operation. While not statistically significant, the odds of reoperation was higher for those that underwent arthroscopic compared to open irrigation and debridement on univariable (OR = 4.05, p = .08) and multivariable analysis (OR = 4.39, p = .10). Additionally, patients were more likely to require a longer hospital stay if they initially underwent arthroscopic rather than open debridement (RR = 1.31, p = .02). Conclusion: Native knee septic arthritis can be treated with a single surgery in the majority of cases. In our sample, there was an increased odds of reoperation in those treated arthroscopically compared to open, though this finding was not statistically significant. We found longer length of stay for patients undergoing arthroscopic rather than open irrigation and debridement - even after controlling for multiple operations, culture status, sex, age, and comorbidities.
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Modern retrosynthetic analysis in organic chemistry is based on the principle of polar relationships between functional groups to guide the design of synthetic routes1. This method, termed polar retrosynthetic analysis, assigns partial positive (electrophilic) or negative (nucleophilic) charges to constituent functional groups in complex molecules followed by disconnecting bonds between opposing charges2-4. Although this approach forms the basis of undergraduate curriculum in organic chemistry5 and strategic applications of most synthetic methods6, the implementation often requires a long list of ancillary considerations to mitigate chemoselectivity and oxidation state issues involving protecting groups and precise reaction choreography3,4,7. Here we report a radical-based Ni/Ag-electrocatalytic cross-coupling of substituted carboxylic acids, thereby enabling an intuitive and modular approach to accessing complex molecular architectures. This new method relies on a key silver additive that forms an active Ag nanoparticle-coated electrode surface8,9 in situ along with carefully chosen ligands that modulate the reactivity of Ni. Through judicious choice of conditions and ligands, the cross-couplings can be rendered highly diastereoselective. To demonstrate the simplifying power of these reactions, concise syntheses of 14 natural products and two medicinally relevant molecules were completed.
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Produtos Biológicos , Técnicas de Química Sintética , Descarboxilação , Eletroquímica , Eletrodos , Preparações Farmacêuticas , Ácidos Carboxílicos/química , Nanopartículas Metálicas/química , Oxirredução , Prata/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Níquel/química , Ligantes , Preparações Farmacêuticas/síntese química , Preparações Farmacêuticas/química , Eletroquímica/métodos , Técnicas de Química Sintética/métodosRESUMO
Background: Periprosthetic joint infection (PJI) is a serious complication following joint replacement surgery, and its diagnosis can be challenging due to the similarity of symptoms to other conditions and the lack of confirmatory imaging tests. Platelet/mean platelet volume ratio (PVR), platelet/lymphocyte ratio, monocyte/lymphocyte ratio, and neutrophil/lymphocyte ratio have been proposed as potential markers to aid in the diagnosis of PJI. This study aimed to further assess the utility of these blood cell ratio combinations for the diagnosis of PJI. Methods: A retrospective chart review was conducted on patients who presented to a university hospital for evaluation for PJI or underwent aseptic revision surgery. All patients were reviewed for inclusion in the study. Data were collected on several markers, including complete blood counts, synovial fluid white blood cell count, and polymorphonuclear percentage. Receiver operator characteristic curve analysis was used to evaluate the diagnostic capabilities of the markers and marker combinations. Results: The combination of erythrocyte sedimentation rate, C-reactive protein, synovial white blood cell count, and synovial polymorphonuclear percentage, with PVR, had the highest area under the curve of 0.97, with a sensitivity of 94.3% and a specificity of 88.9%, and a positive predictive value of 97.1% and a negative predictive value of 80.0%. Conclusions: This study further supports the use of PVR calculated from complete blood count commonly ordered laboratory values obtained during routine complete blood counts when combined with established serum and synovial markers to increase the diagnostic accuracy for diagnosing PJI.
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The co-chaperone BAG3 is a hub for a variety of cellular pathways via its multiple domains and its interaction with chaperones of the HSP70 family or small HSPs. During aging and under cellular stress conditions in particular, BAG3, together with molecular chaperones, ensures the sequestration of aggregated or aggregation-prone ubiquitinated proteins to the autophagic-lysosomal system via ubiquitin receptors. Accumulating evidence for BAG3-mediated selective autophagy independent of cargo ubiquitination led to analyses predicting a direct interaction of BAG3 with LC3 proteins. Phylogenetically, BAG3 comprises several highly conserved potential LIRs, LC3-interacting regions, which might allow for the direct targeting of BAG3 including its cargo to autophagosomes and drive their autophagic degradation. Based on pull-down experiments, peptide arrays and proximity ligation assays, our results provide evidence of an interaction of BAG3 with LC3B. In addition, we could demonstrate that disabling all predicted LIRs abolished the inducibility of a colocalization of BAG3 with LC3B-positive structures and resulted in a substantial decrease of BAG3 levels within purified native autophagic vesicles compared with wild-type BAG3. These results suggest an autophagic targeting of BAG3 via interaction with LC3B. Therefore, we conclude that, in addition to being a key co-chaperone to HSP70, BAG3 may also act as a cargo receptor for client proteins, which would significantly extend the role of BAG3 in selective macroautophagy and protein quality control.