How Toll-like receptors influence Parkinson's disease in the microbiome-gut-brain axis.

Recently, a large number of experimenters have found that the pathogenesis of Parkinson's disease may be related to the gut microbiome and proposed the microbiome-gut-brain axis. Studies have shown that Toll-like receptors, especially Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4), are key mediators of gut homeostasis. In addition to their established role in innate immunity throughout the body, research is increasingly showing that the Toll-like receptor 2 and Toll-like receptor 4 signaling pathways shape the development and function of the gut and enteric nervous system. Notably, Toll-like receptor 2 and Toll-like receptor 4 are dysregulated in Parkinson's disease patients and may therefore be identified as the core of early gut dysfunction in Parkinson's disease. To better understand the contribution of Toll-like receptor 2 and Toll-like receptor 4 dysfunction in the gut to early α-synuclein aggregation, we discussed the structural function of Toll-like receptor 2 and Toll-like receptor 4 and signal transduction of Toll-like receptor 2 and Toll-like receptor 4 in Parkinson's disease by reviewing clinical, animal models, and in vitro studies. We also present a conceptual model of the pathogenesis of Parkinson's disease, in which microbial dysbiosis alters the gut barrier as well as the Toll-like receptor 2 and Toll-like receptor 4 signaling pathways, ultimately leading to a positive feedback loop for chronic gut dysfunction, promoting α-synuclein aggregation in the gut and vagus nerve.

Bioinformatics analysis to identify intersection genes, associated pathways and therapeutic drugs between COVID-19 and Oral candidiasis.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a serious threat to human health. Oral candidiasis (OC) may be one of the causes of morbidity in severe COVID-19 patients. However, there is currently no treatment for oral candidiasis and COVID-19 (OC/COVID-19). The purpose of this study was to use text mining and data analysis to investigate the target genes for treatment and explore potential therapeutic drugs for OC/COVID-19. METHODS: We used the text mining tool pubmed2ensembl to detect genes associated with OC, and the dataset GSE164805 was used for the data analysis. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the two intersection genes using the Database of Annotation, Visualization and Integrated Discovery (DAVID) platform. The protein-protein interaction (PPI) networks were constructed by STRING software, and gene module analysis was performed using Molecular Complex Detection (MCODE), a plug-in in Cytoscape. The most significant genes were selected as hub genes and their functions and pathways were analyzed using Metascape. We revealed the upstream pathway activity of the hub genes. The drug-gene interaction database (DGIdb) and the traditional Chinese medicines integrated database (TCMID) were used to discover potential drugs for the treatment of OC/COVID-19. RESULTS: The analysis indicated that there were 2869 differentially expressed genes (DEGs) in GSE164805. We identified 161 unique genes associated with oral candidiasis through text mining. A total of 20 intersection genes were identified as the therapeutic targets for OC/COVID-19. Based on the bioinformatics analysis, nine genes (TNF, IL1B, IFNG, CSF2, ELANE, CCL2, MMP9, CXCR4, and IL1A) were identified as hub genes that were mainly enriched in the IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications and NOD-like receptor signaling pathway. We identified four of the nine genes that target five existing drugs, including BKT140, mavorixafor, sivelestat, canakinumab, and rilonacept. Furthermore, twenty herb ingredients were also screened as potential drugs. CONCLUSION: In this study, TNF, IL1B, IFNG, CSF2, ELANE, CCL2, MMP9, CXCR4, and IL1A were potentially key genes involved in the treatment of OC/COVID-19. Taken together five drugs and twenty herb ingredients were identified as potential therapeutic agents for OC/COVID-19 treatment and management.

Discovering a Dihydrofluorescein Analogue as a Promising Fluorescence Substrate to HRP

Horseradish peroxidase (HRP) combined with its fluorescence substrates is attracting increasing attention for biochemical analysis. Amplex red is the most widely used fluorescence substrate to HRP;however, it suffers from some drawbacks, such as nonspecific responsiveness toward carboxylesterases. Discovering a new small molecular fluorescence substrate with improved sensitivity and selectivity for HRP is thus desired. Herein, three dihydrofluorescein derivatives (DCFHs) are presented to serve as HRP substrates through fluorescence turn-on methods. The most promising one, 2,7-dichloro-9-(2-(hydroxymethyl)phenyl)-9H-xanthene-3,6-diol (DCFH-1), exhibited excellent sensitivity in the detection of HRP. Moreover, DCFH-1 does not respond to carboxylesterase, thus holding advantages over Amplex red. In the further study, the detection reagent in the commercial ELISA kits was replaced with DCFH-1 to establish a new fluorescence ELISA, which works very well in the quantification of inflammatory cytokine biomarkers from in vitro models.

The monkeypox diagnosis, treatments and prevention: A review.

The world is currently dealing with a second viral outbreak, monkeypox, which has the potential to become an epidemic after the COVID-19 pandemic. People who reside in or close to forest might be exposed indirectly or at a low level, resulting in subclinical disease. However, the disease has lately emerged in shipped African wild mice in the United States. Smallpox can cause similar signs and symptoms to monkeypox, such as malaise, fever, flu-like signs, headache, distinctive rash, and back pain. Because Smallpox has been eliminated, similar symptoms in a monkeypox endemic zone should be treated cautiously. Monkeypox is transmitted to humans primarily via interaction with diseased animals. Infection through inoculation via interaction with skin or scratches and mucosal lesions on the animals is conceivable significantly once the skin barrier is disrupted by scratches, bites, or other disturbances or trauma. Even though it is clinically unclear from other pox-like infections, laboratory diagnosis is essential. There is no approved treatment for human monkeypox virus infection, however, smallpox vaccination can defend counter to the disease. Human sensitivity to monkeypox virus infection has grown after mass vaccination was discontinued in the 1980s. Infection may be prevented by reducing interaction with sick patients or animals and reducing respiratory exposure among people who are infected.

Virtual Care During the COVID-19 Pandemic for Patients With Hematologic Malignancies: A Single-Institution Experience.

PURPOSE: The use of virtual care rapidly increased during the COVID-19 pandemic and has persisted as a routine method of care delivery. Much of the literature on virtual care in oncology has focused on solid tumors, and little is known about its application in malignant hematology. METHODS: We performed a retrospective review of patients with hematologic malignancies at Princess Margaret Cancer Centre from October 2019 to March 2021 to determine the use of virtual care during this period, cost-savings associated with virtual visits, and patient satisfaction. Patient satisfaction was assessed using the Your Voice Matters survey, a provincially administered survey to evaluate patient experience. RESULTS: Overall, 12.1% (1,122/9,295) of patients had a virtual visit during the study period (0% from October 2019 to February 2020, 36% from March to August 2020, and 30% from September 2020 to March 2021), of which 36% were in the lymphoma clinic and 46% were in the myeloma clinic. The mean two-way opportunity cost for an in-person visit was $168.00 CAD per person with public transit, and $120.40 CAD per person driving. Responses to the Your Voice Matters survey indicated that patients with a virtual visit reported that physical symptoms were discussed appropriately (mean 4.73/5), and were more likely to ask for a follow-up virtual visit compared with patients with in-person visits (mean 4.50/5 v 3.02/5, respectively; P < .01). CONCLUSION: These findings suggest that virtual care may be a feasible and well-received tool for delivering care to a substantial proportion of patients with hematologic malignancies, while enabling substantial cost-savings to patients.

Comparing dosimetry of locally advanced cervical cancer patients treated with 3 versus 4 fractions of MRI-guided brachytherapy.

PURPOSE: To demonstrate the feasibility of treating cervical cancer patients with MRI-guided brachytherapy (MRgBT) using 24 Gy in 3 fractions (F) versus a standard, more resource-intensive regimen of 28 Gy in 4F, and its ability to meet EMBRACE II planning aims. METHODS AND MATERIALS: A retrospective review of 224 patients with FIGO Stage IB-IVA cervical cancer treated with 28 Gy/4F (n = 91) and 24 Gy/3F (n = 133) MRgBT between 2016-2021 was conducted. Multivariable linear regression models were fitted to compare dosimetric parameters between the two groups, adjusting for CTVHR and T stage. RESULTS: Most patients had squamous cell carcinoma, T2b disease, and were treated with intracavitary applicator plus interstitial needles (96%). The 28 Gy/4F group had higher CTVHR (median 28 vs. 26 cm3, p = 0.04), CTVIR D98% (mean 65.5 vs. 64.5 Gy, p = 0.03), rectum D2cm3 (mean 61.7 vs. 59.2 Gy, p = 0.04) and bladder D2cm3 (81.3 vs. 77.9 Gy, p = 0.03). There were no significant differences in the proportion of patients meeting the EMBRACE II OAR dose constraints and planning aims, except fewer patients treated with 28 Gy/4F met rectum D2cm3 < 65 Gy (73 vs. 85%, p = 0.027) and ICRU rectovaginal point < 65 Gy (65 vs. 84%, p = 0.005). CONCLUSIONS: Cervical cancer patients treated with 24 Gy/3F MRgBT had comparable target doses and lower OAR doses compared to those treated with 28 Gy/4F. A less-resource intense fractionation schedule of 24 Gy/3F is an alternative to 28 Gy/4F in cervix MRgBT.

Evaluating the Short-Term Environmental and Clinical Effects of a Radiation Oncology Department's Response to the COVID-19 Pandemic (STEER COVID-19).

BACKGROUND: During the COVID-19 pandemic, many radiation oncology departments worldwide adopted the use of shorter and more intense hypofractionated regimens. Hospital foot traffic was reduced through virtual care. This study's primary objective was to assess the collective environmental impact of these strategic changes by identifying sources of carbon dioxide equivalents (CO2e). The rate of radiation-related adverse event from the increased use of hypofractionated treatments was assessed. METHODS: All patients treated with external beam radiation therapy from April 1, 2019 to March 31, 2021 at our single institution were identified (n=10,175) along with their radiotherapy visits (176,423 fractions), and unplanned visits to the radiation nursing clinic (RNC) or emergency (ER) department. Out-patient hospital and virtual visits (n=75,853) during this same period were also analyzed. Environmental impact measures, including linear accelerator power usage, patient travel distances, and personal protection equipment (PPE) consumption were all converted into CO2e. RESULTS: The use of curative hypofractionated regimens increased from 17% to 27% during the pandemic year. Carbon footprint was reduced by 39% during the pandemic year (1,332,388 kg CO2e) as compared to the pre-pandemic year (2,024,823 kg CO2e). Comparing patients in the pre-pandemic vs. pandemic year, there was a significant reduction in the proportion of hypofractionated patients who needed a visit to either the RNC (39% vs. 25%; p<0.001) or ER (6% vs. 2%; p<0.001) during and within 90 days of radiotherapy. DISCUSSION: This is the first study to demonstrate the environmental benefits of increased use of hypofractionated regimens and virtual care, while assuring that there was no added acute radiation-related adverse event. Our findings support their continued use as one of many long-term strategies to reduce the environmental footprint of healthcare delivery.

A Nomogram-Based Study: A Way Forward to Predict the Anxiety Status in Medical Staff During the COVID-19 Pandemic.

Background and Objective: Anxiety influences job burnout and health. This study aimed to establish a nomogram to predict the anxiety status of medical staff during the coronavirus disease (COVID-19) pandemic. Methods: A total of 600 medical members were randomized 7:3 and divided into training and validation sets. The data was collected using a questionnaire. Logistic regression analysis and Akaike information criterion (AIC) were applied to investigate the risk factors for anxiety. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to establish a nomogram. Results: Participation time (OR=44.28, 95% CI=13.13~149.32), rest time (OR=38.50, 95% CI=10.43~142.19), epidemic prevention area (OR=10.16, 95% CI=3.51~29.40), epidemic prevention equipment (OR=15.24, 95% CI=5.73~40.55), family support (OR=9.63, 95% CI=3.55~26.11), colleague infection (OR=6.25, 95% CI=2.18~19.11), and gender (OR=3.30, 95% CI=1.15~9.47) were the independent risk factors (P<0.05) for anxiety in medical staff. The areas under the receiver operating characteristic (ROC) curves of the training and validation sets were 0.987 and 0.946, respectively. The decision curve's net benefit shows the nomogram's clinical utility. Conclusion: The nomogram established in this study exhibited an excellent ability to predict anxiety status with sufficient discriminatory power and calibration. Our findings provide a protocol for predicting and identifying anxiety status in medical staff during the COVID-19 pandemic.

Virtual Care and Electronic Patient Communication During COVID-19: Cross-sectional Study of Inequities Across a Canadian Tertiary Cancer Center.

BACKGROUND: Virtual care (VC) visits (telephone or video) and email-based patient communication have been rapidly adopted to facilitate cancer care during the COVID-19 pandemic. Inequities in access and patient experience may arise as these digital health tools become prevalent. OBJECTIVE: We aimed to characterize inequities in access and patient-reported experience following adoption of digital health tools at a tertiary cancer center during the COVID-19 pandemic. METHODS: We designed a cross-sectional study of outpatients with visits from September to December 2020. Patient characteristics and responses to an email-based patient-experience survey were collated. Inequities in access were assessed across three pairs of comparison groups: (1) patients with VC and in-person visits, (2) patients with and without documented email addresses, and (3) responders and nonresponders to the survey. Inequities in patient-reported experience were assessed among survey responders. Demographics were mapped to area-level averages from national census data. Socioeconomic status was mapped to area-level dimensions of the Canadian Index of Multiple Deprivation. Covariate balance between comparison groups was assessed using standardized mean differences (SMDs), with SMD≥0.2 indicating differences between groups. Associations between patient experience satisfaction scores and covariates were assessed using multivariable analyses, with P<.05 indicating statistical significance. RESULTS: Among the 42,194 patients who had outpatient visits, 62.65% (n=26,435) had at least one VC visit and 31.15% (n=13,144) were emailable. Access to VC and email was similar across demographic and socioeconomic indices (SMD<0.2). Among emailable patients, 21.84% (2870/13,144) responded to the survey. Survey responsiveness was similar across indices, aside from a small difference by age (SMD=0.24). Among responders, 24.4% received VC and were similar to in-person responders across indices (SMD<0.2). VC and in-person responders had similar satisfaction levels with all care domains surveyed (all P>.05). Regardless of visit type, patients had variable satisfaction with care domains across demographic and socioeconomic indices. Patients with higher ethnocultural composition scores were less satisfied with the cultural appropriateness of their care (odds ratio [OR] 0.70, 95% CI 0.57-0.86). Patients with higher situational vulnerability scores were less satisfied with discussion of physical symptoms (OR 0.67, 95% CI 0.48-0.93). Patients with higher residential instability scores were less satisfied with discussion of both physical (OR 0.81, 95% CI 0.68-0.97) and emotional (OR 0.86, 95% CI 0.77-0.96) symptoms, and also with the duration of their visit (OR 0.85, 95% CI 0.74-0.98; P=.02). Male patients were more satisfied with how their health care provider had listened to them (OR 1.64, 95% CI 1.11-2.44; P=.01). CONCLUSIONS: Adoption of VC and email can equitably maintain access and patient-reported experience in cancer care across demographics and socioeconomic indices. Existing health inequities among structurally marginalized patients must continue to be addressed to improve their care experience.

Visualizing the Knowledge Domain in Health Education: A Scientometric Analysis Based on CiteSpace.

OBJECTIVES: This study aimed to visualize the evidence in the global research on health education to better improve the nation's health literacy and to guide future research. METHOD: We searched the Web of Science (Core Collection) electronic databases. The search strategies: topic: ("Health Education" OR "Education, Health" OR "Community Health Education" OR "Education, Community Health" OR "Health Education, Community") AND document: (Article) AND language:(English). Articles of evidence from January 2011 to December 2021 with those words in the title or abstract or keywords will be included in this review. We used the Citespace 5.6.R5 (64-bit) to investigate and determine the thematic patterns, and emerging trends of the knowledge domain, and presented a narrative account of the findings. RESULT: We analyzed 10,273 eligible articles. It showed that BMC Public Health displays the most prolific journals. Author MARCO PAHOR is highlighted in health education. The University of Sydney has published the most studies about health education. The USA plays an important role in these studies. Specifically, the visualization shows several hotspots: disease prevalence surveys and a specific population of knowledge, attitude and practice surveys, health intervention, chronic and non-communicable management, youth-health action, sexual and reproductive health, and physical activity promotion. Furthermore, document co-citation analysis indicated that there are 10 main clusters, which means the research front in health education. Meanwhile, by the citation detected, COVID-19, has achieved universal health coverage in related studies, however, public health education and the health workforce might be more popular in the coming years. CONCLUSION: Health education is an effective measure to shift the concept of public health and improve healthy living standards. The present study facilitates an extensive understanding of the basic knowledge and research frontiers that are pivotal for the developmental process of health education and allows scholars to visualize the identification modes and tendencies.

Visualizing the Knowledge Domain in Health Education: A Scientometric Analysis Based on CiteSpace

Objectives: This study aimed to visualize the evidence in the global research on health education to better improve the nation's health literacy and to guide future research. Method: We searched the Web of Science (Core Collection) electronic databases. The search strategies: topic: ('Health Education';OR 'Education, Health';OR 'Community Health Education';OR 'Education, Community Health';OR 'Health Education, Community';) AND document: (Article) AND language:(English). Articles of evidence from January 2011 to December 2021 with those words in the title or or keywords will be included in this review. We used the Citespace 5.6.R5 (64-bit) to investigate and determine the thematic patterns, and emerging trends of the knowledge domain, and presented a narrative account of the findings. Result: We analyzed 10,273 eligible articles. It showed that BMC Public Health displays the most prolific journals. Author MARCO PAHOR is highlighted in health education. The University of Sydney has published the most studies about health education. The USA plays an important role in these studies. Specifically, the visualization shows several hotspots: disease prevalence surveys and a specific population of knowledge, attitude and practice surveys, health intervention, chronic and non-communicable management, youth-health action, sexual and reproductive health, and physical activity promotion. Furthermore, document co-citation analysis indicated that there are 10 main clusters, which means the research front in health education. Meanwhile, by the citation detected, COVID-19, has achieved universal health coverage in related studies, however, public health education and the health workforce might be more popular in the coming years. Conclusion: Health education is an effective measure to shift the concept of public health and improve healthy living standards. The present study facilitates an extensive understanding of the basic knowledge and research frontiers that are pivotal for the developmental process of health education and allows scholars to visualize the identification modes and tendencies.

A familial cluster of COVID-19 infection in a northern Chinese region.

OBJECTIVE: Currently, coronavirus disease 2019 (COVID-19) has spread worldwide and become a global health concern. Here, we report a familial cluster of six patients infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) in a northern Chinese region and share our local experience with regard the control of COVID-19. METHODS: The demographic data, clinical features, laboratory examinations, and epidemiological characteristics of enrolled cases were collected and analyzed. Two family members (Cases 1 and 2) had Hubei exposure history and were admitted to the hospital with a confirmed diagnosis of COVID-19; eight familial members who had contact with them during the incubation period underwent quarantine in a hospital. We closely followed up all the family members and analyzed their clinical outcome. RESULTS: Case 3 had negative SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) results but was suspected to have COVID-19 because of radiographic abnormalities. Cases 4 and 5 developed symptomatic COVID-19. Case 6 was considered an asymptomatic carrier as his SARS-CoV-2 RT-PCR result was positive. The other four family members with close contacts to COVID-19 patients had no evidence of SARS-CoV-2 infection. CONCLUSIONS: Our findings suggest that COVID-19 has infectivity during the incubation period and preventive quarantine is effective for controlling an outbreak of COVID-19 infection.

Implementation and Outcomes of Virtual Care Across a Tertiary Cancer Center During COVID-19.

Importance: The coronavirus disease 2019 (COVID-19) pandemic has burdened health care resources and disrupted care of patients with cancer. Virtual care (VC) represents a potential solution. However, few quantitative data support its rapid implementation and positive associations with service capacity and quality. Objective: To examine the outcomes of a cancer center-wide virtual care program in response to the COVID-19 pandemic. Design, Setting, and Participants: This cohort study applied a hospitalwide agile service design to map gaps and develop a customized digital solution to enable at-scale VC across a publicly funded comprehensive cancer center. Data were collected from a high-volume cancer center in Ontario, Canada, from March 23 to May 22, 2020. Main Outcomes and Measures: Outcome measures were care delivery volumes, quality of care, patient and practitioner experiences, and cost savings to patients. Results: The VC solution was developed and launched 12 days after the declaration of the COVID-19 pandemic. A total of 22 085 VC visits (mean, 514 visits per day) were conducted, comprising 68.4% (range, 18.8%-100%) of daily visits compared with 0.8% before launch (P < .001). Ambulatory clinic volumes recovered a month after deployment (3714-4091 patients per week), whereas chemotherapy and radiotherapy caseloads (1943-2461 patients per week) remained stable throughout. No changes in institutional or provincial quality-of-care indexes were observed. A total of 3791 surveys (3507 patients and 284 practitioners) were completed; 2207 patients (82%) and 92 practitioners (72%) indicated overall satisfaction with VC. The direct cost of this initiative was CAD$ 202 537, and displacement-related cost savings to patients totaled CAD$ 3 155 946. Conclusions and Relevance: These findings suggest that implementation of VC at scale at a high-volume cancer center may be feasible. An agile service design approach was able to preserve outpatient caseloads and maintain care quality, while rendering high patient and practitioner satisfaction. These findings may help guide the transformation of telemedicine in the post COVID-19 era.

Rapid Adaptation of Breast Radiation Therapy Use During the Coronavirus Disease 2019 Pandemic at a Large Academic Cancer Center in Canada.

PURPOSE: Mitigation strategies to balance the risk of coronavirus disease 2019 (COVID-19) infection against oncologic risk in patients with breast cancer undergoing radiation therapy have been deployed. To this end, shorter hypofractionated regimens have been recommended where appropriate, with prioritization of radiation therapy by oncologic risk and omission or deferral of radiation therapy for lower risk cases. Timely adoption of these measures reduces COVID-19 risk to both patients and health care workers and preserves resources. Herein, we present our early response and adaptation of breast radiation therapy utilization during the COVID-19 pandemic at a large academic cancer center in Canada. METHODS AND MATERIALS: A state of emergency was announced in Ontario on March 17, 2020, owing to the COVID-19 pandemic. Emergency guidelines were instituted. To examine our response, the number of weekly breast radiation therapy starts, type of breast radiation therapy, and patient age were compared from March 1 to April 30, 2020 to the same period in 2019. RESULTS: After the declaration of emergency in Ontario, there was a decrease of 39% in radiation therapy starts in 2020 compared with 2019 (79 vs 129, P < .001). There was a relative increase in the proportion of patients receiving regional nodal irradiation (RNI) in 2020 compared with 2019 (46% vs 29%, respectively), with the introduction of hypofractionated RNI in 2020 (27 of 54 cases, 50%). A smaller proportion of patients starting radiation therapy were aged >50 years in 2020, 66% (78 of 118) versus 83% (132 of 160) in 2019, P = .0027. CONCLUSIONS: A significant reduction in breast radiation therapy starts was noted during the early response to the COVID-19 pandemic, with prioritization of radiation therapy to patients associated with higher oncologic risk requiring RNI. A quick response to a health care crisis is critical and is of particular importance for higher volume cancer sites where the potential effect on resources is greater.