COVID-19 Vaccine Videos: Health Literacy Considerations.

BACKGROUND: Multimedia videos are important tools to inform uptake of the COVID-19 vaccine. Video design using health literacy guidelines may help optimize video usefulness. Many health organizations (HO) (provides information) and health care (HCO) (provides direct health care) organizations have used YouTube to deliver videos about COVID-19 vaccines. OBJECTIVE: We examined HO and HCO COVID-19 vaccine videos shown on YouTube for health literacy guidelines (quality, understandability and actionability). METHODS: The top 30 most viewed COVID-19 vaccine videos posted by HO and HCO were analyzed using the Global Quality Score (GQS) and the Patient Education Assessment Tool for evaluating audiovisual formats (PEMAT-AV). KEY RESULTS: GQS scores averaged 3.12 (standard deviation [SD] .789), which is equivalent to 80%. Using PEMATAV, there was a relationship between actionability and quality (r(28) = .453, p < .05) for HO; for HCO, there was a relationship between usability and quality (r(28) = .455, p < .05). Odds ratio analysis showed quality in HO leading to higher odds of actionability (3.573, 95% confidence interval [CI] [1.480-14.569]) and quality in HCO videos leading to higher understandability (4.093, CI [1.203-17.865]). CONCLUSION: Few organizations applied all health literacy principles to video design. Video creation for mass media health campaigns by HO and HCO should include consideration of evidence-based health literacy measures (quality, understandability, actionability) to ensure intended results across viewers with different health literacy levels including communities who have been disproportionately affected by COVID-19. [HLRP: Health Literacy Research and Practice. 2023;7(2):e111-e118.].

Unraveling attributes of COVID-19 vaccine acceptance and uptake in the U.S.: a large nationwide study.

SARS-CoV-2 vaccines are useful tools to combat the Coronavirus Disease 2019 (COVID-19) pandemic, but vaccine reluctance threatens these vaccines' effectiveness. To address COVID-19 vaccine reluctance and ensure equitable distribution, understanding the extent of and factors associated with vaccine acceptance and uptake is critical. We report the results of a large nationwide study in the US conducted December 2020-May 2021 of 36,711 users from COVID-19-focused smartphone-based app How We Feel on their willingness to receive a COVID-19 vaccine. We identified sociodemographic and behavioral factors that were associated with COVID-19 vaccine acceptance and uptake, and we found several vulnerable groups at increased risk of COVID-19 burden, morbidity, and mortality were more likely to be reluctant to accept a vaccine and had lower rates of vaccination. Our findings highlight specific populations in which targeted efforts to develop education and outreach programs are needed to overcome poor vaccine acceptance and improve equitable access, diversity, and inclusion in the national response to COVID-19.

The Blood-Brain Barrier in Health and Disease.

The blood-brain barrier (BBB) is a complex network of tightly regulated cells and transport proteins that separate the circulating blood from the brain tissue [...].

Barriers and Facilitators to Psychologists' Telepsychology Uptake during the Beginning of the COVID-19 Pandemic.

The COVID-19 pandemic transformed the delivery of psychological services as many psychologists adopted telepsychology for the first time or dramatically increased their use of it. The current study examined qualitative and quantitative data provided by 2619 practicing psychologists to identify variables facilitating and impeding the adoption of telepsychology in the U.S. at the beginning of the COVID-19 pandemic. The top five reported barriers were: inadequate access to technology, diminished therapeutic alliance, technological issues, diminished quality of delivered care or effectiveness, and privacy concerns. The top five reported facilitators were: increased safety, better access to patient care, patient demand, efficient use of time, and adequate technology for telepsychology use. Psychologists' demographic and practice characteristics robustly predicted their endorsement of telepsychology barriers and facilitators. These findings provide important context into the implementation of telepsychology at the beginning of the pandemic and may serve future implementation strategies in clinics and healthcare organizations attempting to increase telepsychology utilization.

Engineering Extracellular Vesicles as Delivery Systems in Therapeutic Applications.

Extracellular vesicles (EVs) are transport vesicles secreted by living cells and released into the extracellular environment. Recent studies have shown that EVs serve as "messengers" in intercellular and inter-organismal communication, in both normal and pathological processes. EVs, as natural nanocarriers, can deliver bioactivators in therapy with their endogenous transport properties. This review article describes the engineering EVs of sources, isolation method, cargo loading, boosting approach, and adjustable targeting of EVs. Furthermore, the review summarizes the recent progress made in EV-based delivery systems applications, including cancer, cardiovascular diseases, liver, kidney, nervous system diseases, and COVID-19 and emphasizes the obstacles and challenges of EV-based therapies and possible strategies.

Evaluation of Drug-Drug Interactions of Ensitrelvir, a SARS-CoV-2 3CL Protease Inhibitor, With Transporter Substrates Based on In Vitro and Clinical Studies.

Drug-drug interaction potentials of ensitrelvir, a novel oral inhibitor of 3C-like protease of severe acute respiratory syndrome coronavirus 2, for drug transporters were evaluated by in vitro and clinical studies. The target drug transporters assessed were P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, OCT2, and multidrug and toxin extrusion 1 and 2K. In vitro study revealed that ensitrelvir is a substrate for P-gp and BCRP and inhibits P-gp, BCRP, OATP1B1, OATP1B3, OCT1, and OAT3. Based on these results, a clinical drug-drug interaction study to evaluate the effect of ensitrelvir on the pharmacokinetics of P-gp, BCRP, OATP1B1, OATP1B3, and OCT1 substrates was conducted with a cocktail approach using digoxin (P-gp substrate), rosuvastatin (BCRP, OATP1B1, and OATP1B3 substrate), and metformin (OCT1 substrate). The cocktail was administered first, and after the washout period, the cocktail was coadministered with 500 mg of ensitrelvir. No treatment-emergent adverse events were observed. Pharmacokinetic analyses demonstrated that the ratios (90% confidence intervals) of "cocktail with ensitrelvir" to "cocktail without ensitrelvir" for maximum plasma concentration and area under the plasma concentration-time curve were, respectively, 2.17 (1.72-2.73) and 1.31 (1.13-1.52) for digoxin, 1.97 (1.73-2.25) and 1.65 (1.47-1.84) for rosuvastatin, and 1.03 (0.91-1.16) and 1.02 (0.94-1.11) for metformin. The results indicate that the exposure levels of digoxin and rosuvastatin increased when coadministered with ensitrelvir, but those of metformin were not changed. In conclusion, ensitrelvir has an impact on the exposure levels of P-gp, BCRP, OATP1B1, and OATP1B3 substrates.

Incidental osteonecrosis in the distal left femur in a case of beta-thalassemia with COVID-19: Role of [99mTc]Tc-MDP whole-body bone scan.

Secondary anemia in hemoglobinopathies like thalassemia can cause expansion of the bone marrow cavities because of compensatory marrow hyperplasia. This case demonstrates spontaneous osteonecrosis of the distal left femur in a patient with ß-thalassemia that may be secondary to ischemic infarction secondary to occlusion of the microvasculature within the expanded cancellous bone. This subject was referred to Hazrat Rasool Akram Hospital because of fever, cough, and bone pain. In the CT scan she had scattered peripheral CGO in both lungs due to COVID-19 with two paravertebral masses due to extramedullary hematopoiesis. The patient had also generalized bone pain so the physician asked for a whole-body bone scan and incidentally, we found a cold lesion with a rim of increased uptake in the distal left femur that with bone biopsy it was consistent with osteonecrosis. This case illustrates the importance of performing a whole-body bone scan in ß-thalassemia for the management of patients and diagnosis of occult osteonecrosis.

Modeling virus transport and dynamics in viscous flow medium.

In this paper, we developed a mathematical model to simulate virus transport through a viscous background flow driven by the natural pumping mechanism. Two types of respiratory pathogens viruses (SARS-Cov-2 and Influenza-A) are considered in this model. The Eulerian-Lagrangian approach is adopted to examine the virus spread in axial and transverse directions. The Basset-Boussinesq-Oseen equation is considered to study the effects of gravity, virtual mass, Basset force, and drag forces on the viruses transport velocity. The results indicate that forces acting on the spherical and non-spherical particles during the motion play a significant role in the transmission process of the viruses. It is observed that high viscosity is responsible for slowing the virus transport dynamics. Small sizes of viruses are found to be highly dangerous and propagate rapidly through the blood vessels. Furthermore, the present mathematical model can help to better understand the viruses spread dynamics in a blood flow.

Wearables in Nephrology: Fanciful Gadgetry or Prêt-à-Porter?

Telemedicine and digitalised healthcare have recently seen exponential growth, led, in part, by increasing efforts to improve patient flexibility and autonomy, as well as drivers from financial austerity and concerns over climate change. Nephrology is no exception, and daily innovations are underway to provide digitalised alternatives to current models of healthcare provision. Wearable technology already exists commercially, and advances in nanotechnology and miniaturisation mean interest is also garnering clinically. Here, we outline the current existing wearable technology pertaining to the diagnosis and monitoring of patients with a spectrum of kidney disease, give an overview of wearable dialysis technology, and explore wearables that do not yet exist but would be of great interest. Finally, we discuss challenges and potential pitfalls with utilising wearable technology and the factors associated with successful implementation.

COVID-19 Biogenesis and Intracellular Transport.

SARS-CoV-2 is responsible for the COVID-19 pandemic. The structure of SARS-CoV-2 and most of its proteins of have been deciphered. SARS-CoV-2 enters cells through the endocytic pathway and perforates the endosomes' membranes, and its (+) RNA appears in the cytosol. Then, SARS-CoV-2 starts to use the protein machines of host cells and their membranes for its biogenesis. SARS-CoV-2 generates a replication organelle in the reticulo-vesicular network of the zippered endoplasmic reticulum and double membrane vesicles. Then, viral proteins start to oligomerize and are subjected to budding within the ER exit sites, and its virions are passed through the Golgi complex, where the proteins are subjected to glycosylation and appear in post-Golgi carriers. After their fusion with the plasma membrane, glycosylated virions are secreted into the lumen of airways or (seemingly rarely) into the space between epithelial cells. This review focuses on the biology of SARS-CoV-2's interactions with cells and its transport within cells. Our analysis revealed a significant number of unclear points related to intracellular transport in SARS-CoV-2-infected cells.

Not Getting Vaccinated? It Is a Matter of Problem-Solving Abilities and Socio-Cognitive Polarization.

The anti-COVID-19 vaccination campaign in the United States provided a significant contribution to the control of the virus spread. Despite the recommendations by public health institutions, vaccine skepticism and hesitancy contributed to low vaccine uptake, thus possibly disrupting the management of preventable diseases associated with the COVID-19 infection. The process that led individuals to accept COVID-19 vaccines required the ability to gather, synthesize, and weigh-up information within a novel, dynamically changing, complex, and ambiguous context. To deal with such complexity, we hypothesized that both the ability of reflection and flexible adaptation played a fundamental role. Based on previous research on cognitive predictors of vaccine refusal, we decided to investigate the combined role of two constructs, namely, problem-solving skills and socio-cognitive polarization (SCP), on vaccine acceptance and uptake. Two-hundred-seventy-seven US participants completed an online survey aimed to measure problem-solving ability, through a rebus puzzles task, and SCP, through a composite measure of absolutist thinking, political conservatism, and xenophobia. Mediation analyses indicated that SCP mediated the association between problem-solving ability and vaccine acceptance, so lower problem-solving abilities associated with higher polarization predicted vaccine rejection. Thus, our findings suggested that low problem-solving skills may represent a risk factor for COVID-19 vaccine refusal, with cognitive and social rigidity playing a crucial role in undermining the anti-COVID-19 vaccine uptake.

Efficacy Validation of SARS-CoV-2-Inactivation and Viral Genome Stability in Saliva by a Guanidine Hydrochloride and Surfactant-Based Virus Lysis/Transport Buffer.

To enhance biosafety and reliability in SARS-CoV-2 molecular diagnosis, virus lysis/transport buffers should inactivate the virus and preserve viral RNA under various conditions. Herein, we evaluated the SARS-CoV-2-inactivating activity of guanidine hydrochloride (GuHCl)- and surfactant (hexadecyltrimethylammonium chloride (Hexa-DTMC))-based buffer, Prep Buffer A, (Precision System Science Co., Ltd., Matsudo, Japan) and its efficacy in maintaining the stability of viral RNA at different temperatures using the traditional real-time one-step RT-PCR and geneLEAD VIII sample-to-result platform. Although Prep Buffer A successfully inactivated SARS-CoV-2 in solutions with high and low organic substance loading, there was considerable viral genome degradation at 35 °C compared with that at 4 °C. The individual roles of GuHCl and Hexa-DTMC in virus inactivation and virus genome stability at 35 °C were clarified. Hexa-DTMC alone (0.384%), but not 1.5 M GuHCl alone, exhibited considerable virucidal activity, suggesting that it was essential for potently inactivating SARS-CoV-2 using Prep Buffer A. GuHCl and Hexa-DTMC individually reduced the viral copy numbers to the same degree as Prep Buffer A. Although both components inhibited RNase activity, Hexa-DTMC, but not GuHCl, directly destroyed naked viral RNA. Our findings suggest that samples collected in Prep Buffer A should be stored at 4 °C when RT-PCR will not be performed for several days.

Effect of Health Insurance Uptake on Hesitancy toward COVID-19 Vaccines in Nigeria: A Recursive Bivariate Probit and Decomposition Estimation.

Moral hazard remains one of the major challenges of health insurance administration. This paper recursively analyzed the effect of health insurance on the willingness to take COVID-19 vaccines in Nigeria. The data comprised 1892 unvaccinated respondents in the 2021/2022 National Longitudinal Phone Survey (NLPS). The data were analyzed with Coban's recursive probit regression and decomposition approaches. The results revealed that 5.87% were health insured, and 7.93% were willing to take COVID-19 vaccines. Health insurance uptake significantly increased (p < 0.05) with an adult being the decision-maker on vaccination, requiring family planning, and urban residence, while it reduced with loss of jobs and residence in the southeast and southwest zones. In addition, health insurance significantly (p < 0.01) increased the willingness to take COVID-19 vaccines, along with each adult, all adults, and households' heads being the major vaccination decision-makers, loss of jobs, and support for making COVID-19 vaccines compulsory. The average treatment effects (ATEs) and average treatment effect on the treated (ATET) of health insurance were significant (p < 0.01), with positive impacts on willingness to be vaccinated. It was concluded that policy reforms to promote access to health insurance would enhance COVID-19 vaccination in Nigeria. In addition, hesitancy toward COVID-19 vaccines can be reduced by targeting adults and household heads with adequate information, while health insurance uptake should target southern states and rural areas.

Endolysosomal cholesterol export: More than just NPC1.

NPC1 plays a central role in cholesterol egress from endolysosomes, a critical step for maintaining intracellular cholesterol homeostasis. Despite recent advances in the field, the full repertoire of molecules and pathways involved in this process remains unknown. Emerging evidence suggests the existence of NPC1-independent, alternative routes. These may involve vesicular and non-vesicular mechanisms, as well as release of extracellular vesicles. Understanding the underlying molecular mechanisms that bypass NPC1 function could have important implications for the development of therapies for lysosomal storage disorders. Here we discuss how cholesterol may be exported from lysosomes in which NPC1 function is impaired.

A phosphoinositide signalling pathway mediates rapid lysosomal repair.

Lysosomal dysfunction has been increasingly linked to disease and normal ageing1,2. Lysosomal membrane permeabilization (LMP), a hallmark of lysosome-related diseases, can be triggered by diverse cellular stressors3. Given the damaging contents of lysosomes, LMP must be rapidly resolved, although the underlying mechanisms are poorly understood. Here, using an unbiased proteomic approach, we show that LMP stimulates a phosphoinositide-initiated membrane tethering and lipid transport (PITT) pathway for rapid lysosomal repair. Upon LMP, phosphatidylinositol-4 kinase type 2α (PI4K2A) accumulates rapidly on damaged lysosomes, generating high levels of the lipid messenger phosphatidylinositol-4-phosphate. Lysosomal phosphatidylinositol-4-phosphate in turn recruits multiple oxysterol-binding protein (OSBP)-related protein (ORP) family members, including ORP9, ORP10, ORP11 and OSBP, to orchestrate extensive new membrane contact sites between damaged lysosomes and the endoplasmic reticulum. The ORPs subsequently catalyse robust endoplasmic reticulum-to-lysosome transfer of phosphatidylserine and cholesterol to support rapid lysosomal repair. Finally, the lipid transfer protein ATG2 is also recruited to damaged lysosomes where its activity is potently stimulated by phosphatidylserine. Independent of macroautophagy, ATG2 mediates rapid membrane repair through direct lysosomal lipid transfer. Together, our findings identify that the PITT pathway maintains lysosomal membrane integrity, with important implications for numerous age-related diseases characterized by impaired lysosomal function.

Design and Development of Nanomaterial-Based Drug Carriers to Overcome the Blood-Brain Barrier by Using Different Transport Mechanisms.

Central nervous system (CNS) diseases are the leading causes of death and disabilities in the world. It is quite challenging to treat CNS diseases efficiently because of the blood-brain barrier (BBB). It is a physical barrier with tight junction proteins and high selectivity to limit the substance transportation between the blood and neural tissues. Thus, it is important to understand BBB transport mechanisms for developing novel drug carriers to overcome the BBB. This paper introduces the structure of the BBB and its physiological transport mechanisms. Meanwhile, different strategies for crossing the BBB by using nanomaterial-based drug carriers are reviewed, including carrier-mediated, adsorptive-mediated, and receptor-mediated transcytosis. Since the viral-induced CNS diseases are associated with BBB breakdown, various neurotropic viruses and their mechanisms on BBB disruption are reviewed and discussed, which are considered as an alternative solution to overcome the BBB. Therefore, most recent studies on virus-mimicking nanocarriers for drug delivery to cross the BBB are also reviewed and discussed. On the other hand, the routes of administration of drug-loaded nanocarriers to the CNS have been reviewed. In sum, this paper reviews and discusses various strategies and routes of nano-formulated drug delivery systems across the BBB to the brain, which will contribute to the advanced diagnosis and treatment of CNS diseases.

Advances in brain barriers and brain fluids research in 2021: great progress in a time of adversity.

This editorial highlights advances in brain barrier and brain fluid research in 2021. It covers research on components of the blood-brain barrier, neurovascular unit and brain fluid systems; how brain barriers and brain fluid systems are impacted by neurological disorders and their role in disease progression; and advances in strategies for treating such disorders.

SARS-CoV-2 ORF6 disrupts nucleocytoplasmic trafficking to advance viral replication.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF6 is an antagonist of interferon (IFN)-mediated antiviral signaling, achieved through the prevention of STAT1 nuclear localization. However, the exact mechanism through which ORF6 prevents STAT1 nuclear trafficking remains unclear. Herein, we demonstrate that ORF6 directly binds to STAT1 with or without IFN stimulation, resulting in the nuclear exclusion of STAT1. ORF6 also recognizes importin α subtypes with different modes, in particular, high affinity to importin α1 but a low affinity to importin α5. Although ORF6 potentially disrupts the importin α/importin ß1-mediated nuclear transport, thereby suppressing the nuclear translocation of the other classical nuclear localization signal-containing cargo proteins, the inhibitory effect of ORF6 is modest when compared with that of STAT1. The results indicate that the drastic nuclear exclusion of STAT1 is attributed to the specific binding with ORF6, which is a distinct strategy for the importin α1-mediated pathway. Combined with the results from a newly-produced replicon system and a hamster model, we conclude that SARS-CoV-2 ORF6 acts as a virulence factor via regulation of nucleocytoplasmic trafficking to accelerate viral replication, resulting in disease progression.