Large libraries of single-chain trimer peptide-MHCs enable antigen-specific CD8+ T cell discovery and analysis.

The discovery and characterization of antigen-specific CD8+ T cell clonotypes typically involves the labor-intensive synthesis and construction of peptide-MHC tetramers. We adapt single-chain trimer (SCT) technologies into a high throughput platform for pMHC library generation, showing that hundreds can be rapidly prepared across multiple Class I HLA alleles. We use this platform to explore the impact of peptide and SCT template mutations on protein expression yield, thermal stability, and functionality. SCT libraries were an efficient tool for identifying T cells recognizing commonly reported viral epitopes. We then construct SCT libraries to capture SARS-CoV-2 specific CD8+ T cells from COVID-19 participants and healthy donors. The immunogenicity of these epitopes is validated by functional assays of T cells with cloned TCRs captured using SCT libraries. These technologies should enable the rapid analyses of peptide-based T cell responses across several contexts, including autoimmunity, cancer, or infectious disease.

The Compassion Club: A New Proposal for Transformation of Tobacco Retail.

INTRODUCTION: One major assumption in the current tobacco industry is the distribution of tobacco products through a system of commercial for-profit retail. However, other models of distribution that do not rely on this mechanism exist. AIMS AND METHODS: In this review, we examine the potential of a nonprofit Compassion Club model and discuss how the current existence of independent vape stores might provide the infrastructure to allow the transformation of tobacco distribution. RESULTS: Compassion Clubs exist internationally with different levels of regulation and legality and have generally been focused on the distribution of illegal drugs or hard-to-access pharmaceuticals. They provide access to drugs for existing users, limit access by novices, limit negative impacts from illicit markets, and provide social support focused on reducing harms associated with drug use. CONCLUSIONS: With decreasing prevalence of tobacco use in many countries and growing interest in a tobacco endgame, a Compassion Club model of distribution could help transition tobacco away from the model of commercial widely available distribution. More work is needed to develop the regulations and policies that might guide a compassion club model. IMPLICATIONS: Compassion clubs are a model for the distribution of psychoactive substances that are focused on harm reduction and social support rather than profit. There has been little discussion about the possibility that this promising model could be applied to help transform the tobacco industry. Many independent vape stores already demonstrate aspects of the compassion club model that could be used to support a transition.

Large libraries of single-chain trimer peptide-MHCs enable rapid antigen-specific CD8+ T cell discovery and analysis.

CD8 + cytotoxic T cell responses against viral infection represent a major element of the adaptive immune response. We describe the development of a peptide antigen - major histompatibility complex (pMHC) library representing the full SARS-CoV-2 viral proteome, and comprised of 634 pMHC multimers representing the A*02.01, A*24.02, and B*07.02 HLA alleles, as well as specific antigens associated with the cytomegalovirus (CMV). These libraries were used to capture non-expanded CD8 + T cells from blood samples collected from 64 infected individuals, and then analyzed using single cell RNA-seq. The discovery and characterization of antigen-specific CD8 + T cell clonotypes typically involves the labor-intensive synthesis and construction of peptide-MHC tetramers. We adapted single-chain trimer (SCT) technologies into a high throughput platform for pMHC library generation, showing that hundreds can be rapidly prepared across multiple Class I HLA alleles. We used this platform to explore the impact of peptide and SCT template mutations on protein expression yield, thermal stability, and functionality. SCT libraries were an efficient tool for identifying T cells recognizing commonly reported viral epitopes. We then constructed SCT libraries designed to capture SARS-CoV-2 specific CD8 + T cells from COVID-19 participants and healthy donors. The immunogenicity of these epitopes was validated by functional assays of T cells with cloned TCRs captured using SCT libraries. These technologies should enable the rapid analyses of peptide-based T cell responses across several contexts, including autoimmunity, cancer, or infectious disease.

You are at rock bottom: A qualitative systematic review of the needs of bereaved parents as they journey through the death of their child to cancer.

PROBLEM IDENTIFICATION: This systematic review will examine the social support needs of bereaved parents in the specific context of pediatric cancer by synthesizing the qualitative evidence. Social support encompasses emotional, practical, informational, and meaning-making support needs. LITERATURE SEARCH: The Joanna Briggs Institute procedures for conducting qualitative systematic reviews guided every stage of this review. Four databases (PsychInfo, CINAHL, Pubmed, and ASSIA) were systematically searched, in addition to the gray literature and scoping review. Through a five-step critical appraisal process 11 out of 668 potential articles were identified as meeting the inclusion criteria. DATA EVALUATION/SYNTHESIS: Relevant findings were synthesized with a thematic-synthesis approach. Findings, which follow the journey of bereaved parents integrated under the core-category "Needs." This encompasses of four higher-level categories: Last days: Parent needs when caring for their dying child Rest in peace: Parent needs during the child's death Feeling abandoned: Parent needs for contact after the child's death Searching for Meaning: Parents needs when making sense of loss. CONCLUSION: Informational support needs is largely unexplored in academic literature. Staff in the treating-hospital are central in offering bereavement-support to parents, who may otherwise feel that they have lost their second home (hospital) and second family (staff).

Endoscopic transnasal septotomy for contralateral orbital apex venous angioma resection and decompression.

Tumors of the orbital apex region are traditionally difficult to approach surgically due to key anatomic structures found in this highly crowded region. We present a case of progressively enlarging orbital apex venous angioma treated with a novel endoscopic transnasal septotomy technique. We highlight the key steps to this approach, as well as specific landmarks necessary to achieve a safe and successful outcome.

Graduated endoscopic multiangle approach for access to the infratemporal fossa: a cadaveric study with clinical correlates.

OBJECTIVE: The infratemporal fossa (ITF) has historically been one of the most difficult regions of the skull base to access surgically. Available open approaches are complex, are associated with high morbidity, and do not always afford optimal visualization. Endoscopic access to the ITF improves visualization for management of many sinonasal and lateral skull base lesions involving this region. The purpose of this study is to evaluate a graduated multiangle approach for endoscopic access to this area using a cadaveric model. STUDY DESIGN AND SETTING: Cadaveric study at an academic medical center. METHODS: Endoscopic dissection was performed on a total of 10 sides of 5 fresh cadaveric heads. Four different approaches to the ITF were studied: ipsilateral endonasal, endoscopically assisted Caldwell-Luc, contralateral endonasal via septotomy, and endoscopically assisted Gillies transtemporal. High-quality endoscopic pictures and high-definition videos of each technique were obtained in order to document the differences in access achieved with each approach. RESULTS: The combination of the 4 different endoscopic techniques allowed complete access to all areas of the ITF. The endoscopically assisted Caldwell-Luc improved anteroposterior access, the contralateral septotomy approach resulted in excellent far lateral access, and the endoscopically assisted Gillies approach allowed posterosuperior visualization and instrumentation. CONCLUSION: Endoscopic access to the ITF can be accomplished by each of the 4 methods described. A multiangle, graduated approach can provide surgeons the ability to customize surgical access depending on the location of a specific lesion within the ITF.

Modified hemi-Lothrop procedure for supraorbital frontal sinus access: a cadaveric feasibility study.

OBJECTIVE: The endoscopic modified Lothrop procedure (EMLP) is a relatively safe and efficacious advanced approach to access the frontal sinus for recalcitrant disease. There have been limited data specifically addressing those patients with advanced but unilaterally limited and supraorbitally based frontal sinus disease. In this study, the authors propose a modification of the EMLP technique, titled a modified hemi-Lothrop procedure (MHLP), which would limit the dissection of the EMLP to removal of the frontal sinus floor of the unilaterally diseased frontal sinus, thereby sparing the mucosa and natural drainage pathways of the nondiseased contralateral frontal sinus. STUDY DESIGN AND SETTING: Cadaveric study at an academic medical center. METHODS: A cadaveric dissection with photodocumentation was performed to demonstrate the MHLP and to quantify the accessibility of this approach to far-laterally based frontal sinus disease. RESULTS: The MHLP dissection was shown to provide adequate access to the most distal supraorbital and laterally based aspects of the frontal sinus. Using 3 cadavers, the authors demonstrated and documented the technique of MHLP to access lateral frontal sinus disease from the contralateral nasal cavity via a superior septectomy window. CONCLUSION: The MHLP was demonstrated to be a feasible approach and alternative to more traditional endoscopic procedures in addressing unilateral frontal sinus disease. This modification may be useful in addressing difficult to access unilateral disease that may otherwise require more extensive resection. This demonstration helps define the accessibility of the lateral frontal sinus via an MHLP and begins to provide estimates of which patients may benefit from this approach.

Laser treatment for ethnic skin.

With the growth of new technology and products over the last 10 years, there has been an increased ability to improve a patient's appearance with procedures that can be performed in an office setting, including laser procedures. Demand for these procedures has grown among all ethnic groups. Patients with ethnic skin can have varying response to lasers. This factor should be considered when planning their treatment. After laser treatment, Patients with ethnic skin are at greater risk for laser energy absorption by melanin, postinflammatory hyperpigmentation, and loss of pigment due to laser effects on melanin production leading to hypopigmentation. Therefore, any laser therapy should be planned carefully, especially in the treatment of patients with darker skin types.

Primary cutaneous mucinous adenocarcinoma of the face: a case report in a 63 year-old.

Primary cutaneous mucinous adenocarcinoma is a rare sweat gland malignancy that most commonly occurs in the head and neck region. The histopathological similarities between primary cutaneous and metastasis from primary visceral tumors allow for both an interesting diagnostic dilemma as well as important management considerations with these patients.

Exploratory tympanotomy revealing incus discontinuity and stapedial otosclerosis as a cause of conductive hearing loss.

OBJECTIVE: To describe a unilateral progressive conductive hearing loss caused by incus discontinuity (without erosion of the long process of the incus), and otosclerosis with fixation of the stapedial footplate. STUDY DESIGN: Case report. SETTING: Department of Otolaryngology, Head and Neck Surgery of the University of Rochester Medical Center, which is a regional tertiary referral center. PATIENT: A 54-year-old woman with multiple otologic complaints including tympanic membrane perforations, otalgia, tinnitus, and hearing loss. Audiography demonstrated 100% speech discrimination bilaterally and a significant conductive right-sided hearing loss. INTERVENTION: The patient underwent a stapedectomy, during which a discontinuity between the long process of the incus and the stapes with no bony erosion was identified. The stapedectomy was completed and an ossicular piston prosthesis was inserted to reestablish ossicular continuity with the tympanic membrane. MAIN OUTCOME MEASURE: Improved subjective hearing confirmed objectively by audiography. CONCLUSION: This is the third reported case of an unusual combination of otosclerosis and ossicular discontinuity, and the first such case report in a patient without head trauma. In addition, it adds a unique item to the differential diagnosis of the pathologic features implicated in an ear with a conductive deficit and normal tympanogram.