ABSTRACT
The rise in antibiotic-resistant pathogens, highly infectious viruses, and chronic diseases has prompted the search for rapid and versatile medical tests that can be performed by the patient. An electronic biosensing platform based on field-effect transistors (FETs) is particularly attractive due to sensitivity, fast turn-around, and compatibility with semiconductor manufacturing. However, the lack of methods for pathogen-specific functionalization of individual FETs prevents parallel detection of multiple pathogens. Indeed, so far functionalization of FET based biosensors is achieved by drop casting without any spatial selectivity. Here, we propose a paradigm shift in FET’s biofunctionalization. Specifically, we use thermal scanning probe lithography (tSPL) with a thermochemically sensitive polymer that can be spin-coated on any FET material. We demonstrate that this scalable, CMOS compatible methodology can be used to functionalize individual FETs with different bioreceptors on the same chip, at sub-20 nm resolution, paving the way for massively parallel FET detection of multiple pathogens. Antibody- and aptamer-modified FET sensors are then realized, achieving an ultra-sensitive detection of 5 aM of SARS-CoV-2 spike proteins and 10 human SARS-CoV-2 infectious live virus particles/ml, and selectivity against human influenza A (H1N1) live virus.
Subject(s)
Severe Acute Respiratory Syndrome , Chronic DiseaseABSTRACT
The SARS-CoV-2 pandemic remains a major public health threat, especially due to newly emerging SARS-CoV-2 Variants of Concern (VoCs), which are more efficiently transmitted, more virulent, and more able to escape naturally acquired and vaccine-induced immunity. Recently, the protease inhibitor Paxlovid®and the polymerase inhibitor molnupiravir, both targeting mutant-prone viral components, were approved for high-risk COVID-19 patients. Nevertheless, effective therapeutics to treat COVID-19 are urgently needed, especially small molecules acting independently of VoCs and targeting genetically stable cellular pathways which are crucial for viral replication. Pamapimod is a selective inhibitor of p38 Mitogen-Activated Protein Kinase alpha (p38 MAPKα) that has been extensively clinically evaluated for the treatment of rheumatoid arthritis. Signaling via p38 has recently been described as a key pathway for the replication of SARS-CoV-2. Here, we reveal that the combination of pamapimod with pioglitazone, an anti-inflammatory and approved drug for the treatment of type 2 diabetes, possesses potent and synergistic activity to inhibit SARS-CoV-2 replication in vitro. Both drugs showed similar antiviral potency across several cultured cell types and similar antiviral activity against SARS-CoV-2 Wuhan type, and the VoCs Alpha, Beta, Gamma, Delta, and Omicron. These data support the combination of pamapimod and pioglitazone as a potential therapy to reduce duration and severity of disease in COVID-19 patients, an assumption currently evaluated in an ongoing phase II clinical study.
ABSTRACT
The current organizational landscape, with its calls for flexibility, innovation, and rapid response to change, has resulted in increased work demands and longer working hours for many employees (Brett & Stroh, 2003;Lewis & Cooper, 2005).Also, access to technology, such as smartphones, widespread internet, social media, and video chatting, has increased the amount of time people spend working (Voydanoff, 1988), thus making work-life balance (WLB) an important social and organizational issue (Kanwar et al., 2009). Many organizations have implemented family-friendly workplaces for their employees (Kossek & Van Dyne, 2008;Lobel & Kossek, 1996). Research has suggested that supportive supervisor behaviors might influence employees' perceptions of family-friendly programs (Batt & Valcour, 2003;Thomas & Ganster, 1995;Thompson & Prottas, 2005). However, few studies have examined the effects of leadership as it relates to promoting the success of family-friendly programs and WLB. The purpose of this qualitative, phenomenological study was to examine the extent to which managers and supervisors practiced and expressed value for work-life balance impacts on their organization's commitment to implementing family-friendly workplace policies. The ultimate goal of this study is to answer the question: "Do middle managers and supervisors practice work-life balance within their own lives?" Both Kahn et al.'s (1981) role theory and Grandey and Cropanzano's (1999) conservation of resources (COR) model were used as theoretical frameworks for this study. This study utilized seven standardized open-ended questions to explore strategies used by 13 managers and supervisors to achieve work-life balance. The findings in this study support the literature surrounding those in the modern-day workforce working long hours and not being able to complete daily tasks by the end of each workday. Also, the managers and supervisors in this study with children at home experienced more challenges in the family domain. Furthermore, the new normal of COVID-19 and its effect on the external environment has created different types of challenges for both the managers and supervisors and the organizations where they are employed. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
ABSTRACT
Introduction: Due to the Covid-19 social distancing restrictions, in March 2020, Weill Cornell Medicine-Qatar decided to replace students’ clinical instruction with novel online electives. Hence, we implemented an innovative online and remote pathology curriculum, anchored on virtual microscopy and Zoom videoconferencing: ideal tools to support online teaching. Objective: To assess a new curriculum implementation at Weill Cornell Medicine-Qatar.Materials and Methods: This for-credit, 2-week elective included 6 synchronous Zoom sessions where complex clinicopathological cases were discussed in small groups. We used open access digital microscopy slides from the University of Leeds’ Virtual Pathology Library (http://www.virtualpathology.leeds.ac.uk/slides/library/). Students independently prepared for these sessions by reviewing cases, slides, readings, and questions in advance (asynchronous self-directed learning anchored on a flipped classroom model), and wrote a final review of a case. An assessment and feedback were given to each student.Results: Four elective iterations were offered to a total of 29 students, with learners and faculty spread over 4 countries. During the Zoom sessions, students controlled the digital slides and offered their own diagnoses, followed by group discussions to strengthen autonomy and confidence. We surveyed learners about the elective’s performance (program evaluation). Students conveyed high levels of satisfaction about the elective’s overall quality, their pathology learning and online interactions, with minimal challenges related to the remote nature of the course.Discussion and conclusions: Technological innovations mitigate sudden disruptions in medical education. A remote curriculum allows instruction at any distance, at any time, from anywhere, enhancing educational exchanges, flexibility and globalization in medical education.