Rational Design of Drugs Targeting G-Protein-Coupled Receptors: Ligand Search and Screening.

G protein-coupled receptors (GPCRs) are transmembrane proteins that participate in many physiological processes and represent major pharmacological targets. Recent advances in structural biology of GPCRs have enabled the development of drugs based on the receptor structure (structure-based drug design, SBDD). SBDD utilizes information about the receptor-ligand complex to search for suitable compounds, thus expanding the chemical space of possible receptor ligands without the need for experimental screening. The review describes the use of structure-based virtual screening (SBVS) for GPCR ligands and approaches for the functional testing of potential drug compounds, as well as discusses recent advances and successful examples in the application of SBDD for the identification of GPCR ligands.

Functional testing is a complementary tool for the diagnosis of vaginitis.

OBJECTIVE: Vaginal microbiota evaluation is a methodology widely used in China to diagnose various vaginal inflammatory diseases. Although vaginal microbiota evaluation has many advantages, it is time-consuming and requires highly skilled and experienced operators. Here, we investigated a six-index functional test that analyzed pH, hydrogen peroxide (H2O2), leukocyte esterase (LEU), sialidase (SNA), ß-glucuronidase (GUS), and acetylglucossidase (NAG), and determined its diagnostic value by comparing it with morphological tests of vaginal microbiota. MATERIALS AND METHODS: The research was conducted using data extracted from the Laboratory Information System of Women and Children's Hospital. A total of 4902 subjects, ranging in age from 35.4 ± 9.7 years, were analyzed. During the consultation, a minimum of two vaginal swab specimens per patient were collected for both functional and morphological testing. Fisher's exact was used to analyze data using SPSS. RESULTS: Of the 4,902 patients, 2,454 were considered to have normal Lactobacillus morphotypes and 3,334 were considered to have normal dominant microbiota. The sensitivity and specificity of H2O2-indicating Lactobacillus morphotypes were 91.3% and 25.28%, respectively, while those of pH-indicating Lactobacillus morphotypes were 88.09% and 59.52%, respectively. The sensitivity and specificity of H2O2-indicating dominant microbiota were 91.3% and 25.3%, respectively, while those of pH-indicating dominant microbiota were 86.27% and 64.45%, respectively. The sensitivity and specificity of NAG for vulvovaginal candidiasis were 40.64% and 84.8%, respectively. For aerobic vaginitis, GUS sensitivity was low at 0.52%, while its specificity was high at 99.93%; the LEU sensitivity and specificity values were 94.73% and 27.49%, respectively. Finally, SNA sensitivity and specificity for bacterial vaginosis were 80.72% and 96.78%, respectively. CONCLUSION: Functional tests (pH, SNA, H2O2, LEU) showed satisfactory sensitivity for the detection of vaginal inflammatory diseases. However, these tests lacked specificity, making it difficult to accurately identify specific pathologies. By contrast, NAG and GUS showed excellent specificity in identifying vaginal inflammatory diseases, but their sensitivity was limited. Therefore, functional tests alone are not sufficient to diagnose various vaginal inflammatory diseases. When functional and morphological tests are inconsistent, morphological tests are currently considered the preferred reference method.

Forward step down test - clinical rating is correlated with joint angles of the pelvis and hip: an observational study.

BACKGROUND: Clinical methods for assessing quality of movement and functional tests are important to clinicians. Typical deviations from normal kinematics during the clinical test of Forward Step Down Test (FSDT) are pelvic tilt and hip adduction which are associated with the risk of knee pain. OBJECTIVES: (1) to examine the correlation between clinical assessment of the FSDT and joint angle measurements of pelvis, hip, knee and ankle joints in males and females; (2) to examine the differences in joint angles between individuals rated as good, fair or poor in a FSDT performance test. METHODS: Ninety-two healthy individuals performing FSDT were video-taped with two-dimensional digital video cameras. The clinical assessment of the FSDT was rated by two experienced physical therapists as good, fair, or poor based on a Crossley et al. (2011) validated scale. Measurements of pelvic drop, hip adduction and knee valgus were taken using Image J software. RESULTS: Out of 177 lower limbs, 74 (37 in each limb) were clinically rated as "good/fair" (41.80%) while 103 (52 in the dominant leg and 51 in the non-dominant leg) were rated as "poor" (58.19%). No significant differences were observed between dominant and non-dominant legs or between males and females in clinical rating of the FSDT. Pelvic drop angle was significantly higher and hip adduction angle was significantly lower for "poor" clinical rating compared to "good/fair" in both dominant and non-dominant legs (p < 0.001) in males and females. Females demonstrated higher pelvic drop, lower hip adduction and higher knee valgus angles compared with males (p < 0.05). CONCLUSIONS: This study showed that the clinical rating of FSDT is correlated with joint angle measurements suggesting that this assessment can be utilized in clinical practice. Individuals with poor quality performance of FSDT showed higher pelvic drop and hip adduction movement. Further studies examining different populations with diverse disorders or pathologies are essential.

Feasibility of return to sports assessment 6 months after patellar instability surgery.

BACKGROUND: The evidence regarding the usefulness of assessment tools to support decisions of return-to-sport after surgery for patellar instability is scarce. The purpose of this study was therefore to explore the feasibility of functional tests assessing readiness for return-to-sport six months after patellar stabilizing surgery. However, there is little evidence on what a functional assessment should include to support these decisions following surgery for patellar instability. Therefore the purpose of this study was to explore the feasibility of functional tests assessing readiness for return-to-sport six months after patellar stabilizing surgery. METHODS: In this cross-sectional study a prospective cohort of 78 patients were subjected to a range of return-to-sport readiness tests at six months after surgery for patellar instability with an "a la carte" approach. Lower Quarter Y-Balance Test (YBT-LQ), single-legged hop tests and isokinetic strength tests were performed. In addition, self-reported function was measured with the Banff Patellofemoral Instability Instrument 2.0 (BPII) and Norwich Patellar Instability score (NPI). Return-to-sport clearance criteria were defined as: ≤4 cm YBT-LQ anterior reach difference between legs, leg-symmetry-index (LSI) ≥ 95% in the YBT-LQ composite score, mean sum score LSI ≥ 85% of all single-leg hop tests and LSI ≥ 90% in isokinetic quadriceps strength. RESULTS: Sixty-four patients (82%) were able to complete all functional tests, while only eleven (14%) patients were deemed ready for return-to-sport, passing all return-to-sport clearance criteria. Patients with bilateral problems demonstrated worse performance in the contralateral leg, which resulted in higher LSI scores compared to individuals with unilateral instability. A supplementary finding was that the extent of surgery (MPFL-R only versus combined surgery) did not predict and mainly did not affect self-reported function or functional performance at the follow-up. CONCLUSION: The functional assessment used in the current study seems feasible to conduct at six months after patellar stabilizing surgery. However, current suggested clearance standards and the use of leg-symmetry-index seems inappropriate for patients with patellar instability. Therefore, further exploration of appropriate tests and return-to-sport clearance criteria is justified. TRIAL REGISTRATION: clinicaltrial.gov, NCT05119088. Registered 12.11.2021 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05119088 .

Longitudinal changes in magnetic resonance imaging biomarkers of the gluteal muscle groups and functional ability in Duchenne muscular dystrophy: a 12-month cohort study.

BACKGROUND: Quantitative magnetic resonance imaging (MRI) is considered an objective biomarker of Duchenne muscular dystrophy (DMD), but the longitudinal progression of MRI biomarkers in gluteal muscle groups and their predictive value for future motor function have not been described. OBJECTIVE: To explore MRI biomarkers of the gluteal muscle groups as predictors of motor function decline in DMD by characterizing the progression over 12 months. MATERIALS AND METHODS: A total of 112 participants with DMD were enrolled and underwent MRI examination of the gluteal muscles to determine fat fraction and longitudinal relaxation time (T1). Investigations were based on gluteal muscle groups including flexors, extensors, adductors, and abductors. The North Star Ambulatory Assessment and timed functional tests were performed. All participants returned for follow-up at an average of 12 months and were divided into two subgroups (functional stability/decline groups) based on changes in timed functional tests. Univariable and multivariable logistic regression methods were used to explore the risk factors associated with future motor function decline. RESULTS: For the functional decline group, all T1 values decreased, while fat fraction values increased significantly over 12 months (P<0.05). For the functional stability group, only the fat fraction of the flexors and abductors increased significantly over 12 months (P<0.05). The baseline T1 value was positively correlated with North Star Ambulatory Assessment and negatively correlated with timed functional tests at the 12-month follow-up (P<0.001), while the baseline fat fraction value was negatively correlated with North Star Ambulatory Assessment and positively correlated with timed functional tests at the 12-month follow-up (P<0.001). Multivariate regression showed that increased fat fraction of the abductors was associated with future motor function decline (model 1: odds ratio [OR]=1.104, 95% confidence interval [CI]: 1.026~1.187, P=0.008; model 2: OR=1.085, 95% CI: 1.013~1.161, P=0.019), with an area under the curve of 0.874. CONCLUSION: Fat fraction of the abductors is a powerful predictor of future motor functional decline in DMD patients at 12 months, underscoring the importance of focusing early on this parameter in patients with DMD.

Effect of nutritional supports on malnutrition, cognition, function and biomarkers of Alzheimer's disease: a systematic review.

AIM: To summarize the nutritional supplementation on biochemical parameters, cognition, function, Alzheimer's Disease (AD) biomarkers and nutritional status. MATERIALS AND METHODS: PubMed, Web of Science, Korean Journal Database, Russian Science Citation Index, SciELO Citation Index, Cochrane Library and Scopus databases were searched until 16 April 2021. 22.193 records in total were reached according to inclusion and exclusion criteria. Included Studies were evaluated through the Modified Jadad Scale and gathered under four subheadings. RESULTS: Forty-eight studies with a total of 7009 AD patients were included. Souvenaid, ONS (368 ± 69 kcal), Vegenat-med, 500 mg Resveratrol, ONS (200 mL) were effective nutritional supplements on promoting weight gain and protecting malnutrition status but showed conflicting results in Body mass index, Mid-Upper-Arm Circumference and Triceps Skin Fold Thickness. ONS and a lyophilized whole supplementation Vegenat-med intake made an increase in MNA scores. While all nutritional supplements showed controversial results in biochemical parameters but caused a decrease in Hcy levels which caused reductions in brain Aß plaque (increase serum Aß), p-Tau and cognitive improvement. Folic acid and vitamin D decreased serum APP, BACE1, BACE1mRNA. Resveratrol, Hericium erinaceus mycelia, vitamin D and Betaine supplements improved cognitive, functional prognosis and quality of life unlike other nutritional supplements had no effect on cognitive scales. CONCLUSIONS: Better designed trials with holistic measures are needed to investigate the effect of nutritional support on the AD biomarkers, cognitive status, biochemical parameters and functional states. Also, more beneficial results can be obtained by examining the simultaneous effects of nutritional supplements with larger sample groups.

Functional performance tests, clinical measurements, and patient-reported outcome measures do not correlate as outcomes 1 year after anterior cruciate ligament reconstruction.

PURPOSE: The results after anterior cruciate ligament reconstruction (ACLR) are evaluated by laxity measures, functional tests, and patients' perception by patient-reported outcome measures (PROMs). It is not known, if one of these evaluation instruments is representative or if outcome scores from all must be reported to obtain a full evaluation of the condition. The aim was to study the correlations between these three types of outcomes 1 year after primary ACLR. METHOD: All adult patients (range 18-45 years) who had an ACLR between 1.1.2019 and 31.12.2021 were offered 1-year follow-up by an independent observer. Preoperative information about knee laxity and peroperative information about the condition of menisci and cartilage were registered. At 1-year follow-up clinical and instrumented knee stability and function assessed by four different hop tests were registered. Patients completed four PROMs (the Subjective International Knee Documentation Committee (IKDC) score, the Knee Numeric-Entity Evaluation Score (KNEES-ACL), the Knee injury and Osteoarthritis Outcome Score (KOOS) and the Lysholm score) and Tegner activity scale and answered anchor questions regarding satisfaction and willingness to repeat the operation. RESULTS: A total of 190 adults attended the 1-year follow-up and 151 had all assessments. There were only a few positive and weak correlations between performance tests and PROMS and between clinical measurements and PROMS (r = 0.00-0.38), and the majority were of negligible strength. Tegner score had in general the highest correlation (low to moderate). The highest correlation was 0.53 (moderate) between the anchor question about patient satisfaction and Lysholm/IKDC scores. There was no difference in the correlations depending on meniscal condition. CONCLUSIONS: In ACLR patients there was no clinically relevant correlation between scores obtained by PROMs, a battery of functional performance tests and instrumented laxity of the knee at 1-year follow-up. Therefore, one type of outcome cannot represent the others. This is an argument for always to include and report all three types of outcomes, and conclusions based on one type of outcome may not be sufficient. LEVEL OF EVIDENCE: II.

Do Patient-Reported Outcomes Reflect Objective Measures of Function? Implications for Total Knee Arthroplasty.

BACKGROUND: Patient-reported outcomes (PROs) are used in research, clinical practice, and by federal reimbursement models to assess outcomes for patients who have knee osteoarthritis (OA) and total knee arthroplasty (TKA). We examined a large cohort of patients to determine if commonly used PROs reflect observed evaluation as measured by standardized functional tests (SFTs). METHODS: We used data from the Osteoarthritis Initiative, a 10-year observational study of knee osteoarthritis patients. Two cohorts were examined: 1) participants who received TKA (n = 281) and 2) participants who have native OA (n = 4,687). The PROs included Western Ontario and McMaster Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), 12-Item Short Form Health Survey (SF-12), and Intermittent and Constant Pain Score (ICOAP). The SFTs included 20 m and 400 meter (m) walks and chair stand pace. Repeated measures correlation coefficients were used to determine the relationship between PROs and SFTs. RESULTS: The PROs and SFTs were not strongly correlated in either cohort. The magnitude of the repeated measures correlation (rrm) between KOOS, WOMAC, SF-12, and ICOAP scores and SFT measurements in native knee OA patients ranged as follows: 400 m walk pace (0.08 to 0.20), chair stand pace (0.05 to 0.12), and 20 m pace (0.02 to 0.21), all with P < .05. In the TKA cohort, values ranged as follows: 400 M walk pace (0.00 to 0.29), chair stand time (0.02 to 0.23), and 20 M pace (0.03 to 0.30). Due to the smaller cohort size, the majority, but not all had P values < .05. CONCLUSION: There is not a strong association between PROs and SFTs among patients who have knee OA or among patients who received a TKA. Therefore, PROs should not be used as a simple proxy for observed evaluation of physical function. Rather, PROs and SFTs are complementary and should be used in combination for a more nuanced and complete characterization of outcome.

Effect of 12-Week BMI-Based Vitamin D3 Supplementation in Parkinson's Disease with Deep Brain Stimulation on Physical Performance, Inflammation, and Vitamin D Metabolites.

Parkinson's disease (PD) is the second most common neurodegenerative disease. To manage motor symptoms not controlled adequately with medication, deep brain stimulation (DBS) is used. PD patients often manifest vitamin D deficiency, which may be connected with a higher risk of falls. We administered a 12-week vitamin D3 supplementation based on BMI (with higher doses given to patients with higher BMI) to investigate its effects on physical performance and inflammation status in PD patients with DBS. Patients were randomly divided into two groups: treated with vitamin D3 (VitD, n = 13), and supplemented with vegetable oil as the placebo group (PL, n = 16). Patients underwent functional tests to assess their physical performance three times during this study. The serum 25(OH)D3 concentration increased to the recommended level of 30 ng/mL in the VitD group, and a significant elevation in vitamin D metabolites in this group was found. We observed significant improvement in the Up and Go and the 6 MWT in the VitD group. In inflammation status, we noticed a trend toward a decrease in the VitD group. To conclude, achieving the optimal serum 25(OH)D3 concentration is associated with better functional test performance and consequently may have a positive impact on reducing falling risk in PD.

Delayed Surgical Treatment in Patients with Chronic Carpal Tunnel Syndrome Is Still Effective in the Improvement of Hand Function.

Background and Objectives: Severe carpal tunnel syndrome (CTS) is the most common compression neuropathy in the upper extremities treated conservatively; later, when advanced, CTS is treated mostly surgically. The most prevalent symptoms comprise numbness, as well as sensation loss in the thumb, index, and middle finger, and thenar muscle strength loss, resulting in impaired daily functioning for patients. Data on the results of CTS treatment in patients with delayed surgical intervention are scarce. The aim of this study was to determine the postoperative results of chronic carpal tunnel syndrome treatment in patients with symptoms lasting for at least 5 years. Materials and Methods: A total of 86 patients (69 females, 17 males) with a mean age of 58 years reporting symptoms of CTS for at least 5 years (mean: 8.5 years) were prospectively studied. The average follow-up time was 33 months. All patients underwent the surgical open decompression of the median nerve at the wrist. A preoperative observation was composed of an interview and a clinical examination. The subjects completed the DASH (the Disabilities of the Arm, Shoulder, and Hand), PRWE (Patient-Rated Wrist Evaluation), and self-report questionnaires. Global grip strength, sensory discrimination, characteristic symptoms of CTS, and thenar muscle atrophy were examined. Postoperatively, clinical and functional examinations were repeated, and patients expressed their opinions by completing a BCTQ (Boston Carpal Tunnel Syndrome Questionnaire). Results: We found improvements in daily activities and hand function postoperatively. Overall, 88% of patients were satisfied with the outcome of surgery. DASH scores decreased after surgery from 44.82 to 14.12 at p < 0.001. PRWE questionnaire scores decreased from 53.34 to 15.19 at p < 0.001. The mean score of the BCTQ on the scale regarding the severity of symptoms was 1.48 and 1.62 on the scale regarding function after surgery. No significant differences were found in the scores between the male and female groups or between age groups (p > 0.05). A significant increase in global grip strength from 16.61 kg to 21.91 kg was observed postoperatively at p < 0.001. No significant difference was detected in the measurement of sensory discrimination (6.02 vs. 5.44). In most of the examined patients, night numbness and wrist pain subsided after surgery at p < 0.001. Thenar muscle atrophy diminished after surgery at p < 0.001. Conclusions: Most patients were satisfied with the results of CTS surgery regarding the open decompression of the median nerve even after 5 years of ineffective conservative treatment. Significant improvement of the hand function was confirmed in the functional studies.

Lower Extremity Physical Performance Tests for the Assessment of Athletes via Telehealth are Reliable.

CONTEXT: Lower extremity physical performance tests (PPTs) have been widely used in sports rehabilitation and are commonly performed in person. However, some situations may disrupt the in-person health care delivery, such as social distancing due to the pandemic, traveling, and living in remote locations. Those situations may require adjustments in planning and applying measurement tests, and telehealth has become an alternative. Nevertheless, the reliability of lower extremity PPT tests via telehealth is still unknown. OBJECTIVES: To verify the test-retest reliability, SEM, and the minimum detectable change (MDC95) of PPTs via telehealth. METHODS: Fifty asymptomatic athletes completed 2 assessment sessions 7 to 14 days apart. The assessment via telehealth consisted of warm-up exercises followed by the single-, triple-, and side-hop tests, and the long jump test, in random order. Intraclass correlation coefficient, SEM, and MDC95 were calculated for each PPT. RESULTS: Single-hop test showed good to excellent reliability, with SEM and MDC95 ranging from 6.06 to 9.24 cm and 16.79 to 25.61 cm, respectively. The triple-hop test showed excellent reliability, with SEM and MDC95 ranging from 13.17 to 28.17 cm and 30.72 to 78.07 cm, respectively. Side-hop tests showed moderate reliability, with SEM and MDC95 ranging from 0.67 to 1.22 seconds and 2.00 to 3.39 seconds, respectively. The long jump test showed excellent reliability, with SEM and MDC95 ranging from 5.34 to 8.34 cm and 14.80 to 23.11 cm, respectively. CONCLUSION: The test-retest reliability of those PPTs via telehealth was acceptable. The SEM and MDC were provided to assist clinicians in interpreting those PPTs.

Physical Performance and Mobility Tests Using Telehealth: A Feasibility Study With Athletes.

CONTEXT: Physical performance tests (PPTs) and mobility tests have been widely used in sports rehabilitation. However, the feasibility of PPTs and mobility tests via telehealth is unknown. OBJECTIVES: To verify the feasibility of PPTs and mobility tests to assess athletes via telehealth. DESIGN: This is a feasibility study. PARTICIPANTS: Athletes enrolled in a sports team or club for at least 2 years and with previous enrollment in a competitive league were recruited through advertisements on social media. The athletes included in this study (mean age = 25.9 y, from different sports) performed a battery of PPTs and mobility tests for the lower-extremity or upper-extremity and trunk, according to their sport modality. MAIN OUTCOME MEASURE: The feasibility was assessed with recruitment, success, and dropout rates. In addition, athletes' perceptions of easiness, satisfaction, and safety during the lower-extremity or upper-extremity and trunk PPTs and mobility tests were assessed. RESULTS: Seventy-three athletes were included, between January and April 2021: 41 were allocated to the lower-extremity and 32 to the upper-extremity and trunk PPTs and mobility test, according to their sports modality. The overall dropout rate was 20.55%; >89% of the athletes agreed that the PPTs and mobility tests via telehealth were easy to perform, >78% were satisfied, and >75% felt safe during the assessments. CONCLUSION: This study indicated that these 2 batteries of performance and mobility tests via telehealth are feasible to assess the lower and upper-extremities, and the trunk of athletes, considering the adherence, athletes' perception of easiness, satisfaction, and safety.

[The possibilities of impulse oscillometry in the diagnosis of the lung function disorders after COVID-19].

BACKGROUND: Impulse oscillometry (IOS) is an effort independent method of studying lung mechanics. AIM: To study the diagnostic significance of IOS in assessing lung mechanics after COVID-19. MATERIALS AND METHODS: Spirometry, body plethysmography, diffusion test (DLco), IOS parameters were analyzed in 315 patients (the median age 48 years), the median period from the beginning of COVID-19 to the study was 50 days. Statistical analysis included descriptive statistics, correlation analysis and one-dimensional logistic regression analysis with an assessment of odds ratios. RESULTS: In general group, spirometry and body plethysmography parameters were in normal values, while DLCO was reduced in 61% of patients. Parameters of IOS were analyzed in the general group and between the groups, depending on the value of DLco and total lung capacity (TLC): normal or reduced. In general group, reactance area (AX), hererogeneity of resistance Rrs5-Rrs20, resistance at 5 Hz (Rrs5), reactance at 5 Hz (ΔXrs5) were increased in 29.8%, 17.8%, 6%, 4.8% of patients, respectively, and were statistically significantly higher in the group with reduced TLC, whereas in the group with reduced DLco AX, Rrs5-Rrs20 were statistically significantly higher. Logistic regression analysis showed that patients with Rrs5-Rrs20>0.07 kPa×sec/l or AX>0.32 kPa/l had a 1.99-fold and 2.24-fold increased risk for decrease DLco, respectively, while the risk of decrease in TLC was 2.25-fold (p=0.012) and 3.16-fold (p<0.001) higher, respectively. CONCLUSION: IOS allow to detect both dysfunction of small airways (if AX or Rrs5-Rrs20 are increased) and the risk of restrictive pattern and lung diffusion impairment after COVID-19.

Exercise Stress Echocardiography for Stable Coronary Artery Disease: Succumbed to the Modern Conceptual Revolution or Still Alive and Kicking?

The modern conceptual revolution in managing patients with stable coronary artery disease (CAD), based on improvement in preventive and pharmacological therapy, advocates coronary artery revascularization only for smaller group of patients with refractory angina, poor left ventricular systolic function, or high-risk coronary anatomy. Therefore, our conventional wisdom about stress testing must be questioned within this new and revolutionary paradigm. Exercise stress echocardiography (ESE) is still a well-known technique for assessing known or suspected stable CAD, it is safe, accessible, and well-tolerated, and there is an widespread evidence base. ESE has been remarkably resilient throughout years of innovation in noninvasive cardiology. Its value is not to be determined over the short portion of diagnostic accuracy but mainly through its prognostic value evident in a wide range of patient subsets. It is coming very close to the modern profile of a leading test that should include, in addition to an essential accettable diagnostic and prognostic accuracy, qualities of low cost, no radiation exposure, and minor environmental traces. In this review, we will discuss advantages, diagnostic accuracy, prognostic value in general and special populations, cost-effectiveness, and changes in referral patterns of ESE in the modern era.

No correlation between symmetry-based performance measures and patient-related outcome prior to and after total knee arthroplasty.

PURPOSE: Standardized outcome measures are crucial for the evaluation of different treatment and rehabilitation regimes in patients after total knee arthroplasty (TKA). Performance-based measures are necessary to capture different aspects of physical function. High reliability and agreement of five performance-based measures were hypothesized to differentiate between measurement error and change in test performance. Secondary outcomes are the correlation of performance-based measurements to KSS and WOMAC prior to surgery (baseline) and 10 weeks thereafter (t3). METHODS: The test-retest reliabilities and agreements of the 1-m walk test, the stair-climbing test, the timed-up-and-go test, the weight-balanced-chair-rising test and the isometric maximum knee extension force in patients undergoing total knee replacements were studied. The intraclass correlation coefficient was calculated and a Bland-Altman analysis performed. RESULTS: The weight-balanced-chair-rising test showed a symmetry at baseline = 0.77, 5 ± 1 days after surgery (t1) = 0.50, 9 ± 1 days (t2) = 0.59 and (t3) = 0.80. All performance tests showed high intraclass correlation coefficients (ICC = 0.81-0.99). The 10-m walk test, stair climbing test, and the timed-up-and-go test showed high agreement in the Bland-Altman analysis. The Bland-Altman analysis for the weight-balanced-chair-rising test and isometric knee extension force indicated high agreement at 5 and 9 days postoperatively, but the relative measurement error increased pre- and 10 weeks postoperatively. CONCLUSION: In conclusion, symmetry, as an important outcome after TKA, is a reliable and rather unique item that should unquestionably be added to established measurements like walking tests or survey-based function assessment. The implementation of standardized performance-based measures to assess physical function in rehabilitation procedures will help to improve the more objectively based assessment of different rehabilitation protocols. LEVEL OF EVIDENCE: II.

Achilles tendon resting angle is able to detect deficits after an Achilles tendon rupture, but it is not a surrogate for direct measurements of tendon elongation, function or symptoms.

PURPOSE: The aim of this study was to investigate how the Achilles tendon resting angle (ATRA), an indirect measurement of tendon elongation, correlates with ultrasonography (US) measurements of the Achilles tendon length 6 and 12 months after an acute ATR and relates to other clinical outcome measurements such as heel-rise height, jumping ability and patient-reported outcome measurements (PROMs). METHODS: Patients were included following acute Achilles tendon rupture (ATR). Achilles tendon length, ATRA, heel-rise height (HRH), drop countermovement jump (Drop CMJ) and PROMs (Achilles tendon total rupture score (ATRS) and physical activity scale (PAS)) were evaluated 6 and 12 months after injury. Achilles tendon length was evaluated using US, while the ATRA was measured with a goniometer. RESULTS: Sixty patients (13 women, 47 men), mean (SD) age 43 (9) years, with an acute ATR undergoing either surgical (35%) or non-surgical (65%) treatment were evaluated. A negative correlation (r = - 0.356, p = 0.010) between relative ATRA and tendon elongation was seen at 12 months after ATR. There were also significant positive correlations at 6 and 12 months between relative ATRA and HRH (r = 0.330, p = 0.011 and r = 0.379, p = 0.004). There were no correlations between ATRA and ATRS or ATRA and Drop CMJ, at either 6 or 12 months after the injury. CONCLUSION: In combination with other clinical evaluations such as HRH and US, ATRA could be a clinical tool for indirect measurements of tendon elongation. However, ATRA cannot be recommended as a direct surrogate for US for determining Achilles tendon length. LEVEL OF EVIDENCE: III.

Does skeletal muscle morphology or functional performance better explain variance in fast gait speed in older adults?

BACKGROUND: Fast gait speed is being increasingly recognized as an important clinical tool in older adults. However, the underlying muscular and functional contributors to fast gait speed performance remain poorly understood. AIM: We sought to determine predictors of fast gait speed in older adults. We hypothesized that lower-extremity skeletal muscle size and quality would be strong predictors. METHODS: Ninety community-dwelling older adults (33 men, 57 women; mean ± SD age = 74 ± 6 years) participated. B-mode ultrasonography was used to capture images of the vastus lateralis, rectus femoris, and gastrocnemius in the transverse plane. Each participant performed 30-second chair stand, heel-rise, functional reach, and grip strength tests. Fast gait speed was measured using the NIH Toolbox 4-Meter Walk Test. ImageJ software was used to quantify cross-sectional area (CSA), subcutaneous tissue thickness, and echo intensity. Two separate stepwise regression analyses were performed, one using muscle morphology variables as independent variables, and another including the functional outcomes. RESULTS: The ultrasound variables exhibited weak-to-moderate correlations with fast gait speed (|r| range = 0.168-0.416). The initial regression analysis indicated that the combination of medial gastrocnemius CSA and subcutaneous tissue thickness explained 22.8% of the variance in fast gait speed. The secondary analysis indicated that 30-second chair stand, heel-rise, and grip strength performance explained 45.5% of the variance. CONCLUSION: While medial gastrocnemius morphology is important, measures of upper and lower-extremity muscle function are better predictors of fast gait speed. These results highlight a dissociation between skeletal muscle morphology and fast gait speed.

[Modern methods in diagnostics of lacrimal system vertical part obliteration]. / Sovremennye metody diagnostiki obliteratsii slezootvodyashchikh putei.

A review of the literature is devoted to the description of modern diagnostic methods that are directed at detecting lacrimal pathway obstruction. The presented analysis is based on the study of data from Russian and foreign literary sources on both routine and high-tech lacrimal system examination methods, as well as on authors' experience in studying the diagnostic efficiency of imaging methods such as lacrimal scintigraphy, computed tomography with lacrimal pathway contrasting, and also single photon emission computed tomography. The article gives information about the advantages and disadvantages of the presented methods, highlights the questions of the prospects of their usage in practical dacryology.

When Would Immunologists Consider a Nanomaterial to be Safe? Recommendations for Planning Studies on Nanosafety.

The immune system is professional in recognizing and responding to non-self, including nanomaterials. Immune responses by professional and nonprofessional immune cells are thus nearly inevitable upon exposure of cells and organisms to such materials. The state of research into taking the immune system into account in nanosafety studies is reviewed and three aspects in which further improvements are desirable are identified: 1) Due to technical limitations, more stringent testing for endotoxin contamination should be made. 2) Since under overdose conditions immunity shows unphysiological responses, all doses used should be justified by being equivalent to tissue-delivered doses. 3) When markers of acute inflammation or cell stress are observed, functional assays are necessary to distinguish between homeostatic fluctuation and genuine defensive or tolerogenic responses. Since immune activation can also indicate that the immune system considers a stimulus to be harmless and induces tolerance, activation markers by themselves do not necessarily imply a danger to the body. Guidelines such as these are necessary to approach the point where specific nanomaterials are classified as safe based on reliable testing strategies.

Physical functional performance and prognosis in patients with heart failure: a systematic review and meta-analysis.

BACKGROUND: Patients with Heart Failure (HF) show impaired functional capacities which have been related to their prognosis. Moreover, physical functional performance in functional tests has also been related to the prognosis in patients with HF. Thus, it would be useful to investigate how physical functional performance in functional tests could determine the prognosis in patients with HF, because HF is the leading cause of hospital admissions for people older than 65 years old. This systematic review and meta-analysis aims to summarise and synthesise the evidence published about the relationship between physical functional performance and prognosis in patients with HF, as well as assess the risk of bias of included studies and the level of evidence per outcome. METHODS: Major electronic databases, such as PubMed, AMED, CINAHL, EMBASE, PEDro, Web of Science, were searched from inception to March 2020 for observational longitudinal cohort studies (prospective or retrospective) examining the relationship between physical functional performance and prognosis in patients with HF. RESULTS: 44 observational longitudinal cohort studies with a total of 22,598 patients with HF were included. 26 included studies reported a low risk of bias, and 17 included studies showed a moderate risk of bias. Patients with poor physical functional performance in the Six Minute Walking Test (6MWT), in the Short Physical Performance Battery (SPPB) and in the Gait Speed Test showed worse prognosis in terms of larger risk of hospitalisation or mortality than patients with good physical functional performance. However, there was a lack of homogeneity regarding which cut-off points should be used to stratify patients with poor physical functional performance from patients with good physical functional performance. CONCLUSION: The review includes a large number of studies which show a strong relationship between physical functional performance and prognosis in patients with HF. Most of the included studies reported a low risk of bias, and GRADE criteria showed a low and a moderate level of evidence per outcome.