Compound Heterozygous Mutations of SACS in a Korean Cohort Study of Charcot-Marie-Tooth Disease Concurrent Cerebellar Ataxia and Spasticity.

Mutations in the SACS gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of Charcot-Marie-Tooth disease (CMT). This study aimed to identify SACS mutations in a Korean CMT cohort with cerebellar ataxia and spasticity by whole exome sequencing (WES). As a result, eight pathogenic SACS mutations in four families were identified as the underlying causes of these complex phenotypes. The prevalence of CMT families with SACS mutations was determined to be 0.3%. All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was performed in four patients and all had fatty replacements. Of note, they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without SACS mutations who had distal dominant fatty involvement. Therefore, these findings were considered a characteristic feature in CMT patients with SACS mutations. Although further studies with more cases are needed, our results highlight lower extremity MRI findings in CMT patients with SACS mutations and broaden the clinical spectrum. We suggest screening for SACS in recessive CMT patients with complex phenotypes of ataxia and spasticity.

Design, synthesis, and evaluation of N1,N3-dialkyldioxonaphthoimidazoliums as antibacterial agents against methicillin-resistant Staphylococcus aureus.

Increasing antibiotic resistance of bacterial pathogens poses a serious threat to human health worldwide. Methicillin-resistant Staphylococcus aureus (MRSA) is among the most deleterious bacterial pathogens owing to its multidrug resistance, necessitating the development of new antibacterial agents against it. We previously identified a novel dioxonaphthoimidazolium agent, c5, with moderate antibacterial activity against MRSA from an anticancer clinical candidate, YM155. In this study, we aimed to design and synthesize several novel cationic amphiphilic N1,N3-dialkyldioxonaphthoimidazolium bromides with enhanced lipophilicity of the two side chains in the imidazolium scaffold and improved antibacterial activities compared to those of c5 against gram-positive bacteria in vitro and in vivo. Our new antibacterial lead, N1,N3-n-octylbenzyldioxonaphthoimidazolium bromide (11), exhibited highly potent antibacterial activities against various gram-positive bacterial strains (MICs: 0.19-0.39 µg/mL), including MRSA, methicillin-sensitive S. aureus, and Bacillus subtilis. Moreover, antibacterial mechanism of 11 against MRSA based on the generation of reactive oxygen species (ROS) was evaluated. Although compound 11 exhibited cytotoxic effects in vitro and lacked a therapeutic index against the HEK293 and HDFa mammalian cell lines, it exhibited low toxicity in the Drosophila animal model. Remarkably, 11 exhibited better in vivo antibacterial efficacy than c5 and the clinically used antibiotic, vancomycin, in SA3-infected Drosophila model. Moreover, the development of bacterial resistance to 11 was not observed after 16 consecutive passages. Therefore, rational design of antibacterial cationic amphiphiles based on ROS-generating pharmacophores with optimized lipophilicity can facilitate the identification of potent antibacterial agents against drug-resistant infections.

Ultrasound and CT findings of subcutaneous metastases in trunk and pelvis: a comprehensive analysis.

OBJECTIVE: This study aimed to describe the ultrasound, CT findings, and clinical manifestations of pathologically confirmed metastases involving the subcutaneous fat layer of the trunk and pelvis. MATERIALS AND METHODS: We included 30 patients with subcutaneous metastases in the trunk and pelvis, verified by ultrasound-guided biopsy. We comprehensively reviewed ultrasound findings of all 30 patients and contrast-enhanced CT findings of 25 patients obtained before biopsy. Medical records were reviewed, including primary malignancy type, presence of coexisting distant metastasis, and detection method leading to biopsy referral. RESULTS: Most subcutaneous metastases were heterogeneously hypoechoic (86.7%) with well-defined margins (80.0%), lobulated (46.7%) or round-to-oval (40.0%) shape, and vascularity (96.7%). Metastases frequently exhibited no contact (53.3%) or focal contact with deep peripheral fascia, resulting in acute contact angle formation (30.0%). Common CT manifestations included central low attenuation with peripheral rim-like enhancement (60.0%) or well-circumscribed lesion with heterogeneous enhancement (32.0%). Lung cancer (46.7%) was the prevalent primary malignancy. CT was the predominant detection method (56.7%). Coexisting subcutaneous metastases were present in 50.0% of cases, and distant metastases (less subcutaneous metastases) were observed in 90.0% of patients. CONCLUSION: This study describes typical imaging findings of subcutaneous metastases involving the trunk and pelvis. CT may play a crucial role in their early detection, and our results may assist radiologists in their diagnosis.

Hemodialysis Efficiency Predictor in End-Stage Kidney Disease Using Real-Time Heart Rate Variability.

BACKGROUND: Autonomic dysfunction as a long-term complication may occur in end-stage kidney disease (ESKD) patients and can be diagnosed using heart rate variability (HRV) analyzed from electrocardiogram (ECG) recordings. There is limited data about HRV using real-time ECG to predict hemodialysis (HD) efficiency in patients with ESKD who are routinely doing HD in the real world. METHODS: A total of 50 patients (62.1 ± 10.7 years) with ESKD underwent continuous real-time ECG monitoring (237.4 ± 15.3 min) during HD for HRV using remote monitoring system. Their electrolyte levels were checked before and after HD. We compared HRV according to electrolyte levels. RESULTS: During the monitor, we checked the ECG and electrolyte levels simultaneously a total of 2374 times for all of the patients. Both time and frequency domain HRV were higher when the patients had lower K+ level (<0.5 mEq/L) and P+ level change (<2 mEq/L) before and after HD as compared to those with a higher K+ level (≥0.5 mEq/L) and P+ level change (≥2 mEq/L). Additionally, patients with lower K+ and P+ level change groups had higher incidences of arrhythmic events including atrial/ventricular premature complexes, despite no difference of mean heart rate (p < 0.001). CONCLUSIONS: Higher HRV was independently associated with a poorly controlled K+ and P+ level during HD in patients with ESKD. This is consistently evidenced by the independent association between higher HRV, K+ and P+ levels in real time, suggesting that low electrolyte changes before and after HD alone may cause cardiac autonomic dysfunction.

Identification of novel Nrf2-activating neuroprotective agents: Elucidation of structural congeners of (-)-galiellalactone and congener-based novel Nrf2 activators.

Herein, (-)-galiellalactone 1 congeners responsible for the nuclear factor erythroid 2-related factor 2 (Nrf2)-activating neuroprotective effects were elucidated. Additionally, novel congener-based Nrf2 activators were identified using a drug repositioning strategy. (-)-Galiellalactone, which comprises a tricyclic lactone skeleton, significantly activates antioxidant response element (ARE)-mediated transcription in neuroblastoma SH-SY5Y cells. Interestingly, two cyclohexene-truncated [3.3] bicyclic lactone analogs, which possess an exocyclic α-methylene-γ-butyrolactone moiety, exhibited higher Nrf2/ARE transcriptional activities than the parent (-)-galiellalactone. We confirmed that the cyclohexene moiety embedding the [3.3] bicyclic lactone congener does not play the essential role of (-)-galiellalactone for Nrf2/ARE activation. Nrf2/ARE activation by novel analogs resulted in the upregulation of downstream antioxidative and phase II detoxifying enzymes, heme oxygenase-1, and NAD(P)H quinone oxidoreductase 1, which are closely related to the cytoprotective effects on neurodegenerative diseases. (-)-Galiellalactone and its [3.3] bicyclic variants 3l and 3p increased the expression of antioxidant genes and exhibited neuroprotective effects against 6-hydroxydopamine-mediated neurotoxicity in the neuroblastoma SH-SY5Y cell line.

Recovery of spatial frequencies in coherent diffraction imaging in the presence of a central obscuration.

Coherent diffraction imaging (CDI) and its scanning version, ptychography, are lensless imaging approaches used to iteratively retrieve a sample's complex scattering amplitude from its measured diffraction patterns. These imaging methods are most useful in extreme ultraviolet (EUV) and X-ray regions of the electromagnetic spectrum, where efficient imaging optics are difficult to manufacture. CDI relies on high signal-to-noise ratio diffraction data to recover the phase, but increasing the flux can cause saturation effects on the detector. A conventional solution to this problem is to place a beam stop in front of the detector. The pixel masking method is a common solution to the problem of missing frequencies due to a beam stop. This paper describes the information redundancy in the recorded data set and expands on how the reconstruction algorithm can exploit this redundancy to estimate the missing frequencies. Thereafter, we modify the size of the beam stop in experimental and simulation data to assess the impact of the missing frequencies, investigate the extent to which the lost portion of the diffraction spectrum can be recovered, and quantify the effect of the beam stop on the image quality. The experimental findings and simulations conducted for EUV imaging demonstrate that when using a beam stop, the numerical aperture of the condenser is a crucial factor in the recovery of lost frequencies. Our thorough investigation of the reconstructed images provides information on the overall quality of reconstruction and highlights the vulnerable frequencies if the beam stop size is larger than the extent of the illumination NA. The outcome of this study can be applied to other sources of frequency loss, and it will contribute to the improvement of experiments and reconstruction algorithms in CDI.

Development of a novel prediction model for differential diagnosis between spinal myxopapillary ependymoma and schwannoma.

Spinal myxopapillary ependymoma (MPE) and schwannoma represent clinically distinct intradural extramedullary tumors, albeit with shared and overlapping magnetic resonance imaging (MRI) characteristics. We aimed to identify significant MRI features that can differentiate between MPE and schwannoma and develop a novel prediction model using these features. In this study, 77 patients with MPE (n = 24) or schwannoma (n = 53) who underwent preoperative MRI and surgical removal between January 2012 and December 2022 were included. MRI features, including intratumoral T2 dark signals, subarachnoid hemorrhage (SAH), leptomeningeal seeding, and enhancement patterns, were analyzed. Logistic regression analysis was conducted to distinguish between MPE and schwannomas based on MRI parameters, and a prediction model was developed using significant MRI parameters. The model was validated internally using a stratified tenfold cross-validation. The area under the curve (AUC) was calculated based on the receiver operating characteristic curve analysis. MPEs had a significantly larger mean size (p = 0.0035), higher frequency of intratumoral T2 dark signals (p = 0.0021), associated SAH (p = 0.0377), and leptomeningeal seeding (p = 0.0377). Focal and diffuse heterogeneous enhancement patterns were significantly more common in MPEs (p = 0.0049 and 0.0038, respectively). Multivariable analyses showed that intratumoral T2 dark signal (p = 0.0439) and focal (p = 0.0029) and diffuse enhancement patterns (p = 0.0398) were independent factors. The prediction model showed an AUC of 0.9204 (95% CI 0.8532-0.9876) and the average AUC for internal validation was 0.9210 (95% CI 0.9160-0.9270). MRI provides useful data for differentiating spinal MPEs from schwannomas. The prediction model developed based on the MRI features demonstrated excellent discriminatory performance.

Correlation of body composition metrics with bone mineral density and computed tomography-based trabecular attenuation.

PURPOSE: To investigate the relationship of body composition metrics with bone mineral density (BMD) and trabecular attenuation in a cohort of healthy individuals. METHODS: We retrospectively analyzed data of consecutively evaluated individuals who underwent dual-energy X-ray absorptiometry (DXA) and abdominopelvic computed tomography (CT) on the same day during routine medical check-ups between January 2021 and December 2021. Trabecular attenuation was measured at L1 level, while body composition metrics, including skeletal muscle index (SMI), skeletal muscle attenuation (SMA), visceral fat index (VFI), and subcutaneous fat index (SFI), were measured at L3 level. The association of body composition metrics with BMD and trabecular attenuation was analyzed using partial correlation analysis. RESULTS: A total of 634 patients (median age, 56 years; range 50-62 years; 392 men) were included. In men, the SMI and SMA were positively correlated with BMD and trabecular attenuation, both before (r, 0.157-0.344; p < 0.05) and after (r, 0.103-0.246; p < 0.05) adjusting for age and body mass index. The VFI showed negative correlations with trabecular attenuation in both men (r, -0.170; p = 0.001) and women (r, -0.394; p < 0.001), which remained significant after adjusting for age and body mass index (r, -0.181 to -0.122; p < 0.05). CONCLUSION: Low skeletal muscle mass and attenuation were significantly correlated with low BMD and trabecular attenuation in men. Visceral adiposity was associated with reduced BMD and trabecular attenuation in both men and women, demonstrating a stronger correlation with trabecular attenuation.

Factors Used by Mobile Applications to Predict Female Fertility Status and Their Reported Effectiveness: A Scoping Review.

Family planning, whether for pregnancy prevention or conception, is of pivotal importance to women of reproductive age. As hormonally driven methods, such as oral contraceptive pills, are widely used but have numerous side effects, women often seek alternative non-hormonal, non-invasive options, including fertility-tracking mobile applications (apps). However, the effectiveness of these apps as a method of contraception and conception planning has not been extensively vetted. The goal of this scoping review is to identify the various factors used by apps marketed as a method of contraception and/or family planning to predict a woman's fertility status, as well as their documented effectiveness. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines, a literature search was performed in CINAHL, MEDLINE, and Alt HealthWatch databases for articles published between October 1, 2017, and October 4, 2022. Quality assessment of eligible full-text articles was conducted using the Joanna Briggs Institute critical appraisal tools. A total of 629 articles were screened. Overall, 596 articles were excluded and the remaining 33 articles underwent full-text review. Seven articles were included in the final analysis, yielding data on the following five apps: Natural Cycles, Ava Fertility, Clearblue Connected, Ovia Fertility, and Dynamic Optimal Timing (DOT). Data supporting the effectiveness of these apps is limited. All apps provided predictions on fertility status throughout a woman's menstrual cycle using proprietary algorithms, biometric data, and self-reported menstrual cycle data. Further research, particularly independent research following a randomized controlled design, on the efficacy of these apps is needed to produce more robust results.

Real-time heart rate variability according to ambulatory glucose profile in patients with diabetes mellitus.

Background: Autonomic neuropathy commonly occurs as a long-term complication of diabetes mellitus (DM) and can be diagnosed based on heart rate variability (HRV), calculated from electrocardiogram (ECG) recordings. There are limited data on HRV using real-time ECG and ambulatory glucose monitoring in patients with DM. The aim of this study was to investigate real-time HRV according to ambulatory glucose levels in patients with DM. Methods: A total of 43 patients (66.3 ± 7.5 years) with DM underwent continuous real-time ECG monitoring (225.7 ± 107.3 h) for HRV and ambulatory glucose monitoring using a remote monitoring system. We compared the HRV according to the ambulatory glucose profile. Data were analyzed according to the target in glucose range (TIR). Results: There were no significant differences in the baseline characteristics of the patients according to the TIR. During monitoring, we checked ECG and ambulatory glucose levels (a total of 15,090 times) simultaneously for all patients. Both time- and frequency-domain HRVs were lower when the patients had poorly controlled glucose levels (TIR < 70%) compared with well controlled glucose levels (TIR > 70%). In addition, heart and respiratory rates increased with real-time glucose levels (P < 0.001). Conclusions: Poorly controlled glucose levels were independently associated with lower HRV in patients with DM. This was further substantiated by the independent continuous association between real-time measurements of hyperglycemia and lower HRV. These data strongly suggest that cardiac autonomic dysfunction is caused by elevated blood sugar levels.

Prognostic significance of body mass index in small-cell lung cancer: Exploring the relationship with skeletal muscle status.

BACKGROUND: We investigated the prognostic significance of body mass index in small-cell lung cancer and explored whether skeletal muscle status affects the body mass index-survival relationship. METHODS: This retrospective study evaluated data from patients who underwent platinum-etoposide chemotherapy for small-cell lung cancer between March 2010 and December 2021. Skeletal muscle status was assessed using non-contrast computed tomography images of baseline positron-emission tomography-computed tomography, with the skeletal muscle index defined as the cross-sectional area of skeletal muscle divided by height squared, and the average attenuation values of skeletal muscle. Cox proportional hazards regression analysis was used to determine the correlations of body mass index, skeletal muscle metrics, and overall survival. RESULTS: We analysed the data of 1146 Asian patients (1006 men and 140 women, with a median age of 67 years [interquartile range: 61-72 years]), including 507 and 639 patients with limited and extensive disease, respectively. Being underweight, defined as a body mass index <18.5 kg/m2 , was associated with shorter overall survival, independent of clinical covariates in both the limited-disease (hazard ratio, 1.77; 95% confidence interval, 1.01-3.09) and extensive-disease (hazard ratio, 1.71; 95% confidence interval, 1.18-2.48) groups. The prognostic value of being underweight remained significant after additional adjustment for skeletal muscle index and attenuation in both limited-disease (hazard ratio, 1.96; 95% confidence interval, 1.09-3.51) and extensive-disease (hazard ratio, 1.75; 95% confidence interval, 1.17-2.61) groups. CONCLUSIONS: Being underweight is an independent poor prognostic factor for shorter overall survival in Asian patients with small-cell lung cancer, regardless of skeletal muscle status.

Effects of the beta-blocker carvedilol on arrhythmia and long-term clinical outcomes in benign prostate hypertrophy patients.

Benign prostatic hypertrophy (BPH) is associated with autonomic dysfunction and sympathetic nervous system mediated by the alpha receptor. However, limited data exist regarding the effects of the beta-blocker (BB) carvedilol on arrhythmia and urologic outcomes in BPH patients. Our database of patients diagnosed with BPH from 2015 to 2020 was used to obtain echocardiography and electrocardiogram data. Inclusion criteria were BPH patients taking BBs. International Prostate Symptom Score questionnaire were used to evaluate the urinary symptoms and quality of life. Among 448 patients with BPH (69.2 ± 10.9 years) taking BBs, 219 patients took carvedilol (48.9%) and 229 patients took a non-carvedilol BB (51.1%; bisoprolol, 184 patients, 80% or nebivolol, 45 patients, 20%). Difference in the baseline characteristics was not observed. During the median 36-month follow-up, a lower incidence of arrhythmic events (P = .029), total urologic events (P < .001), and less use of additive alpha-blocker was observed in the carvedilol group (P = .022). In multivariate analysis, less carvedilol use (P = .019), heart failure (P < .001), stroke (P < .001), and cardiomyopathy (P = .046) were independent risk factors for arrhythmic events. In addition, less carvedilol use (P = .009) and older age (P = .005) were independent risk factors for urologic events based on BB type at the median 36-month follow-up. The use of carvedilol was associated with less arrhythmic events in BPH patients with palpitation and decreased the incidence of urologic events in BPH compared with the use of non-carvedilol BBs in long-term follow-up.

Lactic Acid Bacteria Isolated from Human Breast Milk Improve Colitis Induced by 2,4,6-Trinitrobenzene Sulfonic Acid by Inhibiting NF-κB Signaling in Mice.

Inflammatory bowel disease (IBD), a chronic inflammatory disease, results from dysregulation of the immune responses. Some lactic acid bacteria (LAB), including Lactobacillus, alleviate IBD through immunomodulation. In this study, the anti-colitis effect of LAB isolated from human breast milk was investigated in a mouse model induced acute colitis with 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS remarkably increased weight loss, colon shortening, and colonic mucosal proliferation, as well as the expression levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1ß. Oral administration of LAB isolated from human breast milk resulted in a reduction in TNBS-induced colon shortening, as well as induced cyclooxygenase (COX)-2, nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB). In addition, LAB suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1ß, and thus showed an effect of suppressing the level of inflammation induced by TNBS. Furthermore, LAB alleviated gut microbiota dysbiosis, and inhibited intestinal permeability by increasing the expression of intestinal tight junction protein including ZO-1. Collectively, these results suggest that LAB isolated from human breast milk can be used as a functional food for colitis treatment by regulating NF-κB signaling, gut microbiota and increasing expression of intestinal tight junction protein.

Temporal synchronization between two Q switched pulses in a 1 × 2 array distribution inside a single YAG/Yb:YAG/Cr:YAG laser resonator.

We propose for the first time, to the best of our knowledge, a coupling method of modes guided by gain waveguides to synchronize two Q switched pulses oscillating in a 1 × 2 array distribution inside a single YAG/Yb:YAG/Cr:YAG resonator. To analyze the temporal synchronization of spatially separated Q switched pulses, the buildup time interval, spatial distribution, and longitudinal modes distribution of the two pulse beams are investigated.

Association Between Pelvic Bone Computed Tomography-Derived Body Composition and Patient Outcomes in Older Adults With Proximal Femur Fracture.

OBJECTIVE: To investigate the association between pelvic bone computed tomography (CT)-derived body composition and patient outcomes in older adult patients who underwent surgery for proximal femur fractures. MATERIALS AND METHODS: We retrospectively identified consecutive patients aged ≥ 65 years who underwent pelvic bone CT and subsequent surgery for proximal femur fractures between July 2018 and September 2021. Eight CT metrics were calculated from the cross-sectional area and attenuation of the subcutaneous fat and muscle, including the thigh subcutaneous fat (TSF) index, TSF attenuation, thigh muscle (TM) index, TM attenuation, gluteus maximus (GM) index, GM attenuation, gluteus medius and minimus (Gmm) index, and Gmm attenuation. The patients were dichotomized using the median value of each metric. Multivariable Cox regression and logistic regression models were used to determine the association between CT metrics with overall survival (OS) and postsurgical intensive care unit (ICU) admission, respectively. RESULTS: A total of 372 patients (median age, 80.5 years; interquartile range, 76.0-85.0 years; 285 females) were included. TSF attenuation above the median (adjusted hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.41-4.05), GM index below the median (adjusted HR, 2.63; 95% CI, 1.33-5.26), and Gmm index below the median (adjusted HR, 2.33; 95% CI, 1.12-4.55) were independently associated with shorter OS. TSF index (adjusted odds ratio [OR], 6.67; 95% CI, 3.13-14.29), GM index (adjusted OR, 3.45; 95% CI, 1.49-7.69), GM attenuation (adjusted OR, 2.33; 95% CI, 1.02-5.56), Gmm index (adjusted OR, 2.70; 95% CI, 1.22-5.88), and Gmm attenuation (adjusted OR, 2.22; 95% CI, 1.01-5.00) below the median were independently associated with ICU admission. CONCLUSION: In older adult patients who underwent surgery for proximal femur fracture, low muscle indices of the GM and gluteus medius/minimus obtained from their cross-sectional areas on preoperative pelvic bone CT were significant prognostic markers for predicting high mortality and postsurgical ICU admission.

Structural Congeners of Izenamides Responsible for Cathepsin D Inhibition: Insights from Synthesis-Derived Elucidation.

This study aimed to elucidate the structural congeners of natural izenamides A, B, and C (1-3) responsible for cathepsin D (CTSD) inhibition. Structurally modified izenamides were synthesized and biologically evaluated, and their biologically important core structures were identified. We confirmed that the natural statine (Sta) unit (3S,4S)-γ-amino-ß-hydroxy acid is a requisite core structure of izenamides for inhibition of CTSD, which is closely related to the pathophysiological roles in numerous human diseases. Interestingly, the statine-incorporated izenamide C variant (7) and 18-epi-izenamide B variant (8) exhibited more potent CTSD-inhibitory activities than natural izenamides.

Chemical Glycosylation with p-Methoxyphenyl (PMP) Glycosides via Oxidative Activation.

A novel persulfate-mediated oxidative glycosylation system using p-methoxyphenyl (PMP) glycosides as bench-stable glycosyl donors is developed. This study shows that both K2S2O8 as an oxidant and Hf(OTf)4 as a Lewis acid catalyst play important roles in the oxidative activation of the PMP group into a potential leaving group. This convenient glycosylation protocol proceeds under mild conditions and delivers a wide range of biologically and synthetically valuable glycoconjugates, including glycosyl fluorides.

Effects of Empagliflozin on Diuretics Reduction in Outpatient Heart Failure Patients.

Background and Objectives: Inhibitors of sodium-glucose cotransporter 2 (SGLT2i) reduce the risk of hospitalization for heart failure (HF). We aimed to examine the effect of empagliflozin on change of diuretics dose in outpatient HF patients. Methods: We retrospectively reviewed the medical records of 612 patients who were treated using both empagliflozin and diuretics. We excluded patients who did not meet the criteria for HF. Dose and duration of empagliflozin and diuretics were measured. Results: Of 612 patients, a total of 251 was analyzed and followed for a mean 430.0±175.4 days. The mean age was 69.3, 51.8% were female, and 93.2% had type 2 diabetes. The distribution of initial diuretics type when starting empagliflozin showed that furosemide comprised 24.7%, spironolactone 20.7%, thiazide 36.9%, and others. Total 23.1% of patients reduced diuretic dose, 13.1% increased diuretic dose, 41.4% continued at the same diuretic dose, and 22.3% switched to different diuretics. Among patients who were using furosemide, 36.0% reduced diuretics dose. There was a diuretic reduction in 22.6% of HF preserved ejection fraction (HFpEF, left ventricular ejection fraction [LVEF] ≥50%) and in 26.5% of HF reduced EF (HFrEF, LVEF <50%). The average doses furosemide at the start of empagliflozin decreased from 16.3mg/day to 8.5mg/day at the time of follow-up. Conclusions: Among outpatient clinic HF patients treated with both diuretics and empagliflozin, 23.1% of patients had their diuretics reduced, and the mean dose of furosemide was reduced by about half. This suggests that empagliflozin has clinical advantages in managing outpatient HF patients.

Magnetic resonance imaging-based lower limb muscle evaluation in Charcot-Marie-Tooth disease type 1A patients and its correlation with clinical data.

We aimed to derive comprehensive MRI parameters that reflect intramuscular fat infiltration severity for designated lower extremity levels, based on semiquantitative analyses in Charcot-Marie-Tooth disease type 1A (CMT1A) patients. We reviewed lower extremity MRIs of 116 CMT1A patients. Intramuscular fat infiltration grading using the Mercuri scale was performed for the non-dominant lower extremity at three levels (proximal, mid, and distal) for the thigh and at two levels (proximal and distal) for the lower leg. Based on MRI results, the following parameters were calculated for each level and for entire muscles: fat infiltration proportion (FIP), significant fat infiltration proportion (SigFIP), and severe fat infiltration proportion (SevFIP). The relationships between the MRI parameters and clinical data were evaluated using Spearman's correlation analysis. FIP, SigFIP, and SevFIP measured for entire muscles significantly correlated with Charcot-Marie-Tooth Neuropathy Score (p < 0.001), functional disability scale (p < 0.001), 10-m walk test time (p = 0.0003, 0.0010, and 0.0011), and disease duration (p < 0.001). Similar correlations were demonstrated for FIP, SigFIP, and SevFIP acquired from the lower leg. Our MRI parameters obtained through semiquantitative analyses of muscles significantly correlated with clinical parameters in CMT1A patients, suggesting their potential applicability as imaging markers for clinical severity.

Synthesis of 7,2'-Dihydroxy-4',5'-Dimethoxyisoflavanone, a Phytoestrogen with Derma Papilla Cell Proliferative Activity.

This paper reports a concise and scalable method for the synthesis of the phytoestrogen 7,2'-dihydroxy-4',5'-dimethoxyisoflavanone 1 via an optimized synthetic route. Compound 1 was readily obtained in 11 steps and 11% overall yield on a gram scale from commercially available 3,4-dimethoxyphenol. The key features of the synthesis include the construction of the deoxybenzoin unit through a sequence of Claisen rearrangement, oxidative cleavage, and aryllithium addition and the efficient synthesis of the isoflavanone architecture from highly functionalized 2-hydroxyketone.