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Riad Taher,1 Jaskanwal D Sara,1 Behnam Heidari,1 Takumi Toya,1 Lilach O Lerman,2 Amir Lerman11Division of Cardiovascular Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; 2Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USAPurpose: Metabolic syndrome (MetS) and peripheral endothelial dysfunction (PED) are both independently associated with an increased risk of cardiovascular disease (CVD). PED provides prognostic information beyond that provided by conventional risk factors. However, the association between MetS and PED remains uncertain. We evaluated the association between MetS and PED.Patients and methods: We performed a retrospective analysis of patients who were referred to Mayo Clinic between 2006 and 2014 for evaluation of chest pain and/or an assessment of CVD risk that included an assessment of PED measured with reactive hyperemia peripheral arterial tonometry. MetS was defined as the presence of at least 3 of the following: body mass index≥25 kg/m,2 impaired fasting glucose or diabetes, high blood pressure or hypertension, hypertriglyceridemia, or low high-density lipoprotein cholesterol.Results: Six hundred seventy-eight patients were included (mean age 51.9±13.5 years, 418 (61.6%) women), of which 293 (43.2%) had PED, and 249 (36.7%) had MetS. In multivariable analyses adjusted for age, sex, CVD, smoking status, and elevated low-density lipoprotein, MetS was significantly associated with PED (Odds Ratio (OR) 2.06; P=0.0090). Of the individual MetS components, only being overweight and MetS range high-density lipoprotein had a similar association. After stratifying by sex, the association between MetS and PED persisted only in men (OR 3.16, P=0.0094).Conclusions: MetS is associated with PED in men undergoing an assessment of chest pain and/or CVD risk. Identifying PED in individuals with MetS could provide an abridged assessment of risk, potentially allowing for earlier and more intensive management of risk factors.Keywords: metabolic syndrome, peripheral endothelial dysfunction, reactive hyperemia peripheral arterial tonometry, cardiovascular disease

Background: Chronic pain is common and challenging to treat. Although cognitive behavioral therapy (CBT) is efficacious, its benefit in disadvantaged populations is largely unknown.Objective: To evaluate the efficacy of literacy-adapted and simplified group CBT versus group pain education (EDU) versus usual care.Design: Randomized controlled trial. (ClinicalTrials.gov: NCT01967342).Setting: Community health centers serving low-income patients in Alabama.Patients: Adults (aged 19 to 71 years) with mixed chronic pain.Interventions: CBT and EDU delivered in 10 weekly 90-minute group sessions.Measurements: Self-reported, postintervention pain intensity (primary outcome) and physical function and depression (secondary outcomes).Results: 290 participants were enrolled (70.7% of whom were women, 66.9% minority group members, 72.4% at or below the poverty level, and 35.8% reading below the fifth grade level); 241 (83.1%) participated in posttreatment assessments. Linear mixed models included all randomly assigned participants. Members of the CBT and EDU groups had larger decreases in pain intensity scores between baseline and posttreatment than participants receiving usual care (estimated differences in change scores-CBT: -0.80 [95% CI -1.48 to -0.11]; P = 0.022; EDU: -0.57 [CI, -1.04 to -0.10]; P = 0.018). At 6-month follow-up, treatment gains were not maintained in the CBT group but were still present in the EDU group. With regard to physical function, participants in the CBT and EDU interventions had greater posttreatment improvement than those receiving usual care, and this progress was maintained at 6-month follow-up. Changes in depression (secondary outcome) did not differ between either the CBT or EDU group and the usual care group.Limitations: Participants represented a single health care system. Self-selection bias may have been present.Conclusion: Simplified group CBT and EDU interventions delivered at low-income clinics significantly improved pain and physical function compared with usual care.Primary Funding Source: Patient-Centered Outcomes Research Institute. [ABSTRACT FROM AUTHOR]

Currently, personal mobility vehicles (PMVs) are attracting attention as intermediate- or short-range transportation. Bicycles are familiar PMVs that are also environmentally friendly and convenient. A small-wheel bicycle saves space and is easy to carry. However, a small-wheel bicycle running at low speed has poor upright stability and maneuverability. The purpose of this study is to improve its running stability by adopting a steer-by-wire system, which independently operates the steering gear and the tire. Sensors obtain the handle angle and actuators, instead of force from a mechanical connection, change the steering wheel angle. In this study, we carried out two experiments. First, we carried out straight running experiments to confirm the steering accuracy, upright stability, and maneuverability on a straight course. Second, we carried out turning experiments to confirm the upright stability and maneuverability on a course requiring changes in driving direction. It was confirmed that the proposed mechanism enhanced the upright stability compared with that of a conventional small-wheel bicycle. However, the maneuverability evaluations by the drivers showed that a conventional small wheel bicycle was better than the proposed steer-by-wire bicycle. The delay of motor control and the moment of inertia of the gearing might be the causes of this performance issue.

Human mesenchymal stem cells (hMSC) expressing paracrine factors may enhance therapeutic benefits when transplanted. Here, the authors show that hMSCs stably expressing prostacyclin enhance host regeneration and muscle mass gain in a mouse hindlimb ischaemia model, mediated by the long noncoding RNA H19.

The impact of letermovir (LTV)-an anti-cytomegalovirus (CMV) drug-on human herpesvirus-6 (HHV-6) encephalitis is unclear. We hypothesized that LTV prophylaxis may increase the incidence of HHV-6 encephalitis by reducing anti-CMV therapies after allogeneic hematopoietic stem cell transplantation (HSCT). To evaluate the association between HHV-6 encephalitis and antiviral prophylaxis, 7985 adult patients from a nationwide registry who underwent their first HSCT between January 2019 and December 2021 were analyzed. The incidence of HHV-6 encephalitis on day 100 after HSCT was 3.6%; 11.5% for the broad-spectrum antiviral group (foscarnet, ganciclovir, or valganciclovir); 2.8% for the LTV group, and 3.8% for the other antiviral group (p < 0.001). These differences persisted when cord blood transplantation (CBT) was analyzed separately (14.1%, 5.9%, and 7.4%, p < 0.001). In the multivariate analysis, CBT (hazard ratio [HR]: 2.90), broad-spectrum antiviral prophylaxis (HR: 1.91), and grade II-IV acute graft-versus-host disease requiring systemic corticosteroids (HR: 2.42) were independent risk factors for encephalitis (all p < 0.001). The findings of this large modern database study indicate that broad-spectrum antiviral prophylaxis, rather than LTV prophylaxis, is paradoxically associated with HHV-6 encephalitis in the LTV era. This paradoxical finding needs to be further explored in future studies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Previously, our institution measured peripheral blood CD34 cell counts both pre- and post-peripheral blood stem cell harvest (PBSCH), with both samples analyzed simultaneously post-PBSCH. Since 2021, we have measured pre-CD34 cell counts during PBSCH, adjusting the processed blood volume based on these results. We retrospectively evaluated how this change impacted cellular therapy., Methods: Related healthy donors were included and divided into 1-day and 2-day harvest cohorts. Donors with CD34 cell counts measured post- and during PBSCH were categorized into the previous and current sub-cohorts, respectively., Results: Regarding the 1-day cohort (n = 212), the current sub-cohort had a significantly shorter average harvest duration (151 [standard deviation, SD = 45.1] vs. 180 [SD = 27.8] minutes, respectively) and higher average infusion rates (87.6% [SD = 21.1] vs. 78.1% [SD = 25.7], respectively) than the previous sub-cohort., Conclusion: Adjusting the processed blood volume based on pre-PBSCH CD34 cell counts measured during the harvest may reduce donor burden and enhance workflow efficiency., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

Herein we report that readily available 4-alkenylisocoumarins can be regarded as potent dienolate equivalents. For example, lactol silyl ethers derived from 4-alkenylisocoumarins were selectively converted to the corresponding benzo-homophthalates through a fluoride-induced ring opening step that was followed by a ring closure through a vinylogous intramolecular aldol condensation. Likewise, nucleophilic activation of 4-alkenylisocoumarins directly yields diversely poly-substituted naphthalenes and anthracenes without formation of any regioisomer. Photophysical evaluation of a set of thus obtained 1,3-di- and 1,3,4-trisubstituted anthracenes reveals their distinct intramolecular charge transfer (ICT) character during light absorption in polar solutions and excimer emission from the solid state when a face-to-face π-stacked molecular assembly is present in the crystal packing., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Despite the benefits of pre-exposure prophylaxis (PrEP) in preventing HIV and its potential for reducing racial/ethnic HIV inequities, PrEP remains underutilized among African Americans who may benefit from it. Factors of PrEP uptake include awareness and acceptability of this prevention strategy among this group, yet few community-informed interventions have been developed and evaluated to address these challenges. Thus, this study evaluates the effectiveness of a community-informed, six-month multimedia campaign (print, digital media, internet radio, social media) for African American young adults (age 18-29) in Louisville, Kentucky to increase PrEP awareness and PrEP use intentions. Pretest surveys, posttest surveys, and digital analytic metrics were used to determine campaign effectiveness. Logistic regressions indicate increased PrEP awareness over time ( p  ≤ 0.0001) and greater PrEP intention among participants reporting greater campaign affinity ( p  ≤ 0.05). Campaign digital analytic performance was similar to or exceeded that of industry competitors (e.g., healthcare organizations). Findings indicate that a community-informed multimedia campaign increased PrEP use intentions among those exhibiting greater campaign affinity (the extent to which participants report a favorable view of the campaign) and demonstrated similar or greater effectiveness in digital elements as industry competitors at a cost-effective price. Future studies should incorporate community-engaged approaches in developing health communication products for greater PrEP acceptability and efficiency. Trial registration: ClinicalTrials.gov identifier: NCT0355959.

Disease recurrence remains the principal cause of treatment failure after allogeneic hematopoietic stem cell transplantation. Post-transplant maintenance therapy with azacitidine (AZA) is promising to prevent relapse but the outcomes are unsatisfactory in patients at high risk of recurrence. Herein, we evaluated the outcome in patients who received AZA and gemtuzumab ozogamicin (GO), anti-CD33 antibody-calicheamicin conjugate, as post-transplant maintenance therapy. Twenty-eight patients with high-risk hematologic malignancies harboring CD33-positive leukemic blasts received the maintenance therapy. AZA (30 mg/m 2 ) was administered for 7 days, followed by GO (3 mg/m 2 ) on day 8. The maximum number of cycles was 4. At transplant, 21 patients (75.0%) had active disease. Their 2-year overall survival, disease-free survival, relapse, and non-relapse mortality rates were 53.6%, 39.3%, 50.0%, and 10.7%, respectively. Of these patients, those with minimal residual disease at the start of maintenance therapy (n = 9) had a higher recurrence rate (66.7% vs. 42.1% at 2 years, P = 0.069) and shorter disease-free survival (11.1% vs. 52.6% at 2 years, P = 0.003). Post-transplant maintenance therapy with AZA and GO was generally tolerable but more than half of the patients eventually relapsed. Further improvements are needed to prevent relapse after transplantation in patients with high-risk hematologic malignancies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The Jikei Academic Nursing Practice Center for the Community developed a community nursing practice that matched community health problems and concerns in Chofu and Komae cities, suburban areas of the Tokyo Metropolis. This study aimed to identify health problems and high-risk populations via an understanding of the practice of health behaviors, health literacy, and quality of life. This was an online, cross-sectional study conducted in September 2023. In total, 1520 (Chofu: n = 1170; Komae: n = 350) participants were enrolled. Participants' demographic characteristics, health literacy, health behaviors, and quality of life scores were obtained. Sleep quality was poor compared with national data. Younger participants had higher poor health literacy, did not practice health behaviors, and had a lower quality of life. In addition, parenting and informal nursing care for family members were associated with unhealthy eating, smoking, drinking, and poor quality of life. This study found that health problems and concerns before planning were significant in increasing the salience of interventions for community residents. Based on the findings of this study, an action plan for community-wide nursing practice was created., (© 2024 Wiley Periodicals LLC.)

Anderson-Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a pathological variant of the α-galactosidase A (GLA) gene that results in deficient GLA activity. GLA deficiency leads to the accumulation of globotriaosylceramide (Gb3) and lyso-Gb3 in many tissues. A certain number of FD patients have burning pain or acroparesthesia in the feet and hands since childhood. Enzyme replacement therapy (ERT) is available for FD patients. However, ERT does not dramatically improve these FD-related peripheral neuropathic pain. We generated an adeno-associated virus serotype PHP.eB (AAV-PHP.eB) vector encoding mouse GLA cDNA, which was administered to FD mice intrathecally (it) or intravenously (iv). In the it-administered AAV (it-AAV) FD mice, the GLA enzyme activity in the lumbar dorsal root ganglion (DRG) was significantly greater than that in the untreated (NT) FD mice, and the level of activity was similar to that in wild-type (WT) B6 mice. However, in iv-administered AAV (iv-AAV) FD mice, GLA activity in the DRG did not increase compared to that in NT FD mice. Gb3 storage in the DRG of it-AAV FD mice was reduced compared to that in the DRG of NT FD mice. However, compared with NT FD mice, iv-AAV FD mice did not exhibit a significant reduction in the expression of the Gb3 substrate. Compared with WT mice, FD mice were thermally hyposensitive at 52 °C according to the hot plate test. The it-AAV FD mice showed significant recovery from thermal hyposensitivity. However, the iv-AAV FD mice did not exhibit significant improvement in thermal hyposensitivity. These results suggest that the intrathecal delivery of AAV-PHP.eB-mGLA may be a valuable tool for the treatment of FD-related peripheral neuropathic pain., Competing Interests: Declaration of competing interest H Kobayashi has received research grants from Amicus Therapeutics Icn. (Japan), Sumitomo Pharma Co., Ltd. (Japan), and JCR Pharmaceuticals Co., Ltd. (Japan). T Ohashi is a research advisor for JCR Pharmaceuticals Co., Ltd. (Japan). The other authors declare no conflicting interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The rare sugar D-allulose (Alu), with ca. 10% calories of sucrose (Suc), is a promising alternative sugar that can be used to improve the quality of starch gels in storage. The effects of Alu (compared to Suc) on the hardening and microstructural and molecular order of amylopectin-rich (glutinous rice (GR) and corn amylopectin (CAP)) and amylose-rich (corn (C)) starch gels were investigated. Alu and Suc both suppressed hardening in C gels, while Alu but not Suc was effective in GR and CAP gels. SEM results showed that Alu-containing GR and CAP maintained a relatively large pore size compared to Suc-containing gels. The deconvolution of FTIR spectra revealed that Alu-containing GR and CAP gels had lower ratios of intermolecular hydrogen bonds and higher ratios of loose hydrogen bonds than Suc-containing gels. For amylose-rich C gels, on the other hand, such tendencies were not observed. The influence of Alu on amylopectin-rich gels could be because Alu reduced the ratio of intermolecular hydrogen bonds, which might be involved in amylopectin recrystallization, and increased that of loose hydrogen bonds. The results suggest that Alu is more effective than Suc in inhibiting the hardening of amylopectin-rich starch gels during refrigerated storage.

Background: Fabry disease (FD) is characterized by deficient activity of α-galactosidase A (GLA). Consequently, globotriaosylceramide (Gb3) accumulates in various organs, causing cardiac, renal, and cerebrovascular damage. Gene therapies for FD have been investigated in humans. Strong conditioning is required for hematopoietic stem cell-targeted gene therapy (HSC-GT). However, strong conditioning leads to various side effects and should be avoided. In this study, we tested antibody-based conditioning for HSC-GT in wild-type and FD model mice., Methods: After preconditioning with an antibody-drug conjugate, HSC-GT using a lentiviral vector was performed in wild-type and Fabry model mice. In the wild-type experiment, the EGFP gene was introduced into HSCs and transplanted into preconditioned mice, and donor chimerism and EGFP expression were analyzed. In the FD mouse model, the GLA gene was introduced into HSCs and transplanted into preconditioned Fabry mice. GLA activity and Gb3 accumulation in the organs were analyzed., Results: In the wild-type mouse experiment, when anti-CD45 antibody-drug conjugate was used, the percentage of donor cells at 6 months was 64.5%, and 69.6% of engrafted donor peripheral blood expressed EGFP. When anti-CD117 antibody-drug conjugate and ATG were used, the percentage of donor cells at 6 months was 80.7%, and 73.4% of engrafted donor peripheral blood expressed EGFP. Although large variations in GLA activity among mice were observed in the FD mouse experiment for both preconditioning regimens, Gb3 was significantly reduced in many organs., Conclusions: Antibody-based preconditioning may be an alternative preconditioning strategy for HSC-GT for treating FD., Competing Interests: Declaration of competing interest H Kobayashi has received research grants from Amicus Therapeutics Inc. (Japan), Sumitomo Pharma Co., Ltd. (Japan), and JCR Pharmaceuticals Co., Ltd. (Japan). T Ohashi is an advisor for JCR Pharmaceuticals Co., Ltd. (Japan). The other authors declare no conflicting interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Despite guideline-based recommendation of the interchangeable use of instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) to guide revascularization decision-making, iFR/FFR could demonstrate different physiological or clinical outcomes in some specific patient or lesion subsets. Therefore, we sought to investigate the impact of difference between iFR and FFR-guided revascularization decision-making on clinical outcomes in patients with left main disease (LMD). In this international multicenter registry of LMD with physiological interrogation, we identified 275 patients in whom physiological assessment was performed with both iFR/FFR. Major adverse cardiovascular event (MACE) was defined as a composite of death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization. The receiver-operating characteristic analysis was performed for both iFR/FFR to predict MACE in respective patients in whom revascularization was deferred and performed. In 153 patients of revascularization deferral, MACE occurred in 17.0% patients. The optimal cut-off values of iFR and FFR to predict MACE were 0.88 (specificity:0.74; sensitivity:0.65) and 0.76 (specificity:0.81; sensitivity:0.46), respectively. The area under the curve (AUC) was significantly higher for iFR than FFR (0.74; 95%CI 0.62-0.85 vs. 0.62; 95%CI 0.48-0.75; p = 0.012). In 122 patients of coronary revascularization, MACE occurred in 13.1% patients. The optimal cut-off values of iFR and FFR were 0.92 (specificity:0.93; sensitivity:0.25) and 0.81 (specificity:0.047; sensitivity:1.00), respectively. The AUCs were not significantly different between iFR and FFR (0.57; 95%CI 0.40-0.73 vs. 0.46; 95%CI 0.31-0.61; p = 0.43). While neither baseline iFR nor FFR was predictive of MACE in patients in whom revascularization was performed, iFR-guided deferral seemed to be safer than FFR-guided deferral., (© 2024. The Author(s).)

Primary vitreoretinal lymphoma (PVRL) is a rare malignant lymphoma subtype with an unfavorable prognosis due to frequent central nervous system (CNS) progression. Thus, identifying factors associated with CNS progression is essential for improving the prognosis of PVRL patients. Accordingly, we conducted a comprehensive genetic analysis using archived vitreous humor samples of 36 PVRL patients diagnosed and treated at our institution and retrospectively examined the relationship between genetic alterations and CNS progression. Whole-exome sequencing (n = 2) and amplicon sequencing using a custom panel of 107 lymphomagenesis-related genes (n = 34) were performed to assess mutations and copy number alterations. The median number of pathogenic genetic alterations per case was 12 (range: 0- 22). Pathogenic genetic alterations of CDKN2A, MYD88, CDKN2B, PRDM1, PIM1, ETV6, CD79B, and IGLL5, as well as aberrant somatic hypermutations, were frequently detected. The frequency of ETV6 loss and PRDM1 alteration (mutation and loss) was 23% and 49%, respectively. Multivariate analysis revealed ETV6 loss (hazard ratio [HR]: 3.26, 95% confidence interval [CI]: 1.08-9.85) and PRDM1 alteration (HR: 2.52, 95% CI: 1.03-6.16) as candidate risk factors associated with CNS progression of PVRL. Moreover, these two genetic factors defined slow-, intermediate-, and rapid-progression groups (0, 1, and 2 factors, respectively), and the median period to CNS progression differed significantly among them (52 vs. 33 vs. 20 months, respectively). Our findings suggest that genetic factors predict the CNS progression of PVRL effectively, and the genetics-based CNS progression model might lead to stratification of treatment.

Asbestos, especially chrysotile, continues to be exposed to humans globally. Hence, it should be disposed properly to prevent asbestos-related diseases, including mesothelioma and lung cancer. This study aimed to verify whether forsterite, a heating product of chrysotile, can cause carcinogenicity, particularly mesothelioma. Forsterite (FO-1000) and enstatite (EN-1500) produced by heating chrysotile at 1000°C and 1500°C, respectively, were subjected. We injected 10 mg of chrysotile, FO-1000, or EN-1500 in rats intraperitoneally and observed the development of peritoneal mesothelioma until 24 months. The incidence of peritoneal mesothelioma in the chrysotile group was 91.2%, whereas in the FO-1000 and EN-1500 groups, peritoneal mesothelioma did not develop. Urinary 8-hydroxy-2'-deoxyguanosine and serum N-ERC/mesothelin concentrations significantly increased in the chrysotile group that developed peritoneal mesothelioma, while they only temporarily changed in the FO-1000 or EN-1500 groups during early treatment. Furthermore, there was a significant homozygous deletion of the CDKN2A/p16 gene in the chrysotile group compared to the control group, in contrast to no significant difference in the FO-1000 and EN-1500 groups. Therefore, this study provides clear evidence that forsterite is a nonmesothelioma carcinogen and suggests that forsterite and enstatite are sufficient substances for chrysotile detoxification.

Plant and animal conservation have benefited from the assistance of wildlife detection dogs (WDDs) since 1890, but their application to fungal conservation has not been trialed. In a world-first, we tested the effectiveness of WDDs and human surveyors when searching for experimentally outplanted fungi in natural habitat. We focused on a critically endangered fungus from Australia, Hypocreopsis amplectens, and showed that a WDD outperformed a human surveyor: our WDD detected a greater proportion of targets, had a faster time to first discovery, and had fewer false negatives. Our study highlights the tremendous potential for WDDs to enhance fungal conservation by demonstrating their utility in one of the most challenging fungal systems: a rare species with low population densities and low volatility. Our findings suggest that the application of WDDs to fungal conservation should enhance continuing efforts to document and conserve an understudied kingdom that is threatened by habitat loss and climate change., Competing Interests: The authors declare no competing interests., (Crown Copyright © 2024 Published by Elsevier Inc.)

Abstract: Clinically significant cytomegalovirus infection (csCMVi) is frequently observed after allogeneic hematopoietic stem cell transplantation (HSCT) and prophylaxis with letermovir is commonly adopted. However, the clinical benefit of letermovir prophylaxis according to graft sources has not been sufficiently elucidated. We retrospectively analyzed 2194 recipients of HSCT who were CMV-seropositive (236 with letermovir prophylaxis and 1958 without prophylaxis against CMV). csCMVi was significantly less frequent in patients with letermovir prophylaxis than in those without (23.7% vs 58.7% at 100 days after HSCT, P < .001) and the same trend was seen when recipients of bone marrow (BM), peripheral blood stem cell (PBSC), or cord blood (CB) transplantation were separately analyzed. In recipients of BM, nonrelapse mortality (NRM) was significantly lower in the letermovir group at 6 months after HSCT (5.0% vs 14.9%, P = .018), and the same trend was observed in recipients of PBSCs (14.7% vs 24.8%, P = .062); however, there was no statistical significance at 1 year (BM, 21.1% vs 30.4%, P = .67; PBSCs, 21.2% vs 30.4%, P = .096). In contrast, NRM was comparable between recipients of CB with and without letermovir prophylaxis throughout the clinical course (6 months, 23.6% vs 24.3%, P =.92; 1 year, 29.3% vs 31.0%, P = .77), which was confirmed by multivariate analyses. In conclusion, the impact of letermovir prophylaxis on NRM and csCMVi should be separately considered according to graft sources., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Biological sex is one of the major factors characterizing the heart failure (HF) patient phenotype. Understanding sex-related differences in HF is crucial to implement personalized care for HF patients with various phenotypes. There are sex differences in left ventricular (LV) remodeling patterns in the HF setting, namely, more likely concentric remodeling and diastolic dysfunction in women and eccentric remodeling and systolic dysfunction in men. Recently supra-normal EF (snLVEF) has been recognized as a risk of worse outcome. This pathology might be more relevant in female patients. The possible mechanism may be through coronary microvascular dysfunction and sympathetic nerve overactivation from the findings of previous studies. Further, estrogen deficit might play a significant role in this pathophysiology. The sex difference in body composition may also be related to the difference in LV remodeling and outcome. Lower implementation in guideline-directed medical therapy (GDMT) in female HFrEF patients might also be one of the factors related to sex differences in relation to outcomes. In this review, we will discuss the sex differences in cardiac and clinical phenotypes and their relation to outcomes in HF patients and further discuss how to provide appropriate treatment strategies for female patients.

Unstructured biological macromolecules have attracted attention as protein aggregation inhibitors in living cells. Some are characterized by their free structural configuration, highly charged, and water-soluble. However, the importance of these properties in inhibiting protein aggregation remains unclear. In this study, we investigated the effect of charged poly (amino acids), which mimic these properties, on aggregation of l-lactate dehydrogenase (LDH) and compared their effects to monomeric amino acids and folded proteins. LDH was stable and active at a neutral pH (~7) but formed inactive aggregates at acidic pH (< 6). Adding cationic polyelectrolytes of poly-l-lysine and poly-l-arginine suppressed the acid-induced aggregation and inactivation of LDH under acidic pH values. Adding monomeric amino acids and cationic folded proteins also prevented LDH aggregation but with lower efficacy than cationic polyelectrolytes. These results indicate that unstructured polyelectrolytes effectively stabilize unstable enzymes because they interact flexibly and multivalently with them. Our findings provide a simple method for stabilizing enzymes under unstable conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) show cardiovascular protective effects, regardless of the patient's history of diabetes mellitus (DM). SGLT2is suppressed cardiovascular adverse events in patients with type 2 DM, and furthermore, SGLT-2is reduced the risk of worsening heart failure (HF) events or cardiovascular death in patients with HF. Along with these research findings, SGLT-2is are recommended for patients with HF in the latest guidelines. Despite these benefits, the concern surrounding the increasing risk of body weight loss and other adverse events has not yet been resolved, especially for patients with sarcopenia or frailty. The DAPA-HF and DELIVER trials consistently showed the efficacy and safety of SGLT-2i for HF patients with frailty. However, the Rockwood frailty index that derived from a cumulative deficit model was employed for frailty assessment in these trials, which might not be suitable for the evaluation of physical frailty or sarcopenia alone. There is no fixed consensus on which evaluation tool to use or its cutoff value for the diagnosis and assessment of frailty in HF patients, or which patients can receive SGLT-2i safely. In this review, we summarize the methodology of frailty assessment and discuss the efficacy and safety of SGLT-2i for HF patients with sarcopenia or frailty., Competing Interests: The authors declare no conflicts of interest.

Background: Alabama is one of seven priority states for the National Ending the HIV Epidemic Initiative due to a disproportionate burden of rural infections. To reverse growing infection rates, the state must increase its focus on prevention efforts, including novel strategies. One such approach is to utilize dashboards that visualize real-time data on the pre-exposure prophylaxis (PrEP) care continuum to assist in prioritizing evidence-based preventative care for those most vulnerable for HIV infection., Methods: We conducted a mixed methods evaluation to ascertain stakeholders' perceptions on the acceptability, feasibility, appropriateness, and usability of a PrEP care continuum dashboard, as well as gain insight on ways to improve the activities necessary to sustain it. Clinicians, administrators, and data personnel from participating sites in Alabama completed surveys (n = 9) and participated in key informant interviews (n = 10) to better understand their experiences with the prototype data dashboard and to share feedback on how it can be modified to best fit their needs., Results: Surveys and interviews revealed that all participants find the pilot data dashboard to be an acceptable, feasible, and appropriate intervention for clinic use. Overall, stakeholders find the pilot dashboard to be usable and helpful in administrative efforts, such as report and grant writing; however, additional refining is needed in order to reduce burden and optimize usefulness. Participants voiced concerns about their site's abilities to sustain the dashboard, including the lack of systematized PrEP protocols and limited funds and staff time dedicated to PrEP data collection, cleaning, and upload., Conclusion: Study participants from clinics providing HIV prevention services, including PrEP, in Alabama voiced interest in sustaining and refining a data dashboard that tracks clients across the PrEP care continuum. Despite viewing the platform itself as an acceptable, feasible, and appropriate intervention, participants agreed that efforts need to be focused on standardizing PrEP data collection protocols in order to ensure consistent, accurate data capture and that limited funds and staff time are barriers to the sustained implementation of the dashboard in practice., (© 2024. The Author(s).)

The vagus nerve crucially affects emotions and psychiatric disorders. However, the detailed neurophysiological dynamics of the vagus nerve in response to emotions and its associated pathological changes remain unclear. In this study, we demonstrated that the spike rates of the cervical vagus nerve change depending on anxiety behavior in an elevated plus maze test, and these changes were eradicated in stress-susceptible male mice. Furthermore, instantaneous spike rates of the vagus nerve were negatively and positively correlated with the power of 2-4 Hz and 20-30 Hz oscillations, respectively, in the prefrontal cortex and amygdala. The oscillations also underwent dynamic changes depending on the behavioral state in the elevated plus maze, and these changes were no longer observed in stress-susceptible and vagotomized mice. Chronic vagus nerve stimulation restored behavior-relevant neuronal oscillations with the recovery of altered behavioral states in stress-susceptible mice. These results suggested that physiological vagal-brain communication underlies anxiety and mood disorders., (© 2024. The Author(s).)

A 28-year-old man was diagnosed with acute myelomonocytic leukemia. He achieved complete remission (CR) after two cycles of induction therapy. However, after consolidation therapy, bone marrow aspiration performed to prepare for allogeneic hematopoietic stem cell transplantation revealed disease relapse. Companion diagnostics confirmed the presence of the FLT3-ITD mutation. The patient received gilteritinib monotherapy and achieved CR. Subsequently, he underwent unrelated allogeneic bone marrow transplantation. One year after transplantation, the patient relapsed, and gilteritinib was resumed. However, the leukemia progressed, and panel sequencing using a next-generation sequencer showed that the FLT3-ITD mutation disappeared. A mutation in PTPN11, which regulates the RAS/MAPK signaling pathway, was also detected. Gilteritinib was discontinued, and the patient achieved CR with salvage chemotherapy. He underwent related haploidentical peripheral blood stem cell transplantation but died of relapse. This was a case in which genetic analysis revealed clonal transition and acquisition of resistance to treatment.