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1.
JAC Antimicrob Resist ; 6(3): dlae069, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38716403

RESUMEN

Background: The cefazolin inoculum effect (CzIE) is a phenomenon whereby some MSSA isolates demonstrate resistance to cefazolin when a high bacterial inoculum is used for susceptibility testing. The clinical significance of this phenotypic phenomenon remains unclear. We conducted a systematic review to answer the following question: In patients with serious MSSA infection treated with cefazolin, does infection due to CzIE-positive MSSA isolates result in worse clinical outcomes than infection due to CzIE-negative MSSA isolates? Methods: Ovid MEDLINE, Embase, Cochrane CENTRAL, medRxiv and bioRxiv were searched from inception until 12 April 2023. Studies were included if they tested for CzIE in clinical isolates from MSSA infections in humans. Two independent reviewers extracted data and conducted risk-of-bias assessment. Main outcomes were treatment failure and mortality. Pooling of study estimates was not performed given the heterogeneity of patient populations and outcome definitions. Results: Twenty-three observational studies were included. CzIE presence amidst MSSA isolates ranged from 0% to 55%. There was no statistically significant mortality difference in two studies that compared MSSA infections with and without CzIE, with ORs ranging from 0.72 to 19.78. Of four studies comparing treatment failure, ORs ranged from 0.26 to 13.00. One study showed a significantly higher treatment failure for the CzIE group, but it did not adjust for potential confounders. Conclusions: The evidence on CzIE is limited by small observational studies. In these studies, CzIE did not predict higher mortality in MSSA infections treated with cefazolin. Our findings do not support CzIE testing in clinical practice currently.

2.
Arthritis Res Ther ; 26(1): 99, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38741185

RESUMEN

OBJECTIVES: This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. METHODS: We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. RESULTS: Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. CONCLUSION: Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.


Asunto(s)
Lupus Eritematoso Sistémico , Transcriptoma , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Humanos , Femenino , Adulto , Masculino , Persona de Mediana Edad , Perfilación de la Expresión Génica/métodos , Leucocitos Mononucleares/metabolismo , Mapas de Interacción de Proteínas/genética
3.
Int J Womens Dermatol ; 10(1): e126, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38313363

RESUMEN

Background: Injectable neurotoxins and fillers are potential options for facial gender affirmation for transgender/nonbinary patients. However, the largest barrier to access is cost/insurance coverage. Objective: The purpose of this article is to assess the extent to which Affordable Care Act (ACA) silver plans and Medicaid policies cover gender-affirming injectable neurotoxin and filler procedures. Methods: A cross-sectional study of all ACA silver plans and Medicaid policies was performed from June 22 to August 15, 2021. Plan-specific certificates of coverage, clinical policies of insurance providers, and Medicaid documents were evaluated. Results: A total of 915 plans were reviewed (864 ACA silver plans and all 51 Medicaid policies). None potentially covered neurotoxins. Only 72 (71 ACA and 1 Medicaid) potentially covered fillers, specifically collagen injections and lipofilling. Coverage required demonstration of medical necessity or significant variation of physical appearance from the patient's experienced gender. However, of the 71 ACA plans, 69 outlined cosmetic exclusions, possibly nullifying this coverage. Limitations: Data were sourced from publicly available online information in 2021. Additionally, we were unable to confirm explicit coverage of these procedures with insurance companies. Conclusion: The majority of ACA silver and Medicaid plans did not cover gender-affirming neurotoxin or filler procedures, limiting access to this gender-affirming care.

5.
Exp Dermatol ; 33(1): e14998, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38284186

RESUMEN

In photoaged human skin, type I collagen fragmentation impairs dermal extracellular matrix (ECM) integrity, resulting in collapsed/contracted fibroblasts with reduced type I procollagen synthesis. Injections of cross-linked hyaluronic acid (CL-HA) reverse these deleterious changes. To investigate the time course and effects of biochemical changes induced by injected CL-HA, particularly whether fibroblast activation leads to accumulation/deposition of dermal collagen, we injected CL-HA into photoaged skin of human participants over 60 years-old and performed biochemical/microscopic analyses of skin samples. Beginning 1 week post-injection and lasting 6-9 months, fibroblasts exhibited activation, including increased immunostaining and gene expression of markers of type I collagen synthesis, such as heat shock protein 47 and components of the transforming growth factor-ß pathway. At 1 week post-injection, multiphoton microscopy revealed elongation/stretching of fibroblasts, indicating enhanced dermal mechanical support. At 4 weeks, second-harmonic generation microscopy revealed thick collagen bundles densely packed around pools of injected CL-HA. At 12 months, accumulation of thick collagen bundles was observed and injected CL-HA remained present in substantial amounts. Thus, by occupying space in the dermal ECM, injected CL-HA rapidly and durably enhances mechanical support, stimulating fibroblast elongation and activation, which results in thick, densely packed type I collagen bundles accumulating as early as 4 weeks post-injection and continuing for at least a year. These observations indicate that early and prolonged clinical improvement following CL-HA injection results from space-filling and collagen deposition. As type I collagen has an estimated half-life of 15 years, our data provide the foundations for optimizing the timing/frequency of repeat CL-HA injections.


Asunto(s)
Colágeno Tipo I , Ácido Hialurónico , Humanos , Persona de Mediana Edad , Colágeno Tipo I/metabolismo , Ácido Hialurónico/metabolismo , Colágeno/metabolismo , Piel/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo
6.
Arch Pathol Lab Med ; 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38282571

RESUMEN

CONTEXT.­: Eosinophilic solid and cystic renal cell carcinoma is now defined in the 5th edition of the 2022 World Health Organization classification of urogenital tumors. OBJECTIVE.­: To perform morphologic, immunohistochemical, and preliminary genetic studies about this new entity in China for the purpose of understanding it better. DESIGN.­: The study includes 18 patients from a regional tertiary oncology center in northern China (Tianjin, China). We investigated the clinical and immunohistochemical features of these cases. RESULTS.­: The mean age of patients was 49.6 years and the male to female ratio was 11:7. Macroscopically, 1 case had the classic cystic and solid appearance whereas the others appeared purely solid. Microscopically, all 18 tumors shared similar solid and focal macrocystic or microcystic growth pattern, and the cells were characterized by voluminous and eosinophilic cytoplasm, along with coarse amphophilic stippling. Immunohistochemically, most of the tumors had a predominant cytokeratin (CK) 20-positive feature, ranging from focal cytoplasmic staining to diffuse membranous accentuation. Initially, we separated these cases into different immunohistochemical phenotypes. Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. Group 2 (4 of 18; 23%) was negative for NF2, probably implying a germline mutation of NF2. Group 3 (7 of 18; 38.5%) consisted of the remaining cases. One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression. CONCLUSIONS.­: Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential.

7.
J Adv Nurs ; 80(2): 526-537, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37530449

RESUMEN

AIMS: The aim of the study was to explore plans, considerations and factors influencing long-term care among older sexual minority (SM) women. DESIGN: Qualitative interview study. METHODS: Semi-structured in-depth interviews were conducted with 37 older Taiwanese SM women between May and September 2019. This study analysed interview data using a socio-ecological model and constant comparative analysis. RESULTS: The most frequently reported long-term care plans were housing and institutions, private medical or long-term care insurance, financial planning and medical decisions. Factors associated with women's long-term care plans were categorized using the socio-ecological model level: (1) intrapersonal factors: current physical and mental health status, ageing signs and women's attitudes towards ageing; (2) interpersonal-level factors: receiving support from partners, child(ren), siblings or significant others, concerns about being a caregiver for parents and worries regarding social isolation; (3) community-level factors: receiving support from lesbian, gay, bisexual and transgender (LGBT) organizations; private lesbian online groups; or religious groups; (4) societal-level factors: concerns about negative social environments, concerns about the healthcare system and healthcare providers, inappropriate policies and insufficient resources. CONCLUSION: This study identified multi-level factors related to long-term care plans and concerns among older Taiwanese SM women. Recommendations for nurses, managers of long-term care and healthcare settings, policymakers, and governments have been provided to diminish health disparities and reduce anxiety among older SM women. IMPACT: This study assists nurses in understanding older SM women's long-term care concerns and worries when accessing long-term care and healthcare services and helps nurses provide SM-sensitive services and care for women. PATIENT OR PUBLIC CONTRIBUTION: SM older women were recruited from LGBT organizations, LGBT-friendly bookstores, restaurants, coffee shops and LGBT online chatrooms using purposive and snowball sampling.


Asunto(s)
Homosexualidad Femenina , Minorías Sexuales y de Género , Personas Transgénero , Niño , Humanos , Femenino , Anciano , Cuidados a Largo Plazo , Homosexualidad Femenina/psicología , Personas Transgénero/psicología , Investigación Cualitativa
8.
Clin Exp Dermatol ; 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38060687

RESUMEN

BACKGROUND: During the COVID-19 pandemic, resident didactics at many institutions, including ours, were transitioned from in-person to virtual. OBJECTIVES: We aimed to assess dermatology residents' satisfaction, impression of effectiveness, and preference for virtual didactics, and factors correlating with these sentiments. METHODS: Questionnaire administered to dermatology residents at our institution 3-6 months following transition to virtual didactics. RESULTS: Response rate was 26/31 residents (83.9%), with 20/26 (76.9%) expressing satisfaction, 15/26 (57.7%) effectiveness, and 12/26 (46.2%) preference towards virtual didactics. Factors associated with satisfaction included feeling that virtual didactics positively impacted learning retention, represented time well spent, and utilized high-quality images. Perception of effectiveness correlated with using high-quality images, baseline preference for online instruction, and feeling engaged. Factors associated with preference for virtual didactics included having opportunities for critical thinking, using high-quality images, and utilizing images applicable to teledermatology care. Advantages to virtual didactics included convenience, decreased commuting, and easily hosting guest lecturers. Disadvantages included distractions/decreased focus, reduced social interaction, and difficulty with communication. CONCLUSIONS: Residents expressed satisfaction, effectiveness, and some preference towards virtual didactics, which correlated with numerous factors. Our findings suggest that it is reasonable to maintain a virtual didactic component as part of dermatology resident education. Furthermore, our data provide insights into strategies that residency program directors and educators may consider when/if integrating virtual didactics into future educational curricula.

9.
Artículo en Inglés | MEDLINE | ID: mdl-38141203

RESUMEN

OBJECTIVES: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies. METHODS: RNA-sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analyzed and scored to elucidate the transcriptomic changes during treatment. RESULTS: Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts, and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts. CONCLUSIONS: In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development.

11.
medRxiv ; 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37609199

RESUMEN

Objectives: Oral fluids provide ready detection of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host responses. This study sought to determine relationships between oral virus, oral anti-SARS-CoV-2-specific antibodies, and symptoms. Methods: Saliva/throat wash (saliva/TW) were collected from asymptomatic and symptomatic, nasopharyngeal (NP) SARS-CoV-2 RT-qPCR+, subjects (n=47). SARS-CoV-2 RT-qPCR, N-antigen detection by immunoblot and lateral flow assay (LFA) were performed. RT-qPCR targeting viral subgenomic RNA (sgRNA) was sequence confirmed. SARS-CoV-2-anti-S protein RBD LFA assessed IgM and IgG responses. Structural analysis identified host salivary molecules analogous to SARS-CoV-2-N-antigen. Statistical analyses were performed. Results: At baseline, LFA-detected N-antigen was immunoblot-confirmed in 82% of TW. However, only 3/17 were saliva/TW qPCR+. Sixty percent of saliva and 83% of TW demonstrated persistent N-antigen at 4 weeks. N-antigen LFA signal in three negative subjects suggested potential cross-detection of 4 structurally analogous salivary RNA binding proteins (alignment 19-29aa, RMSD 1-1.5 Angstroms). At entry, symptomatic subjects demonstrated replication-associated sgRNA junctions, were IgG+ (94%/100% in saliva/TW), and IgM+ (75%/63%). At 4 weeks, SARS-CoV-2 IgG (100%/83%) and IgM (80%/67%) persisted. Oral IgG correlated 100% with NP+PCR status. Cough and fatigue severity (p=0.0008 and 0.016), and presence of nausea, weakness, and composite upper respiratory symptoms (p=0.005, 0.037 and 0.017) were negatively associated with oral IgM. Female oral IgM levels were higher than male (p=0.056). Conclusion: Important to transmission and disease course, oral viral replication and persistence showed clear relationships with select symptoms, early Ig responses, and gender during early infection. N-antigen cross-reactivity may reflect mimicry of structurally analogous host proteins.

12.
J Cutan Pathol ; 50(11): 942-946, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37615213

RESUMEN

Malakoplakia is a rare chronic inflammatory condition that most commonly involves the urogenital tract. Cutaneous malakoplakia is extremely rare and many patients diagnosed with skin involvement are immunosuppressed. While the clinical presentation of cutaneous malakoplakia is variable, the histopathologic features are quite distinct and include sheets of closely packed dermal histiocytes with foamy-appearing cytoplasm and Michaelis-Gutmann bodies that are positive with certain immunohistochemical stains. While the exact pathogenesis of malakoplakia is unknown, it has been associated with certain bacterial infections. Treatment generally involves a combination of surgery and antimicrobial agents and/or modulation of immunosuppressant therapy if appropriate. Herein, the authors report a unique case of cutaneous malakoplakia arising in a patient on chronic immunosuppressive therapy for the management of pyoderma gangrenosum.

13.
Bioanalysis ; 15(14): 833-843, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37584364

RESUMEN

Aim: Aur0101 is a cytotoxic and small-molecule microtubule depolymerizing agent, and is the payload conjugated to antibody-drug conjugate PYX-201. Developing and validating a sensitive bioanalytical method to quantitate Aur0101 was novel and crucial in preclinical PYX-201 studies. Materials & methods: Reference standard Aur0101 and its stable isotope labelled internal standard Aur0101-d8 were used in this LC-MS/MS method. Results: This sensitive assay was validated at a lower limit of quantitation of 15 pg/ml and successfully applied to support preclinical rat and monkey toxicology studies. Preclinical plasma toxicokinetic parameters were presented. Conclusion: A sensitive and robust LC-MS/MS assay was validated for Aur0101 in rat and monkey plasma.


Asunto(s)
Antineoplásicos , Inmunoconjugados , Ratas , Animales , Cromatografía Liquida/métodos , Haplorrinos , Espectrometría de Masas en Tándem/métodos , Reproducibilidad de los Resultados
14.
Res Sq ; 2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37645853

RESUMEN

Objectives: Oral fluids provide ready detection of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host responses. This study sought to determine relationships between oral virus, oral anti-SARS-CoV-2-specific antibodies, and symptoms. Methods: Saliva/throat wash (saliva/TW) were collected from asymptomatic and symptomatic, nasopharyngeal (NP) SARS-CoV-2 RT-qPCR+, subjects (n=47). SARS-CoV-2 RT-qPCR, N-antigen detection by immunoblot and lateral flow assay (LFA) were performed. RT-qPCR targeting viral subgenomic RNA (sgRNA) was sequence confirmed. SARS-CoV-2-anti-S protein RBD LFA assessed IgM and IgG responses. Structural analysis identified host salivary molecules analogous to SARS-CoV-2-N-antigen. Statistical analyses were performed. Results: At baseline, LFA-detected N-antigen was immunoblot-confirmed in 82% of TW. However, only 3/17 were saliva/TW qPCR+. Sixty percent of saliva and 83% of TW demonstrated persistent N-antigen at 4 weeks. N-antigen LFA signal in three negative subjects suggested potential cross-detection of 4 structurally analogous salivary RNA binding proteins (alignment 19-29aa, RMSD 1-1.5 Angstroms). At entry, symptomatic subjects demonstrated replication-associated sgRNA junctions, were IgG+ (94%/100% in saliva/TW), and IgM+ (75%/63%). At 4 weeks, SARS-CoV-2 IgG (100%/83%) and IgM (80%/67%) persisted. Oral IgG correlated 100% with NP+PCR status. Cough and fatigue severity (p=0.0008 and 0.016), and presence of nausea, weakness, and composite upper respiratory symptoms (p=0.005, 0.037 and 0.017) were negatively associated with oral IgM. Female oral IgM levels were higher than male (p=0.056). Conclusion: Important to transmission and disease course, oral viral replication and persistence showed clear relationships with select symptoms, early Ig responses, and gender during early infection. N-antigen cross-reactivity may reflect mimicry of structurally analogous host proteins.

15.
bioRxiv ; 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37398270

RESUMEN

The ongoing COVID-19 pandemic has caused millions of deaths and the continued emergence of new variants suggests continued circulation in the human population. In the current time of vaccine availability and new therapeutic development, including antibody-based therapies, many questions about long-term immunity and protection remain uncertain. Identification of protective antibodies in individuals is often done using highly specialized and challenging assays such as functional neutralizing assays, which are not available in the clinical setting. Therefore, there is a great need for the development of rapid, clinically available assays that correlate with neutralizing antibody assays to identify individuals who may benefit from additional vaccination or specific COVID-19 therapies. In this report, we apply a novel semi-quantitative method to an established lateral flow assay (sqLFA) and analyze its ability to detect the presence functional neutralizing antibodies from the serum of COVID-19 recovered individuals. We found that the sqLFA has a strong positive correlation with neutralizing antibody levels. At lower assay cutoffs, the sqLFA is a highly sensitive assay to identify the presence of a range of neutralizing antibody levels. At higher cutoffs, it can detect higher levels of neutralizing antibody with high specificity. This sqLFA can be used both as a screening tool to identify individuals with any level of neutralizing antibody to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or as a more specific tool to identify those with high neutralizing antibody levels who may not benefit from antibody-based therapies or further vaccination.

16.
Nurse Educ Today ; 129: 105914, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37481921

RESUMEN

BACKGROUND: Health disparities exist among lesbian, gay, bisexual, and transgender (LGBT) populations worldwide. However, student nurses and nurse staff have limited knowledge and skills in providing culturally competent nursing care for LGBT patients in Taiwan. OBJECTIVES: This paper describes the development, implementation, and evaluation of an online training program for the cultural competence of student nurses and nurses in Taiwan. DESIGN: A one-group pre-/post-test study design. SETTINGS: The study was conducted in five nursing schools, 10 nursing associations, and 37 long-term care facilities. Two prominent online bulletin boards (PTT Nurse and Dcard Nurse) and one Taiwanese nursing group on Facebook were used to recruit participants. PARTICIPANTS: In total, 301 student nurses and nurses participated in the study and responded to pre- and post-test questionnaires. METHODS: An online training program for culturally competent nursing care was developed and implemented. The pre- and post-test questionnaires contained three sections: (1) demographics, (2) knowledge of LGBT health, and (3) the Sexual Orientation Counselor Competency Scale. Three open-ended questions were included in the post-test questionnaire to evaluate the online training program. RESULTS: The online training program significantly improved the participants' knowledge and cultural competence skills. However, their attitudes towards cultural competence did not change after the program was implemented. Regarding qualitative feedback of the online training program, feedback on the strengths and limitations of the program was summarized under three themes: program content, website design, and online modules. CONCLUSIONS: The results suggest the importance of an online training program which may contribute to reducing health disparities among the LGBT population.


Asunto(s)
Enfermeras y Enfermeros , Minorías Sexuales y de Género , Estudiantes de Enfermería , Personas Transgénero , Humanos , Femenino , Masculino , Competencia Cultural/educación , Conducta Sexual
17.
Med Sci Educ ; : 1-7, 2023 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-37360065

RESUMEN

The COVID-19 pandemic has highlighted a continued need for innovative virtual teaching methods. Chalk talks, or brief illustrated interactive talks, are easily made virtual with an online whiteboard. We evaluated the efficacy of a live virtual chalk talk curriculum for medical students on their dermatology clerkship. A curriculum of one to three 1-h chalk talks was designed on the following topics: papulosquamous diseases, erythroderma, and immunobullous diseases. Talks were delivered monthly via Zoom to dermatology clerkship students. Pre- and post-talk surveys were administered to assess knowledge, confidence, and satisfaction. Compared with pre-talk, students (n = 18) achieved a greater percentage of possible points on knowledge assessment questions after the talks (41.0 ± 27.7% versus 90.4 ± 18.4%, p < 0.001). As assessed on a Likert scale (1 = not at all confident, 5 = extremely confident), students became more confident in differentiating conditions within each disease group and working up the conditions (2.02 ± 0.53 versus 3.53 ± 0.55, p < 0.001, and 2.09 ± 0.44 versus 3.76 ± 0.89, p < 0.001, respectively). Qualitative responses showed that students appreciated the student-teacher interactions. In conclusion, we found that live chalk talks are an effective and engaging way to teach dermatology to medical students in the virtual setting. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01781-4.

18.
J Pharm Biomed Anal ; 233: 115452, 2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37167766

RESUMEN

PYX-201 is an investigative ADC oncology drug composed of a monoclonal human immunoglobulin G (IgG) antibody targeting the extra domain B splice variant of fibronectin (EDB + FN) conjugated to an auristatin payload through a cleavable linker. Effective measurement of PYX-201 tAb is the key to ADC drug PYX-201 preclinical pharmacokinetics (PK) assessment. PYX-201 monoclonal antibody (mAb) was used as the reference standard, goat anti-human IgG polyclonal antibody (pAb) or rabbit anti-human Kappa light chain mAb was employed as the capture antibody, and mouse mAb or goat pAb anti-human IgG the crystallizable fragment (Fc) (horseradish peroxidase (HRP)) was utilized as the detection antibody in this ELISA. This assay was validated with a dynamic range 250 - 10,000 ng/mL and 250 - 6000 ng/mL in rat and monkey K2EDTA plasma, respectively. PYX-201 tAb bioanalytical ELISA assay was reported for the first time in any biological matrix. This is the first time for a bioanalytical method to be validated for a tAb from an ADC drug targeting EDB + FN in any biological matrix.


Asunto(s)
Inmunoconjugados , Ratones , Ratas , Animales , Conejos , Ensayo de Inmunoadsorción Enzimática , Anticuerpos Monoclonales , Peroxidasa de Rábano Silvestre , Inmunoglobulina G
19.
Bioanalysis ; 15(1): 43-52, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36876967

RESUMEN

Aim: PYX-201 is a novel antibody-drug conjugate targeting the extra domain B splice variant of fibronectin in the tumor microenvironment. Accurate quantification of PYX-201 is critical for PYX-201 pharmacokinetics profiling in preclinical studies. Materials & methods: ELISA was performed using reference standard PYX-201, mouse monoclonal anti-monomethyl auristatin E antibody, mouse IgG1, mouse monoclonal anti-human IgG horseradish peroxidase and donkey anti-human IgG horseradish peroxidase. Results: This assay was validated at 50.0-10,000 ng/ml in rat dipotassium EDTA plasma and 250-10,000 ng/ml in monkey dipotassium EDTA plasma. Conclusion: This is the first time for a PYX-201 bioanalytical assay in any matrix to be reported.


Asunto(s)
Inmunoconjugados , Ratas , Ratones , Animales , Ácido Edético , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina G
20.
J Surg Case Rep ; 2023(3): rjad142, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36926621

RESUMEN

Breast cancer is the most common type of cancer diagnosed among women worldwide. It significantly contributes to cancer-related mortality in females. Early-stage breast cancers have a high cure rate. However, distant metastasis of breast cancer due to haematological and lymphatic spread often leads to a poor prognosis. Gastric and duodenal metastasises are rarely observed in invasive lobular carcinoma of the breast. Early diagnosis is challenging due to the non-specific symptoms, the limited specificity of radiological investigations and the difficulty in obtaining adequate tissue biopsy. Herein, we report the clinical, radiological, and macroscopic features of a 72-year-old female with rare gastric metastasis of breast cancer and likely concurrent duodenal metastasis.

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