Locomotive Syndrome is associated with chronic pain and poor quality of life in Brazilian oldest old: LOCOMOV Project

BackgroundIn 2007, the Japanese Orthopedic Association established the term “Locomotive Syndrome” (LS) for the concept of locomotor organ dysfunction with potential loss of independence. The purpose of this study was to identify characteristics of LS and establish a diagnostic cut-off for the Geriatric Locomotive Function Scale (GLFS 25-p) for the Brazilian population.MethodsA cross-sectional observational study of the LOCOMOV Project cohort of independent outpatients aged ≥80 years was conducted. Questionnaires on functional status in Basic and Instrumental Activities of Daily Living (Katz and Lawton, respectively) and quality of life (WHOQOL-Bref) were applied, together with the Geriatric Locomotive Function Scale (GLFS 25-p) to identify individuals with LS. Mobility was assessed using the five-times sit-to-stand test, 4-m gait speed, two-step test, one-leg standing time with eyes open and hand-grip test. The data were analyzed using Student's t-test, the Chi–Square test, and multiple logistic regression (stepwise). The significance level was set at 0.05 (5%).ResultsA sample of 102 individuals with mean age of 87.3 (±4.2) years and predominantly female (73.5%) was assessed. We determined a cut-off score of 19 (sensitivity of 0.86 and specificity of 0.67) for diagnosis of LS, as assessed by the GLFS 25-p, and a high prevalence (55%) of the syndrome was found in the sample. In the multiple regression analysis, LS was directly associated with chronic pain (OR 22.24, 95%CI 3.13–157.87), use of a walking device (OR 17.121, 95%CI 1.94–150.49), and inversely associated with gait speed ≥0.8 m/s (OR 0.42, 95%CI 0.006–0.278), perception of good health (OR 0.153, 95%CI 0.029–0.799) and male gender (OR 0.086, 95%CI 0.0105–0.714).ConclusionThe LS in the oldest old proved a very common condition in this survey, especially in women, and was strongly associated with chronic pain, worse performance on physical tests and poor quality of life.     

Risk factors for pneumothorax associated with isolated congenital diaphragmatic hernia: results of a Japanese multicenter study

This study aimed to elucidate the clinical characteristics of neonates with congenital diaphragmatic hernia (CDH) associated with pneumothorax and evaluate the risk factors for the development of pneumothorax. A retrospective cohort study was conducted in the 15 institutions participating in the Japanese CDH Study Group. A total of 495 neonates with isolated CDH who were born between 2011 and 2018 were analyzed in this study. Among the 495 neonates with isolated CDH, 52 (10.5%) developed pneumothorax. Eighteen (34.6%) patients developed pneumothorax before surgery, while 34 (65.4%) developed pneumothorax after surgery. The log-rank test showed that the cumulative survival rate was significantly lower in patients with pneumothorax than in those without pneumothorax. Univariate analysis revealed significant differences between patients with pneumothorax and those without pneumothorax with regard to the best oxygenation index within 24 h after birth, mean airway pressure (MAP) higher than 16 cmH2O, diaphragmatic defect size, and need for patch closure. Multiple logistic regression analysis indicated that only the MAP was associated with an increased risk of pneumothorax. The cumulative survival rate was significantly lower in isolated CDH patients with pneumothorax than in those without pneumothorax. A higher MAP was a risk factor for pneumothorax in CDH patients.     

Elasticity,friction, and pathway of γ-subunit rotation in FoF1-ATP synthase

We combine molecular simulations and mechanical modeling to explore the mechanism of energy conversion in the coupled rotary motors of F_oF₁-ATP synthase. A torsional viscoelastic model with frictional dissipation quantitatively reproduces the dynamics and energetics seen in atomistic molecular dynamics simulations of torque-driven γ-subunit rotation in the F₁-ATPase rotary motor. The torsional elastic coefficients determined from the simulations agree with results from independent single-molecule experiments probing different segments of the γ-subunit, which resolves a long-lasting controversy. At steady rotational speeds of ∼1 kHz corresponding to experimental turnover, the calculated frictional dissipation of less than k_BT per rotation is consistent with the high thermodynamic efficiency of the fully reversible motor. Without load, the maximum rotational speed during transitions between dwells is reached at ∼1 MHz. Energetic constraints dictate a unique pathway for the coupled rotations of the F_o and F₁ rotary motors in ATP synthase, and explain the need for the finer stepping of the F₁ motor in the mammalian system, as seen in recent experiments. Compensating for incommensurate eightfold and threefold rotational symmetries in F_o and F₁, respectively, a significant fraction of the external mechanical work is transiently stored as elastic energy in the γ-subunit. The general framework developed here should be applicable to other molecular machines.F_oF₁-ATP synthase is essential for life. From bacteria to human, this protein synthesizes ATP from ADP and inorganic phosphate P_i in its F₁ domain, powered by an electrochemical proton gradient that drives the rotation of its membrane-embedded F_o domain (1–5). Its two rotary motors, F₁ and F_o, are coupled through the γ-subunit forming their central shaft (2). ATP synthase is a fully reversible motor, in which the rotational direction switches according to different sources of energy (2, 6). In hydrolysis mode, the F₁ motor pumps protons against an electrochemical gradient across the membrane-embedded F_o part, converting ATP to ADP and P_i (7, 8).F₁ has a symmetric ring structure composed of three αβ-subunits with the asymmetric γ-subunit sitting inside the ring (9, 10). Each αβ-subunit has a catalytic site located at the αβ-domain interface. The F₁ ring has a pseudothreefold symmetry with the three αβ-subunits taking three different conformations, E (empty), TP (ATP-bound), and DP (ADP bound) (9–11). The F_o part is composed of a c ring and an a subunit (3, 12). Driven by protons passing through the interface of the c ring and the a subunit, the c ring rotates together with the γ-subunit (rotor) relative to the a subunit, which is connected to the F₁ ring through the peripheral stalk of the b subunit (stator) (12). Interestingly, in nature, one finds a large variation in the number of subunits in the c ring. In animal mitochondria, one finds c₈ rings, requiring a minimal number of eight proton translocations for the synthesis of three ATP, at least 20% fewer protons than in bacteria and plant chloroplasts with c₁₀–c₁₅ rings (13, 14). The resulting symmetry mismatches between F₁ and F_o (15–17) clearly distinguish the biomolecular motor from macroscopic machines.Key open questions concern the detailed rotational pathway of the two coupled rotary motors, the impact of the rotational symmetry mismatch between the F_o and F₁ motors on the motor mechanics, the resulting need for transient energy storage, the role of frictional dissipation, and the molecular elements associated with stepping of the F₁ motor (18–24). Here we explore these questions by building a dissipative mechanical model of the F₁ motor on the basis of atomistic molecular dynamics (MD) simulations. Friction and torsional elasticity of the γ-subunit are central to the efficient function of the coupled F_oF₁ nanomotors (15, 25, 26). For γ-subunits cross-linked with the α₃β₃-ring, estimates have been obtained by monitoring thermal angle fluctuations in single-molecule experiments (16, 27) and MD simulations (28). To probe the elastic and frictional properties under mechanical load over broad ranges of rotation angles and angular velocities, we induce torque-driven γ-subunit rotation in MD simulations (20, 29). From the resulting mechanical deformation and energy dissipation, we construct a fully quantitative viscoelastic model. We account for the torsional elasticity and friction by describing the rotational motion of the γ-subunit as overdamped Langevin dynamics on a 2D harmonic free energy surface. The model quantifies the magnitude of transient elastic energy storage compensating for the incommensurate rotational symmetries of the F_o and F₁ motors (30). The resulting energetic constraints allow us to map out a detailed pathway for their coupled rotary motions, and to rationalize the finer stepping of the mammalian F₁ motor seen in recent experiments (31), with only eight c subunits in the corresponding F_o motor. By quantifying the frictional dissipation, we identify a key contributor to the high thermodynamic efficiency of the F₁ motor. The general framework developed here for F₁ should be applicable also to other molecular machines.