A Randomized Controlled Trial of Short-term Toe Resistance Training to Improve Toe Pinch Force in Patients with Type 2 Diabetes

Resistance training is effective against type 2 diabetes (T2DM), but the effect of resistance training on toe pinch force (TPF) is unknown. Here we investigated the effect of short-term toe resistance training on TPF in patients with T2DM, in a prospective, parallel-group, single-blind, randomized controlled trial. Twelve patients with T2DM who were hospitalized to improve glycemic control were enrolled. The patients were randomly allocated to the intervention (n=6) and control (n=6) groups. The intervention group performed traditional aerobic exercise and 4 newly developed toe-resistance training exercises. The control group performed aerobic exercise only. After 2 weeks of the exercise intervention program, we evaluated anthropometric parameters, clinical parameters, motor function, and muscle parameters in each patient. After the exercise intervention program, the TPF and toe muscle quality, isometric knee extension force, and knee muscle quality were significantly higher in the intervention group compared to the control group. Two weeks of toe-resistance training significantly increased the TPF in the T2DM patients. Toe resistance training is thus recommended in clinical practice for patients with T2DM

Influence of insulin injection on skin

Aims/Introduction: The influence of repeated insulin injection on subcutaneous tissue is known, but its impact on the skin is unclear. Therefore, this study aimed to elucidate the impact of repeated insulin injections on the skin. Material and Methods: The properties of the skin and the subcutaneous tissue were evaluated in 52 insulin-treated adult patients with diabetes with abnormal findings at the site of self-injection (36 with subcutaneous nodules, 16 with suspected subcutaneous tissue induration) by ultrasonography. In all subjects, both normal and abnormal areas were examined. In addition, skin biopsies were performed in four subjects. Results: The skin thickness of the normal and abnormal skin sites was 1.95 (1.60, 2.50) and 2.80 (2.27, 3.30) mm, respectively (median (first quartile, third quartile)), (P < 0.001). The biopsy specimens revealed slightly thickened and tight bundles of collagen in the dermis. Three patients had amyloid deposits in the subcutaneous tissue, and one also showed these in the dermis. These were positively stained for insulin antibody. Conclusions: Repeated insulin injection procedures result in skin thickening. Increased collagen fibers and possibly amyloid deposition in the dermis may be involved. The results reaffirmed the importance of appropriate site rotation in insulin injection and revealed the usefulness of ultrasonographic skin examination in evaluating the self-injection procedure

Universal adjointation of isometry operations using transformation of quantum supermaps

Identification of possible transformations of quantum objects including quantum states and quantum operations is indispensable in developing quantum algorithms. Universal transformations, defined as input-independent transformations, appear in various quantum applications. Such is the case for universal transformations of unitary operations. However, extending these transformations to non-unitary operations is nontrivial and largely unresolved. Addressing this, we introduce isometry adjointation protocols that convert an input isometry operation into its adjoint operation, which include both unitary operation and quantum state transformations. The paper details the construction of parallel and sequential isometry adjointation protocols, derived from unitary inversion protocols using quantum combs, and achieving optimal approximation error. This error is shown to be independent of the output dimension of the isometry operation. In particular, we explicitly obtain an asymptotically optimal parallel protocol achieving an approximation error $\epsilon = \Theta(d^2/n)$, where $d$ is the input dimension of the isometry operation and $n$ is the number of calls of the isometry operation. The research also extends to isometry inversion and universal error detection, employing semidefinite programming to assess optimal performances. The findings suggest that the optimal performance of general protocols in isometry adjointation and universal error detection is not dependent on the output dimension, and that indefinite causal order protocols offer advantages over sequential ones in isometry inversion and universal error detection.Comment: 65 pages, 6 figures. All codes are available at https://github.com/sy3104/isometry_adjointatio

Toe Pinch Force in Male Type 2 Diabetes Mellitus Patients

We compared the toe pinch force in men with and without type 2 diabetes mellitus (T2DM). Sixty-eight male T2DM patients and 35 apparently healthy men matched for age, sex, and body mass index (BMI) were enrolled in this cross-sectional study. We compared the toe pinch force between the subjects with and without T2DM, and we evaluated the effect of diabetic polyneuropathy on toe pinch force in the patients. The toe pinch force of the T2DM patients was significantly lower than that of the subjects without diabetes (3.12±1.22 kg vs. 4.40±1.19 kg, p<0.001). Multiple regression analysis showed that T2DM was a determinant of reduced toe pinch force. In addition, the toe pinch force of patients with diabetic polyneuropathy was significantly lower than that of patients without diabetic polyneuropathy (2.31±0.93 kg vs. 3.70±1.07 kg, p<0.001). Multiple regression analysis showed that diabetic polyneuropathy was a determinant of the toe pinch force in men with T2DM, even after adjusting for age, BMI, HbA1c, and duration of diabetes. Reduced toe pinch force is a fundamental feature of motor dysfunction in men with T2DM, and diabetic polyneuropathy might be associated with toe pinch force in these patients

DAMPs and radiation injury

The heightened risk of ionizing radiation exposure, stemming from radiation accidents and potential acts of terrorism, has spurred growing interests in devising effective countermeasures against radiation injury. High-dose ionizing radiation exposure triggers acute radiation syndrome (ARS), manifesting as hematopoietic, gastrointestinal, and neurovascular ARS. Hematopoietic ARS typically presents with neutropenia and thrombocytopenia, while gastrointestinal ARS results in intestinal mucosal injury, often culminating in lethal sepsis and gastrointestinal bleeding. This deleterious impact can be attributed to radiation-induced DNA damage and oxidative stress, leading to various forms of cell death, such as apoptosis, necrosis and ferroptosis. Damage-associated molecular patterns (DAMPs) are intrinsic molecules released by cells undergoing injury or in the process of dying, either through passive or active pathways. These molecules then interact with pattern recognition receptors, triggering inflammatory responses. Such a cascade of events ultimately results in further tissue and organ damage, contributing to the elevated mortality rate. Notably, infection and sepsis often develop in ARS cases, further increasing the release of DAMPs. Given that lethal sepsis stands as a major contributor to the mortality in ARS, DAMPs hold the potential to function as mediators, exacerbating radiation-induced organ injury and consequently worsening overall survival. This review describes the intricate mechanisms underlying radiation-induced release of DAMPs. Furthermore, it discusses the detrimental effects of DAMPs on the immune system and explores potential DAMP-targeting therapeutic strategies to alleviate radiation-induced injury

Radiation upregulates macrophage TREM-1 expression to exacerbate injury in mice

IntroductionExposure to high-dose ionizing radiation causes tissue injury, infections and even death due to immune dysfunction. The triggering receptor expressed on myeloid cells-1 (TREM-1) has been demonstrated to critically amplify and dysregulate immune responses. However, the role of TREM-1 in radiation injury remains unknown. Extracellular cold-inducible RNA-binding protein (eCIRP), a new damage-associated molecular pattern, is released from activated or stressed cells during inflammation. We hypothesized that ionizing radiation upregulates TREM-1 expression via eCIRP release to worsen survivalMethodsRAW264.7 cells and peritoneal macrophages collected from C57BL/6 wild-type (WT) mice were exposed to 5- and 10-Gray (Gy) radiation. C57BL/6 WT and CIRP-/- mice underwent 10-Gy total body irradiation (TBI). TREM-1 expression on RAW264.7 cells and peritoneal macrophages in vitro and in vivo were evaluated by flow cytometry. eCIRP levels in cell culture supernatants and in peritoneal lavage isolated from irradiated mice were evaluated by Western blotting. We also evaluated 30-day survival in C57BL/6 WT, CIRP-/- and TREM-1-/- mice after 6.5-Gy TBI.ResultsThe surface protein and mRNA levels of TREM-1 in RAW264.7 cells were significantly increased at 24 h after 5- and 10-Gy radiation exposure. TREM-1 expression on peritoneal macrophages was significantly increased after radiation exposure in vitro and in vivo. eCIRP levels were significantly increased after radiation exposure in cell culture supernatants of peritoneal macrophages in vitro and in peritoneal lavage in vivo. Moreover, CIRP-/- mice exhibited increased survival after 6.5-Gy TBI compared to WT mice. Interestingly, TREM-1 expression on peritoneal macrophages in CIRP-/- mice was significantly decreased compared to that in WT mice at 24 h after 10-Gy TBI. Furthermore, 30-day survival in TREM-1-/- mice was significantly increased to 64% compared to 20% in WT mice after 6.5-Gy TBI.ConclusionOur data indicate that ionizing radiation increases TREM-1 expression in macrophages via the release of eCIRP, and TREM-1 contributes to worse survival after total body irradiation. Thus, targeting TREM-1 could have the potential to be developed as a novel medical countermeasure for radiation injury

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049