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The androgen-induced alterations in adult rodent skeletal muscle fibre cross-sectional area (fCSA), satellite cell content and myostatin (Mstn) were examined in 10-month-old Fisher 344 rats ( n = 41) assigned to Sham surgery, orchiectomy (ORX), ORX + testosterone (TEST; 7.0 mg week−1) or ORX + trenbolone (TREN; 1.0 mg week−1). After 29 days, animals were euthanised and the levator ani/bulbocavernosus (LABC) muscle complex was harvested for analyses. LABC muscle fCSA was 102% and 94% higher in ORX + TEST and ORX + TREN compared to ORX ( p < .001). ORX + TEST and ORX + TREN increased satellite cell numbers by 181% and 178% compared to ORX, respectively ( p < .01), with no differences between conditions for myonuclear number per muscle fibre ( p = .948). Mstn protein was increased 159% and 169% in the ORX + TEST and ORX + TREN compared to ORX ( p < .01). pan-SMAD2/3 protein was ~30-50% greater in ORX compared to SHAM ( p = .006), ORX + TEST ( p = .037) and ORX + TREN ( p = .043), although there were no between-treatment effects regarding phosphorylated SMAD2/3. Mstn, ActrIIb and Mighty mRNAs were lower in ORX, ORX + TEST and ORX + TREN compared to SHAM ( p < .05). Testosterone and trenbolone administration increased muscle fCSA and satellite cell number without increasing myonuclei number, and increased Mstn protein levels. Several genes and signalling proteins related to myostatin signalling were differentially regulated by ORX or androgen therapy. [ABSTRACT FROM AUTHOR]

Permutation problems have captured the attention of the combinatorial optimization community for decades due to the challenge they pose. Although their solutions are naturally encoded as permutations, in each problem, the information to be used to optimize them can vary substantially. In this article, we consider the Quadratic Assignment Problem (QAP) as a case study, and propose using Doubly Stochastic Matrices (DSMs) under the framework of Estimation of Distribution Algorithms. To that end, we design efficient learning and sampling schemes that enable an effective iterative update of the probability model. Conducted experiments on commonly adopted benchmarks for the QAP prove doubly stochastic matrices to be preferred to other four models for permutations, both in terms of effectiveness and computational efficiency. Moreover, additional analyses performed on the structure of the QAP and the Linear Ordering Problem (LOP) show that DSMs are good to deal with assignment problems, but they have interesting capabilities to deal also with ordering problems such as the LOP. The article concludes with a description of the potential uses of DSMs for other optimization paradigms, such as genetic algorithms or model-based gradient search., (© 2025 Massachusetts Institute of Technology.)

Background: Paretic propulsion [measured as anteriorly-directed ground reaction forces (AGRF)] and trailing limb angle (TLA) show robust inter-relationships, and represent two key modifiable post-stroke gait variables that have biomechanical and clinical relevance. Our recent work demonstrated that real-time biofeedback is a feasible paradigm for modulating AGRF and TLA in able-bodied participants. However, the effects of TLA biofeedback on gait biomechanics of post-stroke individuals are poorly understood. Thus, our objective was to investigate the effects of unilateral, real-time, audiovisual TLA versus AGRF biofeedback on gait biomechanics in post-stroke individuals., Methods: Nine post-stroke individuals (6 males, age 63 ± 9.8 years, 44.9 months post-stroke) participated in a single session of gait analysis comprised of three types of walking trials: no biofeedback, AGRF biofeedback, and TLA biofeedback. Biofeedback unilaterally targeted deficits on the paretic limb. Dependent variables included peak AGRF, TLA, and ankle plantarflexor moment. One-way repeated measures ANOVA with Bonferroni-corrected post-hoc comparisons were conducted to detect the effect of biofeedback on gait biomechanics variables., Results: Compared to no-biofeedback, both AGRF and TLA biofeedback induced unilateral increases in paretic AGRF. TLA biofeedback induced significantly larger increases in paretic TLA than AGRF biofeedback. AGRF biofeedback increased ankle moment, and both feedback conditions increased non-paretic step length. Both types of biofeedback specifically targeted the paretic limb without inducing changes in the non-paretic limb., Conclusions: By showing comparable increases in paretic limb gait biomechanics in response to both TLA and AGRF biofeedback, our novel findings provide the rationale and feasibility of paretic TLA as a gait biofeedback target for post-stroke individuals. Additionally, our results provide preliminary insights into divergent biomechanical mechanisms underlying improvements in post-stroke gait induced by these two biofeedback targets. We lay the groundwork for future investigations incorporating greater dosages and longer-term therapeutic effects of TLA biofeedback as a stroke gait rehabilitation strategy. Trial registration NCT03466372., (© 2023. The Author(s).)

Purpose: The primary aim was to evaluate dentoalveolar expansion with Invisalign clear aligners comparing linear measurements in ClinCheck vs. cone beam computed tomography (CBCT). This would enable an assessment of to what extent expansion gained from Invisalign clear aligners was due to buccal tipping and/or bodily translation of the posterior teeth. The study also evaluated the predictive value of Invisalign ClinCheck ® (Align Technology, San Jose, CA, USA) to final outcomes., Methods: The orthodontic records of thirty-two (32) subjects comprised the sample to conduct this study. Linear values of the upper arch width were measured for premolars and molars at two different points (occlusal and gingival) utilized for ClinCheck ® measurements and three different points for CBCT measurements before (T 0 and after treatment (T 1 ). Paired T-tests at a significance level of 0.05 were used for analyses., Results: Expansion was found to be possible with Invisalign clear aligners. However, more expansion was measured at the cusp tips compared to gingival margins ( p < 0.0001), indicating more tipping was occurring than bodily translation. ClinCheck ® also showed a significant overestimation of the amount of expansion capable, with nearly 70% expression in the first premolar area, and the expression decreased as one moved posteriorly with only 35% expressed at the first molar area ( p < 0.0001)., Conclusions: Dentoalveolar expansion with Invisalign is achieved through buccal tipping of posterior teeth and bodily translation; and there is a significant overestimation of the amount of expansion achieved between ClinCheck ® and clinical results.

Objective: The aim of this study was to develop and validate an outcome measure for individuals with motion-provoked dizziness., Study Design: Methodological., Setting: Academic outpatient vestibular and dizziness clinic., Patients/subjects: Adults with and without motion-provoked dizziness., Main Outcome Measures: Scores from the modified Motion Sensitivity Test (mMST) were compared between those with motion-provoked dizziness and controls without complaints of dizziness to evaluate the validity of the mMST. Intrarater and interrater reliability of the total Motion Sensitivity Quotient scores were assessed. Baseline and discharge total Motion Sensitivity Quotient scores were collected in a group of patients to determine the sensitivity of the mMST to measure change in motion-provoked dizziness after vestibular rehabilitation., Results: A 10-item motion sensitivity test was developed and demonstrated discriminant validity to differentiate patients with motion-provoked dizziness and control subjects without dizziness and demonstrated construct validity compared with the Dizziness Handicap Inventory (r = 0.64, p < 0.001). Internal validity of the mMST was excellent (Cronbach α = 0.95). The mMST demonstrated excellent reliability between raters (intraclass correlation coefficient = 1.00) and test sessions (intraclass correlation coefficient = 0.95)., Conclusions: The results indicated that the mMST can be used reliably in clinical practice to develop exercise programs for patients with motion-provoked dizziness and to provide evidence of intervention efficacy. mMST is a valid, reliable measure to use in the clinic for patients with motion-provoked dizziness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

This study explored the performances of waste polyurethane foam (PUF) derived from the shredding of end-of-life refrigerators as an adsorbent for wastewater treatment. The waste PUF underwent a basic pre-treatment (e.g., sieving and washing) prior the adsorption tests. Three target pollutants were considered: methylene blue, phenol, and mercury. Adsorption batch tests were performed putting in contact waste PUF with aqueous solutions of the three pollutants at a solid/liquid ratio equal to 25 g/L. A commercial activated carbon (AC) was considered for comparison. The contact time necessary to reach the adsorption equilibrium was in the range of 60-140 min for waste PUF, while AC needed about 30 min. The results of the adsorption tests showed a better fit of the Freundlich isotherm model (R 2 = 0.93 for all pollutants) compared to the Langmuir model. The adsorption capacity of waste PUF was limited for methylene blue and mercury (K f = 0.02), and much lower for phenol (K f = 0.001). The removal efficiency achieved by waste PUF was lower (phenol 12% and methylene blue and mercury 37-38%) compared to AC (64-99%). The preliminary results obtained in this study can support the application of additional pre-treatments aimed to overcome the adsorption limits of the waste PUF, and it could be applied for "rough-cut" wastewater treatment.

We developed a new class of inhibitors of protein-protein interactions of the SHP2 phosphatase, which is pivotal in cell signaling and represents a central target in the therapy of cancer and rare diseases. Currently available SHP2 inhibitors target the catalytic site or an allosteric pocket but lack specificity or are ineffective for disease-associated SHP2 mutants. Considering that pathogenic lesions cause signaling hyperactivation due to increased levels of SHP2 association with cognate proteins, we developed peptide-based molecules with nanomolar affinity for the N-terminal Src homology domain of SHP2, good selectivity, stability to degradation, and an affinity for pathogenic variants of SHP2 that is 2-20 times higher than for the wild-type protein. The best peptide reverted the effects of a pathogenic variant (D61G) in zebrafish embryos. Our results provide a novel route for SHP2-targeted therapies and a tool for investigating the role of protein-protein interactions in the function of SHP2.

The Src-homology 2 domain containing phosphatase 2 (SHP2) plays a critical role in crucial signaling pathways and is involved in oncogenesis and in developmental disorders. Its structure includes two SH2 domains (N-SH2 and C-SH2), and a protein tyrosine phosphatase (PTP) domain. Under basal conditions, SHP2 is auto-inhibited, with the N-SH2 domain blocking the PTP active site. Activation involves a rearrangement of the domains that makes the catalytic site accessible, coupled to the association between the SH2 domains and cognate proteins containing phosphotyrosines. Several aspects of this transition are debated and competing mechanistic models have been proposed. A crystallographic structure of SHP2 in an active state has been reported (PDB code 6crf), but several lines of evidence suggests that it is not fully representative of the conformations populated in solution. To clarify the structural rearrangements involved in SHP2 activation, enhanced sampling simulations of the autoinhibited and active states have been performed, for wild type SHP2 and its pathogenic E76K variant. Our results demonstrate that the crystallographic conformation of the active state is unstable in solution, and multiple interdomain arrangements are populated, thus allowing association to bisphosphorylated sequences. Contrary to a recent proposal, activation is coupled to the conformational changes of the N-SH2 binding site, which is significantly more accessible in the active sate, rather than to the structure of the central β-sheet of the domain. In this coupling, a previously undescribed role for the N-SH2 BG loop emerged., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

The shredding of end-of-life refrigerators produces every year in Italy 15,000 tons of waste polyurethane foam (PUF), usually destined for energy recovery. This work presents the results of the investigation of the oil sorption potential of waste PUF according to ASTM F726-17 standard. Three oils (diesel fuel and two commercial motor oils) having different densities (respectively, 0.83, 0.87, and 0.88 kg/dm 3 ) and viscosities (respectively, 3, 95, and 140 mm 2 /s at 40 °C) were considered. The waste PUF was sampled in an Italian e-waste treatment plant, and its characterization showed 16.5 wt% particles below 0.71 mm and 13 wt% impurities (paper, plastic, aluminum foil), mostly having dimensions (d) above 5 mm. Sieving at 0.071 mm was applied to the waste PUF to obtain a "coarse" (d > 0.71 mm) and a "fine" fraction (d < 0.71 mm). Second sieving at 5 mm allowed an "intermediate" fraction to be obtained, with dimensions between 0.71 and 5 mm. The oil sorption tests involved the three fractions of waste PUF, and their performances were compared with two commercial oil sorbents (sepiolite and OKO-PUR). The results of the tests showed that the "fine" PUF was able to retain 7.1-10.3 g oil/g, the "intermediate" PUF, 4.2-7.4 g oil/g, and the "coarse" PUF, 4.5-7.0 g oil/g, while sepiolite and OKO-PUR performed worse (respectively, 1.3-1.6 and 3.3-5.3 g oil/g). In conclusion, compared with the actual management of waste PUF (100 wt% sent to energy recovery), the amount destined directly to energy recovery could be limited to 13 wt% (i.e., the impurities). The remaining 87 wt% could be diverted to reuse for oil sorption, and afterward directed to energy recovery, considered as a secondary option.

Background: Reduced forward propulsion during gait, measured as the anterior component of the ground reaction force (AGRF), may contribute to slower walking speeds in older adults and gait dysfunction in individuals with neurological impairments. Trailing limb angle (TLA) is a clinically important gait parameter that is associated with AGRF generation. Real-time gait biofeedback can induce modifications in targeted gait parameters, with potential to modulate AGRF and TLA. However, the effects of real-time TLA biofeedback on gait biomechanics have not been studied thus far., Research Question: What are the effects of unilateral, real-time, audiovisual trailing limb angle biofeedback on gait biomechanics in able-bodied individuals?, Methods: Ten able-bodied adults participated in one session of treadmill-based gait analyses comprising 60-second walking trials under three conditions: no biofeedback, AGRF biofeedback, and TLA biofeedback. Biofeedback was provided unilaterally to the right leg. Dependent variables included AGRF, TLA, ankle moment, and ankle power. One-way repeated measures ANOVA with post-hoc tests were conducted to determine the effect of the biofeedback conditions on gait parameters., Results: Compared to no biofeedback, both AGRF and TLA biofeedback induced significant increases in targeted leg AGRF without concomitant changes to the non-targeted leg AGRF. Targeted leg TLA was significantly larger during TLA biofeedback compared to AGRF biofeedback. Only AGRF biofeedback induced significant increases in ankle power; and only the TLA biofeedback condition induced increases in the non-targeted leg TLA., Significance: Our novel findings provide support for the feasibility and promise of TLA as a gait biofeedback target. Our study demonstrates that comparable magnitudes of feedback-induced increases in AGRF in response to AGRF and TLA biofeedback may be achieved through divergent biomechanical strategies. Further investigation is needed to uncover the effects of TLA biofeedback on gait parameters in individuals with neuro-pathologies such as spinal cord injury or stroke., (Copyright © 2020. Published by Elsevier B.V.)

Here we report the design of membrane-active peptidomimetic molecules with a tunable arrangement of hydrophobic and polar groups. In spite of having the same chemical composition, the effective hydrophobicities of the compounds were different as a consequence of their chemical structure and conformational properties. The compound with lower effective hydrophobicity demonstrated antibacterial activity that was highly selective towards bacteria over mammalian cells. This study, highlighting the role in membrane selectivity of the specific arrangement of the different moieties in the molecular structure, provides useful indications for developing non-toxic antibacterial agents.

We compared immediate post-exercise whey protein (WP, 500 mg) versus L-leucine (LEU, 54 mg) feedings on skeletal muscle protein synthesis (MPS) mechanisms and ribosome biogenesis markers 3 h following unilateral plantarflexor resistance exercise in male, Wistar rats (~250 g). Additionally, in vitro experiments were performed on differentiated C2C12 myotubes to compare nutrient (i.e., WP, LEU) and 'exercise-like' treatments (i.e., caffeine, hydrogen peroxide, and AICAR) on ribosome biogenesis markers. LEU and WP significantly increased phosphorylated-rpS6 (Ser235/236) in the exercised (EX) leg 2.4-fold (P < 0.01) and 2.7-fold (P < 0.001) compared to the non-EX leg, respectively, whereas vehicle-fed control (CTL) did not (+65 %, P > 0.05). Compared to the non-EX leg, MPS levels increased 32 % and 52 % in the EX leg of CTL (P < 0.01) and WP rats (P < 0.001), respectively, but not in LEU rats (+15 %, P > 0.05). Several genes associated with ribosome biogenesis robustly increased in the EX versus non-EX legs of all treatments; specifically, c-Myc mRNA, Nop56 mRNA, Bop1 mRNA, Ncl mRNA, Npm1 mRNA, Fb1 mRNA, and Xpo-5 mRNA. However, only LEU significantly increased 45S pre-rRNA levels in the EX leg (63 %, P < 0.001). In vitro findings confirmed that 'exercise-like' treatments similarly altered markers of ribosome biogenesis, but only LEU increased 47S pre-rRNA levels (P < 0.01). Collectively, our data suggests that resistance exercise, as well as 'exercise-like' signals in vitro, acutely increase the expression of genes associated with ribosome biogenesis independent of nutrient provision. Moreover, while EX with or without WP appears superior for enhancing translational efficiency (i.e., increasing MPS per unit of RNA), LEU administration (or co-administration) may further enhance ribosome biogenesis over prolonged periods with resistance exercise.

The characterization of the first selective orally active and brain-penetrant beta3-adrenoceptor agonist, SR58611A (amibegron), has opened new possibilities for exploring the involvement of this receptor in stress-related disorders. By using a battery of tests measuring a wide range of anxiety-related behaviors in rodents, including the mouse defense test battery, the elevated plus-maze, social interaction, stress-induced hyperthermia, four-plate, and punished drinking tests, we demonstrated for the first time that the stimulation of the beta3 receptor by SR58611A resulted in robust anxiolytic-like effects, with minimal active doses ranging from 0.3 to 10 mg/kg p.o., depending on the procedure. These effects paralleled those obtained with the prototypical benzodiazepine anxiolytic diazepam or chlordiazepoxide. Moreover, when SR58611A was tested in acute or chronic models of depression in rodents, such as the forced-swimming and the chronic mild stress tests, it produced antidepressant-like effects, which were comparable in terms of the magnitude of the effects to those of the antidepressant fluoxetine or imipramine. Supporting these behavioral data, SR58611A modified spontaneous sleep parameters in a manner comparable to that observed with fluoxetine. Importantly, SR58611A was devoid of side effects related to cognition (as shown in the Morris water maze and object recognition tasks), motor activity (in the rotarod), alcohol interaction, or physical dependence. Antagonism studies using pharmacological tools targeting a variety of neurotransmitters involved in anxiety and depression and the use of mice lacking the beta3 adrenoceptor suggested that these effects of SR58611A are mediated by beta3 adrenoceptors. Taken as a whole, these findings indicate that the pharmacological stimulation of beta3 adrenoceptors may represent an innovative approach for the treatment of anxiety and depressive disorders.