Optimization and Characterization of Quercetin Vitamin C Nano-Phytosome Formulation

Objective: To design an optimal formulation for quercetin and vitamin C nano-phytosome. Method(s): Nano-phytosomes are prepared by the thin layer hydration technique using a 2-level-5-factor design experimental. A total of 32 experimental formulas were used for data analysis. The ratio of quercetin: soy lecithin (X1), the ratio of quercetin: cholesterol (X2), stirring speed (X3), stirring temperature (X4), and stirring time (X5) were used as independent factors, while globule size as a dependent factor. Data analysis was carried out by Design Expert12 application. Characterization of the optimal formula included physicochemical evaluation, globule size analysis, zeta potential, polydispersity index, entrapment efficiency, Transition Electron Microscopy (TEM) analysis, and FTIR analysis. Result(s): The optimal formula consisted of quercetin: vitamin C: lecithin: cholesterol ratio of 1: 1: 1.046: 0.105 mol;stirring speed 763.986 rpm;stirring time of 59 min, at temperature 51.73 degreeC which produced 59.26 nm average globule size, PDI value 0.66;zeta potential value-35.93+/-0.95 mV and average SPAN value 0.61. This formulation showed entrapment efficiency of quercetin 91.69+/-0.18 % and vitamin C 90.82+/-0.13 %. The TEM and FITR analysis showed the morphological of the globules and interactions between the drugs, soy lecithin, and cholesterol to form nano-phytosomes. Conclusion(s): The conditions to obtain the optimal formula for quercetin vitamin C nano-phytosome consisted of quercetin: vitamin C: lecithin: cholesterol ratio of 1: 1: 1.046: 0.105 mol;stirring speed 763.986 rpm;stirring time of 59 min, and at temperature 51.73 degreeC.Copyright © 2023 The Authors.

Sleep disturbance and anxiety symptoms among asymptomatic COVID-19 carriers in Shanghai, China: the mediating role of entrapment and defeat.

BACKGROUND: The COVID-19 pandemic increases the risk of psychological problems, especially for the infected population. Sleep disturbance and feelings of defeat and entrapment are well-documented risk factors of anxiety symptoms. Exploring the psychological mechanism of the development of anxiety symptoms is essential for effective prevention. This study aimed to examine the mediating effects of entrapment and defeat in the association between sleep disturbance and anxiety symptoms among asymptomatic COVID-19 carriers in Shanghai, China. METHODS: A cross-sectional study was conducted from March to April, 2022. Participants were 1,283 asymptomatic COVID-19 carriers enrolled from the Ruijin Jiahe Fangcang Shelter Hospital, Shanghai (59.6% male; mean age = 39.6 years). Questionnaire measures of sleep disturbance, entrapment, defeat, anxiety symptoms, and background characteristics were obtained. A mediation model was constructed to test the mediating effects of entrapment and defeat in the association between sleep disturbance and anxiety symptoms. RESULTS: The prevalence rates of sleep disturbance and anxiety symptoms were 34.3% and 18.8%. Sleep disturbance was positively associated with anxiety symptoms (OR [95%CI] = 5.013 [3.721-6.753]). The relationship between sleep disturbance and anxiety symptoms (total effect: Std. Estimate = 0.509) was partially mediated by entrapment (indirect effect: Std. Estimate = 0.129) and defeat (indirect effect: Std. Estimate = 0.126). The mediating effect of entrapment and defeat accounted for 50.3% of the association between sleep disturbance and anxiety symptoms. CONCLUSION: Sleep disturbance and anxiety symptoms were prevalent among asymptomatic COVID-19 carriers. Entrapment and defeat mediate the association between sleep disturbance and anxiety symptoms. More attention is needed to monitoring sleep conditions and feelings of defeat and entrapment to reduce the risk of anxiety.

Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: In-vitro, ex-vivo and in-vivo studies.

The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

Controlled release nanomedicine (CRNM) of aspirin using "biomimetic niosomal nanoparticles (BNNs)”for Covid-19 and cardiovascular treatment: DOE based optimization

Biomimetic strategies can be adopted to improve biopharmaceutical aspects. Subsequently, Biomimetic reconstitutable pegylated amphiphilic lipid nanocarriers have high translational potential for systemic controlled drug delivery;however, such an improvised system for systemic aspirin delivery exploring nanotechnology is not available. Systemic administration of aspirin and its controlled delivery can significantly control blood clotting events, leading to stroke, which has immediate applications in cardiovascular diseases and Covid-19. In this work, we are developing aspirin sustained release pegylated amphiphilic self-assembling nanoparticles to develop reconstitutable aspirin injections by solvent-based co-precipitation method with phase inversion technique that leads to novel "biomimetic niosomal nanoparticles (BNNs).” DOE led optimization is done to develop Design of space for optimized particles. Upon reconstitution of solid powder, the particle size was 144.8 ± 12.90 nm with a surface charge of -29.2 ± 2.24 mV. The entrapment efficiency was found to be 49 ± 0.15%, wherein 96.99 ± 1.57% of the drug was released in 24hr showing super case II transport-based drug release mechanism. The formulation has the least hemolysis while showing significant suppression of platelet aggregation. MTT assay does not show any significant cytotoxicity. This is a potential nanoparticle that can be explored for developing aspirin injection, which is not available.

The Entrapment and Concentration of SARS-CoV-2 Particles with Graphene Oxide: An In Vitro Assay.

Previous studies have suggested that graphene oxide (GO) has some antiviral capacity against some enveloped viruses, including SARS-CoV-2. Given this background, we wanted to test the in vitro antiviral ability to GO using the viral plaque assay technique. Two-dimensional graphene oxide (GO) nanoparticles were synthesized using the modified Hummers method, varying the oxidation conditions to achieve nanoparticles between 390 and 718 nm. The antiviral activity of GO was evaluated by experimental infection and plaque formation units assay of the SARS-CoV-2 virus in VERO cells using a titrated viral clinical isolate. It was found that GO at concentrations of 400 µg/mL, 100 µg/mL, 40 µg/mL, and 4 µg/mL was not toxic to cell culture and also did not inhibit the infection of VERO cells by SARS-CoV-2. However, it was evident that GO generated a novel virus entrapment phenomenon directly proportional to its concentration in the suspension. Similarly, this effect of GO was maintained in assays performed with the Zika virus. A new application for GO nanoparticles is proposed as part of a system to trap viruses in surgical mask filters, air conditioning equipment filters, and air purifier filters, complemented with the use of viricidal agents that can destroy the trapped viruses, an application of broad interest for human beings.

[Meralgia paraesthetica as complication of patient positioning : A not fully controllable risk]. / Meralgia paraesthetica als Lagerungsschaden : Kein voll beherrschbares Risiko.

Meralgia paraesthetica (MP) is the consequence of an entrapment or stretch injury of the lateral femoral cutaneous nerve at the crossing region with the inguinal ligament where the nerve exits the pelvis. It results in temporary or permanent sensory loss, paraesthesia and pain in the anterolateral region of the thigh. Idiopathic forms are known for example as seat belt syndrome or jeans syndrome. An MP can also occur as a complication of surgical or intensive care patient positioning. In focus are the lithotomy position, prone position and beach chair position.We analyzed 21 complaints about MP occurring for the first time postoperatively, which had been submitted to the expert committee for medical treatment errors at the North Rhine Medical Association over the past 10 years. Among these, six cases could be identified as positioning damage after a lithotomy position. In three cases MP occurred after supine positioning but the etiology could not be clarified with certainty. In 12 cases MP was recognized as a direct surgical complication.The pathophysiology, incidence and course as well as legal implications of position-related MP are discussed. Pressure damage to the nerve at its intersection with the inguinal ligament is assumed to be the main pathomechanism. Although all the cases presented here occurred after lithotomy positioning, the complication also appears to occur with other types of positioning according to the literature data, the most common being prone positioning. This also explains the increasingly published case reports of MP after prone positioning in COVID-19 patients for respiratory treatment. Safe avoidance of the positioning-related complication does not appear to be possible due to the anatomical variability of the course of the nerve and the unclear pathomechanisms.

Social Stigma and Depression among Asymptomatic COVID-19 Carriers in Shanghai, China: The Mediating Role of Entrapment and Decadence.

INTRODUCTION: Since the advent of 2019 novel coronavirus (COVID-19), the coexistence between social stigma and depression symptoms (depression hereafter) in COVID-19 patients has been mentioned, but the mechanisms involved remains unclear. This study aimed to explore how the stigma affects depression during the mid-pandemic period. METHODS: A cross-sectional survey using non-probability sampling was conducted among asymptomatic COVID-19 carriers in Shanghai, China (April 2022). An online questionnaire was used to obtain information on demographic characteristics and psychological traits. Logistic regression and path analysis were performed to analyze the depression risk factors and examine the mediation model, respectively. RESULTS: A total of 1283 participants (59.6% men) were involved in this study, in which 44.7% of carriers reported having depression. Univariate analyses found that education level (OR 0.575; 95% CI 0.448-0.737) and doses of vaccine (OR 1.693; 95% CI 1.042-2.750), were significantly associated with depression among asymptomatic carriers. The association between social stigma and depression was fully mediated by their feelings of entrapment and decadence (indirect effect = 0.204, p < 0.001; direct effect = -0.059, p = 0.058). The mediating role of entrapment between stigma and depression was moderated by age group (estimate = 0.116, p = 0.008). CONCLUSION: Mental health issues resulting from the COVID-19 pandemic are increasingly apparent in China and require urgent attention and responses. These findings provide new perspectives for the early prevention of depression in asymptomatic carriers.

Effect of Crosslinking on Control Drug Release of Hydroxychloroquine Sulphate Drug-Using Alginate Beads

Sodium alginate (SA), brown seaweed algae, and Lignosulphonic acid (LS), a plant product, are biodegradable polymers extensively investigated for drug-controlled release. The Hydroxychloroquine sulphate (HCQ) drug, an antimalarial drug, was extensively used in the initial periods of COVID situations. The HCQ drug release from SALS beads is investigated for its control release in a simulated medium (pH1.2 and pH7.4) using different crosslinking agents such as Calcium chloride, Barium chloride and Aluminum chloride. The HCQ release has better controlled in Barium crosslinked beads. They are found to be relatively intact and stable and release the drug for more than 180 minutes in the simulated medium. Further drug entrapment studies prove very high for Ba crosslinked SALS beads. Whereas Aluminum crosslinked beads showed, inferior crosslinking and drug retention in beads is very low and starts degrading in simulated fluids. Drug release kinetics were analyzed using various kinetic model equations to discuss the order of reaction and drug-polymer mechanism. FT-IR investigations of beads show chemical interactions between crosslinking ion and alginate blends. © 2022, Iran University of Science and Technology. All rights reserved.

Questionnaire survey about the effects of new lifestyles during the pandemic of COVID-19 on upper limb diseases.

BACKGROUND: The novel coronavirus (COVID-19) that emerged in 2019 and spread globally in 2020 has resulted in the imposition of lockdowns or a state of emergency in many cities worldwide. In Japan, a "new lifestyle" is being advocated. We hypothesize that the new lifestyle has changed people's use of their upper limbs during the COVID-19 pandemic. Therefore, through this questionnaire study, we aimed to determine the factors associated with exacerbation of symptoms during the pandemic and to investigate the current status of patients who require hand surgery. METHODS: This study was a prospective multi-center questionnaire survey. This study was conducted in Japan from December 2020 to July 2021 at university and general hospitals in nine prefectures. A questionnaire was administered to patients who visited a hospital with symptoms of nerve entrapment syndrome, osteoarthritis, or tenosynovitis. RESULTS: A total of 502 patients with a mean age of 63.8 years responded. The 240 patients who experienced exacerbation (exacerbated and markedly exacerbated) were compared with other patients (unchanged, improved, and markedly improved). An increase in the time spent on personal computers and smartphones was associated with exacerbation of hand symptoms. Patients who wanted to undergo surgery but were postponed due to COVID-19 accounted for 23.5% of the outpatients. The mean scores for pain, jitteriness, and anxious depression in these patients were significantly higher than those of patients who did not want surgery. CONCLUSIONS: Our results suggest that an increase in the time spent on personal computers and smartphones is associated with exacerbation of hand symptoms during the COVID-19 pandemic. Patients who wanted to undergo surgery but were postponed by COVID-19 experienced greater pain, jitteriness, and anxious depression.

Followers' unclear demands during the COVID-19 pandemic can undermine leaders' well-being: A moderated mediation model from an entrapment perspective.

Although effective leaders are important for reducing employee stress during the COVID-19, limited studies have examined how follower behaviors can influence leader stress and well-being during the COVID-19. This study draws on defeat-entrapment theory to examine how followers' unclear demands during the COVID-19 consequently impact leaders' psychological states and well-being. We conducted a three-wave time-lagged investigation with a sample of 281 leaders in the United Kingdom and found that followers' unclear demands could generate feelings of entrapment in leaders, leading to decreased levels of well-being outcomes in leaders. Importantly, we found that leaders who have higher levels of leadership responsibility during the COVID-19 are likely to feel trapped by followers' unclear demands. They are also likely to face higher levels of feelings of entrapment and impaired well-being compared with leaders who have lower levels of leadership responsibility. We discuss the implications for theories and practices, as well as directions for future research.

Lipid Nanoparticles for Drug Delivery

Lipid nanoparticles have attracted significant interests in the last two decades, and have achieved tremendous clinical success since the first clinical approval of Doxil in 1995. At the same time, lipid nanoparticles have also demonstrated enormous potential in delivering nucleic acid drugs as evidenced by the approval of two RNA therapies and mRNA COVID-19 vaccines. In this review, an overview on different classes of lipid nanoparticles, including liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, is first provided, followed by the introduction of their preparation methods. Then the characterizations of lipid nanoparticles are briefly reviewed and their applications in encapsulating and delivering hydrophobic drugs, hydrophilic drugs, and RNAs are highlighted. Finally, various applications of lipid nanoparticles for overcoming different delivery challenges, including crossing the blood-brain barrier, targeted delivery, and various routes of administration, are summarized. Lipid nanoparticles as drug delivery systems offer many attractive benefits such as great biocompatibility, ease of preparation, feasibility of scale-up, nontoxicity, and targeted delivery, while current challenges in drug delivery warrant future studies about structure-function correlations, large-scale production, and targeted delivery to realize the full potential of lipid nanoparticles for wider clinical and pharmaceutical applications in future.

Graphene-based nanocomposite using new modeling molecular dynamic simulations for proposed neutralizing mechanism and real-time sensing of COVID-19

A new virus, the coronavirus (COVID-19), is causing serious respiratory infections in humans. Rapid, specific, and sensitive diagnostic techniques for early-stage detection of SARS-CoV-2 viral protein are developing as a necessary response for effective smart diagnostics, treatment optimization, and exploration of therapeutics with better effectiveness in the fight against the COVID-19 pandemic. Keeping the considerations mentioned above, we propose a new modeling graphene nanocomposite-based biosensing device for detecting COVID-19 at the site of the epidemic as the best way to manage the pandemic. It is important to address the problems of COVID-19 management. With the challenges and aspects of COVID-19 management in mind, we present in this review a collective approach involving electrochemical COVID-19 biosensing required for early-stage COVID-19 diagnosis and the direct interaction with viral surface glycoproteins and metal nanoparticles that can enter cells and neutralize viruses by interacting directly with the viral genome (ribonucleic acid), which identifies the COVID-19 spike protein and antiviral procedure including virus inactivation, host cell receptor inactivation, electrostatic entrapment, and physicochemical destruction of viral species by nucleotide ring opening. The interactions between the graphene composite and virus may be boosted by functionalization of the carbon surface and decoration of metallic components that enhance these interactions. Our proposed new modeling molecular dynamic simulation-based neutralizing mechanism and real-time detection of COVID-19 on graphene nanocomposite-based biosensors are suitable for point-of-care diagnostic applications, and this sensing platform can be modified for the early diagnosis of severe viral infections using real samples. For the potential application, the suggested one is the chemical reaction and bond breaking between the metallic component and molecule of COVID19 with computer simulation data.

Well-known phenomenon, new setting: Digital stress in times of the COVID-19 pandemic

Digital stress caused by the proliferation and omnipresence of digital media has been attracting scientific interest for several years. The physical contact restrictions related to the COVID-19 pandemic have further increased the importance of digital media in people's professional and private lives. This article investigates the consequences of this new situation for people's perceptions of digital stress. It applies a life-world perspective and considers several individual and situational factors. Our study was based on semi-structured interviews with German adults. Five key findings emerged: (1) during the pandemic, digital stress was predominantly caused by home office work;(2) already-known stressors were amplified in home offices;(3) digital devices contributed to the dissolution of boundaries between work and private life;(4) people experienced multiple stressors simultaneously, both digital and analog;(5) the private use of digital media was not associated with stress but perceived as saving social connections. Furthermore, the results show that the experience of digital stress is highly dependent on situational contexts and individual lifestyles.

Were self-described introverts "immune" to increased drug use and entrapment during the pandemic?

BACKGROUND: Social restrictions and other stressors related to the Covid-19 pandemic disrupted daily life in ways that might have increased drug use and undermined mental health. We investigated whether such changes depended on the amount and quality of a person's social activity. We also evaluated the popular idea that effects of pandemic-related restrictions would depend on introversion; to this end, we used self-described introversion as a proxy for preferred frequency of social activity. METHODS: Between September 2020 and March 2021, we obtained online-survey data from 2615 respondents who retrospectively reported alcohol, opioid, or psychostimulant use. We analyzed (1) changes in drug use and entrapment (a psychological construct linked to suicidality) as a function of introversion and the frequency and quality of social activity, and (2) changes in drug use as a function of change in entrapment. RESULTS: Most felt more entrapped during the pandemic, but only a minority increased drug use. Generally: (1) entrapment and drug use increased in respondents unsatisfied with their social activity, (2) introversion and frequency of activity had less influence than satisfaction, (3) introverts reported more symptoms of entrapment, anxiety, depression, and loneliness than non-introverts, (4) when social activity was frequent and unsatisfying, psychostimulant use increased in introverts and opioid use increased in extraverts, (5) alcohol use increased in those who felt increased entrapment, and (6) alcohol and opioid use decreased in those who felt decreased entrapment. CONCLUSIONS: Satisfactory social activity (even in small amounts) was associated with better outcomes, mostly without regard to introversion.

Childhood focal compressive mononeuropathies during the COVID-19 pandemic in Buenos Aires, Argentina.

INTRODUCTION/AIMS: Focal peripheral neuropathies are infrequently seen in pediatric patients. The COVID-19 pandemic has disrupted normal life for many people, including complete lockdowns and school closing for long periods of time in many countries, which prompted children to stay at home. Our aim is to assess whether there has been an increased incidence of focal compressive peripheral neuropathies in the pediatric population during COVID-19-associated lockdown. METHODS: Clinical, electrophysiological, and imaging characteristics were reviewed for patients referred to the electrodiagnostic (EDx) laboratory with suspicion of a focal neuropathy. The incidence of focal compressive peripheral neuropathies seen during the period of March to September 2020 was compared with the same time period in 2019. RESULTS: An increased incidence of focal neuropathies was seen in 2020 (31%) compared with 2019 (6.8%). During 2020, 7 fibular (peroneal) mononeuropathies and 2 ulnar neuropathies were diagnosed. Most patients with focal neuropathies were underweight and acknowledged prolonged screen time periods. Electrophysiological findings consisted of mostly demyelinating lesions with an overall good clinical outcome. DISCUSSION: In this study we raise awareness about a possible increased incidence of focal compressive peripheral neuropathies in children during COVID-19-associated lockdown, which may be prevented with changing positions during sedentary activities.

Peripheral neurological complications during COVID-19: A single center experience.

BACKGROUND AND AIMS: We highlight the peripheral neurologic complications of coronavirus disease 2019 (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an ongoing global health emergency. METHODS: We evaluated twenty-five patients admitted to the COVID-19 Recovery Unit (CRU) at New York-Presbyterian Weill Cornell University Medical Center after intensive care hospitalization with confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whom neurology was consulted for weakness and/or paresthesias. All patients were clinically evaluated by a neuromuscular neurologist who performed electrodiagnostic (EDX) studies when indicated. Magnetic resonance imaging (MRI) of the affected regions, along with nerve and muscle biopsies were obtained in select patients to better elucidate the underlying diagnosis. RESULTS: We found fourteen out of twenty-five patients with prolonged hospitalization for COVID-19 infection to have peripheral neurological complications, identified as plexopathies, peripheral neuropathies and entrapment neuropathies. The other eleven patients were not found to have peripheral neurologic causes for their symptoms. Patients with peripheral neurological complications often exhibited more than one type of concurrently. Specifically, there were four cases of plexopathies, nine cases of entrapment neuropathies, and six cases of peripheral neuropathies, which included cranial neuropathy, sciatic neuropathy, and multiple mononeuropathies. CONCLUSIONS: We explore the possibility that the idiopathic peripheral neurologic complications could be manifestations of the COVID-19 disease spectrum, possibly resulting from micro-thrombotic induced nerve ischemia.

Feelings of Entrapment during the COVID-19 Pandemic Based on ACE Star Model: A Concept Analysis.

This study aimed to analyze the concept of the "feelings of entrapment" during the COVID-19 (coronavirus disease 2019) pandemic using a systematic review. We included literature based on content and outcomes related to feelings of entrapment, such as antecedents, attributes, and consequences. The exclusion criteria were studies that did not have inappropriate subject, content, conceptual definition, and degree thesis was excluded. Walker and Avant's process of concept analysis was used in this systematic literature review. The attributes of the concept of feelings of entrapment during the COVID-19 pandemic were found to be feelings of: (1) being out of control, (2) no escape, (3) being trapped, (4) being robbed, and (5) hopelessness. The causes for these were identified as (1) the COVID-19 pandemic, (2) lockdown system, (3) restricted situation, (4) uncertain future, (5) economic hardship, and (6) poor coping abilities. Consequences of the concept were: (1) increased suicide, (2) decreased mental health, and (3) decreased well-being. In situations such as COVID-19, it is important need to know what feelings of entrapment's antecedents and attributes are to prevent suicide and enhance mental health and well-being. Based on the results of this study, counseling services, policies, and systems for relieving feelings of entrapment in the COVID-19 situation are recommended.