RING Program: The CFAR Diversity, Equity, and Inclusion Pathway Initiative.

BACKGROUND: Case Western Reserve University (CWRU)/University Hospitals Cleveland Medical Center in Cleveland, OH, and the University of Pittsburgh (Pitt) in Pittsburgh, PA, forged a strategic alliance to form the Rustbelt Center for AIDS Research. The Rustbelt Center for AIDS Research developed a National Institutes of Health-supported diversity, equity, and inclusion pathway initiative termed the "Rustbelt Investigators for the Next Generation (RING) Program" that provides research training experiences for Puerto Rican students that will help them pursue a biomedical research career in HIV. SETTING: The RING Program provides 10-week research training experiences in different disciplines of HIV/AIDS for under-represented minority undergraduate and masters students from 4 campuses (Río Piedras, Mayagüez, Humacao, and Cayey) at the University of Puerto Rico. Mentors are drawn from both CWRU and Pitt. RESULTS: The RING Program recently completed our first wave of recruitment. Recruitment sessions were either virtual or on site at the University of Puerto Rico campuses and included an overview presentation, a Q&A session, and in-person interviews. We interviewed 32 eligible applicants and accepted 10 into the program, of which 9 were female. Five students were matched with faculty at CWRU and 5 with faculty at Pitt. CONCLUSIONS: The RING Program is a comprehensive program in laboratory and implementation science that aims to enhance under-represented Hispanic undergraduate and masters students' passion for pursuing a biomedical research career in HIV.

Ichthyosis: case report in a Colombian man with genetic alterations in ABCA12 and HRNR genes.

BACKGROUND: Ichthyosis is a heterogeneous group of diseases caused by genetic disorders related to skin formation. They are characterized by generalized dry skin, scaling, hyperkeratosis and frequently associated with erythroderma. Among its different types, harlequin ichthyosis (HI) stands out due to its severity. HI is caused by mutations in the ABCA12 gene, which encodes essential proteins in epidermal lipid transport, and it helps maintain the homeostasis of the stratum corneum of the epidermis. However, due to the wide spectrum of genetic alterations that can cause ichthyosis, holistic medical care, and genetic studies are required to improve the diagnosis and outcomes of these diseases. CASE PRESENTATION: Here, we presented the case of a 19 years old male patient who was a premature infant and exhibited clinical features consistent with HI, including bright yellow hyperkeratotic plates with erythematous fissures that covered his entire body like a collodion baby. Currently, he exhibited erythroderma, photosensitivity, ectropion, auricular pavilion alterations, and musculoskeletal disorders, such as equinovarus feet, fingers, hands, and hypoplastic feet with contractures in flexion and marked difficulty in fine motor skills. In addition, he presented dyschromatopsia, Achilles reflex hyporeflexia, slight speech, dental alteration and deficient cognitive performance. After the genetic sequencing, variants were found in ABCA12 and HRNR which are related to several skin diseases, including ichthyosis. CONCLUSIONS: Although in clinical practice, ichthyosis is a common entity, a severe type of ichthyosis is presented, highlighting the importance of appropriate genetic diagnosis, given the broad spectrum of genetic alterations with similar phenotypic and clinical characteristics. These pathologies must be known to guarantee initial support measures to prevent complications and offer multidisciplinary management to those patients.

Trastorno del comportamiento alimentario de difícil tratamiento: Caso clínico / Eating behavior disorders difficult to treat: A clinical case

La incidencia de los trastornos de la conducta alimentaria (TCA), integrados por la bulimia nerviosa (BN) y la anorexia nerviosa (AN) ha aumentado en los últimos años. Su etiología es multifactorial. Las edades de presentación son cada vez más tempranas, afectando a individuos de ambos sexos. Son trastornos crónicos, que asocian importante morbi-mortalidad y que frecuentemente se presentan con múltiples recaídas. El tratamiento requiere la participación de un equipo multidisciplinario, sin claras evidencias que indiquen la efectividad de diversas estrategias terapéuticas. Se analiza el caso clínico de una adolescente portadora de TCA: AN con componente purgativo. Presentaba varios de los factores de riesgo descriptos para la enfermedad, la forma de presentación fue característica y presentó algunas de las complicaciones más frecuentes. El tratamiento se inició con la paciente hospitalizada, realizando un abordaje multidisciplinario. La respuesta inicial no fue buena, por lo que fue necesario cambiar la estrategia terapéutica. Como objetivo terapéutico principal se planteó el cuidado de la integridad física y mental. Se buscó recuperar el estado nutricional instaurando cambios en la conducta alimentaria.

The incidence of eating behaviour disorders (EBD), represented by bulimia nervosa (BN) and anorexia nervosa (AN) has increased in recent years. Its aetiology is multifactorial. Currently, the age at presentation is increasingly younger, affecting individuals of both sexes. EBDs are chronic disorders, associated with high morbidity and mortality and often present with multiple relapses. Treatment requires the involvement of a multidisciplinary team, although there is no evidence indicating the effectiveness of various treatment strategies. The study presents the case of a EBD carrier teen (AN with purgative component). This patient had several risk factors described for the disease, the presentation was characteristic and presented some of the most frequent complications. Treatment was initiated with hospitalization and a multidisciplinary approach. The initial response was not good, so it was necessary to change the therapeutic strategy. The major therapeutic target was the physical and mental integrity care. Recovery of nutritional status was initiated and sought to establish changes in eating behaviour.

Magneto-responsive liquid crystalline elastomer nanocomposites as potential candidates for dynamic cell culture substrates.

Recently, liquid crystalline elastomers (LCEs) have been proposed as active substrates for cell culture due to their potential to attach and orient cells, and impose dynamic mechanical signals through the application of external stimuli. In this report, the preparation of anisotropic and oriented nematic magnetic-sensitized LCEs with iron oxide nanoparticles, and the evaluation of the effect of particle addition at low concentrations on the resultant structural, thermal, thermo-mechanical, and mechanical properties is presented. Phase transformations produced by heating in alternating magnetic fields were investigated in LCEs in contact with air, water, and a common liquid cell culture medium was also evaluated. The inclusion of nanoparticles into the elastomers displaced the nematic-to-isotropic phase transition, without affecting the nematic structure as evidenced by similar values of the order parameter, while reducing the maximum thermomechanical deformations. Remote and reversible deformations of the magnetic LCEs were achieved through the application of alternating magnetic fields, which induces the nematic-isotropic phase transition through nanoparticle heat generation. Formulation parameters can be modified to allow for remote actuation at values closer to the human physiological temperature range and within the range of deformations that can affect the cellular behavior of fibroblasts. Finally, a collagen surface treatment was performed to improve compatibility with NIH-3T3 fibroblast cultures, which enabled the attachment and proliferation of fibroblasts on substrates with and without magnetic particles under quiescent conditions. The LCEs developed in this work, which are able to deform and experience stress changes by remote contact-less magnetic stimulation, may allow for further studies on the effect of substrate morphology changes and dynamic mechanical properties during in vitro cell culture.

Hydrophobicity of Antifungal ß-Peptides Is Associated with Their Cytotoxic Effect on In Vitro Human Colon Caco-2 and Liver HepG2 Cells.

The widespread distribution of fungal infections, with their high morbidity and mortality rate, is a global public health problem. The increase in the population of immunocompromised patients combined with the selectivity of currents treatments and the emergence of drug-resistant fungal strains are among the most imperative reasons to develop novel antifungal formulations. Antimicrobial ß-peptides are peptidomimetics of natural antimicrobial peptides (AMPs), which have been proposed as developmental platforms to enhance the AMPs selectivity and biostability. Their tunability allows the design of sequences with remarkable activity against a wide spectrum of microorganisms such as the human pathogenic Candida spp., both in planktonic and biofilm morphology. However, the ß-peptide's effect on surrounding host cells remains greatly understudied. Assessments have mainly relied on the extent of hemolysis that a candidate peptide is able to cause. This work investigated the in vitro cytotoxicity of various ß-peptides in the Caco-2 and HepG2 mammalian cell lines. Results indicated that the cytotoxic effect of the ß-peptides was influenced by cell type and was also correlated to structural features of the peptide such as hydrophobicity. We found that the selectivity of the most hydrophobic ß-peptide was 2-3 times higher than that of the least hydrophobic one, for both cell types according to the selectivity index parameter (IC50/MIC). The IC50 of Caco-2 and HepG2 increased with hydrophobicity, which indicates the importance of testing putative therapeutics on different cell types. We report evidence of peptide-cell membrane interactions in Caco-2 and HepG2 using a widely studied ß-peptide against C. albicans.

Trastorno del comportamiento alimentario de difícil tratamiento. Caso clínico / Eating behavior disorders difficult to treat. A clinical case

La incidencia de los trastornos de la conducta alimentaria (TCA), integrados por la bulimia nerviosa (BN) y la anorexia nerviosa (AN) ha aumentado en los últimos años. Su etiología es multifactorial. Las edades de presentación son cada vez más tempranas, afectando a individuos de ambos sexos. Son trastornos crónicos, que asocian importante morbi-mortalidad y que frecuentemente se presentan con múltiples recaídas. El tratamiento requiere la participación de un equipo multidisciplinario, sin claras evidencias que indiquen la efectividad de diversas estrategias terapéuticas. Se analiza el caso clínico de una adolescente portadora de TCA: AN con componente purgativo. Presentaba varios de los factores de riesgo descriptos para la enfermedad, la forma de presentación fue característica y presentó algunas de las complicaciones más frecuentes. El tratamiento se inició con la paciente hospitalizada, realizando un abordaje multidisciplinario. La respuesta inicial no fue buena, por lo que fue necesario cambiar la estrategia terapéutica. Como objetivo terapéutico principal se planteó el cuidado de la integridad física y mental. Se buscó recuperar el estado nutricional instaurando cambios en la conducta alimentaria.

Synthetic antimicrobial ß-peptide in dual-treatment with fluconazole or ketoconazole enhances the in vitro inhibition of planktonic and biofilm Candida albicans.

Fungal infections are a pressing concern for human health worldwide, particularly for immunocompromised individuals. Current challenges such as the elevated toxicity of common antifungal drugs and the emerging resistance towards these could be overcome by multidrug therapy. Natural antimicrobial peptides, AMPs, in combination with other antifungal agents are a promising avenue to address the prevailing challenges. However, they possess limited biostability and susceptibility to proteases, which has significantly hampered their development as antifungal therapies. ß-peptides are synthetic materials designed to mimic AMPs while allowing high tunability and increased biostability. In this work, we report for the first time the inhibition achieved in Candida albicans when treated with a mixture of a ß-peptide model and fluconazole or ketoconazole. This combination treatment enhanced the biological activity of these azoles in planktonic and biofilm Candida, and also in a fluconazole-resistant strain. Furthermore, the in vitro cytotoxicity of the dual treatment was evaluated towards the human hepatoma cell line, HepG2, a widely used model derived from liver tissue, which is primarily affected by azoles. Analyses based on the LA-based method and the mass-action law principle, using a microtiter checkerboard approach, revealed synergism of the combination treatment in the inhibition of planktonic C. albicans. The dual treatment proved to be fungicidal at 48 and 72 h. Interestingly, it was also found that the viability of HepG2 was not significantly affected by the dual treatments. Finally, a remarkable enhancement in the inhibition of the highly azole-resistant biofilms and fluconazole resistant C. albicans strain was obtained.