Obesity Is a Major Determinant of Impaired Cardiac Energy Metabolism in Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major health problem with limited treatment options. Although optimizing cardiac energy metabolism is a potential approach to treating heart failure, it is poorly understood what alterations in cardiac energy metabolism actually occur in HFpEF. To determine this, we used mice in which HFpEF was induced using an obesity and hypertension HFpEF protocol for 10 weeks. Next, carvedilol, a third-generation ß-blocker and a biased agonist that exhibits agonist-like effects through ß arrestins by activating extracellular signal-regulated kinase, was used to decrease one of these parameters, namely hypertension. Heart function was evaluated by invasive pressure-volume loops and echocardiography as well as by ex vivo working heart perfusions. Glycolysis and oxidation rates of glucose, fatty acids, and ketones were measured in the isolated working hearts. The development of HFpEF was associated with a dramatic decrease in cardiac glucose oxidation rates, with a parallel increase in palmitate oxidation rates. Carvedilol treatment decreased the development of HFpEF but had no major effect on cardiac energy substrate metabolism. Carvedilol treatment did increase the expression of cardiac ß arrestin 2 and proteins involved in mitochondrial biogenesis. Decreasing bodyweight in obese HFpEF mice increased glucose oxidation and improved heart function. This suggests that the dramatic energy metabolic changes in HFpEF mice hearts are primarily due to the obesity component of the HFpEF model. SIGNIFICANCE STATEMENT: Metabolic inflexibility occurs in heart failure with preserved ejection fraction (HFpEF) mice hearts. Lowering blood pressure improves heart function in HFpEF mice with no major effect on energy metabolism. Between hypertension and obesity, the latter appears to have the major role in HFpEF cardiac energetic changes. Carvedilol increases mitochondrial biogenesis and overall energy expenditure in HFpEF hearts.

Diagnosis and management of longitudinal erythronychia: A clinical review by an expert panel.

Longitudinal erythronychia (LE) is defined as a longitudinal red band of the nail(s) and is classified as localized (involvement of 1 nail) or polydactylous (involvement of more than 1 nail). The differential diagnosis is distinct for these classifications. The etiologies of localized longitudinal erythronychia are most frequently benign subungual neoplasms and less often malignancies. Polydactylous longitudinal erythronychia is typically secondary to regional or systemic diseases, including lichen planus and Darier disease. LE is a common but underrecognized clinical finding. Increased dermatologist awareness of the clinical characteristics and differential diagnosis for LE is necessary given the possibility for malignancy and associated systemic disease. In this clinical review, the clinical features, differential diagnosis, evaluation, and management of LE are described.

Dermatologic Fungal Neglected Tropical Diseases-Part I. Epidemiology and Clinical Features.

In this part 1 of a 2-part continuing medical education series, the epidemiology, clinical features, and diagnostic methods for fungal skin neglected tropical diseases (NTDs), which include eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis, are reviewed. These infections, several of which are officially designated as NTDs by the World Health Organization (WHO), cause substantial morbidity and stigma worldwide and are receiving increased attention due to the potential for climate change-related geographic expansion. Domestic incidence may be increasing in the setting of global travel and immunosuppression. United States dermatologists may play a central role in early detection and initiation of appropriate treatment, leading to decreased morbidity and mortality.

Dermatologic Fungal Neglected Tropical Diseases-Part II. Management and Morbidity.

In this part 2 of a 2-part continuing medical education series, the management, outcomes, and morbidities for fungal skin neglected tropical diseases (NTDs), including eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis are reviewed. While fungal skin NTDs are associated with poverty in resource-limited settings, they are more often associated with immunosuppression and global migration in the United States. These infections have a high morbidity burden, including disfigurement, physical disability, coinfection, malignant transformation, mental health issues, and financial impact. For most fungal skin NTDs, management is difficult and associated with low cure rates. Dermatologists play a central role in initiating appropriate treatment early in disease course in order to improve patient outcomes.

Digital Reimbursement Systems in a Student-Run Clinic.

The increasing reliance on digital tools for standard healthcare practices in uninsured populations is poorly understood. This study aims to assess the impacts of a newly implemented digital reimbursement system at a student-run primary care clinic associated with an academic medical institution serving uninsured New York City residents. Pharmacy records of 94 unique patients receiving a total of 2770 reimbursements between October 17th, 2016, and May 18th, 2023, were analyzed. Patients were divided into two groups (in-person vs. digital) based on their reimbursement preferences type. Demographic analyses were performed in addition to assessing reimbursement volumes, number of refunds, and duration until receipt of payment for each group. The clinic's total monthly reimbursement volume, number of prescriptions, and number of patients for the period before introduction of digital refunds was compared to the period after. The mean age (in-person = 52.7 ± 14.7 years, digital = 54.9 ± 12.9 years) was not statistically different between the groups. Patients in the digital group requested on average more refunds (digital = 47 refunds, in-person = 14 refunds), received higher total reimbursement amount (digital = $1131.24, in-person = $289.36), and they were reimbursed faster (digital = 56 days, in-person = 62 days). Since the introduction of the digital reimbursement option, our three-month reimbursement volume more than doubled from $481 to $1298. The average number of monthly reimbursements increased from 27 to 45 refunds, and the number of monthly patients increased from 6 to 9 patients. In summary, digital reimbursement options can facilitate medication reimbursement among uninsured patients. These results suggest that digital reimbursement systems result in higher utilization, faster refunds, and larger total reimbursements amount for uninsured and underserved patients.

Biopriming of maize seeds with plant growth-promoting bacteria isolated from the earthworm Aporrectodea molleri: effect on seed germination and seedling growth.

Earthworms have become a potential source of multi-beneficial bacteria and effective bioinoculants. Seed biopriming is an efficient inoculation method to apply bacteria prior to sowing, which enhances the chances of bacterial candidates to colonize the rhizosphere and/or establish a liaison with the plant. In this study, we evaluated plant growth-promoting traits of bacterial strains isolated from the earthworm's Aporrectodea molleri chloragogenous tissue. In addition, we investigated their prospective use as biopriming agents to enhance Zea mays germination and seedling growth. Results were subjected to principal component analysis for potential correlations between the studied parameters. The bacterial strains displayed different in vitro plant growth-promoting characteristics and were efficient when applied in vivo as they significantly increased maize germination rate (26-78%), root elongation (67-84%), seedlings fresh weight and dry weight. Aeromonas encheleia TC22 was the most significant strain to influence germination due to its high ability to produce indole-3-acetic acid, and along with Pseudomonas azotoformans TC1, they were the most proficient at enhancing seedling root elongation and biomass, which was significantly correlated with their in vitro plant growth-promoting traits. Our findings indicate that isolates TC22 and TC1 are potent bio-primers for maize seeds and should be tested further for their use as biopriming inoculants.

Enhanced Quadrupole and Octupole Strength in Doubly Magic

The first 2^{+} and 3^{-} states of the doubly magic nucleus ^{132}Sn are populated via safe Coulomb excitation employing the recently commissioned HIE-ISOLDE accelerator at CERN in conjunction with the highly efficient MINIBALL array. The ^{132}Sn ions are accelerated to an energy of 5.49 MeV/nucleon and impinged on a ^{206}Pb target. Deexciting γ rays from the low-lying excited states of the target and the projectile are recorded in coincidence with scattered particles. The reduced transition strengths are determined for the transitions 0_{g.s.}^{+}→2_{1}^{+}, 0_{g.s.}^{+}→3_{1}^{-}, and 2_{1}^{+}→3_{1}^{-} in ^{132}Sn. The results on these states provide crucial information on cross-shell configurations which are determined within large-scale shell-model and Monte Carlo shell-model calculations as well as from random-phase approximation and relativistic random-phase approximation. The locally enhanced B(E2;0_{g.s.}^{+}→2_{1}^{+}) strength is consistent with the microscopic description of the structure of the respective states within all theoretical approaches. The presented results of experiment and theory can be considered to be the first direct verification of the sphericity and double magicity of ^{132}Sn.

Vitamins for the Management of Nail Disease: A Literature Review.

Background: Vitamins have gained popularity among physicians and patients for purported benefits to hair, skin, and nail health. Safe and efficacious therapies for nail disorders, many of which are chronic conditions, are needed. Summary: We conducted a literature review of studies assessing the efficacy of oral, topical, and intralesional vitamin/vitamin derivatives for the treatment of nail disorders, including yellow nail syndrome, brittle nail syndrome, onychomycosis, habit-tic nail deformity, periungual/subungual verruca, and nail psoriasis. Forty-nine articles were reviewed. There is good evidence to support the use of topical tazarotene and vitamin D analogs for nail psoriasis treatment. We found overall limited evidence for treatment of other nail disorders with vitamin/vitamin derivatives, and further research is needed to support their use. Key Messages: Besides topical tazarotene and vitamin D analogs for nail psoriasis treatment, there is limited evidence for treatment of nail disorders with topical, oral, and intralesional vitamin/vitamin derivatives.

Body-Focused Repetitive Behaviors in Patients with FOXP1 Syndrome: An International Cross-Sectional Survey-Based Study.

Introduction: FOXP1 syndrome is a rare neurodevelopmental disorder due to forkhead box protein 1 (FOXP1) gene mutations and is associated with intellectual disability, dysmorphic features, and autism spectrum disorder. We aimed to assess body-focused repetitive behavior (BFRB) prevalence in this patient population using a cross-sectional survey-based study. Methods: A validated survey assessing for BFRBs was administered to parents attending the International FOXP1 Foundation conference on June 21, 2023, and was sent to a FOXP1 syndrome listserv. Results: Excoriation disorder, onychophagia, onychotillomania, and trichotillomania were reported by 58.6%, 38.6%, 29.7%, and 10.0% of subjects, with 63.4%, 59.3%, 54.5%, and 14.3% having moderate to severe disease, respectively. Overall, 28.6%, 30.0%, and 10.0% had one, two, and three BFRBs, respectively. Conclusion: Prevalence of BFRBs is high among FOXP1 syndrome patients surveyed, affecting quality of life for patients and their families and causing significant sequelae.

Enhancing Cosmetic and Functional Improvement of Recalcitrant Nail Lichen Planus With Resin Nail.

Lichen planus (LP) is one of the few conditions that may cause permanent and debilitating nail loss. Recurrence is common despite treatment with first-line therapies including intralesional and systemic corticosteroids. We describe application of a resin nail for recalcitrant LP of the fingernail for improved cosmesis and functionality.