Functional Evaluation Research Articles

In silico Analysis of Natural Inhibitors against HPV E6 Protein.

Drug re-purposing is one of the cost-effective methods to establish novel therapeutics against many diseases. Established natural products are collected from databases and used to potentially screen them against HPV E6 protein, a critical viral protein. This study aims to design potential small molecule inhibitors against HPV E6 protein using structure-based approaches. Ten natural anti-cancerous compounds (Apigenin, Baicalein, Baicalin, Ponicidin, Oridonin, Lovastatin, Triterpenoid, Narirutin, Rosmarinic Acid, and Xanthone) were selected by review of the literature. These compounds were screened using Lipinski Rule of Five. Out of ten compounds, seven were found to satisfy Rule of five. Docking of these seven compounds was carried out using AutoDock software and corresponding Molecular Dynamics Simulations were performed by GROMACS. Among the seven compounds docked with the E6 target protein, six compounds showed lesser binding energy than the reference compound, Luteolin. The three-dimensional structures of E6 protein and the corresponding ligand complexes were visualised and analysed using PyMOL whereas the two-dimensional images of protein-ligand interactions were obtained by LigPlot⁺ software to study the specific interactions. ADME analysis using SwissADME software revealed that all the compounds except Rosmarinic acid have good gastrointestinal absorption and solubility characteristics while Xanthone and Lovastatin showed blood brain barrier penetration properties. Considering the binding energy and ADME analysis, Apigenin and Ponicidin are found to be most suitable for de novo</i> designing of potential inhibitors against the HPV16 E6 protein. Further, synthesis and characterization of these potential HPV16 E6 inhibitors will be carried out and their functional evaluation using cell culture-based assays will be undertaken.

The six minute walk test in healthy young women

ObjectivesThe Six Minute Walk Test (6MWT) assesses functional capacity. We determined the reference range distance walked, heart rate change, and breathlessness in healthy women. DesignProspective observational study. Methods100 nulliparous women aged 18–40 performed two 6MWTs, with the second performed after heart rate returned to baseline. Borg scales compared expected and true breathlessness. ResultsReference range was 472–758 ​m, with distance mean (SD) of 615 (73.0) metres. Heart rate increase during exercise was 11 (11.8) beats per minute, recovering to baseline in 4.5 (3.9) minutes. 63 ​% of women overestimated breathlessness. ConclusionsThese data represent reference values for functional evaluation of healthy young women.

Approximation in the extended functional tensor train format

This work proposes the extended functional tensor train (EFTT) format for compressing and working with multivariate functions on tensor product domains. Our compression algorithm combines tensorized Chebyshev interpolation with a low-rank approximation algorithm that is entirely based on function evaluations. Compared to existing methods based on the functional tensor train format, the adaptivity of our approach often results in reducing the required storage, sometimes considerably, while achieving the same accuracy. In particular, we reduce the number of function evaluations required to achieve a prescribed accuracy by up to over 96%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$96\\%$$\\end{document} compared to the algorithm from Gorodetsky et al. (Comput. Methods Appl. Mech. Eng. 347, 59–84 2019).

Fitwalking: A New Frontier for Kidney Patients. A Center' s Experience.

Physical inactivity is common in patients with chronic kidney disease (CKD) and is an important modifiable risk factor for mortality, morbidity, and reduced quality of life. The present single-centre pilot study evaluated the possibility of performing structured physical exercise using a specific walking model, Fitwalking, in a population of patients with CKD and, according to the American College of Rheumatology guidelines, also in a population with immuno-rheumatological disease. Patients were recruited from the nephrology, haemodialysis, peritoneal dialysis, transplantation, and immuno-rheumatology outpatient clinics. After general and functional clinical evaluation and exercise prescription at the Department of Sports Medicine, we performed scientifically proven tests on CKD (Six-minute walk test and Sit to stand test), before and after the Fitwalking technique training course, and again after 6 and 12 months, to evaluate its effectiveness and identify any critical issues. We enrolled 80 patients, (41 males, 51.2%), mean age 53±12 years; the clinical data showed statistically significant improvements in systolic, average, and differential blood pressure, average speed, and physical strength. Participants also adapted to muscle fatigue, experienced a reduction in BMI with stable lean mass and reduced fat mass, and reported improved perceptions of physical and mental health, and quality of life. All enrolled patients successfully completed the process. A specific prescription was used that provided health education and allowed for the implementation of structured physical activity that could be performed safely and independently even after the training period. The activity was sustainable thanks to the training of in-house medical and nursing staff, demonstrating that it is possible to overcome this type of barrier to physical activity in CKD and in immuno-rheumatological patients.

A New Approach to Postoperative Rehabilitation Following Mosaicplasty and Bone Marrow Aspiration Concentrate (BMAC) Augmentation

Background: Chondral defects in the knee present a significant challenge due to their limited self-healing capacity, often leading to joint degeneration and functional disability. Current treatments, including surgical approaches like mosaicplasty and regenerative therapies such as bone marrow aspirate concentrate (BMAC) augmentation, aim to address these defects and improve patient outcomes. Materials and Methods: This study conducted a single-center, randomized controlled trial to evaluate the efficacy of different treatment approaches and rehabilitation protocols for chondral defects. Thirty-seven subjects presenting with symptomatic chondral or osteochondral defects (&gt;3 cm2) in the weight-bearing region of the femoral condyle were partitioned into three groups, and underwent mosaicplasty with or without BMAC augmentation, followed by either a 6-week or 12-week rehabilitation program. Group 1 (n = 10) received mosaicplasty combined with BMAC augmentation and engaged in a twelve-week two-phase rehabilitation protocol. Group 2 (n = 15) underwent mosaicplasty alone and participated in the same twelve-week two-phase rehabilitation regimen. Meanwhile, Group 3 (n = 12) underwent mosaicplasty and underwent a shorter six-week one-phase rehabilitation program. Clinical assessments were performed using the visual analog scale (VAS) for pain, goniometry for the knee’s range of motion (ROM), manual muscle testing (MMT) for quadricep strength, and the Western Ontario and McMaster University Arthritis Index (WOMAC) for functional evaluation in three test phases. Results: Significant differences in WOMAC scale scores were observed between the three groups at the intermediate (F(2, 34) = 5.24, p &lt; 0.010) and final (F(2, 34) = 111, p &lt; 0.000) stages, with post hoc Tukey tests revealing variations shared among all three groups. The between-group analysis of the VAS scale demonstrated no statistically significant difference initially (F(2, 34) = 0.18, p &lt; 0.982), but significant differences emerged following the intermediate (F(2, 34) = 11.40, p &lt; 0.000) and final assessments (F(2, 34) = 59.87, p &lt; 0.000), with post hoc Tukey tests revealing specific group variations, notably between Group 1 and both Group 2 and Group 3, and also between Group 3 and Group 2. The between-group analysis of quadricep muscle strength using MMT scores revealed no statistically significant differences initially (F(2, 34) = 0.376, p &lt; 0.689) or following the intermediate assessment (F(2, 34) = 2.090, p &lt; 0.139). The one-way ANOVA analysis showed no significant difference in the knee ROM initially (F(2, 34) = 1.037, p &lt; 0.366), but significant differences emerged following intermediate (F(2, 34) = 9.38, p &lt; 0.001) and final assessments (F(2, 34) = 11.60, p &lt; 0.000). Post hoc Tukey tests revealed significant differences between Groups 1 and 2, Groups 1 and 3, and Groups 2 and 3 at intermediate and final assessments. Conclusions: The patients who received BMAC augmentation and completed a 12-week rehabilitation protocol had significantly better outcomes in pain relief, knee function, and ROM when compared to those who did not receive BMAC augmentation or those who completed a shorter rehabilitation period. Our findings suggest that combining mosaicplasty with BMAC augmentation and a comprehensive rehabilitation program can lead to superior clinical outcomes for patients with chondral defects in the knee.

From Hospital to Home: Validating a Cognitive-Functional Evaluation of Elders (COFEE-HD).

Background. Increase in hospitalizations of older adults emphasizes the need for efficient hospital discharge planning to enable optimal reentry upon returning home. Yet few assessments offer an extensive picture of the older adult's functional-cognitive state. A comprehensive assessment for discharge planning together with a written summary can be beneficial to the older adult and family. Purpose. This quantitative study compared a modified version of a previously validated tool COFEE (cognitive OT functional evaluation of elders), for use in the hospital, HD (hospital discharge) with standard hospitals assessments. Methods. Of the 77 participants recruited in hospital, home assessments were conducted 4 months later on 64 participants. Findings. The COFEE-HD scores (physical functioning, personal and environmental safety and meta cognitive functioning) were significantly correlated with standard hospital measures and with the home assessment. Implications. The COFEE-HD was found to have a high level of validity in a hospital setting, and the resulting evaluation can provide important insights into function, safety and cognitive function for post-discharge behaviors.

#2295 Can we detect the evolution of GFR with estimated GFR in patients with ADPKD?

Abstract Background and Aims ADPKD affects about 10% of the patients with CKD. In the disease the formation of cysts replace normal renal parenchyma leading to renal function loss. The evolution of the disease is irregular: some patients lose renal function very fast while others remain stable or have a slow loss. This may have consequences in clinical care. In day-to-day practice, GFR is evaluated by means of formulas, which are algorithms that use creatinine and others markers like age and gender to estimate GFR. However, the accuracy and precision of eGFR in reflecting real GFR in ADPKD is not clear, being this the objective of our study. Method To analyse the capacity of eGFR by creatinine-based formulas in predicting mGFR changes over time. We evaluated patients with ADPKD, who underwent mGFR and eGFR by a group 5 equations at baseline, month 6 and then annually. mGFR was evaluated by the clearance of iohexol using dried blood spots (iohexol-DBS) and eGFR with the following creatinine-based equations: Cockcroft-Gault, aMDRD, CKD-EPI, FAS and EKFC. We calculated renal function decline (GFR decline) using repeated measured with mGFR and eGFR. All subjects have at least 3 repeated evaluations of renal function. The agreement between mGFR and eGFR declines was analysed by the concordance correlation coefficient (CCC). Also, we evaluated the capacity of eGFR decline in detecting diverse degree of GFR decline (a) rapid progressors: mGFR of −5 ml/min/y; (b) moderate progressors: −2 to −5 ml/min/y; (c) stable: &amp;gt; −2 ml/min/y. Results We evaluated 111 (43; 37% men); age: 42 y ± 14, with a 5 ± 1 evaluations of GFR over time (mGFR and eGFR). The average GFR decline was: −2,8 ml/min/year (mGFR); −3,1 (Cockcroft-Gault), −2,9 (aMDRD), −3,0 (CKD-EPI), −2,8 (FAS) and −2,6 (EFKC) According with mGFR decline, 21 patients (19%) were rapid progressors; 46 (41%) moderate progressors and 44 (40%) stable. The agreement between eGFR decline and mGFR decline was poor, reflected by a low CCC: 0.37 (Cockcroft-Gault); 0.76 (aMDRD); 0.80 (CKD-EPI), 0.77 (FAS); 0.81 (EFKC). In general, eGFR decline failed to detect progression of renal function over time. On average, 43% of the rapid progressors, 53% of the moderate progressors and 54% of the stable patients were not detected by any formula, respectively. Finally, a total of 12% and 6% of those stable or moderate progressors were falsely classified as rapid progressors. Conclusion eGFR is not able to reflect properly renal function changes over time in patients with ADPKP in about half of the patients. A relevant number of cases are erroneously considered as rapid progressors or even stable patients. This may have clinical consequences. Whenever possible, mGFR could be considered in this population.

Peritendinous Submembrane Access Technique for Management of Acute Ruptures of the Achilles Tendon: A Retrospective Study of 249 Cases.

Percutaneous repair is an alternative to open surgical repair of the Achilles tendon with comparable, functional results and low re-rupture and infection rates; however, sural nerve injury is a known complication. The purpose of this study is to design a new surgical procedure, the minimally invasive peritendinous submembrane access technique (MIS-PSAT). It offers optimal results, with excellent functional outcomes, and with minimal soft tissue complications and sural nerve injury. This retrospective study included 249 patients with acute closed Achilles tendon ruptures treated at our institution between 2009 and 2019. All patients underwent MIS-PSAT at our institution and were followed up for 8-48 months. Functional evaluation was based on the Achilles tendon total rupture score (ATRS) and the American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS-AHS), associated with local complications and isokinetic tests. None of the patients had infection, necrosis, or sural nerve injury. Re-rupture occurred in two cases. The average times to return to work and sports was 10.4 and 31.6 weeks, respectively. The average ATRS and AOFAS-AHS scores were 90.2 and 95.7, respectively, with an excellent rate of 99.5%. Isokinetic tests showed that ankle function on the affected side was comparable with that on the healthy side (p > 0.05). The MIS-PSAT for acute Achilles tendon rupture is easy to perform with few complications. Importantly, the surgical technique reduces the risk of sural nerve injuries. Patients have high postoperative satisfaction, low re-rupture rates, and muscle strength, and endurance can be restored to levels similar to those on the healthy side.

Use of transcranial magnetic stimulation (TMS) for studying cognitive control in depressed patients: A systematic review.

Major depressive disorder (MDD) is a debilitating mental disorder and the leading cause of disease burden. Major depressive disorder is associated with emotional impairment and cognitive deficit. Cognitive control, which is the ability to use perceptions, knowledge, and information about goals and motivations to shape the selection of goal-directed actions or thoughts, is a primary function of the prefrontal cortex (PFC). Psychotropic medications are one of the main treatments for MDD, but they are not effective for all patients. An alternative treatment is transcranial magnetic stimulation (TMS). Previous studies have provided mixed results on the cognitive-enhancing effects of TMS treatment in patients with MDD. Some studies have found significant improvement, while others have not. There is a lack of understanding of the specific effects of different TMS protocols and stimulation parameters on cognitive control in MDD. Thus, this review aims to synthesize the effectiveness of the TMS methods and a qualitative assessment of their potential benefits in improving cognitive functioning in patients with MDD. We reviewed 21 studies in which participants underwent a treatment of any transcranial magnetic stimulation protocol, such as repetitive TMS or theta-burst stimulation. One of the primary outcome measures was any change in the cognitive control process. Overall, the findings indicate that transcranial magnetic stimulation (TMS) may enhance cognitive function in patients with MDD. Most of the reviewed studies supported the notion of cognitive improvement following TMS treatment. Notably, improvements were predominantly observed in inhibition, attention, set shifting/flexibility, and memory domains. However, fewer significant improvements were detected in evaluations of visuospatial function and recognition, executive function, phonemic fluency, and speed of information processing. This review found evidence supporting the use of TMS as a treatment for cognitive deficits in patients with MDD. The results are promising, but further research is needed to clarify the specific TMS protocol and stimulation locations that are most effective.

CD62-L down-regulation after L18-MDP stimulation as a complementary flow cytometry functional assay for the diagnosis of XIAP deficiency.

X-linked inhibitor of apoptosis (XIAP) deficiency is an infrequent inborn error of immunity caused by mutations in XIAP gene. Most cases present with absence of XIAP protein which can be detected by flow cytometry (FC), representing a rapid diagnostic method. However, since some genetic defects may not preclude protein expression, it is important to include a complementary functional test in the laboratory workup of these patients. L-selectin (CD62-L) is a molecule that is cleaved from the surface membrane of leukocytes upon stimulation of different receptors such as toll like receptors (TLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs), including NOD2. Considering that XIAP deficiency impairs NOD2 signaling, we decided to assess CD62-L down-regulation by FC post-stimulation of neutrophils and monocytes with L18-muramyl Di-Peptide (L18-MDP), a NOD2 specific agonist, in order to develop a novel assay for the functional evaluation of patients with suspicion of XIAP defects. Whole blood samples from 20 healthy controls (HC) and four patients with confirmed molecular diagnosis of XIAP deficiency were stimulated with 200 ng/mL of L18-MDP for 2 h. Stimulation with 100 ng/mL of lipopolysaccharide (LPS) was carried out in parallel as a positive control of CD62-L shedding. CD62-L expression was evaluated by FC using an anti CD62-L- antibody and down-regulation was assessed by calculating the difference in CD62-L expression before and after stimulation, both in terms of percentage of CD62-L expressing cells (Δ%CD62-L) and median fluorescence intensity (ΔMFI%). Neutrophils and monocytes from XIAP deficient patients displayed a significantly diminished response to L18-MDP stimulation compared with HC (p < 0.0001), indicating a severely altered mechanism of CD62-L down-regulation following activation of NOD2-XIAP axis. On the other hand, the response to LPS stimulation was comparable between patients and heathy controls, suggesting preserved CD62-L shedding with a different stimulus. FC detection of CD62-L down-regulation in monocytes and neutrophils after whole blood stimulation with L18-MDP results in an effective and rapid functional test for the identification of XIAP deficient patients.

Differences in the Evaluation of Malnutrition and Body Composition Using Bioelectrical Impedance Analysis, Nutritional Ultrasound, and Dual-Energy X-ray Absorptiometry in Patients with Heart Failure.

Although malnutrition is frequently observed in patients with heart failure (HF), this diagnosis should be performed carefully since HF itself is associated with increased inflammatory activity, which affects body weight, functionality, and some nutritional parameters; thus, its isolated interpretation can erroneously identify surrogate markers of severity as markers of malnutrition. In this context, we aimed to evaluate the prevalence of malnutrition using different classification systems and perform a comprehensive nutritional evaluation to determine the reliability of different diagnostic techniques. Eighty-three patients with a recent hospital admission due to HF were evaluated. GLIM diagnosis criteria and subjective global assessment (SGA) were performed; a comprehensive anthropometric, functional, and biochemical nutritional evaluation was performed, in which bioelectrical impedance analysis (BIA), nutritional ultrasound, and dual-energy X-ray absorptiometry (DXA) were performed. Additionally, mortality and additional admissions due to HF were determined after a mean follow up of 18 months. Malnutrition according to the GLIM criteria (54%) accurately distinguished patients with impaired functionality, lower lean mass, skeletal mass index, and appendicular muscle mass (BIA), as well as lower trunk fat mass, trunk lean mass, fat-free mass (DXA), and decreased albumin and increased C-reactive protein serum levels. According to SGA, there were significant changes in body composition parameters determined by BIA, muscle ultrasound, and functional tests between well-nourished patients and patients with risk of malnutrition (53.7%) or who had malnutrition (7.1%), but not when the last two groups were compared. BIA and DXA showed strong correlations when evaluating muscle and fat mass in HF patients, but correlations with nutritional ultrasound were limited, as well as functional tests. A multivariate analysis showed that no significant association was observed between body composition and mortality, but preperitoneal fat was associated with an increased risk of new hospital admissions (OR: 0.73). GLIM criteria identified a lower percentage of patients with HF and malnutrition compared with SGA; thus, SGA could have a role in preventing malnutrition in HF patients. Nutritional evaluation with BIA and DXA in patients with HF showed reliable results of body composition parameters in HF, and both help with the diagnosis of malnutrition according to the GLIM or SGA criteria and could provide complementary information in some specific cases.

Pediatric three-dimensional quantitative cardiovascular computed tomography.

High-resolution, isotropic, 3-dimensional (D) data from pediatric cardiovascular computed tomography (CT) offer great potential for the accurate quantitative evaluation of pediatric cardiovascular and pulmonary vascular diseases. Recent pilot studies using pediatric 3-D cardiovascular CT have shown promising results in assessing cardiac function in conditions such as tetralogy of Fallot, cardiac defects with a hypoplastic ventricle, Ebstein anomaly, and in quantifying myocardial mass. In addition, the quantitative assessment of pulmonary vascularity is useful for evaluating differential right-to-left pulmonary vascular volume ratio, the effectiveness of pulmonary angioplasty, and predicting pulmonary hypertension. These initial experiences could broaden the role of pediatric cardiovascular CT in clinical practice. Furthermore, the current barriers to its widespread use, pertinent solutions to these problems, and new applications are discussed. In this review, the 3-D quantitative evaluations of cardiac function and pulmonary vascularity using high-resolution pediatric cardiovascular CT data are illustrated.

Evaluation of the Physicochemical and Micromeritic Properties of Exudate Gum of Cussonia arborea Stem Bark in Conventional Tablet Formulation

Pharmaceutical excipients are classified based on the function(s) in the processing and/or finished product. However, functionality evaluations, procedures, and related acceptance criteria for excipients tend to depend on the dosage form, and assessment is usually done on a case-by-case basis. This means that any useful and reliable evaluation of the overall functionality-related properties is only possible within the context of the specific formulation method. This study evaluated the physicochemical, functional, and related properties of purified gum obtained from the stem bark of the Cussonia arborea tree. The purified gum was acidic (pH 5.32–5.50) with percentage (%) moisture content and insoluble matter of 13.33 ± 0.33 and 0.47 ± 0.01, respectively. Moreover, it was soluble in all the aqueous-based solvents but insoluble in all the organic solvents. The total ash of the gum was higher than that of international standard gum Arabic. Micromeritic properties indicated the need for a flow aid to improve flowability. Six formulated batches of tablets containing 0.5–5%w/w of gum, respectively, were generally soft with none passing the USP T80 standard of drug dissolution indicating poor tablet binding and drug-releasing properties. The disintegration action of CAPG was poor (only batches containing 0.5 and 1% CAPG passed) and was not comparable to that of the standard corn starch. The gum was therefore considered a poor disintegrant and binder in the formulation of conventional release tablets.

Comparison of Conservative and Arthroplasty Treatment for 3 or 4 Part Proximal Humerus Fractures in the Elderly

Aim: Proximal humerus fractures are common injuries in the elderly population. This study hypothesizes that arthroplasty is not superior to conservative treatment in the management of multi-part proximal humerus fractures in elderly patients. Material and Method: Patients aged 65 and above with 3–4-part proximal humerus fractures, treated either conservatively or with arthroplasty, were included in the study. The minimum follow-up period was set at 12 months. Functional evaluations of the patients were performed using the Quick Disabilities of Arm, Shoulder and Hand (Q-DASH) scoring system. Statistical analysis comparing the two groups was conducted using the SPSS software. The mean values of numerical data were analyzed using the Mann-Whitney U test, while categorical data were compared using the Chi-square test. A significant level of 0.05 was considered. Results: A total of 67 patients who received adequate clinical follow-up were included in the study (50 conservative 17 arthroplasty). The average age of the patients was 76.12 years, with 9 male and 58 female patients. The average follow-up period was 22.61 months (range: 12-82). There were no statistically significant differences in age, gender, side, follow-up period, and fracture type distribution between the two groups. However, a significant difference in Q-DASH scores was observed (p

Spectral-like conjugate gradient methods with sufficient descent property for vector optimization.

Several conjugate gradient (CG) parameters resulted in promising methods for optimization problems. However, it turns out that some of these parameters, for example, 'PRP,' 'HS,' and 'DL,' do not guarantee sufficient descent of the search direction. In this work, we introduce new spectral-like CG methods that achieve sufficient descent property independently of any line search (LSE) and for arbitrary nonnegative CG parameters. We establish the global convergence of these methods for four different parameters using Wolfe LSE. Our algorithm achieves this without regular restart and assumption of convexity regarding the objective functions. The sequences generated by our algorithm identify points that satisfy the first-order necessary condition for Pareto optimality. We conduct computational experiments to showcase the implementation and effectiveness of the proposed methods. The proposed spectral-like methods, namely nonnegative SPRP, SHZ, SDL, and SHS, exhibit superior performance based on their arrangement, outperforming HZ and SP methods in terms of the number of iterations, function evaluations, and gradient evaluations.

Periosteal wrapping of the hamstring tendon autograft improves graft healing and prevents tunnel widening after anterior cruciate ligament anatomic reconstruction.

The periosteum is a readily available tissue at the hamstring harvest site that could be utilized to enhance graft healing and prevent tunnel widening without additional cost or morbidity. This study aimed to compare graft healing using magnetic resonance imaging (MRI) and functional clinical outcome scores in a matched cohort of patients who underwent anterior cruciate ligament (ACL) reconstruction with hamstring autografts with or without periosteal augmentation. Forty-eight patients who underwent ACL reconstruction (ACLR) were prospectively enrolled: 25 with standard ACLR (ST-ACLR) and 23 with periosteal augmented grafts (PA-ACLR). The same surgical techniques, fixation methods, and postoperative protocol were used in both groups. Signal-to-noise quotient (SNQ), graft healing at the bone-graft interface, graft signal according to the Howell scale, and femoral tunnel widening were evaluated using MRI after 1 year of follow-up. International knee documentation score (IKDC), Lysholm, Tegner activity scale, and visual analog scale for pain were used for functional evaluation at a minimum of 2years postoperative. The mean SNQ of the proximal part of the graft was 9.6 ± 9.2 and 2.9 ± 3.3 for the ST-ACLR and PA-ACLR groups, respectively (P = 0.005). The mean femoral tunnel widening was 30.3% ± 18.3 and 2.3% ± 9.9 for the ST-ACLR, PA-ACLR groups, respectively (P < 0.001). Complete graft tunnel healing was observed in 65% and 28% of cases in the PA-ACLR and ST-ACLR groups, respectively. Both groups showed marked improvements in functional scores, with no statistically significant differences. Periosteal wrapping of hamstring tendon autografts is associated with better graft healing and maturation and lower incidence of femoral tunnel widening based on MRI analysis 1year after ACL reconstruction. However, patient-reported outcomes and measured laxity were similar between the two groups at 2years follow up. Trail registration number: PACTR202308594339018, date of registration: 1/5/2023, retrospectively registered at the Pan African Clinical Trial Registry (pactr.samrc.ac.za) database.

Relationship between pulmonary, cough, and swallowing functions in individuals with amyotrophic lateral sclerosis.

Evaluations of pulmonary, cough, and swallow function are frequently performed to assess disease progression in amyotrophic lateral sclerosis (ALS), yet the relationship between these functions remains unknown. We therefore aimed to determine relationships between these measures in individuals with ALS. One hundred individuals with ALS underwent standardized tests: forced vital capacity (FVC), maximum expiratory/inspiratory pressure (MEP, MIP), voluntary cough peak expiratory flow (PEF), and videofluoroscopic swallow evaluation (VF). Duplicate raters completed independent, blinded ratings using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale. Descriptives, Spearman's Rho correlations, Kruskal-Wallis analyses, and Pearson's chi-squared tests were completed. Mean and standard deviation across pulmonary and cough measures were FVC: 74.2% predicted (± 22.6), MEP: 91.6 cmH2O (± 46.4), MIP cmH2O: 61.1 (± 28.9), voluntary PEF: 352.7 L/min (± 141.6). DIGEST grades included: 0 (normal swallowing): 31%, 1 (mild dysphagia): 48%, 2 (moderate dysphagia): 10%, 3 (severe dysphagia): 10%, and 4 (life-threatening dysphagia): 1%. Positive correlations were observed: MEP-MIP: r = .76, MIP-PEF: r = .68, MEP-PEF: r = .61, MIP-FVC: r = .60, PEF-FVC: r = .49, and MEP-FVC: r = .46, p < .0001. MEP (p = .009) and PEF (p = .04) differed across DIGEST safety grades. Post hoc analyses revealed significant between group differences in MEP and PEF across DIGEST safety grades 0 versus 1 and grades 0 versus 3, (p < .05). In this cohort of individuals with ALS, pulmonary function, and voluntary cough were associated. Expiratory metrics (MEP, PEF) were diminished in individuals with unsafe swallowing, increasing their risk for effectively defending the airway.

Development and functional evaluation of a hyaluronic acid coated nano-formulation with kaempferol as a novel intra-articular agent for Knee Osteoarthritis treatment

Knee osteoarthritis (OA) involves articular cartilage degradation driven mainly by inflammation. Kaempferol (KM), known for its anti-inflammatory property, holds potential for OA treatment. This study investigated the potential of hyaluronic acid (HA)-coated gelatin nanoparticles loaded with KM (HA-KM GNP) for treating knee OA. KM was encapsulated into gelatin nanoparticles (KM GNP) and then coated with HA to form HA-KM GNPs. Physical properties were characterized, and biocompatibility and cellular uptake were assessed in rat chondrocytes. Anti-inflammatory and chondrogenic properties were evaluated using IL-1β-stimulated rat chondrocytes, compared with HA-coated nanoparticles without KM (HA GNP) and KM alone. Preclinical efficacy was tested in an anterior cruciate ligament transection (ACLT)-induced knee OA rat model treated with intra-articular injection of HA-KM GNP. Results show spherical HA-KM GNPs (88.62 ± 3.90 nm) with positive surface charge. Encapsulation efficiency was 98.34 % with a sustained release rate of 18 % over 48 h. Non-toxic KM concentration was 2.5 μg/mL. In IL-1β-stimulated OA rat chondrocytes, HA-KM GNP significantly down-regulated RNA expression of IL-1β, TNF-α, COX-2, MMP-9, and MMP-13, while up-regulating SOX9 compared to HA GNP, and KM. In vivo imaging demonstrated significantly higher fluorescence intensity within rat knee joints for 3 hours post HA-KM GNP injection compared with KM GNP (185.2% ± 34.1% vs. 45.0% ± 16.7%). HA-KM GNP demonstrated significant effectiveness in reducing subchondral sclerosis, attenuating inflammation, inhibiting matrix degradation, restoring cartilage thickness, and reducing the severity of OA in the ACLT rat model. In conclusion, HA-KM GNP holds promise for knee OA therapy.

Estimation-of-distribution algorithms for multi-valued decision variables

The majority of research on estimation-of-distribution algorithms (EDAs) concentrates on pseudo-Boolean optimization and permutation problems, leaving the domain of EDAs for problems in which the decision variables can take more than two values, but which are not permutation problems, mostly unexplored. To render this domain more accessible, we propose a natural way to extend the known univariate EDAs to this setting. Different from a naïve reduction to the binary case, our approach avoids additional constraints.Since understanding genetic drift is crucial for an optimal parameter choice, we extend the known quantitative analysis of genetic drift to EDAs for multi-valued, categorical variables. Roughly speaking, when the variables take r different values, the time for genetic drift to become significant is r times shorter than in the binary case. Consequently, the update strength of the probabilistic model has to be chosen r times lower now.To investigate how desired model updates take place in this framework, we undertake a mathematical runtime analysis on the r-valued LeadingOnes problem. We prove that with the right parameters, the multi-valued UMDA solves this problem efficiently in O(rln⁡(r)2n2ln⁡(n)) function evaluations. This bound is nearly tight as our lower bound Ω(rln⁡(r)n2ln⁡(n)) shows.Overall, our work shows that our good understanding of binary EDAs naturally extends to the multi-valued setting, and it gives advice on how to set the main parameters of multi-values EDAs.

Use of Uncemented Humeral Stem in Reverse Arthroplasties for Fractures of The Proximal End of the Humerus: Radiographic and Functional Evaluation

Use of Uncemented Humeral Stem in Reverse Arthroplasties for Fractures of The Proximal End of the Humerus: Radiographic and Functional Evaluation