An Analysis of Lesbian, Gay, Bisexual, Transgender, and Queer Curricula Inclusion: A National Study of Physician Assistant Programs.

INTRODUCTION: The health professions education literature shows an increased focus on inclusion of lesbian, gay, bisexual, transgender, and queer (LGBTQ) content in curricula; however, it does not address hours of content or methods for content delivery. The purpose of this study was to describe the delivery of LGBTQ content in physician assistant (PA) education through a national survey of PA programs. METHODS: In 2021, a national program survey was sent to all US-accredited PA Programs (n = 284) and had a completion rate of 71.8% (n = 204). Descriptive statistics were conducted to describe trends and make comparisons in the delivery of LGBTQ content. RESULTS: Most PA programs are incorporating LGBTQ content into preclinical phases of PA education (81%) and describe that LGBTQ curricula align with institutional values (82%). Most report 1 to 3 hours of preclinical education for all LGBTQ population groups and cite medical interviewing courses as the most frequently used course to address LGTBQ care. Many programs (43%) do not provide instructional hours on LGBTQ content in the clinical phase, and the majority do not offer clinical rotations focused on this care. The results show variability in the level of preparedness that programs report on their students caring for LGBTQ populations. DISCUSSION: Physician assistant programs are generally integrating the content throughout their didactic curricula; however, few offer clinical experiences focused on caring for patients who are LGBTQ. Offering clinical experiences and assessing student competencies are areas of growth in health professions education as related to LGBTQ health.

[Caecum hernia of foramen of Winslow]. / Hernie caecale du foramen de Winslow.

Winslow's foramen hernia, or Blandin's hernia, is a rare internal hernia with a non-specific clinical presentation and its diagnosis may be difficult. The hernia occurs across the omental hiatus, bounded by the inferior vena cava posteriorly and the portal triad anteriorly. CT imaging provides several diagnostic clues in this condition. Prompt surgical management allows reduction before complications arise. We present a case of caecal internal herniation through Winslow's foramen in a patient who underwent gastrojejunal bypass about ten years ago. Laparoscopy with reduction of the caecal bascule and closure of the foramen is performed successfully.

La hernie du foramen de Winslow, ou hernie de Blandin, est une hernie interne rare, avec une présentation clinique non spécifique et son diagnostic peut être difficile. La hernie se produit au travers de l'hiatus omental, limité par la veine cave inférieure en arrière et la triade portale en avant. L'imagerie médicale par tomodensitométrie nous fournit plusieurs indices diagnostiques dans cette pathologie. La prise en charge chirurgicale rapide permet une réduction avant la survenue de complications. Nous présentons un cas de hernie interne caecale par le foramen de Winslow chez un patient ayant bénéficié d'un bypass gastro-jéjunal une dizaine d'années auparavant. Une laparoscopie avec réduction de la bascule caecale et fermeture du foramen est réalisée avec succès.

Two MP2CL5 Antigen Vaccines from Naegleria fowleri Stimulate the Immune Response against Meningitis in the BALB/c Model.

Naegleria fowleri is an etiological agent that generates primary amoebic meningoencephalitis; unfortunately, no effective treatment or vaccine is available. The objective of this work was to determine the immunoprotective response of two vaccine antigens, as follows: (i) the polypeptide band of 19 kDa or (ii) a predicted immunogenic peptide from the membrane protein MP2CL5 (Smp145). Both antigens were administered intranasally in mice using cholera toxin (CT) as an adjuvant. The survival rate and immune response of immunized mice with both antigens and challenged with N. fowleri trophozoites were measured in the nose-associated lymphoid tissue (NALT) and nasal passages (NPs) by flow cytometry and enzyme-linked immunosorbent assay (ELISA). We also determined the immunolocalization of both antigens in N. fowleri trophozoites by confocal microscopy. Immunization with the polypeptide band of 19 kDa alone or coadministered with CT was able to confer 80% and 100% of protection, respectively. The immunization with both antigens (alone or coadministered with CT) showed an increase in T and B lymphocytes. In addition, there was an increase in the expression of integrin α4ß1 and IgA in the nasal cavity of protected mice, and the IgA, IgG, and IgM levels were increased in serum and nasal washes. The immunolocalization of both antigens in N. fowleri trophozoites was observed in the plasma membrane, specifically in pseudopod-like structures. The MP2CL5 antigens evaluated in this work were capable of conferring protection which would lead us to consider them as potential candidates for vaccines against meningitis caused by N. fowleri.

Oil-Based Double Emulsion Microcarriers for Enhanced Stability and Bioaccessibility of Betalains and Phenolic Compounds from Opuntia stricta var. dillenii Green Extracts.

Opuntia cactus fruit (prickly pear flesh and agricultural residues such as peels and stalks) is an important source of bioactive compounds, including betalains and phenolic compounds. In this work, two double emulsion W1/O/W2 formulations (A and B) were designed to encapsulate green extracts rich in betalains and phenolic compounds obtained from Opuntia stricta var. dillenii (OPD) fruits with the aim of improving their stability and protecting them during the in vitro gastrointestinal digestion process. In addition, the characterization of the double emulsions was studied by microscopy and the evaluation of their physical and physico-chemical parameters. Formulation A, based on Tween 20, showed smaller droplets (1.75 µm) and a higher physical stability than Formulation B, which was achieved with sodium caseinate (29.03 µm). Regarding the encapsulation efficiency of the individual bioactives, betalains showed the highest values (73.7 ± 6.7 to 96.9 ± 3.3%), followed by flavonoids (68.2 ± 5.9 to 95.9 ± 7.7%) and piscidic acid (71 ± 1.3 to 70.2 ± 5.7%) depending on the formulation and the bioactive compound. In vitro digestive stability and bioaccessibility of the individual bioactives increased when extracts were encapsulated for both formulations (67.1 to 253.1%) in comparison with the non-encapsulated ones (30.1 to 64.3%), except for neobetanin. Both formulations could be considered as appropriate microcarrier systems for green OPD extracts, especially formulation A. Further studies need to be conducted about the incorporation of these formulations to develop healthier foods.

Identification of peptide epitopes of the gp120 protein of HIV-1 capable of inducing cellular and humoral immunity.

The Human Immunodeficiency Virus (HIV-1) causes Acquired Immunodeficiency Syndrome (AIDS) and a high percentage of deaths. Therefore, it is necessary to design vaccines against HIV-1 for the prevention of AIDS. Bioinformatic tools and theoretical algorisms allow us to understand the structural proteins of viruses to develop vaccines based on immunogenic peptides (epitopes). In this work, we identified the epitopes: P1, P2, P10, P27 and P30 from the gp120 protein of HIV-1. These peptides were administered intranasally alone or with cholera toxin (CT) to BALB/c mice. The population of CD4+, CD8+ T lymphocytes and B cells (CD19/CD138+, IgA+ and IgG+) from nasal-associated lymphoid tissue, nasal passages, cervical and inguinal nodes was determined by flow cytometry. In addition, anti-peptides IgG and IgA from serum, nasal and vaginal washings were measured by ELISA. The results show that peptides administered by i.n. can modulate the immune response of T and B lymphocyte populations, as well as IgA and IgG antibodies secretion in the different sites analyzed. In conclusion, bioinformatics tools help us to select peptides with physicochemical properties that allow the induction of the humoral and cellular responses that depend on the peptide sequence.

Physician assistant and nurse practitioner onboarding in primary care: The participant perspective.

BACKGROUND: Many new graduate primary care physician assistants (PAs) and nurse practitioners (NPs) can experience stress and difficulty as they transition to practice. Feelings of anxiety and role ambiguity are common and can lead to costly turnover, impact care continuity, and place patients at risk for poor clinical outcomes. Onboarding, the process of helping new hires adjust to social and performance aspects of their new job and has the potential to ease transition to practice for PAs and NPs. Recent research has linked PA/NP onboarding programs to increased engagement, decreased turnover, and higher clinical productivity. PURPOSE: To describe new graduate PA and NP perspectives of onboarding programs they completed in their first primary care position. METHODOLOGY: Thirteen semistructured interviews were conducted with new graduate PAs and NPs who participated in onboarding programs. Interviews were transcribed and then analyzed using an inductive coding methodology. RESULTS: Analyses revealed nine thematic concepts that are described within two frameworks. Structural components include improving competence, training on the electronic health record, promoting mentorship, orienting to organizational dynamics, tailoring ramp-up of patient scheduling, clarifying expectations, and providing clear organizational support. Psychosocial factors include creating comfort and building self-confidence. CONCLUSION: Understanding participants' experiences with onboarding programs is essential for ensuring successful transition to practice for new graduate PAs and NPs. IMPLICATIONS: These findings are beneficial to the health care workforce. Administrators can incorporate these findings into existing and future programs, and new graduate PAs and NPs can negotiate for the inclusion of these components in their first position.

PA and NP onboarding in primary care: The participant perspective.

OBJECTIVE: To describe new graduate physician associate/assistant (PA) and NP perspectives of onboarding programs in their first primary care position. METHODS: Thirteen semistructured interviews were conducted with new graduate PAs and NPs who participated in onboarding programs. Interviews were transcribed and then analyzed using an inductive coding methodology. RESULTS: Analyses revealed nine thematic concepts that are described in two frameworks. Structural components are improving competence, training on the electronic health record (EHR), promoting mentorship, orienting to organizational dynamics, tailoring ramp-up of patient scheduling, clarifying expectations, and providing clear organizational support. Psychosocial factors are creating comfort and building self-confidence. DISCUSSION: The results describe and delineate important components for onboarding that administrators can incorporate into existing and future programs. CONCLUSION: Understanding participants' experiences with onboarding programs is essential for ensuring successful transition to practice for new graduate PAs and NPs.

Quality of life and gastric acid-suppression medication post-laparoscopic fundoplication: a ten years retrospective study.

Background: Although medical treatment is the best approach for treating gastroesophageal reflux disease (GERD), surgery has a significant role to play not only in cases of failure of medical treatment but also as in a long-term approach, specifically in young patient. On the other hand, alarming reports have been published concerning the outcomes and usefulness of antireflux surgery (ARS). The aim of this study was to evaluate medium and long-term functional outcomes following ARS performed in our institution over a 10 year period.Methods: This was a retrospective review of patients in our department who underwent primary or redo laparoscopic fundoplication between 2005 and 2015. Evaluation of the outcomes was made using a validated questionnaire specifically dedicated to GERD (the Gastroesophageal Reflux Disease - Health-Related Quality of Life (GERD-HRQL) questionnaire) and by investigation about the continued use of proton-pump inhibitors (PPIs). Exclusion criteria were patients treated for GERD with Roux-en-Y gastric bypass, emergency reduction of hiatal hernia, patients missing from follow-up and patients deceased from unrelated causes.Results: 296 patients out of 309 met the inclusion criteria. Primary procedures included 214 Nissen, 35 Toupet, and 23 Collis gastroplasty; there were additionally 62 redo operations. Neither postoperative mortality nor conversion was observed. The mean follow-up was 8 years post-surgery, and contact was made with 96% of the original group. 85% of the patients had stopped PPI use since their operation (86% after Nissen, 73% after Toupet, 94% after Collis and 82% after redos). 90% of the patients had good to excellent functional results as reported by their GERD-HRQL score, and independent of the type of previous procedure. 31 patients were dissatisfied due to dysphagia in 7 and GERD recurrence in 24. Again 75% were extremely satisfied and 15% satisfied. Our own incidence of redo procedures was 11% but the functional result and satisfaction index were comparable between redo and primary procedures. The addition of Collis gastroplasty in cases of real short oesophagus did not alter the final result.Conclusions: Laparoscopic ARS presents a superior alternative to lifetime medication use and can provide long-term control of GERD symptoms in the majority of patients if it is performed skillfully and in carefully evaluated patients. Based on the present study, we believed that significant improvement in GERD health-related quality of life can be attained following both primary and reoperative ARS.

Preclinical Pharmacokinetics and Acute Toxicity in Rats of 5-{[(2E)-3-Bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic Acid: A Novel 5-Aminosalicylic Acid Derivative with Potent Anti-Inflammatory Activity.

Compound 5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (C1), a new 5-aminosalicylic acid (5-ASA) derivative, has proven to be an antioxidant in vitro and an anti-inflammatory agent in mice. The in vivo inhibition of myeloperoxidase was comparable to that of indomethacin. The aim of this study was to take another step in the preclinical evaluation of C1 by examining acute toxicity with the up-and-down OECD method and pharmacokinetic profiles by administration of the compound to Wistar rats through intravenous (i.v.), oral (p.o.), and intraperitoneal (i.p.) routes. According to the Globally Harmonized System, C1 belongs to categories 4 and 5 for the i.p. and p.o. routes, respectively. An RP-HPLC method for C1 quantification in plasma was successfully validated. Regarding the pharmacokinetic profile, the elimination half-life was approximately 0.9 h with a clearance of 24 mL/min after i.v. administration of C1 (50 mg/kg). After p.o. administration (50 mg/kg), the maximum plasma concentration was reached at 33 min, the oral bioavailability was about 77%, and the compound was amply distributed to all tissues evaluated. Therefore, C1 administered p.o. in rats is suitable for reaching the colon where it can exert its effect, suggesting an important advantage over 5-ASA and indomethacin in treating ulcerative colitis and Crohn's disease.

Emerging practices in onboarding programs for PAs: Strategies for onboarding.

OBJECTIVE: This is the final article in a series that examines the role of onboarding programs for new physician assistants (PAs) and NPs. On-the-job learning is highly relevant for this workforce. Here we examine the strategies organizations use to impart information and skills in onboarding programs. METHODS: In 2018, we interviewed 13 administrators of onboarding programs. Interviews were transcribed and analyzed for themes by a team of researchers, with feedback from interviewees. RESULTS: Seven strategies were identified and are described in this article: Clinical mentoring, personal and professional mentoring, meeting with/shadowing other professionals, checking in by administrators, delivering didactic content, tailoring content or ramp-up, and assessing/ensuring competency. CONCLUSIONS: This article describes commonly used strategies in onboarding programs for PAs and NPs and can provide guidance to those designing their own onboarding programs. The programs we examined relied heavily on mentoring and other strategies appropriate for adult learners. Future work should evaluate the effectiveness of onboarding programs.

In vitro gastrointestinal stability, bioaccessibility and potential biological activities of betalains and phenolic compounds in cactus berry fruits (Myrtillocactus geometrizans).

Cactus berry (Myrtillocactus geometrizans) is a scarcely studied Mexican wild fruit. These fruits could contribute to reduce the risk of degenerative chronic diseases due to their bioactive profile. The aim of this work was to study the betalains and phenolic profile in cactus berry, their in vitro biological activities and gastrointestinal digestive stability and bioaccessibility. 43 metabolites were identified by HPLC-DAD-ESI-QTOF (8 betaxanthins, 8 betacyanins, 13 flavonoids, 6 phenolic acids). Phyllocactin and Isorhamnetin rhamnosyl-rutinoside (IG2) were the most abundant metabolites (5876 and 396 µg/g dw) which were also bioaccessible (16 and 21%, respectively). Pulps showed higher (p ≤ 0.05) antioxidant activity by the Oxygen Radical Absorbance Capacity (27 mM Trolox equivalents). The anti-hyperglycemic activity was highest (p ≤ 0.05) in peel and pulp tissues (85% α-glucosidase and 8% α-amylase inhibition). An 83% inhibition of hyaluronidase showed high anti-inflammatory activity. Cactus berry fruit should be considered a promising fruit candidate for a sustainable healthy diet.

Emerging practices in onboarding programs for PAs: Program content.

OBJECTIVE: Healthcare organizations are interested in creating onboarding programs to assist new PA and NP employees as they transition to practice settings. There is a need for information on what the ideal content and topic areas are for clinics to include in their onboarding programs. METHODS: In 2018, we interviewed 13 administrators of onboarding programs. Interviews were transcribed and analyzed for themes by a team of researchers, with feedback from interviewees. RESULTS: Eight content areas were identified and described in this paper: culture and values; goals and strategies; task proficiency; rules and policies; structure; working relationships; wellness; and navigation and politics. CONCLUSIONS: These common content areas may provide a starting point for organizations designing onboarding programs for their unique organizations.

Identification of Immunogenic Antigens of Naegleria fowleri Adjuvanted by Cholera Toxin.

The intranasal administration of Naegleria fowleri lysates plus cholera toxin (CT) increases protection against N. fowleri meningoencephalitis in mice, suggesting that humoral immune response mediated by antibodies is crucial to induce protection against the infection. In the present study, we applied a protein analysis to detect and identify immunogenic antigens from N. fowleri, which might be responsible for such protection. A Western blot assay of N. fowleri polypeptides was performed using the serum and nasal washes from mice immunized with N. fowleri lysates, either alone or with CT after one, two, three, or four weekly immunizations and challenged with trophozoites of N. fowleri. Immunized mice with N. fowleri plus CT, after four doses, had the highest survival rate (100%). Nasal or sera IgA and IgG antibody response was progressively stronger as the number of immunizations was increased, and that response was mainly directed to 250, 100, 70, 50, 37, and 19 kDa polypeptide bands, especially in the third and fourth immunization. Peptides present in these immunogenic bands were matched by nano-LC-ESI-MSMS with different proteins, which could serve as candidates for a vaccine against N. fowleri infection.

Identification of differential protein recognition pattern between Naegleria fowleri and Naegleria lovaniensis.

Many pathogenicity factors are involved in the development of primary amoebic meningoencephalitis (PAM) caused by N fowleri. However, most of them are not exclusive for N fowleri and they have not even been described in other nonpathogenic Naegleria species. Therefore, the objective of this work was to identify differential proteins and protein pattern recognition between Naegleria fowleri and Naegleria lovaniensis using antibodies anti-N fowleri as strategy to find vaccine candidates against meningoencephalitis. Electrophoresis and Western blots conventional and 2-DE were performed for the identification of antigenic proteins, and these were analysed by the mass spectrometry technique. The results obtained in 2-DE gels and Western blot showed very notable differences in spot intensity between these two species, specifically those with relative molecular weight of 100, 75, 50 and 19 kDa. Some spots corresponding to these molecular weights were identified as actin fragment, myosin II, heat shock protein, membrane protein Mp2CL5 among others, with differences in theoretical post-translational modifications. In this work, we found differences in antigenic proteins between both species, proteins that could be used for a further development of vaccines against N fowleri infection.

Emerging practices in onboarding programs for PAs and NPs.

OBJECTIVE: To describe administrative factors that should be considered when designing an onboarding program for physician assistants (PAs) and NPs. METHODS: Interview study of 13 administrators of onboarding programs. Interviews were transcribed and analyzed for themes by a team of researchers, with feedback from interviewees. RESULTS: Five administrative themes are summarized: goals of onboarding, critical organization factors, organizational fit, designing the program, and costs of onboarding. CONCLUSIONS: Careful planning and administration are essential to the success of onboarding programs. Although onboarding programs must be designed with unique institutional needs in mind, the considerations identified by our project might serve as a useful guide to PA and NP employers in the process of creating an onboarding program.

In silico search, chemical characterization and immunogenic evaluation of amino-terminated G4-PAMAM-HIV peptide complexes using three-dimensional models of the HIV-1 gp120 protein.

Peptide epitopes have been widely used to develop synthetic vaccines and immunotherapies. However, peptide epitopes may exhibit poor absorption or immunogenicity due to their low molecular weights. Conversely, fourth-generation polyamidoamine (G4-PAMAM) dendrimers are nonimmunogenic and relatively nontoxic synthetic nanoparticles that have been used as adjuvants and nanocarriers of small peptides and to improve nasal absorption. Based on this information, we hypothesized that the combination of intranasal immunization and G4-PAMAM dendrimers would be useful for enhancing the antibody responses of HIV-1 gp120 peptide epitopes. Therefore, we first used structural data, peptide epitope predictors and docking and MD simulations on MHC-II to identify two peptide epitopes on the CD4 binding site of HIV-1 gp120. The formation of G4-PAMAM-peptide complexes was evaluated in silico (molecular docking studies using different G4-PAMAM conformations retrieved from MD simulations as well as the MMGBSA approach) and validated experimentally (electrophoresis, 1H NMR and cryo-TEM). Next, the G4-PAMAM dendrimer-peptide complexes were administered intranasally to groups of female BALB/cJ mice. The results showed that both peptides were immunogenic at the systemic and mucosal levels (nasal and vaginal), and G4-PAMAM dendrimer-peptide complexes improved IgG and IgA responses in serum and nasal washes. Thus, G4-PAMAM dendrimers have potential for use as adjuvants and nanocarriers of peptides.

Pharmacokinetics in Wistar Rats of 5-[(4-Carboxybutanoyl)Amino]-2-Hydroxybenzoic Acid: A Novel Synthetic Derivative of 5-Aminosalicylic Acid (5-ASA) with Possible Anti-Inflammatory Activity.

5-[(4-carboxybutanoyl)amino]-2-hydroxybenzoic acid (C2) is a novel synthetic derivative of 5-aminosalicylic acid (5-ASA), which is currently being evaluated ex vivo as an anti-inflammatory agent and has shown satisfactory results. This study aimed to obtain the pharmacokinetic profiles, tissue distribution and plasma protein binding of C2 in Wistar Rats. Additionally, an HPLC method was developed and validated to quantify C2 in rat plasma. The pharmacokinetic profiles of intragastric, intravenous and intraperitoneal administration routes at singles doses of 100, 50, and 100 mg/kg, respectively, were studied in Wistar rats. The elimination half-life of intravenously administered C2 was approximately 33 min. The maximum plasma level of C2 was reached approximately 24 min after intragastric administration, with a Cmax value of 2.5 g/mL and an AUCtot value of 157 µg min-1/mL; the oral bioavailability was approximately 13%. Following a single intragastric or oral dose (100 mg/kg), C2 was distributed and detected in all examined tissues (including the brain and colon). The results showed that C2 accumulates over time. The plasma protein binding results indicated that the unbound fraction of C2 at concentrations of 1 to 20 µg/mL ranged from 89.8% to 92.5%, meaning that this fraction of C2 is available to cross tissues. Finally, the blood-plasma partitioning (BP ratio) of C2 in rat plasma was 0.71 and 0.6 at concentrations of 5 and 10 µg/mL, respectively, which indicates that C2 is free in the plasmatic phase and not inside blood cells. The results of this study suggest that a fraction of the administered C2 dose is absorbed in the stomach, and the fraction that is not absorbed reaches the small intestine and colon. This distribution constitutes the main advantage of C2 compared with 5-ASA for the treatment of ulcerative colitis (UC) and Crohn's disease (CD).

In vivo dual targeting of the oncogenic Ether-à-go-go-1 potassium channel by calcitriol and astemizole results in enhanced antineoplastic effects in breast tumors.

BACKGROUND: The oncogenic ether-à-go-go-1 potassium channel (EAG1) activity and expression are necessary for cell cycle progression and tumorigenesis. The active vitamin D metabolite, calcitriol, and astemizole, a promising antineoplastic drug, target EAG1 by inhibiting its expression and blocking ion currents, respectively. We have previously shown a synergistic antiproliferative effect of calcitriol and astemizole in breast cancer cells in vitro, but the effect of this dual therapy in vivo has not been studied. METHODS: In the present study, we explored the combined antineoplastic effect of both drugs in vivo using mice xenografted with the human breast cancer cell line T-47D and a primary breast cancer-derived cell culture (MBCDF). Tumor-bearing athymic female mice were treated with oral astemizole (50 mg/kg/day) and/or intraperitoneal injections of calcitriol (0.03 µg/g body weight twice a week) during 3 weeks. Tumor sizes were measured thrice weekly. For mechanistic insights, we studied EAG1 expression by qPCR and Western blot. The expression of Ki-67 and the relative tumor volume were used as indicators of therapeutic efficacy. RESULTS: Compared to untreated controls, astemizole and calcitriol significantly reduced, while the coadministration of both drugs further suppressed, tumor growth (P < 0.05). In addition, the combined therapy significantly downregulated tumoral EAG1 and Ki-67 expression. CONCLUSIONS: The concomitant administration of calcitriol and astemizole inhibited tumor growth more efficiently than each drug alone, which may be explained by the blocking of EAG1. These results provide the bases for further studies aimed at testing EAG1-dual targeting in breast cancer tumors expressing both EAG1 and the vitamin D receptor.