A phase I study to evaluate the safety, tolerance and pharmacokinetics of anti-Shiga toxin hyperimmune equine F (ab')2 fragments in healthy volunteers.

AIMS: Shiga toxin-producing Escherichia coli-haemolytic uraemic syndrome (STEC-HUS) is considered a toxaemic disorder in which early intervention with neutralizing antibodies may have therapeutic benefits. INM004, composed of F (ab')2 fragments from equine immunoglobulins, neutralizes Stx1/Stx2, potentially preventing the onset of HUS. METHODS: A single-centre, randomized, phase 1, single-blind, placebo-controlled clinical trial to evaluate INM004 safety, tolerance and pharmacokinetics (PK) in healthy adult volunteers, was conducted; in stage I, eight subjects were divided in two cohorts (n = 4) to receive a single INM004 dose of 2 or 4 mg kg-1, or placebo (INM004:placebo ratio of 3:1). In stage II, six subjects received three INM004 doses of 4 mg kg-1 repeated every 24 h, or placebo (INM004:placebo ratio of 5:1). RESULTS: Eight subjects (57.1%) experienced mild treatment-emergent adverse events (TEAEs); most frequent were rhinitis, headache and flushing, resolved within 24 h without changes in treatment or additional intervention. No serious AEs were reported. Peak concentrations of INM004 occurred within 2 h after infusion, with median Cmax values of 45.1 and 77.7 µg mL-1 for 2 and 4 mg kg-1, respectively. The serum concentration of INM004 declined in a biphasic manner (t1/2 range 30.7-52.9 h). Systemic exposures increased with each subsequent dose in a dose-proportional manner, exhibiting accumulation. Geometric median Cmax and AUC values were 149 and 10 300 µg h mL-1, respectively, in the repeated dose regimen. Additionally, samples from subjects that received INM004 at 2 mg kg-1 showed neutralizing capacity against Stx1 and Stx2 in in vitro assays. CONCLUSIONS: The results obtained in this first-in-human study support progression into the phase 2 trial in children with HUS.

RadioLab project: knowledge of radon gas in Italy.

RadioLab is an Italian project, addressed to school-age people, and designed for the dissemination of scientific culture on the theme of environmental radioactivity, with particular regards to the importance of knowledge of radon gas exposure. The project is a nationwide initiative promoted by the National Institute of Nuclear Physics- INFN. First tool used by the project, and of immediate impact to assess the public awareness on radon, is the administration of the survey "do you know the radon gas?". In the survey, together with the knowledge of radon and of its sources, information on personal, cultural and territorial details regarding the interviewees are also taken. Reasonably, the survey invests not only young people, but also their relatives, school workers and, gradually, the public. The survey is administrated during exhibitions or outreach events devoted to schools, but also open to the public. The survey is in dual form: printed and online. The online mode clearly leads RadioLab project even outside the school environment. Based on the results of the survey, several statistical analyses have been performed and many conclusions are drawn about the knowledge of the population on the radon risk. The RadioLab benefit and the requirement to carry on the project goals, spreading awareness of environmental radioactivity from radon, emerge. The dataset involves all twenty Italian regions and consists of 28,612 entries covering the 5-year period 2018-2022.

Use of direct oral anticoagulants and low molecular weight heparin in venous thromboembolism associated with cancer: real-world evidence in Argentina.

BACKGROUND: Venous thromboembolism (VTE) and major bleeding (MB) are common in cancer patients. Reduced-doses of antithrombotics as secondary prophylaxis have limited data. This work aims to describe and to compare treatments and outcomes for cancer-associated VTE. RESEARCH DESIGN AND METHODS: Retrospective study. Adults with cancer-associated VTE were included. After 3-6 months of full-doses of anticoagulants, three strategies were considered: A) lowering the doses; B) maintaining full-doses; C) stopping treatment. The strategy and medication used were shown in a descriptive analysis and the rate of bleeding and VTE-recurrence between those in a comparative analysis. RESULTS: A total of 420 patients were included, 56.2% received DOACs, 43.8% enoxaparin. Strategy was defined in 257 patients: A (50.2%), B (46.3%), and C (3.5%). Forty-one (9.8%) had VTE-recurrence and 15 (3.6%) had MB or clinically relevant non-major bleeding (CRNMB).According to strategy, recurrent-VTE was 8.5% (A), 4.2% (B), and 11.1 (C) (p = 0.22), MB or CRNMB was 0.8% (A), 1.7% (B), and 0% (C) (p = 0.64). CONCLUSIONS: DOACs and strategy A were the most frequently used agent and strategy, respectively. There were no differences between medications or strategies used. The results must be interpreted with caution, and it is a retrospective single-center study, probably with information and selection bias.

Reversal of MYB-dependent suppression of MAFB expression overrides leukaemia phenotype in MLL-rearranged AML.

The transcription factor MYB plays a pivotal role in haematopoietic homoeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). We have previously demonstrated that not all AML subtypes display the same dependency on MYB expression and that such variability is dictated by the nature of the driver mutation. However, whether this difference in MYB dependency is a general trend in AML remains to be further elucidated. Here, we investigate the role of MYB in human leukaemia by performing siRNA-mediated knock-down in cell line models of AML with different driver lesions. We show that the characteristic reduction in proliferation and the concomitant induction of myeloid differentiation that is observed in MLL-rearranged and t(8;21) leukaemias upon MYB suppression is not seen in AML cells with a complex karyotype. Transcriptome analyses revealed that MYB ablation produces consensual increase of MAFB expression in MYB-dependent cells and, interestingly, the ectopic expression of MAFB could phenocopy the effect of MYB suppression. Accordingly, in silico stratification analyses of molecular data from AML patients revealed a reciprocal relationship between MYB and MAFB expression, highlighting a novel biological interconnection between these two factors in AML and supporting new rationales of MAFB targeting in MLL-rearranged leukaemias.

Maternal responsiveness and toddler body mass index z-score: Prospective analysis of maternal and child mealtime interactions.

Responsive feeding, where parents are guided by children's hunger and satiation cues and provide appropriate structure and support for eating, is believed to promote healthier weight status. However, few studies have assessed prospective associations between observed parental feeding and toddler growth. We characterized toddler growth from 18 to 36 months and, in a subset of families, examined whether observed maternal responsiveness to toddler satiation cues and encouraging prompts to eat at 18 and 24 months were associated with toddler body mass index z-score (BMIz) from 18 to 36 months. Participants included 163 toddlers and their mothers with overweight/obesity who had participated in a lifestyle intervention during pregnancy. Anthropometrics were measured at 18, 24, and 36 months. In a subsample, mealtime interactions were recorded in families' homes at 18 (n = 77) and 24 (n = 75) months. On average, toddler BMIz remained stable from 18 to 36 months with 31.3% (n = 51) categorized with a healthy weight, 56.4% (n = 92) with at risk for overweight and 12.3% (n = 20) with overweight. Fewer maternal prompts to eat at 18 months was associated with both higher probability of having at risk for overweight/overweight (p < .05), and higher child 36-month BMIz (p = .002). Higher child weight status at 12 months was also associated with both higher probability of having at risk for overweight/overweight (p < .05), and higher child 36-month BMIz (p < .001). Neither 24-month maternal prompts nor 18 or 24 month responsiveness to satiation cues were associated with toddler BMIz. In this diverse sample, weight status was relatively stable from 18 to 36 months. Maternal prompts to eat measured earlier in toddlerhood and prior child weight status were associated with toddler BMIz.

Management of isolated anterior talofibular ligament lesion in patients suffering from chronic ankle instability: comparison of two minimally invasive surgical techniques.

OBJECTIVE: The aim of the present study was to retrospectively compare the outcomes of two minimally invasive surgical techniques in patients with isolated anterior talofibular ligament (ATFL) lesion suffering from chronic ankle instability (CAI). PATIENTS AND METHODS: Thirty-six patients with ATFL lesion suffering from CAI were treated at our department from 2010 to 2017 and retrospectively reviewed after an average time of 4 years (2 to 9 years). Eighteen patients underwent a four-step operative protocol, including: synovectomy, debridement of ATFL lesion borders, capsular shrinkage, and 21-day immobilization and non-weightbearing. Eighteen patients underwent arthroscopic Broström procedure. Patients were assessed pre-operatively and at follow-up with American Orthopedic Foot & Ankle Society Score (AOFAS) scale, Karlsson-Peterson score, Tegner activity level, and objective examination comprehending range of motion, anterior drawer test, and talar tilt test. Wilcoxon test was utilized to compare the pre-operative and follow-up status. The Mann-Whitney U test was used to make comparisons between the two surgical techniques. Statistical significance was established at p < 0.05. RESULTS: Mean overall AOFAS, Karlsson-Peterson and Tegner scores significantly increased at follow-up compared to pre-operatory status (p < 0.05). However, no statistically significant differences concerning mean AOFAS score (90.2 in the four-step group vs. 89.2 in the Broström arthroscopic group), mean Karlsson-Peterson score (88.1 and 85.9 respectively), and median Tegner activity level (6.0 vs. 5.5) were reported between the two groups (p = n.s.). The complications in the arthroscopic four-step treatment group included damage to the superficial branch of the peroneal nerve in one case. The complications in the arthroscopic Broström included nerve injury in one case and persistent local pain nearby suture knot in one case. CONCLUSIONS: Both arthroscopic Broström and a four-step operative procedure including synovectomy, debridement of ATFL lesion borders, capsular shrinkage and immobilization, improved functional outcomes in patients with ATFL lesion suffering from CAI.

A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia.

BACKGROUND: Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely on the basis of observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomized, controlled trials. METHODS: We randomly assigned hospitalized adult patients with severe Covid-19 pneumonia in a 2:1 ratio to receive convalescent plasma or placebo. The primary outcome was the patient's clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death. RESULTS: A total of 228 patients were assigned to receive convalescent plasma and 105 to receive placebo. The median time from the onset of symptoms to enrollment in the trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the most frequent severity criterion for enrollment. The infused convalescent plasma had a median titer of 1:3200 of total SARS-CoV-2 antibodies (interquartile range, 1:800 to 1:3200). No patients were lost to follow-up. At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83; 95% confidence interval [CI], 0.52 to 1.35; P = 0.46). Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of -0.46 percentage points (95% CI, -7.8 to 6.8). Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups. CONCLUSIONS: No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo. (PlasmAr ClinicalTrials.gov number, NCT04383535.).

Reproductive traits in different Nile tilapia genetic groups / [Características reprodutivas em diferentes grupos genéticos de tilápia do Nilo]

The aim of this study was to evaluate the reproductive traits of the non-inbred and inbred AquaAmérica, GIFT and AquaAmérica × GIFTgenetic groups. Six fish from each genetic group were used (2 females:1 male). Females were examined for the presence of eggs in their mouth at every four days, for 12 weeks. Reproduction occurred in all genetic groups (GIFT: 100%; non-inbred AquaAmérica and AquaAmérica ×GIFT: 75%; inbred AquaAmérica: 50%). Female weight, female standard length, total spawning weight, absolute fecundity, relative fecundity, spawn index and hatching rate did not differ significantly between the genetic groups. However, the non-inbred AquaAmérica variety showed lower values (P<0.05) for egg diameter (2.4mm) and egg weight (4.2mg) and higher values (P<0.05) for relative number of eggs (247.6 eggs/g of egg) than GIFT (egg diameter: 2.8mm; egg weight: 5.7mg; relative number of eggs: 175.4 eggs/g of egg) and AquaAmérica ×GIFT (egg diameter: 2.8mm; egg weight: 5.9mg; relative number of eggs: 168.8 eggs/g of egg). In conclusion, the non-inbred AquaAmérica variety produces smaller, lighter eggs but a higher relative number of eggs than the GIFT variety and the AquaAmérica ×GIFT cross; and inbreeding negatively affects spawning rate.(AU)

O objetivo deste estudo foi avaliar as características reprodutivas dos grupos genéticos AquaAmérica não endogâmicos e endogâmicos, GIFT e AquaAmérica × GIFT. Foram utilizados seis peixes de cada grupo genético (duas fêmeas:um macho). As fêmeas foram examinadas quanto à presença de ovos na boca a cada quatro dias, durante 12 semanas. A reprodução ocorreu em todos os grupos genéticos (GIFT: 100%; AquaAmérica não endogâmica e AquaAmérica × GIFT: 75%; AquaAmérica endogâmica: 50%). Peso e comprimento padrão de fêmea, peso total de desova, fecundidade absoluta, fecundidade relativa, índice de desova e taxa de eclosão não diferiram significativamente entre os grupos genéticos. Entretanto, a variedade não endogâmica da AquaAmérica apresentou valores mais baixos (P<0,05) para diâmetro do ovo (2,4mm) e peso do ovo (4,2mg) e maiores valores (P<0,05) para número relativo de ovos (247,6 ovos/g de ovo ) que GIFT (diâmetro do ovo: 2,8mm; peso do ovo: 5,7mg; número relativo de ovos: 175,4 ovos/g de ovo) e AquaAmérica × GIFT (diâmetro do ovo: 2,8mm; peso do ovo: 5,9mg; número relativo de ovos: 168,8 ovos/g de ovo). Em conclusão, a variedade AquaAmérica não endogâmica produz ovos menores e mais leves, mas um número relativo maior de ovos que a variedade GIFT e o cruzamento AquaAmérica × GIFT; a consanguinidade afeta negativamente a taxa de desova.(AU)

Lipid domain formation and membrane shaping by C24-ceramide.

Ceramides are an important group of sphingolipids that modulate several cellular events. The mechanisms underlying biological actions of ceramides are not fully known, but evidence suggests that ceramides can act through regulation of the biophysical properties of the membrane. However, ceramide-induced changes on membrane properties are complex and depend on several factors. To gain further insight into this subject, we characterized the biophysical impact of very-long acyl chain C24-ceramide in a fluid model membrane under thermodynamic equilibrium and non-equilibrium conditions. Our results show that C24-ceramide readily forms two types of gel domains with distinct properties, likely corresponding to different interdigitated metastable gel phases. Upon reaching thermodynamic equilibrium, only partially interdigitated gel phase coexists with the fluid phase. In addition, C24-ceramide promotes strong changes in the shape of the vesicles, including domains with sharp edges and tubule-like structures. The results suggest that the formation of very long acyl chain ceramides in response to stress stimuli will initially induce a multitude of changes in the organization and fluidity of biological membranes that might be responsible for the activation of different cellular processes.

Caffeine exposure ameliorates acute ischemic cell death in avian developing retina.

In infants, the main cause of blindness is retinopathy of prematurity that stems in a hypoxic-ischemic condition. Caffeine is a psychoactive compound that at low to moderate concentrations, selectively inhibits adenosine A1 and A2A receptors. Caffeine exerts beneficial effects in central nervous system of adult animal models and humans, whereas it seems to have malefic effect on the developing tissue. We observed that 48-h exposure (during synaptogenesis) to a moderate dose of caffeine (30 mg/kg of egg) activated pro-survival signaling pathways, including ERK, CREB, and Akt phosphorylation, alongside BDNF production, and reduced retinal cell death promoted by oxygen glucose deprivation in the chick retina. Blockade of TrkB receptors and inhibition of CREB prevented caffeine protection effect. Similar signaling pathways were described in previously reported data concerning chemical preconditioning mechanism triggered by NMDA receptors activation, with low concentrations of agonist. In agreement to these data, caffeine increased NMDA receptor activity. Caffeine decreased the levels of the chloride co-transporter KCC2 and delayed the developmental shift on GABAA receptor response from depolarizing to hyperpolarizing. These results suggest that the caffeine-induced delaying in depolarizing effect of GABA could be facilitating NMDA receptor activity. DPCPX, an A1 adenosine receptor antagonist, but not A2A receptor inhibitor, mimicked the effect of caffeine, suggesting that the effect of caffeine occurs through A1 receptor blockade. In summary, an in vivo caffeine exposure could increase the resistance of the retina to ischemia-induced cell death, by triggering survival pathways involving CREB phosphorylation and BDNF production/TrkB activation.

Medication for addiction treatment and acute care utilization in HIV-positive adults with substance use disorders.

Medication for addiction treatment (MAT) could reduce acute care utilization in HIV-positive individuals with substance use disorders. The study objective was to determine if HIV-positive people with substance use disorders treated with MAT report less acute care utilization than those not receiving MAT. We assessed the association between MAT and acute care utilization among HIV-positive individuals with alcohol or opioid use disorder. Acute care utilization 6 months later was defined as any past 3-month self-reported (1) emergency department (ED) visit and (2) hospitalization. Of 153 participants, 88% had alcohol use disorder, 41% had opioid use disorder, and 48 (31%) were treated with MAT. Fifty-five (36%) participants had an ED visit and 38 (25%) participants had a hospitalization. MAT was not associated with an ED visit (AOR 1.12, 95% CI 0.46-2.75) or hospitalization (AOR 1.09, 95% CI 0.39-3.04). MAT was not associated with acute care utilization. These results highlight the need to increase MAT prescribing in HIV-positive individuals with substance use disorders, and to address the many factors that influence acute care utilization.

The Italian version of rheumatoid arthritis pain scale (IT-RAPS): psychometric properties on community and clinical samples.

This paper describes the validation process of the Italian version of the Rheumatoid Arthritis Pain Scale (ITRAPS), describing its translation and adaptation to Italian culture. The cultural adaptation and validation were based on data from a sample of people affected by rheumatoid arthritis (RA). The process required a forward and backward translation of the original language, reviewed by an expert panel. The adapted version of the RAPS was then tested on a community and clinical sample, in order to test its psychometric properties. The IT-RAPS was submitted to 122 people affected by RA. The data was analyzed using Cronbach's coefficient alpha and the Pearson product-moment correlation coefficients. The IT-RAPS showed an internal consistency reliability coefficient of 0.96. This is the first study reporting the validation and cross-cultural adaptation of the RAPS in Italian. The study's findings provided support for the IT-RAPS as a reliable and valid measurement of multidimensional pain in RA patients.

Reducing transfusion requirements following total knee arthroplasty: effectiveness of a double infusion of tranexamic acid.

OBJECTIVE: Blood loss following joint replacement surgery represents a relevant issue for orthopedic surgeons. The use of tranexamic acid (TXA) to reduce transfusion requirements has become mainstream. However, consensus about the starting time, methods, or volume of usage of TXA in joint replacement surgery has yet to be found. A retrospective study was conducted comparing pre- and post-operative infusion of TXA 15 mg/kg to a single pre-operative infusion. PATIENTS AND METHODS: 291 patients undergoing TKA were retrospectively reviewed. 109 received a single pre-operative dose of 15 mg/ kg TXA (single dose, SD group), 182 received a single pre- operative dose of 15 mg/ kg TXA followed by a second post-operative dose of 15 mg/kg TXA (double dose, DD group). The primary outcome was blood loss calculated from haematological values and perioperative transfusions. Secondary outcomes included the occurrence of major complications within the first postoperative year. RESULTS: None of the patients reported adverse events. Blood transfusions were administered to 63 patients (13.5%) in the SD and 36 in the DD group (5.7%). Significant difference between the groups was observed (p < 0.005). No significant difference between the two groups was found concerning mean blood loss in drainage after the 24th hour and postoperative hemoglobin values (p = n.s.). CONCLUSIONS: The study demonstrated that TXA possesses a good safety profile. In addition, pre- and post-operative infusion of TXA 15 mg/kg is more effective compared to single pre-operative infusion in reducing need for transfusion requirements.

Three-dimensional evaluation of rapid maxillary expansion anchored to primary molars: direct effects on maxillary arch and spontaneous mandibular response.

AIM: The purpose of this study was to evaluate the effects of rapid maxillary expansion (RME) on maxillary and mandibular arch in the mixed dentition. MATERIALS AND METHODS: Forty-four consecutive patients with transverse maxillary deficiency were recruited. Test group: 21 patients (10 male, 11 female; 7.4 ± 1.2 years) who underwent RME (Haas type) therapy banded on the primary second molars. CONTROL GROUP: 17 patients (10 male, 7 female; 7.3 ± 1.1 years old) who did not receive any orthodontic treatment. Dental casts obtained pre-treatment and after appliance removal (11 months) were processed by means of a three-dimensional scanner (3Shape D250 laser, DK). Digital landmarks were traced using the VAM software (Canfield Scientific Inc., Fairfield-NJ, USA). Arch Length, interdental width and torque differences were measured before and after the removal of the appliance. The t-test (P<0.05) for paired data was applied to evaluate the measurements values before and after treatment. The linear regression model was employed to assess the correlations between treatment effects. RESULTS: The efficacy of the RME was confirmed both on maxillary and mandibular arch. Mandibular intermolar width (+2.02 mm) together with primary intermolar (+1.39 mm), intercanine width (+0.95mm) and torque variations significantly increased. The untreated control group showed no significant statistical differences between T0 and T1. The linear regression between maxillary and mandibular data showed correlations between the torque of the teeth 16/46 and 65/85 (P<0.05). CONCLUSIONS: RME anchored on primary molars is an effective treatment option to correct tranverse maxillary deficiencies. All the measurements increased significantly confirming the indirect effect of RME on the mandibular arch.

'Ripple' effect on infant zBMI trajectory of an internet-based weight loss program for low-income postpartum women.

BACKGROUND: Weight loss interventions can have positive 'ripple' effects on untreated partners in the home, but ripple effects on infants are unknown. OBJECTIVE: To examine whether a 12-month internet-based weight loss intervention for postpartum mothers had a positive ripple effect on participants' infants. METHODS: A 12-month cluster randomized, assessor-blind, clinical trial enrolling 371 postpartum women at 12 Women, Infants, Children clinics in CA. Clinics were randomized to standard Women, Infants, Children or an internet-based weight loss intervention for mothers. RESULTS: A total of 333 of the 371 (89.8%) mothers assented for infant participation. Infants were 5.3 ± 3.2 months; 75.9% were Hispanic and 64% were breastfeeding. Infant retention was 272/333 (82.7%) at 6 months post enrollment and 251/333 (75.3%) at 12 months post enrollment. In intent-to-treat analysis, a significant interaction between group and time was observed (p = 0.008) with the offspring of intervention mothers exhibiting lower zBMI change from study entry through 6 months (0.23 [CI, 0.03, 0.44] vs. 0.65 [0.50, 0.79] zBMI change, respectively; p = 0.001) but was not significant through 12 months (p = 0.16). Regardless of group, maternal reports at the final assessment indicated that infants (aged =17.2 ± 3.4 months) consumed sweetened beverages (0.93 ± 1.5/week), juice (2.0 ± 1.4/day), 'junk food' (7.8 ± 5.4/week) and fast food (2/month), and 46.7% of the infants had a TV in their bedroom. CONCLUSIONS: An internet-based weight loss program for low-income, postpartum mothers had a positive 'ripple' effect on the zBMI of infants in the home during the first 6 months of treatment.

Deficits in rate of torque development are accompanied by activation failure in patients with knee osteoarthritis.

Aim of this study was to investigate if knee extensor maximal voluntary contraction (MVC) torque and rate of torque development (RTD) deficits are accompanied by neuromuscular activation failure in patients with knee osteoarthritis (KOA). Nineteen patients with unilateral KOA completed gradual MVCs, from which MVC torque, voluntary activation and maximal EMG activity were recorded, and explosive MVCs, from which RTD and rate of EMG rise were recorded. For gradual MVCs, MVC torque (-28%), voluntary activation (-6%) and maximal EMG activity (-30%) were lower on the involved than on the uninvolved side (p < 0.001). Asymmetries in MVC torque and maximal EMG activity were positively correlated (r = 0.70; p < 0.001). For explosive MVCs, involved-side RTD (-19%) and rate of EMG rise (-20%) were lower compared to the uninvolved side (p < 0.05-0.001). Asymmetries in RTD and rate of EMG rise were positively correlated (r = 0.61-0.80; p < 0.01). Deficits in isometric knee extensor strength were accompanied by neuromuscular activation failure during gradual MVCs and, more importantly, during the early phase of explosive MVCs. Such inability to rapidly activate the quadriceps may have functional consequences and warrants greater attention in the evaluation and rehabilitation of patients with KOA.