Nonequilibrium fluctuations for a single-particle analog of gas in a soft wall

We investigate the motion of a colloidal particle driven out of equilibrium by a time-varying stiffness of the optical trap that produces persistent nonequilibrium work. Measurements of work production for repeated cycles composed of the compression and expansion processes for the optical potential show huge fluctuations due to thermal motion. Using a precise technique to modulate the stiffness in time, we accurately estimate the probability distributions of work produced for the compression and expansion processes. We confirm the fluctuation theorem from the ratio of the two distributions. We also show that the average values of work for the two processes comply with the Jarzynski equality. This system has an analogy with a gas in a breathing soft wall. We discuss about its applicability to a heat engine and an information engine operated by feedback control.open1

Correlation of Femoral Muscle Volume Using Three-Dimensional Modeling and Locomotor Function After Unilateral Trans-femoral Amputation

Objective To evaluate the relationship between femoral muscle volume (FMV) and physiological outcomes after trans-femoral amputations (TFAs) affecting overall locomotor function in patients. Methods Seven individuals who underwent TFA and had been using a prosthesis participated in this cross-sectional study. Gait and balance were assessed using clinical tests, such as 10-m walk test, 6-minute walk test, Berg Balance Scale, and automatic balance system. Respiratory gas analysis was performed to check oxygen consumption rate. Five participants were evaluated for bilateral FMV by MR imaging and FMV was reconstructed using three-dimentional remodeling. Results In five participants, significant differences were found between the non-involved and involved sides in femur length, total FMV, and functional muscle volume (all p<0.01) in all groups except for the hip adductor volume. The %mean difference between the non-involved and involved sides was 30% for femur length, 52.55% for hip flexor volume, 26.55% for hip adductor volume, 51.86% for hip extensor volume, and 60.21% for knee extensor volume. The hip flexor volume to hip extensor volume ratio in the involved limb and oxygen consumption rate during comfortable gait were negatively correlated (r=-0.96, p=0.04). Conclusion In individuals who underwent unilateral TFA, hip girdle muscle imbalance in the involved limbs may be associated with oxygen consumption rate while using a prosthesis

Factors affecting the long-term outcomes of idiopathic membranous nephropathy

Abstract Background We attempted to describe the clinical features and determine the factors associated with renal survival in idiopathic membranous nephropathy (iMN) patients with nephrotic syndrome (NS) and to determine the factors associated with spontaneous complete remission (sCR) and progression to NS in iMN patients with subnephrotic proteinuria. Methods This retrospective study involved 166 iMN patients with NS and 65 patients with subnephrotic proteinuria. The primary end point was a doubling of serum creatinine or initiation of dialysis. In patients with subnephrotic proteinuria, we determined the factors associated with sCR and factors associated with progression to NS. Results Remission of NS was achieved in 125 out of 166 patients (75.3%). Of those who reached remission, 26 patients (20.8%) experienced relapse that was followed by second remission. The relapse or persistence of proteinuria was associated with the primary end points (hazard ratio [HR] = 12.40, P = 0.037, HR = 173, P < 0.001, respectively). In patients with subnephrotic proteinuria, sCR occurred in 35.4% of the patients. The patients with sCR had lower proteinuria and serum creatinine levels and higher serum albumin concentrations at baseline. The serum albumin level at diagnosis was a prognostic factor for progression to NS (Odds ratio [OR] = 0.015, P < 0.001). Conclusions The occurrence of relapse or persistence of proteinuria had negative effects on renal survival in iMN patients with NS, and low serum albumin levels at baseline were associated with non-achievement of sCR and progression to NS

Electronic structures of hexagonal RMnO3 (R = Gd, Tb, Dy, and Ho) thin films

We investigated the electronic structure of multiferroic hexagonal RMnO3 (R = Gd, Tb, Dy, and Ho) thin films using both optical spectroscopy and first-principles calculations. Using artificially stabilized hexagonal RMnO3, we extended the optical spectroscopic studies on the hexagonal multiferroic manganite system. We observed two optical transitions located near 1.7 eV and 2.3 eV, in addition to the predominant absorption above 5 eV. With the help of first-principles calculations, we attribute the low-lying optical absorption peaks to inter-site transitions from the oxygen states hybridized strongly with different Mn orbital symmetries to the Mn 3d3z2-r2 state. As the ionic radius of the rare earth ion increased, the lowest peak showed a systematic increase in its peak position. We explained this systematic change in terms of a flattening of the MnO5 triangular bipyramid

Variables affecting new drug prices in South Korea’s pricing system

Objective: The price of pharmaceuticals is important from the economic and industrial perspectives but as well as patients’ access to treatment. This study aimed to analyze the variables affecting the prices of new drugs in South Korea’s pricing system.Methods: Data on 192 new drugs listed in South Korea from 2012 to 2022 were collected from the official website of the Health Insurance Review and Assessment Service. The independent variables included drugs for severe diseases, alternatives, number of patients, number of advanced 7 countries listed, budget impact, and listing period. The dependent variables included annual treatment cost and the price ratio to the advanced 7 country’s average adjusted price. Descriptive statistics of variables, linear correlations between quantitative independent and dependent variables, and associations between independent and dependent variables were analyzed.Results: The mean annual treatment cost and price ratio to the advanced 7 country’s average adjusted price were higher for drugs for severe diseases and those with no alternatives. Annual treatment cost and price ratio to the advanced 7 country’s average adjusted price were negatively correlated with the number of patients and positively correlated with the number of advanced 7 countries listed. Annual treatment cost was affected by the variables drugs for severe diseases, alternatives, number of patients, number of advanced 7 countries listed, and budget impact. The price ratio to the advanced 7 country’s average adjusted price was affected by drugs for severe diseases, alternatives, and the number of patients.Conclusion: This study revealed the effect of different variables on the prices of new drugs in South Korea, allowing for the development of a more effective assessment system to evaluate the prices of new drugs while ensuring profitability for pharmaceutical companies, sustainability of public insurance, and accessibility to drugs by patients

Phosphatidylcholine induces apoptosis of 3T3-L1 adipocytes

<p>Abstract</p> <p>Background</p> <p>Phosphatidylcholine (PPC) formulation is used for lipolytic injection, even though its mechanism of action is not well understood.</p> <p>Methods</p> <p>The viability of 3T3-L1 pre-adipocytes and differentiated 3T3-L1 cells was measured after treatment of PPC alone, its vehicle sodium deoxycholate (SD), and a PPC formulation. Western blot analysis was performed to examine PPC-induced signaling pathways.</p> <p>Results</p> <p>PPC, SD, and PPC formulation significantly decreased 3T3-L1 cell viability in a concentration-dependent manner. PPC alone was not cytotoxic to CCD-25Sk human fibroblasts at concentrations <1 mg/ml, whereas SD and PPC formulation were cytotoxic. Western blot analysis demonstrated that PPC alone led to the phosphorylation of the stress signaling proteins, such as p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, and activated caspase-9, -8, -3 as well as cleavage of poly(ADP-ribose) polymerase. However, SD did not activate the apoptotic pathways. Instead, SD and PPC formulation induced cell membrane lysis, which may lead to necrosis of cells.</p> <p>Conclusions</p> <p>PPC results in apoptosis of 3T3-L1 cells.</p

Intestinal Pseudo-Obstruction as an Initial Manifestation of Systemic Lupus Erythematosus

Intestinal pseudo-obstruction (IPO) is an uncommon, severe complication that occurs in a small subgroup of patients with systemic lupus erythematosus (SLE). To our knowledge, approximately 30 cases of IPO in SLE have been reported in the literature. Moreover, IPO is rare as an initial manifestation of SLE. We report a case of a 43-year-old woman with SLE who initially presented with IPO

Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study

Background Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population. Methods Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0–4), and the sum of quartiles (0–12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model. Results During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m2, and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death. Conclusion Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors

Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses

<p>Abstract</p> <p>Background</p> <p>Immunization with the spike protein (S) of severe acute respiratory syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K (PEI) is a cationic polymer which effectively delivers the plasmid DNA.</p> <p>Results</p> <p>In the present study, the immune responses of BALB/c mice immunized via intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form have been examined. The size of the PEI/pci-S nanoparticles appeared to be around 194.7 ± 99.3 nm, and the expression of the S mRNA and protein was confirmed <it>in vitro</it>. The mice immunized with i.n. PEI/pci-S nanoparticles produced significantly (<it>P </it>< 0.05) higher S-specific IgG1 in the sera and mucosal secretory IgA in the lung wash than those in mice treated with pci-S alone. Compared to those in mice challenged with pci-S alone, the number of B220⁺cells found in PEI/pci-S vaccinated mice was elevated. Co-stimulatory molecules (CD80 and CD86) and class II major histocompatibility complex molecules (I-A^d) were increased on CD11c⁺dendritic cells in cervical lymph node from the mice after PEI/pci-S vaccination. The percentage of IFN-γ-, TNF-α- and IL-2-producing cells were higher in PEI/pci-S vaccinated mice than in control mice.</p> <p>Conclusion</p> <p>These results showed that intranasal immunization with PEI/pci-S nanoparticles induce antigen specific humoral and cellular immune responses.</p