Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) With Severe Hyponatremia As the Initial and Sole Presentation of COVID-19 Infection: A Case Report and Pathophysiologic Insights.

Hyponatremia is one of the common electrolyte imbalances among hospitalized patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) being a common etiology for hyponatremia. There are multiple pathophysiologic considerations in the differential diagnosis of the etiologic factor for SIADH, including infections such as pneumonia and meningitis, as well as coronavirus disease 2019 (COVID-19) infection. However, SIADH, as the sole initial presentation of the infection of COVID-19, is rarely reported. In this report, we present a case of SIADH as the initial and only presentation of a COVID-19 infection, highlighting the clinical course and treatment strategy while providing the putative pathophysiologic insights into this unusual and potentially serious complication of COVID-19 infection.

Structural basis for substrate selection by the SARS-CoV-2 replicase.

The SARS-CoV-2 RNA-dependent RNA polymerase coordinates viral RNA synthesis as part of an assembly known as the replication-transcription complex (RTC)1. Accordingly, the RTC is a target for clinically approved antiviral nucleoside analogues, including remdesivir2. Faithful synthesis of viral RNAs by the RTC requires recognition of the correct nucleotide triphosphate (NTP) for incorporation into the nascent RNA. To be effective inhibitors, antiviral nucleoside analogues must compete with the natural NTPs for incorporation. How the SARS-CoV-2 RTC discriminates between the natural NTPs, and how antiviral nucleoside analogues compete, has not been discerned in detail. Here, we use cryogenic-electron microscopy to visualize the RTC bound to each of the natural NTPs in states poised for incorporation. Furthermore, we investigate the RTC with the active metabolite of remdesivir, remdesivir triphosphate (RDV-TP), highlighting the structural basis for the selective incorporation of RDV-TP over its natural counterpart adenosine triphosphate3,4. Our results explain the suite of interactions required for NTP recognition, informing the rational design of antivirals. Our analysis also yields insights into nucleotide recognition by the nsp12 NiRAN (nidovirus RdRp-associated nucleotidyltransferase), an enigmatic catalytic domain essential for viral propagation5. The NiRAN selectively binds guanosine triphosphate, strengthening proposals for the role of this domain in the formation of the 5' RNA cap6.

Inactivation strategies for SARS-CoV-2 on surgical masks using light-activated chemical dyes.

BACKGROUND: Methylene blue (MB) and riboflavin (RB) are light-activated dyes with demonstrated antimicrobial activity. They require no specialized equipment, making them attractive for widespread use. Due to COVID-19-related worldwide shortages of surgical masks, simple, safe, and effective decontamination methods for reusing masks have become desirable in clinical and public settings. MATERIAL AND METHODS: We examined the decontamination of SARS-CoV-2 Beta variant on surgical masks and Revolution-Zero Environmentally Sustainable (RZES) reusable masks using these photoactivated dyes. We pre-treated surgical masks with 2 MB concentrations, 2 RB concentrations, and 2 combinations of MB and RB. We also tested 7 MB concentrations on RZES masks. RESULTS: Photoactivated MB consistently inactivated SARS-CoV-2 at >99.9% for concentrations of 2.6 µM or higher within 30 min on RZES masks and 5 µM or higher within 5 min on disposable surgical masks. RB alone showed a lower, yet still significant inactivation (∼93-99%) in these conditions. DISCUSSION: MB represents a cost-effective, rapid, and widely deployable decontamination method for SARS-CoV-2. The simplicity of MB formulation makes it ideal for mask pre-treatment in low-resource settings. CONCLUSIONS: The results demonstrate that MB effectively decontaminates SARS-CoV-2 at concentrations above 5 µM on surgical masks and above 10 µM on RZES masks.

Methylene blue applied to N95 respirators and medical masks for SARS-CoV-2 decontamination: What is the likelihood of inhaling methylene blue?

BACKGROUND: Global shortage of personal protective equipment (PPE), as consequence of the COVID-19 global pandemic, has unmasked significant resource inequities prompting efforts to develop methods for safe PPE decontamination for reuse. The World Health Organization (WHO) in their Rational Use of PPE bulletin cited the use of a photodynamic dye, methylene blue, and light exposure as a viable option for N95 respirator decontamination. Because WHO noted that methylene blue (MB) would be applied to surfaces through which health care workers breathe, we hypothesized that little to no MB will be detectable by spectroscopy when the PPE is subjected to MB at supraphysiologic airflow rates. METHODS: A panel of N95 respirators, medical masks, and cloth masks were sprayed with 5 cycles of 1,000 uM MB solution. Mask coupons were subjected to the equivalent of 120 L/min of 100% humidified air flow. Effluent gas was trapped in an aqueous solution and the resultant fluid was sampled for MB absorbance with a level of detection of 0.004 mg/m3. RESULTS: No detectable MB was identified for any mask using Ultraviolet-Visible spectroscopy. CONCLUSIONS: At 500-fold the amount of MB applied to N95 respirators and medical masks as were used for the decontamination study cited in the WHO Rational Use of PPE bulletin, no detectable MB was observed, thus providing safety evidence for the use of methylene blue and light exposure for mask decontamination.

“Why couldn’t we do this more often?”: exploring the feasibility of virtual and distributed work in product design engineering

Lower costs and higher employee satisfaction are some of the benefits driving organizations to adopt dispersed and virtual working arrangements. Despite these advantages, product design engineering teams—those who develop physical products—have not widely adopted this working style due to perceived critical dependence on physical facilities and the belief that it is ineffective to communicate technical details virtually. This paper uses the mass shift in working conditions caused by the COVID-19 pandemic to explore the feasibility of virtual and distributed work in product design engineering. We conducted 20 semi-structured interviews with product design engineers working virtually to uncover current challenges of, and the beginning of promising strategies for, effective virtual engineering work. We categorize and analyze Tangible Design activities, Intangible Design activities, and Communication and Project Management activities throughout the product design process. Contrary to present opinions, we found that much of a product design engineer's work is realizable in a virtual and distributed setting. However, there are still many challenges, especially when attempting Tangible Design activities—those that require physical products and tools—from home. These challenges, missing from existing virtual product design engineering literature, include but are not limited to individuals’ lessened sense of accountability, fewer de-risking opportunities before product sign-off, and limited supervision of production staff. Product design engineers described novel strategies that emerged organically to mitigate these challenges, such as creating digital alternatives for engineering reviews and sign-offs and leveraging rapid prototyping. Recent advances in technology, an increased commitment to reducing environmental impact, and better work-life balance expectations from new generations of workers will only push society faster towards a distributed working model. Thus, it is critical that we use this opportunity to understand the existing challenges for distributed product design engineers, so that organizations can best prepare and become resilient to future shocks.

The Relationships among Authentic Leadership, Social Exchange Relationships, and Trust in Organizations during COVID-19 Pandemic

Purpose: Trust is essential for organizations' cooperative relationships during COVID-19. Authentic leadership and social exchange relationships are required to increase trust during a crisis. However, leader behaviors during COVID-19 have effects on the relationships among authentic leadership, social exchange relationships, and trust in organizations to understand their effects. The moderating effects of leader behaviors during COVID-19 on the relationships among authentic leadership, social exchange relationships, and trust in organizations are investigated. Design/ Methodology/Approach: Hierarchical multiple regression with interaction terms is used to examine interactions of leader behaviors during COVID-19 on the relationships between variables. Moreover, bootstrapping is performed to explore the mediating role of social exchange relationships between authentic leadership and trust in organizations. Findings: The findings indicate that authentic leadership positively affects social exchange relationships and trust, whereas social exchange relationships positively affect trust. Moreover, a social exchange relationship has a mediating effect between authentic leadership and trust. Both leader behaviors are regrading (a) managerial ability with ethics and (b) a positive working relationship based on work from home as moderators, positively influencing authentic leadership, social exchange relationships, and trust. Practical implications: This paper suggests that authentic leadership increases the quality of social exchange relationships and trust. Leader behavior qualities and leader-follower relationships based on social exchange theory are essential for improving trust even after postCOVID-19. Finally, based on the social exchange theory, leader behavior qualities and leaderfollower relationships can motivate positive relationships in organizations. The chief executive officers (CEOs) and the organizational management teams benefit from the outcomes of this paper to comprehend which factors affect relationships and trust changes in organizations.

Authentic Leadership, Trust, and Social Exchange Relationships under the Influence of Leader Behavior

During the pandemic, government policies such as social distancing and telework have impacted trust and working or social exchange relationships in the workplace. The behavior of leaders is critical for good leadership, employees' trust, and social exchange relationships. Therefore, the main objective of this study was to assess the associations among authentic leadership, trust, and social exchange relationships under the influence of leader behavior. A regression-based approach was used to test the moderating and mediating effects. The results show that authentic leadership positively impacts trust and social exchange relationships, whereas trust directly affects social exchange relationships. During COVID-19, leader behaviors with ability, ethics, and positive relationships have had a positive impact on the association between authentic leadership, trust, and social exchange relationships. Additionally, trust positively mediates authentic leadership and social exchange relationships. The findings of this paper suggest that authentic leadership promotes trust and high-quality social exchange relationships. Moreover, based on leader behaviors during COVID-19, the ability to manage change effectively, boost employees' work motivation, provide support, and take appropriate action is essential for authentic leadership to increase trust and foster a positive working relationship based on social exchange. Finally, regarding social exchange theory, high-quality leader behaviors and the leader–follower relationships drive positive associations among variables. These results will help organizational management teams to find methods to improve their organizational working relationships. The implication is that the abilities, ethics, and supportive and positive relationship behaviors of leaders are essential for effective management to improve leadership, trust, and social exchange relationships. Leaders should have the ability to manage work and people, even with teleworkers. Therefore, leader behaviors are important to maintain organizational sustainability. Further discussion on theoretical and practical implications is provided in the section.

Ensemble cryo-EM reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication-transcription complex.

The SARS-CoV-2 nonstructural proteins coordinate genome replication and gene expression. Structural analyses revealed the basis for coupling of the essential nsp13 helicase with the RNA-dependent RNA polymerase (RdRp) where the holo-RdRp and RNA substrate (the replication-transcription complex or RTC) associated with two copies of nsp13 (nsp132-RTC). One copy of nsp13 interacts with the template-RNA in an opposing polarity to the RdRp and is envisaged to drive the RdRp backward on the RNA template (backtracking), prompting questions as to how the RdRp can efficiently synthesize RNA in the presence of nsp13. Here we use cryogenic-electron microscopy and molecular dynamics simulations to analyze the nsp132-RTC, revealing four distinct conformational states of the helicases. The results indicate a mechanism for the nsp132-RTC to turn backtracking on and off, using an allosteric mechanism to switch between RNA synthesis or backtracking in response to stimuli at the RdRp active site.

Burnout and work-work imbalance in radiology- wicked problems on a global scale. A baseline pre-COVID-19 survey of US neuroradiologists compared to international radiologists and adjacent staff.

PURPOSE: Worldwide, radiologists are experiencing increasing clinical workloads with associated increased burnout. This paper will review burnout definitions, prevalence, and causes. We will also share data from a survey of US neuroradiologists as an example of the impact of work-work imbalances from clinical overload. This article examines the impact on several key job indicators and upon the quality of the neuroradiology work environment in one nation. Finally, we will review proposals for ameliorating and preventing radiologist burnout. METHOD: A survey was sent to members of the American Society of Neuroradiology (ASNR) practicing in the US. Selected measures included workhours and volume, burnout symptoms, subjectively reported errors, participation in non-clinical activities, perceived interpretation quality, results communication, and consideration of early retirement. RESULTS: Survey respondents (n = 412) included 57.5% with teaching responsibilities. Cutbacks in teaching, mentoring, research and/or practice building were reported by 86.2% of respondents. Subjective errors were reported as occurring sometimes or more frequently in the majority of respondents (56.9%) and were increased with faster than optimal speeds of interpretation (P < 0.001) and signing (P < 0.001). At least one burnout measure was reported by 85.2% of respondents. CONCLUSIONS: Increasing clinical demands in conjunction with a more challenging work environment impacts the ability of radiologists to perform core non-interpretive duties that are critical for success in both private and academic practice and is associated with burnout symptoms and adverse effects on quality. While this survey does not prove causation, the trends and findings are concerning and warrant both close monitoring and appropriate intervention.

Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex

SARS-CoV-2 is the causative agent of the 2019-2020 pandemic. The SARS-CoV-2 genome is replicated-transcribed by the RNA-dependent RNA polymerase holoenzyme (subunits nsp7/nsp82/nsp12) along with a cast of accessory factors. One of these factors is the nsp13 helicase. Both the holo-RdRp and nsp13 are essential for viral replication and are targets for treating the disease COVID-19. Here we present cryo-electron microscopic structures of the SARS-CoV-2 holo-RdRp with an RNA template-product in complex with two molecules of the nsp13 helicase. The Nidovirus-order-specific N-terminal domains of each nsp13 interact with the N-terminal extension of each copy of nsp8. One nsp13 also contacts the nsp12-thumb. The structure places the nucleic acid-binding ATPase domains of the helicase directly in front of the replicating-transcribing holo-RdRp, constraining models for nsp13 function. We also observe ADP-Mg2+ bound in the nsp12 N-terminal nidovirus RdRp-associated nucleotidyltransferase domain, detailing a new pocket for anti-viral therapeutic development.

A Pattern New in Every Moment: The Temporal Clustering of Markets for Crude Oil, Refined Fuels, and Other Commodities

The identification of critical periods and business cycles contributes significantly to the analysis of financial markets and the macroeconomy. Financialization and cointegration place a premium on the accurate recognition of time-varying volatility in commodity markets, especially those for crude oil and refined fuels. This article seeks to identify critical periods in the trading of energy-related commodities as a step toward understanding the temporal dynamics of those markets. This article proposes a novel application of unsupervised machine learning. A suite of clustering methods, applied to conditional volatility forecasts by trading days and individual assets or asset classes, can identify critical periods in energy-related commodity markets. Unsupervised machine learning achieves this task without rules-based or subjective definitions of crises. Five clustering methods—affinity propagation, mean-shift, spectral, k-means, and hierarchical agglomerative clustering—can identify anomalous periods in commodities trading. These methods identified the financial crisis of 2008–2009 and the initial stages of the COVID-19 pandemic. Applied to four energy-related markets—Brent, West Texas intermediate, gasoil, and gasoline—the same methods identified additional periods connected to events such as the September 11 terrorist attacks and the 2003 Persian Gulf war. t-distributed stochastic neighbor embedding facilitates the visualization of trading regimes. Temporal clustering of conditional volatility forecasts reveals unusual financial properties that distinguish the trading of energy-related commodities during critical periods from trading during normal periods and from trade in other commodities in all periods. Whereas critical periods for all commodities appear to coincide with broader disruptions in demand for energy, critical periods unique to crude oil and refined fuels appear to arise from acute disruptions in supply. Extensions of these methods include the definition of bull and bear markets and the identification of recessions and recoveries in the real economy.

Addressing personal protective equipment (PPE) decontamination: Methylene blue and light inactivates severe acute respiratory coronavirus virus 2 (SARS-CoV-2) on N95 respirators and medical masks with maintenance of integrity and fit.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus. DESIGN: The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance. METHODS: MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method. RESULTS: Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3. CONCLUSIONS: MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.

Clustering commodity markets in space and time: Clarifying returns, volatility, and trading regimes through unsupervised machine learning

Unsupervised machine learning can interpret logarithmic returns and conditional volatility in commodity markets. This article applies machine learning in order to visualize and interpret log returns and conditional volatility in commodities trading. We emphasize two classes of unsupervised learning methods: clustering and manifold learning for the reduction of dimensionality. We source daily prices from September 18, 2000 through July 31, 2020, for precious metals, base metals), energy commodities and agricultural commodities. Our results highlight that at the very least, returns-based clusters conform more closely to traditional boundaries between precious metals, base metals, fuels, temperate-climate agricultural commodities, and tropical agricultural commodities. On the other hand, volatility-based clustering succeeds in identifying periods of extreme market distress, such as the global financial crisis of 2008–09 and the Covid-19 pandemic.

BIM for Smart Hospital Management during COVID-19 Using MCDM

In context of the recent COVID-19 pandemic, smart hospitals’ contributions to pre-medical, remote diagnosis, and social distancing has been further vetted. Smart hospital management evolves with new technology and knowledge management, which needs an evaluation system to prioritize its associated criteria and sub-criteria. The global effect of the COVID-19 pandemic further necessitates a comprehensive research of smart hospital management. This paper will utilize Analytical Hierarchy Process (AHP) within Multiple Criteria Decision Making (MCDM) to establish a smart hospital evaluation system with evaluation criteria and sub-criteria, which were then further prioritized and mapped to BIM-related alternatives to inform asset information management (AIM) practices. This context of this study included the expert opinions of six professionals in the smart hospital field and collected 113 responses from hospital-related personnel. The results indicated that functionalities connected to end users are critical, in particular IoT’s Network Core Functionalities, AI’s Deep Learning and CPS’s Special Network Technologies. Furthermore, BIM’s capability to contribute to the lifecycle management of assets can relate and contribute to the asset-intensive physical criteria of smart hospitals, in particular IoT, service technology innovations and their sub-criteria.

Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex.

Backtracking, the reverse motion of the transcriptase enzyme on the nucleic acid template, is a universal regulatory feature of transcription in cellular organisms but its role in viruses is not established. Here we present evidence that backtracking extends into the viral realm, where backtracking by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) may aid viral transcription and replication. Structures of SARS-CoV-2 RdRp bound to the essential nsp13 helicase and RNA suggested the helicase facilitates backtracking. We use cryo-electron microscopy, RNA-protein cross-linking, and unbiased molecular dynamics simulations to characterize SARS-CoV-2 RdRp backtracking. The results establish that the single-stranded 3' segment of the product RNA generated by backtracking extrudes through the RdRp nucleoside triphosphate (NTP) entry tunnel, that a mismatched nucleotide at the product RNA 3' end frays and enters the NTP entry tunnel to initiate backtracking, and that nsp13 stimulates RdRp backtracking. Backtracking may aid proofreading, a crucial process for SARS-CoV-2 resistance against antivirals.

A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients.

SARS coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Although most COVID-19 cases are asymptomatic or involve mild upper respiratory tract symptoms, a significant number of patients develop severe or critical disease. Patients with severe COVID-19 commonly present with viral pneumonia that may progress to life-threatening acute respiratory distress syndrome (ARDS). Patients with COVID-19 are also predisposed to venous and arterial thromboses that are associated with a poorer prognosis. The present study identified the emergence of a low-density inflammatory neutrophil (LDN) population expressing intermediate levels of CD16 (CD16Int) in patients with COVID-19. These cells demonstrated proinflammatory gene signatures, activated platelets, spontaneously formed neutrophil extracellular traps, and enhanced phagocytic capacity and cytokine production. Strikingly, CD16Int neutrophils were also the major immune cells within the bronchoalveolar lavage fluid, exhibiting increased CXCR3 but loss of CD44 and CD38 expression. The percentage of circulating CD16Int LDNs was associated with D-dimer, ferritin, and systemic IL-6 and TNF-α levels and changed over time with altered disease status. Our data suggest that the CD16Int LDN subset contributes to COVID-19-associated coagulopathy, systemic inflammation, and ARDS. The frequency of that LDN subset in the circulation could serve as an adjunct clinical marker to monitor disease status and progression.

Perspective on COVID-19 Pandemic Factors Impacting Organizational Leadership

Employees are important assets of an organization. Therefore, the employee engagement in teamwork is extremely vital for long-term organizational development. Good managers need excellent leadership skills. However, as the COVID-19 pandemic rapidly spreads around the world, many countries implemented strategies to avoid infection, such as working from home, isolation of infected people from others, and 14 days of self-quarantine. These strategies impact the trust, communal relationships, and social exchange relationships among organizational employees. However, communal and social exchange relationships are necessary for organizational leadership, and they are considered as the basis of social networks. The trust, communal relationships, social exchange relationships, and leadership in an organization are an interesting issue, particularly in the COVID-19 time, since the role of leaders is very crucial for maintaining organizational sustainability. The main objective of this study is to investigate the impact of COVID-19 on leadership in organizations based on trust, communal relationships, and social exchange relationships. The study employed correlation analysis to explore the interrelationships between variables. The 220 samples collected consisted of basic, middle, and high managers of organizations. The findings show that COVID-19 impacted organizational leadership. COVID-19 (F1) and (F2) factors integrated with each variable: (1) trust, (2) communal relationships, and (3) social exchange relationships created a stronger relationship between trust and leadership, communal relationships and leadership, and also social exchange relationship and leadership in organizations. On the contrary, Covid-19 (F3) factors integrated with each variable: (1) trust, (2) communal relationships, and (3) social exchange relationships decreased a relationship between trust and leadership, communal relationships and leadership, and also social exchange relationships and leadership in organizations. These results can help CEOs in organizations to perceive what factors have a positive impact or a negative impact on leadership in organizations in order to improve their leadership skills, even post COVID-19. The managerial implications are that (1) leaders need good communication skills to share true information with empathy and optimism and (2) leaders need to be thoughtful and capable to handle change in uncertain situations ethically.

Digital Screen Time During the COVID-19 Pandemic: Risk for a Further Myopia Boom?

PURPOSE: To review the impact of increased digital device usage arising from lockdown measures instituted during the COVID-19 pandemic on myopia and to make recommendations for mitigating potential detrimental effects on myopia control. DESIGN: Perspective. METHODS: We reviewed studies focused on digital device usage, near work, and outdoor time in relation to myopia onset and progression. Public health policies on myopia control, recommendations on screen time, and information pertaining to the impact of COVID-19 on increased digital device use were presented. Recommendations to minimize the impact of the pandemic on myopia onset and progression in children were made. RESULTS: Increased digital screen time, near work, and limited outdoor activities were found to be associated with the onset and progression of myopia, and could potentially be aggravated during and beyond the COVID-19 pandemic outbreak period. While school closures may be short-lived, increased access to, adoption of, and dependence on digital devices could have a long-term negative impact on childhood development. Raising awareness among parents, children, and government agencies is key to mitigating myopigenic behaviors that may become entrenched during this period. CONCLUSION: While it is important to adopt critical measures to slow or halt the spread of COVID-19, close collaboration between parents, schools, and ministries is necessary to assess and mitigate the long-term collateral impact of COVID-19 on myopia control policies.