Optimization of a micro-scale air-liquid-interface model of human proximal airway epithelium for moderate throughput drug screening for SARS-CoV-2.

Background: Many respiratory viruses attack the airway epithelium and cause a wide spectrum of diseases for which we have limited therapies. To date, a few primary human stem cell-based models of the proximal airway have been reported for drug discovery but scaling them up to a higher throughput platform remains a significant challenge. As a result, most of the drug screening assays for respiratory viruses are performed on commercial cell line-based 2D cultures that provide limited translational ability.

The effect of mandibular advancement on pharyngeal airway space in patients with oral squamous cell carcinoma: A monocentric prospective study with computed tomography.

Objectives: The presented study aimed to evaluate the effect of mandibular protrusion with a temporarily applied mandibular advancement device (MAD) on the posterior airway space and to determine a reliable metric constant based on a three-dimensional computed tomography (CT) evaluation.

Materials And Methods: The study population consisted of patients with oral squamous cell carcinoma who were treated at least six months prior to the follow-up CT in supine position. Each patient received an individually adjusted MAD that was temporarily applied with three different protrusion distances (P = 0 mm, P = 4 mm, and P = 8 mm) during follow-up CT.

Synthesis and Structure-Activity Relationship of Covalent Inhibitors of SARS-CoV-2 Papain-Like Protease with Antiviral Potency.

The papain-like protease (PLpro) is a highly conserved domain encoded by the coronavirus (CoV) genome and it plays an essential role in the replication and maturation of the virus in addition to weakening host immune response. Due to the virus's reliance on PLpro for survival and propagation, small-molecule inhibitors of PLpro serve as an attractive model for direct-acting antiviral therapeutic agents against SARS-CoV-2. Building upon existing work aimed at designing covalent inhibitors against PLpro, we report the synthesis and structure-activity relationship of analogs based on the known covalent inhibitor 1 (Sanders, et al.

An oral non-covalent non-peptidic inhibitor of SARS-CoV-2 Mpro ameliorates viral replication and pathogenesis in vivo.

Safe, effective, and low-cost oral antiviral therapies are needed to treat those at high risk for developing severe COVID-19. To that end, we performed a high-throughput screen to identify non-peptidic, non-covalent inhibitors of the SARS-CoV-2 main protease (Mpro), an essential enzyme in viral replication. NZ-804 was developed from a screening hit through iterative rounds of structure-guided medicinal chemistry.

Impact of tumor localization and choice of microvascular flap on posterior airway changes following ablative surgery in primary oral squamous cell carcinoma: A monocentric cross-sectional study.

Background: The aim of this study was to determine the influence of intraoral reconstructions following oral squamous cell carcinoma (OSCC) resection with a free microvascular flap on the posterior airway space (PAS) and to correlate these results with the potential risk of developing an obstructive sleep apnea syndrome (OSAS).

Materials And Methods: Only primary OSCC cases of the tongue or floor of the mouth which were operated and reconstructed. The PAS displayed in computed tomography (CT) scans at three time points were analyzed: t = preoperative, t = first postoperative CT, and t = most recent situation.

Reprint of: Impact of outpatient pharmacist dispensing in an opioid use disorder clinic.

Background: Medications for opioid use disorder are effective in reducing opioid deaths, but access can be an issue. Relocating an outpatient pharmacist for weekly buprenorphine dispensing in an outpatient clinic may facilitate coverage for buprenorphine and mitigate access and counseling barriers.

Objectives: This study aimed to evaluate whether staffing an outpatient resident pharmacist to dispense in the buprenorphine clinic had a positive impact on (1) mean cost per prescription charged to charity care and (2) basic elements of patient satisfaction with the on-site pharmacist.

Pre- and post-pandemic risk perceptions and worries.

Introduction: The present study is a cross-sectional investigation of worry and risk perceptions regarding various hazards and destinations, measured before, during, and after the COVID-19 pandemic.

Methods: Questionnaire data were collected from tourists in Norway during the summer seasons of 2012 ( = 2,669), 2019 ( = 1,666), and 2022 ( = 956), and from a representative sample of Norwegians in 2020 ( = 1,003).

Results: The results show a general decline in the level of worry and risk perceptions post-pandemic compared to those pre-pandemic, with the exception of infectious diseases, whose perceived risk slightly increased in 2022.

Using the refractive index of latent fingerprints for the quantification and characterisation of sample deposition.

Latent fingerprints (LFPs) are predominantly used for personal identification, but in recent years research has shown their potential for drug screening. Despite this there is no standardised collection method to allow accurate drug test interpretation. We sought to help address this by characterising different variables related to sweat deposition in LFPs as the knowledge is limited.

CRISPR/Cas9-mediated knock out of ITGB6 in human OSCC cells reduced migration and proliferation ability.

Background: The treatment of oral squamous cell carcinoma (OSCC) remains challenging and survival rates have not been improved significantly over the past decades. Integrins have been recognized driving the cancer progression and high expression levels cause poor outcomes in patients afflicted with OSCC. Integrin αvβ6 and its subunit integrin beta 6 (ITGB6) were discovered to enhance the invasiveness by providing beneficial effects on downstream pathways promoting the cancer progression.

Pharmacist-community-based organization collaboration to address health-related social needs.

Background: Community-based organizations (CBOs) help address community issues, including health-related social needs (HRSNs). Community pharmacies are positioned to collaborate with CBOs to help their patients identify and address HRSNs to optimize medication use.

Objectives: To develop and evaluate 2 models of community pharmacy-CBO collaboration to address HRSNs facing patients taking medications.

Postoperative Opioid-Prescribing Practice in Limb Preservation Surgery.

Background: Limb preservation surgery affects more than 100,000 Americans annually. Current postoperative pain management prescribing practices of podiatric physicians in the United States are understudied. We examined prescribing practices for limb preservation surgery to identify prescriber characteristics' that may be associated with postoperative opioid-prescribing practices.

Impact of outpatient pharmacist dispensing in an opioid use disorder clinic.

Background: Medications for opioid use disorder are effective in reducing opioid deaths, but access can be an issue. Relocating an outpatient pharmacist for weekly buprenorphine dispensing in an outpatient clinic may facilitate coverage for buprenorphine and mitigate access and counseling barriers.

Objectives: This study aimed to evaluate whether staffing an outpatient resident pharmacist to dispense in the buprenorphine clinic had a positive impact on (1) mean cost per prescription charged to charity care and (2) basic elements of patient satisfaction with the on-site pharmacist.

Oral rehabilitation and associated quality of life following mandibular reconstruction with free fibula flap: a cross-sectional study.

Introduction: Mandibular reconstruction with the free fibula flap (FFF) has become a standardized procedure. The situation is different with oral rehabilitation, so the purpose of this study was to investigate the frequency of implant placement and prosthetic restoration. Additionally, the patients' situation, motivation, and treatment course were structurally assessed.

A review of analytical parameters in 'rapid' liquid chromatographic methods for bioanalysis: Can we do better?

Rapid bioanalysis is beneficial to many applications. However, how 'rapid' a method is, or could be, is often an unanswered question. In this statistical review, the authors have assessed multiple pre-analytical (i.

Contrast-enhanced computed tomography of retromandibular vein position and course patterns relative to the mandible during sagittal split ramus osteotomy.

Background: Sagittal split ramus osteotomy is an established procedure used in oral and maxillofacial surgery. Major bleeding is representative intraoperative complication involves vessels such as the inferior alveolar, facial, and maxillary arteries and accompanying veins, in particular the retromandibular vein (RMV). We previously described the RMV course patterns using embalmed cadavers.

An Integrative Medicine Educational Program for Radiation Oncology Patients: Patient-Reported Outcomes.

Purpose: Complementary health approaches (CHAs) equip patients to self-manage radiation therapy (RT)-related symptoms and fulfill unmet needs, but few disclose CHA use to their radiation oncologist. An integrative medicine educational program (IMEP) was developed to assess its ability to improve patient self-efficacy for symptom management and CHA use disclosure.

Methods And Materials: The IMEP included 4 1-hour sessions covering topics of (1) meditation, (2) yoga, (3) massage therapy, and (4) nutrition.

Discovery of CMX990: A Potent SARS-CoV-2 3CL Protease Inhibitor Bearing a Novel Warhead.

There remains a need to develop novel SARS-CoV-2 therapeutic options that improve upon existing therapies by an increased robustness of response, fewer safety liabilities, and global-ready accessibility. Functionally critical viral main protease (M, 3CL) of SARS-CoV-2 is an attractive target due to its homology within the coronaviral family, and lack thereof toward human proteases. In this disclosure, we outline the advent of a novel SARS-CoV-2 3CL inhibitor, , bearing an unprecedented trifluoromethoxymethyl ketone warhead.

'Floating things' and methodological drift: Accounting for haunted materialities in the North Pacific Ocean.

In this article I follow the mystery of millions of tons of materials washed out to sea by the March 2011 Japan tsunami: a massive wave of lost materials expected to reach North American shores that never seems to officially arrive. I bring Gordon's conceptualization of haunting together with STS conversations about absence and invisibility to build on feminist approaches that do not take as given what is missing or what should be done. I begin by situating efforts to respectfully distinguish materials survivors call 'floating things' amidst a sea of concern for ocean plastic pollution.

Comparison of three-dimensional imaging of the nose using three different 3D-photography systems: an observational study.

Background: New 3D technologies for superficial soft tissue changes, especially in plastic and reconstructive surgical procedures, can improve the planning and documentation of facial surgeries. The purpose of this study was to compare and determine the applicability and feasibility of three different 3D-photography systems in clinical practice imaging the nose.

Methods: A total of 16 healthy non-operated noses were included in this prospective study.

The Value of Surveillance Imaging of Oral Squamous Cell Carcinoma.

The evaluation of surveillance imaging of OSCC patients is a difficult task physicians have to face daily. Multiple patients experience a recurrence of this disease, which underlines the importance of regular patient monitoring programs. Our study analysed the value of surveillance imaging, such as computed tomography (CT) and nuclear magnetic resonance imaging (NMRI), as a patient monitoring programme and its effectiveness in achieving improvement in early recurrence detection.

Determinants Affecting the Clinical Implementation of a Molecularly Informed Molecular Tumor Board Recommendation: Experience from a Tertiary Cancer Center.

Molecular Tumor Boards (MTBs) converge state-of-the-art next-generation sequencing (NGS) methods with the expertise of an interdisciplinary team consisting of clinicians, pathologists, human geneticists, and molecular biologists to provide molecularly informed guidance in clinical decision making to the treating physician. In the present study, we particularly focused on elucidating the factors impacting on the clinical translation of MTB recommendations, utilizing data generated from gene panel mediated comprehensive genomic profiling (CGP) of 554 patients at the MTB of the Comprehensive Cancer Center Erlangen, Germany, during the years 2016 to 2020. A subgroup analysis of cases with available follow-up data ( = 332) revealed 139 cases with a molecularly informed MTB recommendation, which was successfully implemented in the clinic in 44 (31.