Illuminated Devices: A Sociotechnical System to Broaden Access to Digital Assistance

User training and support are crucial factors in bridging the digital divide. The Illuminated Devices sociotechnical system, inspired by our experiences providing online support during COVID-19, will provide personal digital tutoring, accessible anywhere, even with limited prior technology experience. System development leverages a human-centered, design-based research approach. The project will culminate in a pilot rollout and evaluation at three community sites. © ISLS.

COVID-19 disease is associated with a hypofibrinolytic state driven by elevated plasminogen activator inhibitor-1 and its cofactor vitronectin

Background: COVID-19 disease arises from infection with severe acute respiratory cornonavirus-2 (SARS-CoV- 2). Severe disease is associated with a coagulopathy characterised by elevated D-dimer levels, fibrin deposition in the lung, and a thrombotic incidence of approximately 30%, indicating catastrophic derailment of the haemostatic system. Aim(s): To investigate whether SARS-CoV- 2- induced coagulopathy arises due to an imbalance in the fibrinolysis. Method(s): Citrated plasma was collected from 139 patients presenting with symptomatic COVID-19, 24 patients with non-COVID- 19 respiratory infection and 30 healthy controls in a dual-centre study. Fibrinolytic biomarkers were evaluated including plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), plasminogen, vitronectin and thrombin activatable fibrinolysis inhibitor (TAFI). Furthermore, diagnostic biomarkers including, fibrinogen, C-reactive protein (CRP), D-dimer and inflammatory cytokines were quantified. Clot lysis was evaluated using turbidity assays, plasma clot structure visualised by confocal microscopy and plasmin generation quantified by chromogenic substrate. Result(s): PAI-1 antigen, activity, and the cofactor for this serpin, vitronectin, were significantly elevated in patients with COVID-19 compared to healthy controls and non-COVID- 19 respiratory infection. Patients with COVID-19 exhibit attenuated plasmin generation compared to healthy volunteers despite significant elevation in tPA. PAI-1 correlated with inflammatory cytokines (IL-1beta, IL-8 and TNF-alpha). In line with this acute phase proteins, fibrinogen and CRP were high in patients with COVID-19 but only CRP was increased compared to non-COVID- 19 respiratory infections. Levels of PAI-1 and vitronectin were associated with escalating oxygen support and a corresponding decrease in plasminogen. Importantly, patients with COVID-19 disease exhibit resistance to fibrinolytic degradation by Actilyse, however, this could be overcome by the PAI-1 resistant form of tPA, Metalyse. Conclusion(s): We reveal that COVID-19 disease promotes a hypofibrinolytic state due to elevated PAI-1 and its stabilizing cofactor vitronectin. PAI-1 correlates with inflammatory cytokines and disease severity thereby highlighting its potential prognostic power in the development of severe COVID-19 disease.

POLLINATOR-FLOWER INTERACTIONS IN GARDENS DURING THE COVID-19 PANDEMIC LOCKDOWN OF 2020

During the main COVID-19 global pandemic lockdown period of 2020 an impromptu set of pollination ecologists came together via social media and personal contacts to carry out standardised surveys of the flower visits and plants in gardens. The surveys involved 67 rural, suburban and urban gardens, of various sizes, ranging from 61.18° North in Norway to 37.96° South in Australia, resulting in a data set of 25,174 rows, with each row being a unique interaction record for that date/site/plant species, and comprising almost 47,000 visits to flowers, as well as records of flowers that were not visited by pollinators, for over 1,000 species and varieties belonging to more than 460 genera and 96 plant families. The more than 650 species of flower visitors belong to 12 orders of invertebrates and four of vertebrates. In this first publication from the project, we present a brief description of the data and make it freely available for any researchers to use in the future, the only restriction being that they cite this paper in the first instance. The data generated from these global surveys will provide scientific evidence to help us understand the role that private gardens (in urban, rural and suburban areas) can play in conserving insect pollinators and identify management actions to enhance their potential. © 2022 The authors.

JAPAN 2021: THE LIBERAL DEMOCRATIC PARTY EMERGES STRONGER DESPITE DOMESTIC TUMULT

The COVID-19 pandemic continued to impact the Japanese economy as well as the political fortunes of Japan’s leader in 2021. For the second year in a row, Japan’s Prime Minister was forced to stand down, portending a return to the revolving door of one-year prime ministerships that characterized the politically tumultuous period between 2006 and 2012. Prime Minister Suga Yoshihide’s announcement that he would not seek reappointment as president of the ruling Liberal Democratic Party (LDP), therefore effectively resigning as prime minister, precipitated the most competi-tive race for the LDP leadership in a decade in September. Suga’s anointed replace-ment was former record-setting Minister of Foreign Affairs Kishida Fumio. Kishida was not the most popular choice for Japan’s next prime minister among the public or even the LDP party cadres. His initial cabinet ratings reflected this and the fact that Kishida had triumphed over then «vaccine minister» Kōno Tarō in the party contest primarily due to factional manoeuvrings facilitated by former Prime Minister Abe Shinzō. To the traditionally dovish Kishida’s credit, he demonstrated great prag-matism in 2021. He managed to win the backing of Abe and other conservatives by adapting his own political positions and adopting others from the conservative wing of the LDP, particularly on Taiwan policy, national security, and economic security policy. Kishida survived Japan’s October House of Representatives election in better-than-expected shape and went on to improve his cabinet ratings in the last two months of 2021. Kishida entered 2022 in a strong position with both the COVID-19 and economic situation heading in the right direction ahead of the mid-2022 House of Councillors election—the last national election Kishida will have to face for three years if he prevails. © Viella s.r.l. & Associazione Asia Maior.

SPIKE PLUS NUCLEOCAPSID VACCINE PROTECTS AGAINST SARS-CoV-2 DELTA INFECTION in NHPs

Background: SARS-CoV-2 vaccines capable of inducing broad and cross-reactive humoral and T cell responses help to fight against emerging variants. In this study we compared the immunogenicity and efficacy of modified vaccinia Ankara (MVA) based SARS-CoV-2 vaccine expressing furin-cleavage site inactivated stabilized spike (SdFCS) and nucleocapsid (N) delivered via intramuscular (IM), buccal or sublingual (SL) routes in rhesus macaques (RMs). Methods: Three groups (n=5/group) of RMs were immunized with MVA/SdFCS-N vaccine on weeks 0 and 4, via IM, buccal, or SL route. An additional group (control) received non-recombinant MVA via IM. IM vaccinations were delivered using needle and SL and buccal vaccinations were delivered using a needle-free injection device. All RMs were challenged with B.1.617.2 strain (Delta) of SARS-CoV-2 at week 8 via intratracheal and intranasal routes simultaneously. Various humoral and cellular immune parameters were determined post vaccination and challenge. SARS-CoV-2 subgenomic RNA (sgRNA) was measured to monitor virus replication in the upper (nose) and lower (lung) respiratory tract. Results: IM vaccination induced strong RBD-specific IgG antibody in serum, nose, throat, lung, and rectum. The serum antibody showed strong live virus neutralizing activity against WA-1/2020 (median of 415) and B.1.617.2 strains (median of 317). Serum from IM vaccinated animals also demonstrated strong non-neutralizing effector functions such as ADCD, ADCP and ADNKA. In addition, IM vaccination induced strong CD4 and CD8 T cell response in the blood that was directed against both S and N. In contrast, the SL and buccal vaccination-induced antibody showed lower neutralization titer against WA-1/2020 (143 and 302, respectively), and showed 4.5-fold lower cross reactivity neutralization titer against B.1.617.2 compared to WA-1/2020. Following challenge with B.1.617.2, the IM group RMs showed superior protection with 3 of the 5 animals being negative in upper and lower respiratory airways at Day 2. In contrast, no significant protection was observed in the SL group. Vaccine induced neutralizing and non-neutralizing antibody effector functions showed direct association with protection. Conclusion: Our findings showed that IM vaccination with improved MVA-based SARS-CoV-2 vaccine elicits cross-reactive antibody and T cell responses and protect against heterologous SARS-CoV-2 Delta challenge in RMs. They also showed IM vaccinations are superior to oral vaccinations.

Need for tracheostomy in major head and neck ablative surgery: a paradigm shift during the COVID-19 pandemic.

INTRODUCTION: Management of the airway in the perioperative period for patients requiring major head and neck ablative surgery has commonly included the performance of elective surgical tracheostomy. This has been standard practice in most maxillofacial units across the UK, including ours. However, the COVID-19 pandemic and emerging guidelines on aerosol-generating procedures required us to revisit the need for a perioperative tracheostomy. METHODS: We present our series of 29 consecutive cases, cared for during the first wave of the COVID-19 pandemic, that were managed either using surgical tracheostomy or overnight tracheal intubation. RESULTS: Out of 29 patients 3 received a surgical tracheostomy. The average duration of tracheostomy use was 8 days. Twenty patients were managed using a period of overnight tracheal intubation. Average duration of tracheal intubation was 1.2 days, with an average intensive care unit stay of 1.7 days. The average duration of hospital stay was 15.8 days for patients managed with overnight tracheal intubation and 30.1 days for patients who received a surgical tracheostomy. The return to theatre rate was 13.8% for reasons including flap failure and neck space infection. There were no airway issues reported in this series of patients. CONCLUSIONS: Our findings suggest that overnight tracheal intubation can be a safe alternative to surgical tracheostomy in the majority of cases.

Acute Rehabilitation in a Lung Transplant Recipient Infected with Covid-19: Case Report

We report a case of a 68-year-old female with idiopathic pulmonary fibrosis who underwent bilateral lung transplantation with concurrent Covid-19 infection. Physical and Occupational therapy were initiated immediately following transplantation. Physical therapy interventions included bed mobility, functional transfers, ambulation, balance training, aerobic and breathing exercises. Occupational therapy interventions worked on cognitive and grooming tasks, total body dressing, anxiety reduction and energy conservation. Despite the presence of respiratory and physical impairments, the patient achieved significant improvements in functional mobility and ADLs. The patient improved her activity tolerance and was discharged to an inpatient rehabilitation facility. Rehabilitation management of lung transplant recipients with Covid-19 has not been studied and therefore it is crucial to investigate the effects of early evaluation and treatment of impairments exhibited by these patients, as they will likely require acute and long-term rehabilitation. Further research is needed to provide clinical practice guidelines for lung transplant recipients with Covid-19. © 2021 Taylor & Francis Group, LLC.

Seropositivity in blood donors and pregnant women during the first year of SARS-CoV-2 transmission in Stockholm, Sweden.

BACKGROUND: In Sweden, social restrictions to contain SARS-CoV-2 have primarily relied upon voluntary adherence to a set of recommendations. Strict lockdowns have not been enforced, potentially affecting viral dissemination. To understand the levels of past SARS-CoV-2 infection in the Stockholm population before the start of mass vaccinations, healthy blood donors and pregnant women (n = 5,100) were sampled at random between 14 March 2020 and 28 February 2021. METHODS: In this cross-sectional prospective study, otherwise-healthy blood donors (n = 2,600) and pregnant women (n = 2,500) were sampled for consecutive weeks (at four intervals) throughout the study period. Sera from all participants and a cohort of historical (negative) controls (n = 595) were screened for IgG responses against stabilized trimers of the SARS-CoV-2 spike (S) glycoprotein and the smaller receptor-binding domain (RBD). As a complement to standard analytical approaches, a probabilistic (cut-off independent) Bayesian framework that assigns likelihood of past infection was used to analyse data over time. SETTING: Healthy participant samples were randomly selected from their respective pools through Karolinska University Hospital. The study was carried out in accordance with Swedish Ethical Review Authority: registration number 2020-01807. PARTICIPANTS: No participants were symptomatic at sampling, and blood donors were all over the age of 18. No additional metadata were available from the participants. RESULTS: Blood donors and pregnant women showed a similar seroprevalence. After a steep rise at the start of the pandemic, the seroprevalence trajectory increased steadily in approach to the winter second wave of infections, approaching 15% of all individuals surveyed by 13 December 2020. By the end of February 2021, 19% of the population tested seropositive. Notably, 96% of seropositive healthy donors screened (n = 56) developed neutralizing antibody responses at titres comparable to or higher than those observed in clinical trials of SARS-CoV-2 spike mRNA vaccination, supporting that mild infection engenders a competent B-cell response. CONCLUSIONS: These data indicate that in the first year since the start of community transmission, seropositivity levels in metropolitan in Stockholm had reached approximately one in five persons, providing important baseline seroprevalence information prior to the start of vaccination.

Altered mental status presenting to the pediatric emergency department

Case Report Introduction Hyperosmolar hyperglycemic state (HHS) represents a syndrome of acute diabetic decompensation characterized by marked hyperglycemia, hyperosmolality, dehydration and decreased mental status that may progress to coma. About 20% of patients have no known history of type 2 diabetes. Case A 15 yo male presented to the emergency department with altered mental status. Mom reported that he had malaise, polydipsia and polyuria for 1 week and 2 days of right flank pain. She denied fever, cough, headache, diarrhea, vomiting and rash. Prior to arrival he was found unresponsive with urinary incontinence. Vital signs: HR 136 RR 20 BP 140/62 T 101.2 90% on RA Responsive only to deep sternal rub. HEENT: PERRL. Respiratory: CTAB. Cardiac: Tachycardic, gallop present. Skin: Cool periphery, no edema, or petechiae. Abdomen: soft, NTND. Neuro: No obvious focal deficit. Labs: VBG: pH 7.18, pCO2 49.9, pO2 59, HCO3 19, Lactic acid 7.5, Glucose >700 Lipid Panel: normal CMP: Na 131, K 3.4,Bicarb 9, Bun 42,Cr 2.93, Albumin 5.0, liver enzymes normal, Phos 2.3, Mg 3.55, Ca 10.9, glucose 2238, lipase 1600. CT head revealed cerebral edema, MRV negative for dural sinus thrombosis. COVID PCR positive, VRP negative. Hospital course: ED: Patient was given 2L of LR boluses, mannitol and insulin drip was started. 2 LPM of supplemental oxygen was given for hypoxia to 88%. ICU: Patient was intubated for acute respiratory failure and shock. Received >8L volume and was started on epinephrine, vasopressin and milrinone. He was given steroids for fluid resistant shock, vancomycin, cefepime and flagyl. Echocardiogram showed hyperdynamic function. Elevated ferritin, ddimer and inflammatory markers were concerning for multisystem inflammatory syndrome (MIS-C), so he received IVIG. Became oliguric with AKI requiring dialysis. Discussion Associated diseases in HHS are gram-negative pneumonia, GI bleeding and gram negative sepsis. There is insufficient data on SARS-CoV-2 and HHS. Case reports indicate that MIS-C may present with clinical entities as varied as appendicitis, pseudotumor and encephalopathy. We present a unique case of HHS and MIS-C. Pediatric HHS has a higher incidence of fatal cerebral edema and warrants early recognition and further investigation as our clinical understanding of MIS-C continues to evolve.