RESUMO
A ~10-11 bp periodicity in dinucleotides imparting DNA bending, with shorter periods found in organisms with positively-supercoiled DNA and longer periods found in organisms with negatively-supercoiled DNA, was previously suggested to assist in DNA compaction. However, when measured with more robust methods, variation in the observed periods between organisms with different growth temperatures is not consistent with that hypothesis. We demonstrate that dinucleotide periodicity does not arise solely by mutational biases but is under selection. We found variation between genomes in both the period and the suite of dinucleotides that are periodic. Whereas organisms with similar growth temperatures have highly variable periods, differences in periods increase with phylogenetic distance between organisms. In addition, while the suites of dinucleotides under selection for periodicity become more dissimilar among more distantly-related organisms, there is a core set of dinucleotides that are strongly periodic among genomes in all domains of life. Notably, this core set of periodic motifs are not involved in DNA bending. These data indicate that dinucleotide periodicity is an ancient genomic architecture which may play a role in shaping the evolution of genes and genomes.
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DNA/genética , Repetições de Dinucleotídeos/genética , Evolução Molecular , Motivos de Nucleotídeos/genética , Archaea/genética , Genoma Bacteriano/genética , Genômica , Mutação/genética , Nucleossomos/genética , Paleontologia , Filogenia , Seleção Genética/genéticaRESUMO
PURPOSE: The objective of this study was to determine if intra-operatively measured joint gaps are associated with 2-year pain outcomes in total knee arthroplasty (TKA) and whether balance and laxity windows could be defined throughout flexion to optimize 2-year pain outcomes. Our hypothesis is that intra-operative joint gaps are associated with 2 year post-operative pain outcome. METHODS: A prospective study investigating 310 robotically assisted TKAs was performed. Final intra-operative joint gap data were recorded using a digital tensioner and component alignment data were recorded by the robotics system. Patient demographics and Knee Injury and Osteoarthritis Outcome Score (KOOS) were recorded pre-operatively and KOOS and Hospital for Special Surgery (HSS) satisfaction were recorded at 2 years post-op. A random search Simulated Annealing (SANN) optimisation algorithm was used to determine global optimum laxity and balance windows at different flexion angles which maximized the 2-year KOOS pain scores. The windows were combined to determine the impact of achieving optimal laxity and balance throughout flexion. To improve clinical utility, boundaries identified by the SANN algorithm were rounded to the nearest 0.5 mm before statistical analysis. RESULTS: Laxity and balance windows were defined in extension (Med lax: -2.0 to 2.5 mm, Lat lax: -0.5 to 2.5 mm, Balance: -3.0 to 0.0 mm), mid-flexion (Med lax: -1.0 to 2.5 mm, Lat lax: -0.5 to 3.0 mm, Balance: -2.0 to 2.0 mm), and flexion (Med lax: -2.0 to 3.5 mm, Lat lax: -2.0 to 1.5 mm, Balance: -3.0 to 3.0 mm). When all windows were satisfied, the greatest difference in KOOS pain score was observed (100.0 vs 94.4, p < 0.0001). The highest percentage of knees satisfying the Patient Acceptable Symptom State (PASS) for KOOS pain was also observed in knees which satisfied all windows compared to knees which did not (93% vs 71%, p = 0.0009). The proportion of knees which satisfy the PASS threshold decreased in knees which only satisfied 1-3 (29%) or 4-6 (69%) windows (p ≤ 0.0018). No optimal windows were found between component alignment and KOOS pain outcome (p ≥ 0.1180). High satisfaction was found across all groups (≥ 95%). CONCLUSION: Intra-operatively measured joint gaps are associated with all KOOS sub-score outcomes at 2 years after TKA. Optimal windows for a clinically relevant improvement in post-operative KOOS pain were defined for laxity and balance but not for alignment indicating balance may have a greater impact on outcome than alignment. LEVEL OF EVIDENCE: II.
Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Articulação do Joelho/cirurgia , Estudos Prospectivos , Osteoartrite do Joelho/cirurgia , Amplitude de Movimento Articular , Dor/cirurgiaRESUMO
Crystal polymorphism of pharmaceutical compounds directly impacts resulting physicochemical characteristics, a critical aspect in active pharmaceutical ingredient (API) production. Tools to characterize and chemically map these polymorphs at the single particle scale remain important to advancing directed manufacture of targeted polymorphs. Here, time-of-flight secondary ion mass spectrometry (ToF-SIMS) was employed for chemically imaging inkjet printed acetaminophen samples. ToF-SIMS generates large data sets of high spatial resolution images. Extracting relevant data and peaks of interest can be laborious for, and biased by, users. Advances in machine learning approaches have introduced many supervised and unsupervised methods for data analysis. In this study, we apply non-negative matrix factorization (NMF) for the unsupervised analysis of ToF-SIMS chemical image data. More specifically, an expanded variant of NMF, NMFk, was employed to determine the data set's latent dimensionality. NMFk combines the spectral unmixing of traditional NMF with k-means clustering of the resulting factors and an optimization of the reconstruction and clustering. The method was used to identify the number of polymorph phases-and their representative mass spectra-generated from inkjet printed acetaminophen samples. Amorphous, crystalline form I, and crystalline form II polymorphs were observed. The learned polymorph mass spectra were then used to map the learned polymorphs onto subsequent particle samples of acetaminophen. Finally, NMFk also enabled the decomposition of mixed particle samples (i.e., migraine medicine), learning the number of compounds and their composition. The extracted constituent phase mass spectra-representing single compounds-were searched against mass spectral libraries for identification.
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Acetaminofen , Espectrometria de Massa de Íon Secundário , Espectrometria de Massa de Íon Secundário/métodos , Algoritmos , Análise por Conglomerados , Preparações FarmacêuticasRESUMO
PURPOSE: Achieving a balanced knee is accepted as an important goal in total knee arthroplasty; however, the definition of ideal balance remains controversial. This study therefore endeavoured to determine: (1) whether medio-lateral gap balance in extension, midflexion, and flexion are associated with improved outcome scores at one-year post-operatively and (2) whether these relationships can be used to identify windows of optimal gap balance throughout flexion. METHODS: 135 patients were enrolled in a multicenter, multi-surgeon, prospective investigation using a robot-assisted surgical platform and posterior cruciate ligament sacrificing gap balancing technique. Joint gaps were measured under a controlled tension of 70-90 N from 10°-90° flexion. Linear correlations between joint gaps and one-year KOOS outcomes were investigated. KOOS Pain and Activities of Daily Living sub-scores were used to define clinically relevant joint gap target thresholds in extension, midflexion, and flexion. Gap thresholds were then combined to investigate the synergistic effects of satisfying multiple targets. RESULTS: Significant linear correlations were found throughout extension, midflexion, and flexion. Joint gap thresholds of an equally balanced or tighter medial compartment in extension, medial laxity ± 1 mm compared to the final insert thickness in midflexion, and a medio-lateral imbalance of less than 1.5 mm in flexion generated subgroups that reported significantly improved KOOS pain scores at one year (median ∆ = 8.3, 5.6 and 2.8 points, respectively). Combining any two targets resulted in further improved outcomes, with the greatest improvement observed when all three targets were satisfied (median ∆ = 11.2, p = 0.002). CONCLUSION: Gap thresholds identified in this study provide clinically relevant and achievable targets for optimising soft tissue balance in posterior cruciate ligament sacrificing gap balancing total knee arthroplasty. When all three balance windows were achieved, clinically meaningful pain improvement was observed. LEVEL OF EVIDENCE: Level II.
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Artroplastia do Joelho , Osteoartrite do Joelho , Atividades Cotidianas , Artroplastia do Joelho/métodos , Humanos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Dor/cirurgia , Estudos Prospectivos , Amplitude de Movimento ArticularRESUMO
BACKGROUND: The objective of this study was to investigate the impact of alignment and soft tissue release on patient outcomes following total knee arthroplasty (TKA). METHODS: In a multicenter study, soft tissue releases during TKA were prospectively documented in 330 robotic-assisted TKAs. Knee Injury and Osteoarthritis Outcome Scores (KOOS) were captured postoperatively. Delphi analysis was used to determine inlier and outlier component alignment boundaries: Tibia Coronal (TC): ±3°, Femur Coronal (FC): ±3°, Femoral Axial (FA): 3°Int-6°Ext, Hip-Knee-Ankle (HKA): 3°Val-4°Var, and Tibiofemoral Axial (TFA): 3°Int-6°Ext. Kruskal-Wallis analysis of variance tests were used to compare groups. RESULTS: No significant differences were found between any individual or grouped inlier and outlier alignment criterion and KOOS at any timepoint. Outlier alignment frequencies were: TC: 0%, FC: 12%, FA: 8%, HKA: 9%, TFA: 8%, and Any: 23%. Soft tissue releases were performed in 18% of cases. Knees with soft tissue releases reported significantly worse KOOS scores at: 6M: Symptoms (80.0 versus 75.3, P = .03), activities of daily living (ADL) (86.2 versus 80.8, P = .030), quality of life (70.1 versus 60.9, P = .008), 12M ADL (90.0 versus 85.1, P = .023), and 24M ADL (91.9 versus 87.2, P = .016). A higher proportion of patients achieved Minimal Clinically Important Difference for pain at 6 months for those having no releases versus released (92.3% versus 81.0%, P = .021). No significant associations were found between preoperative deformity and preoperative or postoperative KOOS. CONCLUSION: The addition of soft tissue releases after bony cuts is associated with worse KOOS scores out to 2 years and was more prevalent in knees with worse deformity, while no such association was found for alignment.
Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Atividades Cotidianas , Humanos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Tíbia/cirurgiaRESUMO
Despite significant frequencies of lateral gene transfer between species, higher taxonomic groups of bacteria show ecological and phenotypic cohesion. This suggests that barriers prevent panmictic dissemination of genes via lateral gene transfer. We have proposed that most bacterial genomes have a functional architecture imposed by Architecture IMparting Sequences (AIMS). AIMS are defined as 8 base pair sequences preferentially abundant on leading strands, whose abundance and strand-bias are positively correlated with proximity to the replication terminus. We determined that inversions whose endpoints lie within a single chromosome arm, which would reverse the polarity of AIMS in the inverted region, are both shorter and less frequent near the replication terminus. This distribution is consistent with the increased selection on AIMS function in this region, thus constraining DNA rearrangement. To test the hypothesis that AIMS also constrain DNA transfer between genomes, AIMS were identified in genomes while ignoring atypical, potentially laterally-transferred genes. The strand-bias of AIMS within recently acquired genes was negatively correlated with the distance of those genes from their genome's replication terminus. This suggests that selection for AIMS function prevents the acquisition of genes whose AIMS are not found predominantly in the permissive orientation. This constraint has led to the loss of at least 18% of genes acquired by transfer in the terminus-proximal region. We used completely sequenced genomes to produce a predictive road map of paths of expected horizontal gene transfer between species based on AIMS compatibility between donor and recipient genomes. These results support a model whereby organisms retain introgressed genes only if the benefits conferred by their encoded functions outweigh the detriments incurred by the presence of foreign DNA lacking genome-wide architectural information.
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Bactérias/genética , Cromossomos/genética , Rearranjo Gênico/genética , Transferência Genética Horizontal , Seleção Genética , Inversão Cromossômica , Replicação do DNA , Genoma Bacteriano , FilogeniaRESUMO
INTRODUCTION: New technologies exist which may assist surgeons to better predict final intra-operative joint balance. Our objectives were to compare the impact of (1) a predictive digital joint tensioning tool on intra-operative joint balance; and (2) joint balance and flexion joint laxity on patient-reported outcomes. MATERIALS AND METHODS: Two-hundred Eighty patients received posterior cruciate ligament sacrificing TKA with ultra-congruent tibial inserts using a robotic-assisted navigation platform. Patients were divided into those in which a Predictive Plan with a digital joint-tensioning device was used (PP) and those in which it was not (NPP), in all cases final post-operative joint gaps were collected immediately before final implantation. Demographics and KOOS were collected pre-operatively. KOOS, complications and satisfaction were collected at 3, 6 and 12 months post-operatively. Optimal balance difference between PP and NPP was defined and compared using area-under-the-curve analysis (AUC). Outcomes were then compared according to the results from the AUC. RESULTS: AUC analysis yielded a balance threshold of 1.5 mm, in which the PP group achieved a higher rate of balance throughout flexion compared to the NPP group: extension: 83 vs 52%; Midflexion: 82 vs 55%; Flexion 89 vs 68%; Flexion to Extension 80 vs 49%; p ≤ 0.003. Higher KOOS scores were observed in knees balanced within 1.5 mm across all sub-scores at various time points, however, differences did not exceed the minimum clinically important difference (MCID). Patients with > 1.5 mm flexion laxity medially or laterally had an increased likelihood of 2.2 (1.1-4.4) and 2.5 (1.3-4.8), respectively, for failing to achieve the Patient Acceptable Symptom State for KOOS Pain at 12 months. Patient satisfaction was high in both the PP and NPP groups (97.4 and 94.7%, respectively). CONCLUSIONS: Use of a predictive joint tensioning tool improved the final balance in TKA. Improved outcomes were found in balanced knees; however, this improvement did not achieve the MCID, suggesting further studies may be required to define optimal balance targets. Limiting medial and lateral flexion laxity resulted in an increased likelihood of achieving the Patient Acceptable Symptom State for KOOS Pain.
Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Articulação do Joelho/cirurgia , Ligamentos , Osteoartrite do Joelho/cirurgia , Estudos ProspectivosRESUMO
Portable analytical instrumentation that can provide an alarm indication for the presence of explosives and related components is critical for the identification of explosives-based hazards and threats. Many explosives incident reports involve an inorganic oxidizer-fuel mixture which can include pyrotechnics, fireworks, flash powders, black powders, black powder substitutes, and improvised or homemade explosives. A portable CE instrument with targeted analysis of common inorganic oxidizer ions, for example, chlorate, perchlorate, and nitrate, was used here as a rapid detection platform. Unlike frequently used gas-phase separation and detection instrumentation such as ion mobility spectrometry (IMS), an automated liquid extraction mechanism is required for CE separation using acetate paper sample collection wipes. Target inorganic oxidizers were inkjet-printed onto sample wipes to investigate instrument response relative to the collected analyte spatial distribution. Overall, analyte signal intensities increased with off-center sample deposition due to improved sample extraction from wipes and no change in response was observed for varied array distributions across wipes. The system demonstrated sub 200 ng detection limits for all target analytes, with further improvement when normalizing to an internal standard.
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Eletroforese Capilar/métodos , Substâncias Explosivas/análise , Substâncias Explosivas/química , Substâncias Explosivas/isolamento & purificação , Limite de Detecção , Nitratos/química , Percloratos/química , PósRESUMO
BACKGROUND: Insurance, racial, and socioeconomic health disparities continue to pose significant challenges for access to dermatologic care. Studies applying teledermatology to increase access to underinsured individuals and ethnic minorities are limited. OBJECTIVE: To determine how the implementation of a teledermatology program affects access to health care and patient outcomes. METHODS: A cross-sectional evaluation was performed of all ambulatory dermatology referrals and electronic dermatology consultations (eConsults) at Ohio State University within a 25-month period. RESULTS: Compared with ambulatory referrals, eConsults served more nonwhite patients (612 of 1698 [36.0%] vs 4040 of 16,073 [25.1%]; P < .001) and more Medicaid enrollees (459 of 1698 patients [27.0%] vs 3266 of 16,073 [20.3%]; P < .001). In addition, ambulatory referral patients were significantly less likely to attend their scheduled appointment compared with eConsult patients, as either "no-shows" (246 of 2526 [9.7%] vs 3 of 62 [4.8%]) or cancellations (742 of 2526 [29.4%] vs 8 of 62 [12.9%]; P = .003). There were fewer median days to extirpation for eConsult patients compared with ambulatory referral patients (interquartile range; 80.7 ± 79.8 vs 116.9 ± 86.6 days; P = .004). CONCLUSION: Integrating dermatologic care through a telemedicine system can result in improved access for underserved patients through improved efficiency outcomes.
Assuntos
Dermatologia/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Consulta Remota/estatística & dados numéricos , Dermatopatias/diagnóstico , Adulto , Agendamento de Consultas , Estudos Transversais , Dermatologia/métodos , Dermatologia/organização & administração , Feminino , Implementação de Plano de Saúde , Acessibilidade aos Serviços de Saúde/organização & administração , Disparidades em Assistência à Saúde/estatística & dados numéricos , Hospitais Universitários/organização & administração , Humanos , Masculino , Pessoa de Meia-Idade , Ohio , Avaliação de Programas e Projetos de Saúde , Consulta Remota/organização & administração , Estudos Retrospectivos , Dermatopatias/terapia , Fatores Socioeconômicos , Populações Vulneráveis/estatística & dados numéricosRESUMO
Highly Iterated Palindrome 1 (HIP1, GCGATCGC) is hyper-abundant in most cyanobacterial genomes. In some cyanobacteria, average HIP1 abundance exceeds one motif per gene. Such high abundance suggests a significant role in cyanobacterial biology. However, 20 years of study have not revealed whether HIP1 has a function, much less what that function might be. We show that HIP1 is 15- to 300-fold over-represented in genomes analyzed. More importantly, HIP1 sites are conserved both within and between open reading frames, suggesting that their overabundance is maintained by selection rather than by continual replenishment by neutral processes, such as biased DNA repair. This evidence for selection suggests a functional role for HIP1. No evidence was found to support a functional role as a peptide or RNA motif or a role in the regulation of gene expression. Rather, we demonstrate that the distribution of HIP1 along cyanobacterial chromosomes is significantly periodic, with periods ranging from 10 to 90 kb, consistent in scale with periodicities reported for co-regulated, co-expressed and evolutionarily correlated genes. The periodicity we observe is also comparable in scale to chromosomal interaction domains previously described in other bacteria. In this context, our findings imply HIP1 functions associated with chromosome and nucleoid structure.
Assuntos
Proteínas de Bactérias/genética , Cianobactérias/genética , Genoma Bacteriano/genética , Seleção Genética , Proteínas de Bactérias/metabolismo , Sequência de Bases , Cromossomos Bacterianos/genética , Cianobactérias/classificação , Cianobactérias/metabolismo , DNA Bacteriano/genética , Regulação Bacteriana da Expressão Gênica , Periodicidade , FilogeniaRESUMO
The opioid crisis and emergence of fentanyl, fentanyl analogues, and other synthetic opioids has highlighted the need for sensitive and robust detection for interdiction at screening points, notably vehicles at border crossings and packages at postal facilities. This work investigates the discriminative potential, sensitivity and specificity, of ion mobility spectrometry (IMS) for the detection of fentanyl and fifteen (15) fentanyl-related compounds (analogues, other opioids, and metabolites) relative to confounding environmental interferents. The environmental background interferent levels, frequency and intensity, were derived from over 10 000 screening samples collected from delivery vehicles entering a federal site. A receiver operating characteristic (ROC) curve methodology was employed to quantify the relationship between sensitivity and specificity for these target compounds on two instruments/configurations. These instrument configurations differed in desorption and drift tube temperatures, reactant ion dopant chemistry, and analysis time. This work identified reduced mobility areas of high interference that resulted in increased false positive rates (FPR), effectively reducing sensitivity (true positive rate: TPR) in those regions. Except for a few target compounds on either of the instruments that exhibited elevated FPRs, detection of fentanyl and fentanyl-related species was achieved at single to tens of nanograms with ≥90% TPR and ≤2% FPR. This work established the importance of systematic environmental background characterization at each specific screening setting in evaluating a platform's true performance.
Assuntos
Fentanila/análogos & derivados , Fentanila/análise , Espectrometria de Mobilidade Iônica/métodos , Meio Ambiente , Limite de Detecção , Curva ROCRESUMO
Antigenically distinct members of bacterial species can be differentially distributed in the environment. Predators known to consume antigenically distinct prey with different efficiencies are also differentially distributed. Here we show that antigenically distinct, but otherwise isogenic and physiologically indistinct, strains of Salmonella enterica show differential survival in natural soil, sediment and intestinal environments, where they would face a community of predators. Decline in overall cell numbers is attenuated by factors that inhibit the action of predators, including heat and antiprotozoal and antihelminthic drugs. Moreover, the fitness of strains facing these predators - calculated by comparing survival with and without treatments attenuating predator activity - varies between environments. These results suggest that relative survival in natural environments is arbitrated by communities of natural predators whose feeding preferences, if not species composition, vary between environments. These data support the hypothesis that survival against natural predators may drive the differential distribution of bacteria among microenvironments.
RESUMO
Despite the importance of host attributes for the likelihood of associated microbial transmission, individual variation is seldom considered in studies of wildlife disease. Here, we test the influence of host phenotypes on social network structure and the likelihood of cuticular bacterial transmission from exposed individuals to susceptible group-mates using female social spiders (Stegodyphus dumicola). Based on the interactions of resting individuals of known behavioural types, we assessed whether individuals assorted according to their behavioural traits. We found that individuals preferentially interacted with individuals of unlike behavioural phenotypes. We next applied a green fluorescent protein-transformed cuticular bacterium,Pantoeasp., to individuals and allowed them to interact with an unexposed colony-mate for 24 h. We found evidence for transmission of bacteria in 55% of cases. The likelihood of transmission was influenced jointly by the behavioural phenotypes of both the exposed and susceptible individuals: transmission was more likely when exposed spiders exhibited higher 'boldness' relative to their colony-mate, and when unexposed individuals were in better body condition. Indirect transmission via shared silk took place in only 15% of cases. Thus, bodily contact appears key to transmission in this system. These data represent a fundamental step towards understanding how individual traits influence larger-scale social and epidemiological dynamics.
Assuntos
Aranhas/microbiologia , Aranhas/fisiologia , Animais , Feminino , Pantoea/isolamento & purificação , Fenótipo , Seda , Comportamento SocialRESUMO
PURPOSE: The purpose of this study was to explore the effectiveness of the aromatherapy product QueaseEASE (QE) for decreasing postdischarge nausea (PDN) in patients undergoing outpatient abdominal surgery. DESIGN: Prospective exploratory study. METHODS: Informed Consent was obtained preoperatively from a convenience sample of adult patients scheduled for outpatient abdominal surgery procedures. Prior to discharge, subjects were instructed in the use of QE and given instructions on how to rate their nausea on a 0-10 scale. They recorded nausea scales > 0 any time they occurred for the next 24 hours, used the QE, and recorded their nausea scales 3 minutes later. A study nurse called subjects the next day to collect the information. FINDINGS: The sample included 70 outpatients who underwent abdominal surgery. Twenty-five participants (36%) reported experiencing PDN and their concomitant use of QE. There was a significant difference in mean age of those reporting PDN (37 years) versus those without nausea (48 years, P = .004) as well as a significant difference in mean intravenous fluid intake during hospitalization of those reporting PDN (1,310 mL) versus those without nausea (1,511 mL, P = .04). The PDN group had more female participants (72% vs 42%, P = .02), more participants that were less than 50 years of age (84% vs 53%, P = .02), and received more opioids (100% vs 76%, P = .006) than the no nausea group. The 25 PDN participants reported 47 episodes of PDN in which they used QE. For all of the 47 PDN episodes experienced, participants reported a decrease in nausea scale (0 to 10) after the use of QE; for 22 (47%) of the PDN episodes experienced, a nausea scale of 0 after using QE was reported. The mean decrease in nausea scale for all 25 participants was 4.78 (±2.12) after using QE. CONCLUSION: This study found that the aromatherapy QE was an effective treatment of PDN in select same-day abdominal surgery patients.
Assuntos
Abdome/cirurgia , Procedimentos Cirúrgicos Ambulatórios , Aromaterapia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Adulto JovemRESUMO
The optimal force applied during ligament balancing in total knee arthroplasty (TKA) is not well understood. We quantified the effect of increasing distraction force on medial and lateral gaps throughout the range of knee motion, both prior to and after femoral resections in tibial-first gap-balancing TKA. Twenty-five consecutive knees in 21 patients underwent robotic-assisted TKA. The posterior cruciate ligament was resected, and the tibia was cut neutral to the mechanical axis. A digital ligament tensioning tool recorded gaps and applied equal mediolateral loads of 70 N (baseline), 90 N, and 110 N from 90 degrees to full extension. A gap-balancing algorithm planned the femoral implant position to achieve a balanced knee throughout flexion. After femoral resections, gap measurements were repeated under the same conditions. Paired t-tests identified gap differences between load levels, medial/lateral compartments, and flexion angle. Gaps increased from 0 to 20 degrees in flexion, then remain consistent through 90 degrees of flexion. Baseline medial gap was significantly smaller than lateral gap throughout flexion (p <0.05). Increasing load had a larger effect on the lateral versus medial gaps (p <0.05) and on flexion versus extension gaps. Increasing distraction force resulted in non-linear and asymmetric gap changes mediolaterally and from flexion to extension. Digital ligament tensioning devices can give better understanding of the relationship between joint distraction, ligament tension, and knee stiffness throughout the range of flexion. This can aid in informed surgical decision making and optimal soft tissue tensioning during TKA.
Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Procedimentos Cirúrgicos Robóticos , Humanos , Artroplastia do Joelho/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Osteoartrite do Joelho/cirurgia , Articulação do Joelho/cirurgia , Ligamentos Articulares/cirurgia , Amplitude de Movimento Articular , Fenômenos BiomecânicosRESUMO
ABSTRACT: In this article, we describe our experience developing and implementing a multipronged approach to improve performance across a strategic subset of quality measures within primary care. Detailed techniques include data visualization and analytics, process reengineering, team engagement, visual project management, continuous improvement methods and training, and incentives and recognition. We achieved positive change across 12 high priority measures which we deemed the "High Value Framework (HVF)" by fostering a collaborative, nonpunitive, problem-solving culture. We focused on measures that had the greatest potential for impact from a clinical, reimbursement, and reputational perspective. More importantly, we sustained gains despite the challenges posed by the COVID-19 pandemic, thereby demonstrating programmatic resilience and high process reliability. This systematic approach serves as a practical blueprint for other healthcare entities seeking to navigate the complexities of quality improvement in a dynamic environment. The model provides a strategic framework for prioritizing and standardizing quality measures, effectively engaging stakeholders, and managing organizational change. Our model emerged from a need to address real-world operational challenges, rather than as an academic or theoretical exercise, and was developed independently of existing literature on measure prioritization and standardization at the time of its inception.
Assuntos
COVID-19 , Melhoria de Qualidade , SARS-CoV-2 , Humanos , Melhoria de Qualidade/organização & administração , Pandemias , Atenção Primária à Saúde/organização & administração , Atenção Primária à Saúde/normas , Assistência Ambulatorial/organização & administração , Assistência Ambulatorial/normas , Inovação OrganizacionalRESUMO
The objective of this study was to determine relationships between intraoperative posterior cruciate ligament (PCL) sacrificing posterior stabilized (PS) total knee arthroplasty (TKA) laxity measurements throughout flexion and patient outcomes at 2 years post-TKA and to define clinically relevant laxity thresholds to optimize patient outcomes.In a single-surgeon study, PCL sacrificing TKA using a robotics-assisted platform with a digital joint tensioning device was performed in 115 knees in 115 patients. Final intraoperative joint laxity was recorded, and 2-year Knee Injury and Osteoarthritis Outcome Scores (KOOSs) were obtained. A Simulated Annealing optimization algorithm was used to identify medial and lateral laxity windows which maximized the 2-year KOOS pain score. Wilcoxon nonparametric tests were used to compare outcomes between groups.Significant associations were found between intraoperative joint laxity and 2-year KOOS pain outcomes throughout flexion. Clinically relevant laxity windows were defined medially and laterally in mid-flexion and flexion for improved outcomes, whereas only a lateral laxity window could be defined in extension. When all laxity windows were satisfied, a 14.5-KOOS point improvement was found (97.2 vs. 77.8, p = 0.0060) compared to knees which did not satisfy any window. Improvements in Activities of Daily Living (Δ8.8, p = 0.0143), Sports (Δ22.5, p = 0.0108), and Quality of Life (Δ18.7, p = 0.0011) KOOS subscores were also found in knees which satisfied all windows versus 0-1 window.Intraoperative joint laxity is associated with postoperative outcomes in a PS knee design, wherein patients balanced within identified laxity targets reported improved outcomes over those that did not. Clinically significant thresholds were defined and were predominately found in mid-flexion and flexion for medial and lateral laxity. When target windows were combined further improved outcomes were identified.
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In bacteria, physiological change may be effected by a single gene acquisition, producing ecological differentiation without genetic isolation. Natural selection acting on such differences can reduce the frequency of genotypes that arise from recombination at these loci. However, gene acquisition can only account for recombination interference in the fraction of the genome that is tightly linked to the integration site. To identify additional loci that contribute to adaptive differences, we examined orthologous genes in species of Enterobacteriaceae to identify significant differences in the degree of codon selection. Significance was assessed using the Adaptive Codon Enrichment metric, which accounts for the variation in codon usage bias that is expected to arise from mutation and drift; large differences in codon usage bias were identified in more genes than would be expected to arise from stochastic processes alone. Genes in the same operon showed parallel differences in codon usage bias, suggesting that changes in the overall levels of gene expression led to changes in the degree of adaptive codon usage. Most significant differences between orthologous operons were found among those involved with specific environmental adaptations, whereas "housekeeping" genes rarely showed significant changes. When considered together, the loci experiencing significant changes in codon selection outnumber potentially adaptive gene acquisition events. The identity of genes under strong codon selection seems to be influenced by the habitat from which the bacteria were isolated. We propose a two-stage model for how adaptation to different selective regimes can drive bacterial speciation. Initially, gene acquisitions catalyze rapid ecological differentiation, which modifies the utilization of genes, thereby changing the strength of codon selection on them. Alleles develop fitness variation by substitution, producing recombination interference at these loci in addition to those flanking acquired genes, allowing sequences to diverge across the entire genome and establishing genetic isolation (i.e., protection from frequent homologous recombination).
Assuntos
Adaptação Biológica/genética , Bactérias/genética , Códon/genética , Meio Ambiente , Transferência Genética Horizontal/genética , Filogenia , Seleção Genética/genética , Análise de Variância , Funções Verossimilhança , Modelos Genéticos , Óperon/genética , Análise de Componente Principal , Especificidade da EspécieRESUMO
The proper folding, assembly, and maintenance of cellular proteins is a highly regulated process and is critical for cellular homeostasis. Multiple cellular compartments have adapted their own systems to ensure proper protein folding, and quality control mechanisms are in place to manage stress due to the accumulation of unfolded proteins. When the accumulation of unfolded proteins exceeds the capacity to restore homeostasis, these systems can result in a cell death response. Unfolded protein accumulation in the endoplasmic reticulum (ER) leads to ER stress with activation of the unfolded protein response (UPR) governed by the activating transcription factor 6 (ATF6), inositol requiring enzyme-1 (IRE1), and PKR-like endoplasmic reticulum kinase (PERK) signaling pathways. Many xenobiotics have been shown to influence ER stress and UPR signaling with either pro-survival or pro-death features. The ultimate outcome is dependent on many factors including the mechanism of action of the xenobiotic, concentration of xenobiotic, duration of exposure (acute vs. chronic), cell type affected, nutrient levels, oxidative stress, state of differentiation, and others. Assessing perturbations in activation or inhibition of ER stress and UPR signaling pathways are likely to be informative parameters to measure when analyzing mechanisms of action of xenobiotic-induced toxicity.
Assuntos
Estresse do Retículo Endoplasmático/fisiologia , Resposta a Proteínas não Dobradas/fisiologia , Xenobióticos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Dobramento de Proteína , Transdução de Sinais , Resposta a Proteínas não Dobradas/efeitos dos fármacosRESUMO
Because the properties of horizontally-transferred genes will reflect the mutational proclivities of their donor genomes, they often show atypical compositional properties relative to native genes. Parametric methods use these discrepancies to identify bacterial genes recently acquired by horizontal transfer. However, compositional patterns of native genes vary stochastically, leaving no clear boundary between typical and atypical genes. As a result, while strongly atypical genes are readily identified as alien, genes of ambiguous character are poorly classified when a single threshold separates typical and atypical genes. This limitation affects all parametric methods that examine genes independently, and escaping it requires the use of additional genomic information. We propose that the performance of all parametric methods can be improved by using a multiple-threshold approach. First, strongly atypical alien genes and strongly typical native genes would be identified using conservative thresholds. Genes with ambiguous compositional features would then be classified by examining gene context, including the class (native or alien) of flanking genes. By including additional genomic information in a multiple-threshold framework, we observed a remarkable improvement in the performance of several popular, but algorithmically distinct, methods for alien gene detection.