Immunotherapy: ALLOGENEIC UMBILICAL CORD BLOOD REGULATORY T CELLS DECREASE INFLAMMATION AND PRESERVE ANTI-TUMOR ACTIVITY OF CAR T CELLS

Background & Aim: With larger accessibility and increased number of patients being treated with CART cell therapy, real-world toxicity continues to remain a significant challenge to its widespread adoption. We have previously shown that allogeneic umbilical cord blood derived (UCB) regulatory T cells (Tregs) can resolve uncontrolled inflammation and can treat acute and immune mediated lung injury in a xenogenic model as well as in patients suffering from COVID-19 acute respiratory distress syndrome. The unique properties of UCB Tregs including: i) lack of plasticity when exposed to inflammatory micro-environments;ii) no requirement for HLA matching;iii) long shelf life of cryopreserved Tregs;and iv) immediate product availability for on demand treatment, makes them an attractive source for treating acute inflammatory syndromes. Therefore, we hypothesized that add-on therapy with UCB derived Tregs may resolve uncontrolled inflammation responsible for CART cell therapy associated toxicity. Methods, Results & Conclusion(s): UCB Tregs were added in 1:1 ratio to CART cells, where no interference in their ability to kill CD19+ Raji cells, was detected at different ratios : 8:1 (80.4% vs. 81.5%);4:1 (62.0% vs. 66.2%);2:1 (50.1% vs. 54.7%);1:1 (35.4% vs. 44.1%) (Fig 1A). In a xenogenic B cell lymphoma model, multiple injections of Tregs were administered after CART injection (Fig 1B), which did not impact distribution of CD8+ T effector cells (Fig 1C) or CART cells cells (Fig 1D) in different organs. No decline in the CAR T levels was observed in the Tregs recipients (Fig 1E). Specifically, no difference in tumor burden was detected between the two arms (Fig 2A). No tumor was detected in CART+Tregs in liver (Fig 2B) or bone marrow (Fig 2C). A corresponding decrease in multiple inflammatory cytokines in peripheral blood was observed in CART+Tregs when compared to CART alone (Fig 2D). Here we show "proof of concept" for add-on therapy with Tregs to mitigate hyper-inflammatory state induced by CART cells without interference in their on-target anti-tumor activity. The timing of Tregs administration after CART cells have had sufficient time for forming synapse with tumor cells allows for preservation of their anti-tumor cytotoxicity, such that the infused Tregs home to the areas of tissue damage to bind to the resident antigen presenting cells which in turn collaborate with Tregs to resolve inflammation. Such differential distribution of cells allow for a Treg "cooling blanket" and lays ground for clinical study. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy

Assessment of Jordanian physicians' knowledge about venous thromboembolism risk and management among COVID-19 patients

Objectives: The aim of this study was to assess Jordanian physicians' awareness about venous thromboembolism (VTE) risk among COVID-19 patients and its treatment protocol. Method(s): This was a cross-sectional-based survey that was conducted in Jordan in 2020. During the study period, a convenience sample of physicians working in various Jordanian hospitals were invited to participate in this study. Physicians' knowledge was evaluated and physicians gained one point for each correct answer. Then, a knowledge score out of 23 was calculated for each. Key Findings: In this study, 102 physicians were recruited. Results from this study showed that most of the physicians realize that all COVID-19 patients need VTE risk assessment (n = 69, 67.6%). Regarding VTE prophylaxis, the majority of physicians (n = 91, 89.2%) agreed that low molecular weight heparin (LMWH) is the best prophylactic option for mild-moderate COVID-19 patients with high VTE risk. Regarding severe/critically ill COVID-19 patients, 75.5% of physicians (n = 77) recognized that LMWH is the correct prophylactic option in this case, while 80.4% of them (n = 82) knew that mechanical prevention is the preferred prophylactic option for severe/critically ill COVID-19 patients with high bleeding risk. Moreover, 77.5% of physicians (n = 79) knew that LMWH is the treatment of choice for COVID-19 patients diagnosed with VTE. Finally, linear regression analysis showed that consultants had an overall higher knowledge score about VTE prevention and treatment in COVID-19 patients compared with residents (P = 0.009). Conclusion(s): All physicians knew about VTE risk factors for COVID-19 patients. However, consultants showed better awareness of VTE prophylaxis and treatment compared with residents. We recommend educational workshops be conducted to enhance physicians' knowledge and awareness about VTE thromboprophylaxis and management in COVID-19 patients.Copyright © 2022 The Author(s). Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved.

Repurposing of poly-gamma-glutamic acid, immunotherapeutic drug for cervical intraepithelial neoplasia 1, as covid-19 treatment

Covid-19 virus variants identified so far are due to viral genetic diversity, genetic evolution, and variable infectivity, suggesting that high infection rates and high mortality rates may be contributed by these mutations. And it has been reported that the targeting strategies for innate immunity should be less vulnerable to viral evolution, variant emergence and resistance. Therefore, the most effective solution to Covid-19 infection has been proposed to prevent and treat severe exacerbation of patients with moderate disease by enhancing human immune responses such as NK cell and T cell. In previous studies, we demonstrated for the first time that gamma-PGA induced significant antitumor activity and antiviral activity by modulating NK cell-mediated cytotoxicity. Especially intranasal administration of gamma-PGA was found to effectively induce protective innate and CTL immune responses against viruses and we found out that gamma-PGA can be an effective treatment for cervical intraepithelial neoplasia 1 through phase 2b clinical trial. In this study, the possibility of gamma-PGA as a Covid-19 immune modulating agent was confirmed by animal experiments infected with Covid-19 viruses. After oral administration of gamma-PGA 300mug/mouse once a day for 5 days in a K18-hACE2 TG mouse model infected with SARS-CoV-2 (NCCP 43326;original strain) and SARS-CoV-2 (NCCP 43390;Delta variant), virus titer and clinical symptom improvement were confirmed. In the RjHan:AURA Syrian hamster model infected with SARS-CoV-2 (NCCP 49930;Delta variant), 350 or 550 mug/head of gamma-PGA was administered orally for 10 days once a day. The virus for infection was administered at 5 x 104 TCID50, and the titer of virus and the improvement of pneumonia lesions were measured to confirm the effectiveness in terms of prevention or treatment. In the mouse model infected with original Covid-19 virus stain, the weight loss was significantly reduced and the survival rate was also improved by the administration of gamma-PGA. And gamma-PGA alleviated the pneumonic lesions and reduced the virus titer of lung tissue in mice infected with delta variant. In the deltavariant virus infected hamster model, gamma-PGA showed statistically significant improvement of weight loss and lung inflammation during administration after infection. This is a promising result for possibility of Covid-19 therapeutics along with the efficacy results of mouse model, suggesting gammaPGA can be therapeutic candidate to modulate an innate immune response for Covid-19.

Enabling mRNA medicine for brain tumors

mRNA is a new class of drugs that has the potential to revolutionize the treatment of brain tumors. Thanks to the COVID-19 mRNA vaccines and numerous therapy-based clinical trials, it is now clear that lipid nanoparticles (LNPs) are a clinically viable means to deliver RNA therapeutics. However, LNP-mediated mRNA delivery to brain tumors remains elusive. Over the past decade, numerous studies have shown that tumor cells communicate with each other via small extracellular vesicles, which are around 100 nm in diameter and consist of lipid bilayer membrane similar to synthetic lipidbased nanocarriers. We hypothesized that rationally designed LNPs based on extracellular vesicle mimicry would enable efficient delivery of RNA therapeutics to brain tumors without undue toxicity. We synthesized LNPs using four components similar to the formulation used in the mRNA COVID19 vaccines (Moderna and Pfizer): ionizable lipid, cholesterol, helper lipid and polyethylene glycol (PEG)-lipid. For the in vitro screen, we tested ten classes of helper lipids based on their abundance in extracellular vesicle membranes, commercial availability, and large-scale production feasibility while keeping rest of the LNP components unchanged. The transfection kinetics of GFP mRNA encapsulated in LNPs and doped with 16 mol% of helper lipids was tested using GL261, U87 and SIM-A9 cell lines. Several LNP formations resulted in stable transfection (upto 5 days) of GFP mRNA in all the cell lines tested in vitro. The successful LNP candidates (enabling >80% transfection efficacy) were then tested in vivo to deliver luciferase mRNA to brain tumors via intrathecal administration in a syngeneic glioblastoma (GBM) mouse model, which confirmed luciferase expression in brain tumors in the cortex. LNPs were then tested to deliver Cre recombinase mRNA in syngeneic GBM mouse model genetically modified to express tdTomato under LoxP marker cassette that enabled identification of LNP targeted cells. mRNA was successfully delivered to tumor cells (70-80% transfected) and a range of different cells in the tumor microenvironment, including tumor-associated macrophages (80-90% transfected), neurons (31- 40% transfected), neural stem cells (39-62% transfected), oligodendrocytes (70-80% transfected) and astrocytes (44-76% transfected). Then, LNP formulations were assessed for delivering Cas9 mRNA and CD81 sgRNA (model protein) in murine syngeneic GBM model to enable gene editing in brain tumor cells. Sanger sequencing showed that CRISPR-Cas9 editing was successful in ~94% of brain tumor cells in vivo. In conclusion, we have developed a library of safe LNPs that can transfect GBM cells in vivo with high efficacy. This technology can potentially be used to develop novel mRNA therapies for GBM by delivering single or multiple mRNAs and holds great potential as a tool to study brain tumor biology.

Solidarity with everyone? Intergroup helping and COVID‐19

This study investigates peoples' prosocial attitudes and real‐life prosocial behaviour towards different ethnic groups during the COVID‐19 pandemic, taking Germany as an empirical example. In a preregistered multi‐study design, we examined: (a) who receives help, (b) who helps and (c) what explains prosocial behaviour. In study 1, we conducted a large‐scale, nation‐wide field experiment (1,980 help requests across 11 cities, resulting in 769 help offers in response). In study 2, we conducted an online survey with a general population sample (N = 1,033, Mage = 40 years, 43% females). Tests of proportions revealed high levels of prosocial attitudes as well as behaviour, favouring the ethnic ingroup (study 1), while regression analysis highlights the importance of empathy, compared to other theoretical predictors, for explaining prosocial behaviour (study 2). Findings underscore the relevance of ethnic boundaries during the pandemic crisis: Ethnic minority members benefit less from solidarity than ethnic majority members. However, we observe an attitude‐behaviour gap between field experimental and survey data, indicating the importance of observational studies when studying prosocial behaviour during the pandemic. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement. [ FROM AUTHOR] Copyright of Journal of Community & Applied Social Psychology is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Biodegradable Polyester Nanoparticle Vaccines Deliver Self-Amplifying mRNA in Mice at Low Doses

Delivery of self-amplifying mRNA (SAM) has high potential for infectious disease vaccination due to its self-adjuvanting and dose-sparing properties. Yet a challenge is the susceptibility of SAM to degradation and the need for SAM to reach the cytosol fully intact to enable self-amplification. Lipid nanoparticles are successfully deployed at incredible speed for mRNA vaccination, but aspects such as cold storage, manufacturing, efficiency of delivery, and the therapeutic window can benefit from further improvement. To investigate alternatives to lipid nanoparticles, a class of >200 biodegradable end-capped lipophilic poly(beta-amino ester)s (PBAEs) that enable efficient delivery of SAM in vitro and in vivo as assessed by measuring expression of SAM encoding reporter proteins is developed. The ability of these polymers to deliver SAM intramuscularly in mice is evaluated, and a polymer-based formulation that yields up to 37-fold higher intramuscular (IM) expression of SAM compared to injected naked SAM is identified. Using the same nanoparticle formulation to deliver a SAM encoding rabies virus glycoprotein, the vaccine elicits superior immunogenicity compared to naked SAM delivery, leading to seroconversion in mice at low RNA injection doses. These biodegradable nanomaterials may be useful in the development of next-generation RNA vaccines for infectious diseases.Copyright © 2023 The Authors. Advanced Therapeutics published by Wiley-VCH GmbH.

Child, adolescent, and parent mental health in general population during a year of COVID-19 pandemic in belgium: a cross-sectional study

Background: This study aims to evaluate the mental health status of children, adolescents and their parents during the first year of COVID-19 pandemic in Belgium. Method(s): Analysis compared results before and during the second national lockdown, which started on November 2nd 2020. A cross-sectional online survey was conducted between May 2020 and April 2021. Result(s): Two hundred and eighteen adults and 273 children fully completed the survey. Almost one in five children (17.9%) presented moderate-to-severe scores of depression. Adolescents presented a higher level of depression than children (p = 0.007). The rate of moderate-to-severe depression scores (10.8% to 21%, p = 0.007) and internalized symptoms increased during the second lockdown (p < 0.001). Parents' depression (p < 0.001) and anxiety (p = 0.027) levels also increased during the second lockdown. Logistic regression showed that the use of psychotropic medication in parents and parents' depression scores were risk factors for children to have worse depression scores. Conclusion(s): The second lockdown appears to worsen the effects of the pandemic on children's and parents' mental health. There is a need to implement specific interventions targeting both children/adolescents and their parents to support them during lockdown periods and improve mental health outcomes.Copyright © 2022, The Author(s).

Fast de novo antibody structure prediction with atomic accuracy

Background: In the field of antibody engineering, an essential task is to design a novel antibody whose paratopes bind to a specific antigen with correct epitopes. Understanding antibody structure and its paratope can facilitate a mechanistic understanding of its function. Therefore, antibody structure prediction from its sequence alone has always been a highly valuable problem for de novo antibody design. AlphaFold2 (AF2), a breakthrough in the field of structural biology, provides a solution to this protein structure prediction problem by learning a deep learning model. However, the computational efficiency and undesirable prediction accuracy on antibody, especially on the complementarity-determining regions limit its applications in de novo antibody design. Method(s): To learn informative representation of antibodies, we trained a deep antibody language model (ALM) on curated sequences from observed antibody space database via a well-designed transformer model. We also developed a novel model named xTrimoABFold++ to predict antibody structure from antibody sequence only based on the pretrained ALM as well as efficient evoformers and structural modules. The model was trained end-to-end on the antibody structures in PDB by minimizing the ensemble loss of domain-specific focal loss on CDR and the frame aligned point loss. Result(s): xTrimoABFold++ outperforms AF2 and OmegaFold, HelixFold-Single with 30+% improvement on RMSD. Also, it is 151 times faster than AF2 and predicts antibody structure in atomic accuracy within 20 seconds. In recently released antibodies, for example, cemiplimab of PD1 (PDB: 7WVM) and cross-neutralizing antibody 6D6 of SARS-CoV-2 (PDB: 7EAN), the RMSD of xTrimoABFold++ are 0.344 and 0.389 respectively. Conclusion(s): To the best of our knowledge, xTrimoABFold++ achieved the state-of-the-art in antibody structure prediction. Its improvement on both accuracy and efficiency makes it a valuable tool for de novo antibody design, and could make further improvement in immuno-theory.

The preventive effect and mechanism of Dayuanyin in hypoxic pulmonary hypertension through NF-kappaB signaling pathway.

Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg.kg-1), and positive control sildenafil group (100 mg.kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% +/- 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF- kappaB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF- kappaB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-kappaB and signal transducer and activator of transcription 3 (STAT3) by DYY.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.

Low- and mid-level equine assisted services improved mood and state anxiety levels in health-care workers

The aim of this study was to measure the effect of equine assisted services (EAS) on mood and anxiety in health-care workers. While the emotional toll of the COVID-19 pandemic has been felt in every aspect of our society, health-care workers have been hit especially hard. A survey conducted by Mental Health America during June - September in 2020, found 93% of health-care workers were experiencing stress and 86% reported experiencing anxiety. There is research to support a wide range of interventions to address stress, low mood, and anxiety, including pharmaceuticals, physical exercise, and animal interaction. While several studies have shown an improvement in anxiety and mood after interaction with horses, few studies have included a physically active control group to consider the effect of exercise on results. In this study conducted in October 2021, participants were recruited from area hospitals and randomly assigned to a control group (30-min guided walk with no horse interaction, n = 17), a low level EAS group (30-min self-guided farm tour, n = 20), or a mid-level EAS group (30 min of grooming a horse, n = 19). Before the intervention, participants completed a demographic survey. Pre and post activity, participants completed the Brief Mood Introspection Scale (BMIS) and State Anxiety Inventory for AdultsTM that measured currentfeelings of mood and anxiety, respectively. Data were analyzed using the repeated measures one-way ANOVA procedure in SPSS. This study was approved by the MSU Human Research and Protection Program and the Institutional Animal Care and Use Committee. Fifty-six health-care workers participated in the study, with 32% having worked in health care for less than 5 years and 33.9% having worked in health care for over 20 years. All participants had a significant improvement in State-Anxiety scores after completing their group activity (P < 0.001), with no differences among groups. Similarly, all groups had an improved BMIS score (P < 0.001). However, there was significantly greater improvement in BMIS scores in the mid-level EAS (P < 0.01) when compared with the control group. While all participants in this study improved both their current feelings of anxiety and mood after completing an activity on the farm, there was a greater improvement in mood in those individuals who spent 30 min grooming a horse when compared with the walk group without horse interaction. The results from this study provide further support for the impact of equine assisted services as a means of improving mood.Copyright © 2023

Assessment of the knowledge, attitudes, and behaviors of individuals presenting to family medicine polyclinics for COVID-19 and influenza vaccines: a study in a Turkish population

BACKGROUND: Vaccines are one of the most important weapons in protection against diseases, especially pandemics lacking available treatment. The objective of this study was to investigate the knowledge, attitudes, and behaviors of individuals presenting to family medicine polyclinics for COVID-19 and influenza vaccines. METHOD(S): The cross-sectional descriptive study comprised healthy individuals who presented to family medicine polyclinics in Ankara Training and Research Hospital, Ankara, Turkiye between 10 December 2020 and 31 January 2021. Data on participants' knowledge and attitudes for COVID-19 and influenza vaccines were collected through questionnaire surveys. In total, 521 individuals aged older than 18 years were included in the study. RESULT(S): If a COVID-19 vaccine were available, 34.4% (N.=179) of respondents would be vaccinated, and 35.3% (N.=184) of respondents would not consider vaccination. Of those considering COVID-19 vaccination, 55.3% (N.=99) of respondents deemed the vaccine an effective way of providing protection against the virus. Increased willingness to have the COVID-19 vaccine was associated with the following factors: considering the influenza vaccine an effective protection method (P<0.001), a history of influenza vaccination (P=0.003), and concern about COVID-19 related death rates (P=0.008). CONCLUSION(S): The most common reasons for COVID-19 vaccine hesitancy and refusal were fear of vaccine-related side effects and a lack of perceived research evidence on the vaccine. Having a positive view of the influenza vaccine had a positive impact on attitudes toward the COVID-19 vaccine.Copyright © 2022 EDIZIONI MINERVA MEDICA.

A qualitative study exploring how youth use TikTok to learn about mental health and mental health services in British Columbia, Canada

Aims: Youth are increasingly seeking health information through online platforms, such as websites, social media, and online forums. TikTok emerged as a popular platform for disseminating and consuming health information during the COVID-19 pandemic. As such, this study aimed to explore how youth used TikTok to access information about mental health and mental health services during the pandemic. Method(s): Twenty-one interviews were conducted over Zoom with youth (ages 12-24) who lived in British Columbia, Canada and had accessed TikTok for mental health information during the pandemic. Interviews were audio-recorded, transcribed verbatim, and analysed thematically using an inductive approach. Result(s): Youth described TikTok as a safe place to talk about mental health and share personal experiences. This helped youth feel less alone with their struggles and facilitated conversations about mental health with friends, family, and service providers. Participants also described how mental health content on TikTok helped them be more mindful of their own mental health and the different resources and coping strategies available and encouraged them to seek services. For those hesitant or unable to access services, TikTok provided immediate support. Youth appreciated the ease of accessing this information, given the platform's engaging and digestible format (i.e., short videos) and predictive nature of its algorithm. However, participants expressed concerns with the spread of misinformation and the lack of verifiable information on the platform. Conclusion(s): TikTok is as a practical platform to disseminate mental health information to youth. However, efforts to establish strategies for preventing and reporting misinformation are warranted.

Innovative Methods for Integrating Social Determinants of Health Data with Administrative Claims to Facilitate Health Equity Research

Objectives: The Covid-19 pandemic highlighted the importance of considering Social Determinants of Health (SDoH) in healthcare research. Administrative claims databases are widely used for research, but often lack SDoH data or sufficient transparency in how these data were obtained. This study describes innovative methods for integrating SDoH data with administrative claims to facilitate health equity research. Method(s): The HealthCore Integrated Research Database (HIRD) contains medical and pharmacy claims from a large, national US payer starting in 2006 and includes commercial (Comm), Medicare Advantage (MCare), and Medicaid (MCaid) populations. The HIRD includes individually identifiable information, which was used for linking with SDoH data from the following sources: national neighborhood-level data from the American Community Survey, the Food Access Research Atlas, and the National Center for Health Statistics' urbanicity classification;and member-level data on race/ethnicity from enrollment files, medical records, self-attestation, and imputation algorithms. We examined SDoH metrics for members enrolled as of 05-July-2022 and compared them to the respective US national data using descriptive statistics. We also examined telehealth utilization in 2022. Result(s): SDoH data were available for ~95% of currently active members in the HIRD (Comm/MCare/MCaid 12.5m/1m/7.6m). Socioeconomic characteristics at the neighborhood-level differed by membership type and vs. national data: % of members with at least a high-school education (90/88/84 vs. 87);median family income ($98k/$76k/$70k vs. $82k);% of members living in low-income low-food-access tracts (9/14/18 vs. 13);urban (57/52/47 vs. 61). At the member-level, the % of White Non-Hispanics, Black Non-Hispanics, Asian Non-Hispanics, and Hispanics were 61/6/5/6 (Comm), 76/12/2/2 (MCare), and 45/26/5/19 (MCaid). Imputation contributed 15-60% of race/ethnicity values across membership types. Telehealth utilization increased with socioeconomic status. Conclusion(s): We successfully integrated SDoH data from a variety of sources with administrative claims. SDoH characteristics differed by type of insurance coverage and were associated with differences in telehealth utilization.Copyright © 2023

Lipid nanoparticle library towards development next generation genomic medicines

Ionizable amino lipids are a major constituent of the lipid nanoparticles for delivering nucleic acid therapeutics (e.g., DLin-MC3-DMA in ONPATTRO , ALC-0315 in Comirnaty , SM-102 in Spikevax ). Scarcity of lipids that are suitable for cell therapy, vaccination, and gene therapies continue to be a problem in advancing many potential diagnostic/therapeutic/vaccine candidates to the clinic. Herein, we describe the development of novel ionizable lipids to be used as functional excipients for designing vehicles for nucleic acid therapeutics/vaccines in vivo or ex vivo use in cell therapy applications. We first studied the transfection efficiency (TE) of LNP-based mRNA formulations of these ionizable lipid candidates in primary human T cells and established a workflow for engineering of primary immune T cells. We then adapted this workflow towards bioengineering of CAR constructs to T cells towards non-viral CAR T therapy. Lipids were also tested in rodents for vaccine applications using self-amplifying RNA (saRNA) encoding various antigens. We have then evaluated various ionizable lipid candidates and their biodistribution along with the mRNA/DNA translation exploration using various LNP compositions. Further, using ionizable lipids from the library, we have shown gene editing of various targets in rodents. We believe that these studies will pave the path to the advancement in nucleic acid based therapeutics and vaccines, or cell gene therapy agents for early diagnosis and detection of cancer, and for targeted genomic medicines towards cancer treatment and diagnosis.

Self-medication among university students during the COVID-19 pandemic: a comparative analysis of different faculties

Self-medication is a widespread public health concern. University students are likely to be more prone to it since self-medication rates increase with educational level. Studies have shown that self-medication rates vary among academics belonging to different faculties, and medical students have the highest self-medication rates. However, it is unknown whether this holds in a vulnerable situation, such as the COVID-19 pandemic. It is also unknown whether differences in technical knowledge of drugs influence self-medication rates among students. Thus, this study analyzes and compares prophylactic self-medication among graduate students of different faculties in the context of the COVID-19 pandemic. This cross-sectional observational study was conducted at a private university in southern Brazil. Students from the medicine, law, life sciences, and fine arts faculties were surveyed, and their responses were compared using a chi-square test. Among 396 respondents, 29.5% reported using preventive medication for COVID-19, and medical students were the least likely to do so. The self-medication rate was 13.6% among respondents, and self-medication did not differ significantly between students of different faculties. Of the students who self-medicated 63% reported having studied the medication before using them. Furthermore, the media did not induce drug use among 81.8% respondents. These results show that medical students used fewer preventive medications during the pandemic and refute the assertion that self-medication rates are higher among medical students. They also show that self-medication rates during the pandemic were significantly lower than those before the pandemic. These revelations show a new aspect of self-medication.Copyright © 2021 Muslim OT et al.

Low-intensity online intervention (LiON) for distressed young people in Hong Kong: Preliminary findings

Previous studies have demonstrated that low-intensity intervention is effective in improving mental health in young people. Whilst interventions have majorly been offered online during COVID-19 pandemic, it is not known whether low-intensity interventions delivered online can also help reduce the level of distress experienced by young people. The study aimed to determine whether a low-intensity online intervention (LiON) can reduce levels of distress in young people greater than those in similar initial distress levels but received no intervention. Young people aged 15 to 24 were recruited for the 4-weekly LiON intervention consisting of three modules namely sleep and relaxation, stress-coping and problem-solving. The reductions in distress level after intervention were compared to those that occurred over a period of 3 months among community young people with similar baseline K6 distress levels. Seventy-four young people (mean age 20.24 [SD 2.26] years, 71.6% female) received the LiON intervention from December 2021 to July 2022. We observed a greater improvement in their distress levels after receiving the intervention than those with no intervention in the community (beta -4.13, 95%CI -5.12, -3.07, p < .001, Cohen's f2 0.027). The findings offered evidence that the LiON intervention significantly reduced young people's distress level in addition to the improvement that may occur naturally. The use of LiON is adaptable to a wider variety of frontline community organizations. Future evaluation of its cost-effectiveness is warranted.

Heterologous prime-boost viral vector vaccines for the treatment of a P1A-expressing BGL-1 glioblastoma model

Glioblastoma is an extremely aggressive and difficult cancer to treat, which may partly be due to its limited ability to induce T-cell responses. However, combining viral vector vaccines with other therapies to generate tumor-specific T cells may provide a meaningful benefit to patients. Here, we investigated whether heterologous prime-boost vaccination with chimpanzee-derived adenoviral vector ChAdOx1 and modified vaccinia Ankara (MVA) vaccines could generate therapeutically effective CD8+ T-cell responses against a model antigen P1A, a mouse homolog of human tumorassociated Melanoma Antigen GenE (MAGE)-type antigens, expressed by a BGL-1 mouse glioblastoma cell line. We demonstrated that heterologous prime-boost vaccination with ChAdOx1/MVA vaccines targeting P1A generated a high magnitude of CD8+ T cells specific for the P1A35-43 epitope presented by the MHC class I molecule H-2Ld . Prophylactic vaccination with ChAdOx1/MVA-P1A significantly prolonged the survival of syngeneic mice subcutaneously challenged with P1A-expressing BGL-1 tumors. Furthermore, different vaccination schedules significantly impact the magnitude of antigen-specific CD8+ T-cell responses and may impact protective efficacy. However, the substantial induction of myeloid-derived suppressor cells (MDSCs) by this tumor model presents a significant challenge in the therapeutic setting. Future work will investigate the efficacy of this vaccination strategy on intracranial P1A-expressing BGL-1 models.

Factors Influencing Work Satisfaction and Compliance of Using Ppe among Shop Assistants during Covid-19

Objectives: The objectives of the study was to assess the level of work satisfaction, assess compliance of using PPE among shop assistants during COVID-19 and to find the factors influencing work satisfaction. Method(s): A quantitative approach with descriptive design was used for the study. Eighty samples were selected by using convenient sampling technique. The study was conducted in 4 districts of Kerala through online platform as well as through offline mediums. Result(s): From the study, it is evident that majority of the subjects (55%) were satisfied with their work at the time of COVID-19 and more than half (55%) of the samples have enough compliance with the use of PPE and only 7.5% have less compliance with the use of PPE. Demographic variables such age, relationship status, and work experience were found to be statically significant (p<0.05) with work satisfaction, and other variables did not have a significant association. Conclusion(s): This study provides a baseline for assessing the level of work satisfaction and compliance of PPE among shop assistants in selected areas. Periodic reinforcements, proper education, availability and trainings on the use of PPE can reduce the spread of Corona Virus and improve PPE compliance to an extend. Good working environment support from family and good rapport with colleagues can help to improve work satisfaction .Copyright © 2023 The Authors.

SARS-CoV-2 spike S1 mediated lung tumor regression in a mouse model

Lung cancer is the leading cause of cancer related deaths worldwide, with a relatively low 5-year survival rate. Although there are some therapies against lung cancer, new effective treatment options are urgently required. Recently during the COVID-19 pandemic, we have seen that SARSCoV-2 binds to its receptor angiotensin-converting enzyme 2 (ACE2) via spike S1 to enter the cells. This study underlines the importance of SARS-CoV-2 spike S1 in inducing death in human lung cancer cells. Interestingly, we have seen that recombinant spike S1 treatment at very low doses led to death of human A549 lung cancer cells. On the other hand, boiled recombinant SARS-CoV-2 spike S1 remained unable to induce death, suggesting that the induction of cell death in A549 cells was due to native SARS-CoV-2 spike S1 protein. SARS-CoV-2 spike S1-induced A549 cell death was also inhibited by neutralizing antibodies against spike S1 and ACE2. Moreover, our newly designed wild type ACE2-interacting domain of SARS-CoV-2 (wtAIDS), but not mAIDS, peptide also attenuated SARS-CoV-2 spike S1-induced cell death, suggesting that SARS-CoV-2 spike S1- induced death in lung cancer cells depends on its interaction with ACE2 receptor. Similarly, recombinant spike S1 treatment also led to death of H1299 and H358 human lung cancer cells. Finally, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) intoxication led to the formation tumors in lungs of A/J mice and alternate day intranasal treatment with low dose of recombinant SARS-CoV-2 spike S1 from 22-weeks of NNK insult (late stage) led to induced apoptosis and tumor regression in the lungs. These studies indicate that recombinant SARS-CoV-2 Spike S1 protein may have implications in the treatment of lung cancer.