Search

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of antidiabetic drugs. Guidelines for the proper use of SGLT2 inhibitors recommend caution regarding urinary tract infections (UTIs). However, little evidence has been reported on the relationship between SGLT2 inhibitors and UTIs in large epidemiological studies. We investigated (1) the relationship between diabetes mellitus (DM) and UTIs and (2) the relationship between SGLT2 inhibitor prescriptions and the likelihood of developing UTIs in patients with DM, using a nationwide Japanese health insurance claims database by MDV analyzer®. We found that the incidence of UTIs was significantly higher among patients with DM than among those without DM (odds ratio (OR), 1.71; 95% confidence interval (CI), 1.69–1.72, for male; OR, 1.90; 95% CI, 1.89–1.92 for female). In contrast, in male patients with DM, the prescription of SGLT2 inhibitors was negatively associated with the likelihood of developing UTIs (OR, 0.74; 95% CI, 0.72–0.75). Among female patients with DM, there was no significant difference in the incidence of UTIs with or without an SGLT2 inhibitor prescription (OR, 0.99; 95% CI, 0.96–1.01). Subgroup analyses by age confirmed similar relationships between SGLT2 inhibitor prescriptions and UTIs, except for female patients aged ≤39 years, in whom SGLT2 inhibitor prescription was negatively associated with the likelihood of developing UTIs. In conclusion, our analysis of a nationwide claims database found no evidence that SGLT2 inhibitors increase UTIs in Japanese patients with DM, regardless of sex or age.

Thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a rare condition with diverse clinical and pathological characteristics related to multi-organ damage. We report a case of TAFRO syndrome complicated by immune thrombocytopenia with prolonged fever and thrombocytopenia for several weeks. A 61-year-old man was transferred with sepsis caused by Enterococcus faecalis, and developed disseminated intravascular coagulation. Antibiotics treatment was initiated: however, low-grade fever and thrombocytopenia persisted despite the adequate antimicrobial treatment. Systemic edema, pleural effusion, and ascites had developed before hospitalization, and renal and liver function had deteriorated, resulting in progressive multi-organ damage. Prednisolone 40 mg/day was initiated based on the assumption of a condition in which excessive production of inflammatory cytokines would lead to systemic deterioration and fatal organ damage. Subsequently, the fever resolved, and renal function began to normalize. However, thrombocytopenia did not show much recovery trend after Helicobacter pylori eradication therapy and initiation of thrombopoietin receptor agonists. Bone marrow biopsy results showed normal bone marrow with no malignant findings. Alternatively, significant clinical signs met the diagnostic criteria for TAFRO syndrome, and a renal biopsy revealed thrombotic microangiopathy, which is also reasonable for renal involvement in TAFRO syndrome. The use of cyclosporine remarkably corrected the thrombocytopenia. We considered this a case of TAFRO syndrome that developed after sepsis with disseminated intravascular coagulation and performed the differential diagnosis of prolonged thrombocytopenia and excluded it. Although TAFRO syndrome is a unique disease concept, diagnostic criteria may consist of nonspecific elements such as generalized edema, thrombocytopenia, persistent fever, and elevated inflammatory response, and there are many differential conditions to exclude, requiring caution in diagnosing TAFRO syndrome.

Fabry disease (FD) is an X-linked disorder of the sphingolipid metabolism, caused by deficiency or decreased activity of α-galactosidase A. We report a rare case of Fabry nephropathy (FN) in a 21-year-old Japanese female patient presenting with only urinary mulberry bodies; she was treated with pharmacological chaperone therapy (PCT) after renal biopsy. The patient underwent a detailed examination because her mother was diagnosed with FD in the Division of Community Medicine of our hospital. She did not have renal dysfunction or proteinuria, and only mulberry bodies were detected in the urine. The activity of α-galactosidase A was low, and genetic analysis revealed the R301Q mutation. A percutaneous renal biopsy was performed, and the findings revealed enlargement and vacuolation of glomerular podocytes by light microscopy, and myelin and zebra bodies were detected in podocytes by electron microscopy. She was diagnosed with FN by renal biopsy and gene analysis. PCT was selected as the treatment to prevent cardiac events and renal dysfunction. The present case suggests that renal biopsy may be necessary even for young women with only mulberry bodies for the diagnosis of FN. It could be useful to evaluate the effect of treatment using the counts of mulberry bodies in the urine. In addition, due to its oral administration, PCT may be suitable for patients who are unable to visit the hospital frequently.

Uremic sarcopenia is a serious clinical problem associated with physical disability and increased morbidity and mortality. Methylglyoxal (MG) is a highly reactive, dicarbonyl uremic toxin that accumulates in the circulatory system in patients with chronic kidney disease (CKD) and is related to the pathology of uremic sarcopenia. The pathophysiology of uremic sarcopenia is multifactorial; however, the details remain unknown. We investigated the mechanisms of MG-induced muscle atrophy using mouse myoblast C2C12 cells, focusing on intracellular metabolism and mitochondrial injury. We found that one of the causative pathological mechanisms of uremic sarcopenia is metabolic flow change to fatty acid synthesis with MG-induced ATP shortage in myoblasts. Evaluation of cell viability revealed that MG showed toxic effects only in myoblast cells, but not in myotube cells. Expression of mRNA or protein analysis revealed that MG induces muscle atrophy, inflammation, fibrosis, and oxidative stress in myoblast cells. Target metabolomics revealed that MG induces metabolic alterations, such as a reduction in tricarboxylic acid cycle metabolites. In addition, MG induces mitochondrial morphological abnormalities in myoblasts. These changes resulted in the reduction of ATP derived from the mitochondria of myoblast cells. Our results indicate that MG is a pathogenic factor in sarcopenia in CKD.

Background and Objectives: Peritoneal dialysis (PD)-related peritonitis is a critical problem. However, preoperative risk factors for PD-related peritonitis have not been established. Thus, we aimed to determine the preoperative risk factors for PD-related peritonitis. Materials and Methods: This is a single-center prospective observational study. All peritonitis episodes during the study period were recorded, and preoperative and intraoperative clinical parameters were compared between patients with and without peritonitis to examine risk factors for PD-related peritonitis. Furthermore, subcutaneous and abdominal fat volumes were evaluated using computed tomography. Results: Among a total of 118 patients, 24 patients developed peritonitis. The proportion of male patients (83% vs. 61%, p = 0.04), body mass index (25 vs. 22 kg/m2, p = 0.04), and subcutaneous fat area (120 vs. 102 cm2, p = 0.01) were significantly higher and the proportion of patients living with family members (75% vs. 94%, p = 0.02) was significantly lower in the peritonitis group than in the non-peritonitis group. There were no significant differences in age, operation method, surgeon experience, previous abdominal surgery, medical history of diabetic nephropathy, serum albumin level, and renal function between the two groups. Conclusions: Male patients with high subcutaneous fat who are living alone might be at higher risk of PD-related peritonitis. These characteristics might be useful in risk assessment and patient education before PD induction.

Abstract Kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) is a light-gated channel used for optogenetic silencing of mammalian neurons. It selects K+ over Na+ in the absence of the canonical tetrameric K+ selectivity filter found universally in voltage- and ligand-gated channels. The genome of H. catenoides also encodes a highly homologous cation channelrhodopsin (HcCCR), a Na+ channel with >100-fold larger Na+ to K+ permeability ratio. Here, we use cryo-electron microscopy to determine atomic structures of these two channels embedded in peptidiscs to elucidate structural foundations of their dramatically different cation selectivity. Together with structure-guided mutagenesis, we show that K+ versus Na+ selectivity is determined at two distinct sites on the putative ion conduction pathway: in a patch of critical residues in the intracellular segment (Leu69/Phe69, Ile73/Ser73 and Asp116) and within a cluster of aromatic residues in the extracellular segment (primarily, Trp102 and Tyr222). The two filters are on the opposite sides of the photoactive site involved in channel gating.

IntroductionVirtual reality-based mirror therapy (VRMT) has recently attracted attention as a novel and promising approach for treating upper extremity dysfunction in patients with stroke. However, the clinical efficacy of VRMT has not been investigated.MethodsThis study aimed to conduct a meta-analysis to evaluate the effects of VRMT on upper extremity dysfunction in patients with stroke. We screened articles published between January 2010 and July 2022 in PubMed, Scopus, MEDLINE, and Cochrane Central Register of Controlled Trials. Our inclusion criteria focused on randomized controlled trials (RCTs) comparing VRMT groups with control groups (e.g., conventional mirror therapy, occupational therapy, physical therapy, or sham therapy). The outcome measures included the Fugl–Meyer assessment upper extremity test (FMA-UE), the box and block test (BBT), and the manual function test (MFT). Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool 2.0. We calculated the standardized mean differences (SMD) and 95% confidence intervals (95% CI). The experimental protocol was registered in the PROSPERO database (CRD42022345756).ResultsThis study included five RCTs with 148 stroke patients. The meta-analysis showed statistical differences in the results of FMA-UE [SMD = 0.81, 95% CI (0.52, 1.10), p

IntroductionConcerns regarding the ecological validity of movement-related cortical potential (MRCP) experimental tasks that are related to motor learning have recently been growing. Therefore, we compared MRCP during real movement task (RMT) and simulated movement task (SMT) from an ecological validity perspective.MethodsThe participants performed both RMT and SMT, and MRCP were measured using electroencephalogram (EEG). EEG was based on the 10-20 method, with electrodes placed in the motor cortex (C3 and C4) and supplementary motor cortex (FCz [between Fz and Cz] and Cz) areas. This experiment examined the MRCP using Bereitschaftspotential (BP) and negative slope (NS’) onset times, and BP, NS’, and motor potential (MP) amplitudes during the task.ResultsThe results revealed that the SMT exhibited later BP and NS’ onset times and smaller BP, NS’, and MP amplitudes than the RMT. Furthermore, in RMT, the onset time of MRCP was delayed, and the amplitude of MRCP was smaller in the second half of the 200 times task than in the first half, whereas in SMT, there was no change in onset time and amplitude. The SMT showed a different MRCP than the RMT, suggesting that the ecological validity of the task should be fully considered when investigating the cortical activity associated with motor skill learning using MRCP.ConclusionEcological validity of the study should be fully considered when investigating the cortical activity associated with motor skill learning using MRCP. Moreover, it is important to understand the differences between the two methods when applied clinically.

In this scoping review, we aimed to comprehensively clarify the methodology of Mental practice (MP) by systematically mapping studies documenting the application of MP to post-stroke paralytic upper-extremity function. Specifically, when is an MP intervention most commonly applied after stroke onset? What is the corresponding MP load (intervention time, number of intervention days, and intervention period)? What are the most common methods of Motor Imagery (MI) recall and MI tasks used during the application of MP? Is MP often used in conjunction with individual rehabilitation? What are the paralyzed side’s upper-limb and cognitive function levels at the start of an MP intervention? The research questions were identified according to PRISMA-ScR. The PubMed, Scopus, Medline, and Cochrane Library databases were used to screen articles published until 19 July 2022. In total, 694 English-language articles were identified, of which 61 were finally included. Most of the studies were conducted in the chronic phase after stroke onset, with limited interventions in the acute or subacute phase. The most common intervention time was ≤30 min and intervention frequency was 5 times/week in MP. An audio guide was most commonly used to recall MI during MP, and 50 studies examined the effects of MP in combination with individual rehabilitation. The Fugl-Meyer Assessment mean for the 38 studies, determined using the Fugl-Meyer Assessment, was 30.3 ± 11.5. Additional research with the aim of unifying the widely varying MP methodologies identified herein is warranted.

Approaches to preserve corticomotor excitability (CE) are attracting interest as a treatment for pain-induced changes in neural plasticity. We determined the effects of mirror therapy (MT) on skeletal muscle pain. Fifteen healthy adults who received hypertonic saline injections (5.8% NaCl, 0.2 mL) into the first dorsal interosseous (FDI) muscle of the right hand to induce experimental skeletal muscle pain were assigned to either the “MT and injection” or “injection only” group. Post-injection, the “MT and injection” group observed their left index finger abducting and adducting for 4 min, creating the illusion that the right index finger was moving. The “injection only” group remained at rest. CE and pain were assessed by measuring motor-evoked potentials (MEPs) of the right FDI triggered by transcranial magnetic stimulation and the numerical rating scale (NRS), respectively. MEP amplitudes were significantly higher in the “MT and injection” group, a trend that persisted post-MT intervention (MT intervention; p < 0.01, post-1; p < 0.05). The time for the NRS score to reach 0 was notably shorter in the “MT and injection” group (p < 0.05). Our preliminary results suggested that MT decreases CE and pain in skeletal muscles, potentially preventing neural plasticity changes associated with skeletal muscle pain and providing early pain relief.

Abstract Within the microbial rhodopsin family, heliorhodopsins (HeRs) form a phylogenetically distinct group of light-harvesting retinal proteins with largely unknown functions. We have determined the 1.97 Å resolution X-ray crystal structure of Thermoplasmatales archaeon SG8-52-1 heliorhodopsin (TaHeR) in the presence of NaCl under acidic conditions (pH 4.5), which complements the known 2.4 Å TaHeR structure acquired at pH 8.0. The low pH structure revealed that the hydrophilic Schiff base cavity (SBC) accommodates a chloride anion to stabilize the protonated retinal Schiff base when its primary counterion (Glu-108) is neutralized. Comparison of the two structures at different pH revealed conformational changes connecting the SBC and the extracellular loop linking helices A–B. We corroborated this intramolecular signaling transduction pathway with computational studies, which revealed allosteric network changes propagating from the perturbed SBC to the intracellular and extracellular space, suggesting TaHeR may function as a sensory rhodopsin. This intramolecular signaling mechanism may be conserved among HeRs, as similar changes were observed for HeR 48C12 between its pH 8.8 and pH 4.3 structures. We additionally performed DEER experiments, which suggests that TaHeR forms possible dimer-of-dimer associations which may be integral to its putative functionality as a light sensor in binding a transducer protein.

Evidence suggests that optimism has a positive impact on health status. Attentional bias modification (ABM) may be beneficial for enhancing optimism, but its effective application requires a detailed investigation of the association between attentional bias and optimism. This study aimed to determine the association between attentional bias and optimism based on different task types. Eighty-four participants completed the attentional bias measures using the dot-probe task (DPT), emotional visual search task (EVST) paradigms, and psychological assessments. Optimism was assessed using the Life Orientation Test-Revised with subscales for optimism and pessimism. Pearson’s correlation coefficient and multivariate linear regression analysis were applied to investigate the association between optimism and attentional bias. Neither the attentional bias derived from DPT nor EVST was significantly correlated with optimism total score or subscales. Regression analysis also showed no association between attentional bias and optimism (DPT, β = 0.12; EVST, β = 0.09), optimism subscales (DPT, β = 0.09; EVST, β = 0.17), or pessimism subscales (DPT, β = −0.10; EVST, β = 0.02). Our findings showed no evidence that attentional biases derived from either the DPT or EVST measures are associated with optimism or pessimism. Further studies are needed to effectively adapt the ABM to enhance optimism.

Continuous repetition of motor imagery leads to mental fatigue. This study aimed to examine whether fatigue caused by motor imagery training affects improvement in performance and the change in corticospinal excitability. The participants were divided into “physical practice training” and “motor imagery training” groups, and a visuomotor task (set at 50% of maximal voluntary contraction in participants) was performed to assess the training effect on fatigue. The measurements were recorded before and after training. Corticospinal excitability at rest was measured by transcranial magnetic stimulation according to the Neurophysiological Index. Subjective mental fatigue and muscle fatigue were assessed by using the visual analog scale and by measuring the pinch force, respectively. Additionally, the error area was evaluated and calculated at pre-, mid-, and post-terms after training, using a visuomotor task. After training, muscle fatigue, subjective mental fatigue, and decreased corticospinal excitability were noted in both of the groups. Moreover, the visuomotor task decreased the error area by training; however, there was no difference in the error area between the mid- and post-terms. In conclusion, motor imagery training resulted in central fatigue by continuous repetition, which influenced the improvement in performance in the same manner as physical practice training.