Comparative analysis of variation in the quality and completeness of local outbreak control plans for SARS-CoV-2 in English local authorities.

BACKGROUND: Local outbreak control plans (LOCPs) are statutory documents produced by local authorities (LAs) across England. LOCPs outline LAs' response to Coronavirus Disease 19 (COVID19) outbreaks and the coordination of local resources, data and communication to support outbreak response. LOCPs are therefore crucial in the nation's response to COVID-19. However, there has been no previous systematic assessment of these documents. We performed this study to systematically assess the quality of LOCPs and to offer recommendations of good practice. METHODS: All published LOCPs were assessed for basic characteristics. A framework based on Department of Health and Social Care guidelines was used to assess a random sample of LOCPs. Qualitative analysis was undertaken for LOCPs with highest completeness. RESULTS: Hundred and thirty-seven of 150 LAs publicly published a full LOCP; 9 were drafts. Statistical analysis demonstrated the significant difference between reporting of mainstream schools, care homes and the homeless population and other educational settings, high-risk settings and other vulnerable groups. LOCPs varied in approach when structuring outbreak response information and focused on different areas of outbreak management. CONCLUSIONS: The majority of LAs are publicly accessible. There is significant variation between the reporting of high-risk settings and groups. Suggested recommendations may help to improve future LOCP updates.

Apatinib in patients with extensive-stage small-cell lung cancer after second-line or third-line chemotherapy: a phase II, single-arm, multicentre, prospective study.

BACKGROUND: Small-cell lung cancer (SCLC) remains an aggressive cancer with short-term survival due to limited therapeutic options. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor-2. This study aimed to investigate the efficacy and safety of apatinib in patients with extensive-stage (EC) SCLC who had progressed after two or three previous therapies. METHODS: Eligible patients were histologically confirmed ES-SCLC after two or three previous treatments, including a platinum-based regimen. Patients received apatinib at an initial dose of 500 mg once daily. The primary endpoint was the objective response rate. RESULTS: Forty patients were enrolled. At the data cut-off time (November 15, 2018), the median follow-up was 7.4 months; no patients remained on treatment, and five were still in follow-up. An objective response was achieved in 7 of 40 patients (17.5%) in the intention-to-treat population, and 7 of 38 patients (18.4%) in the per-protocol population. The median progression-free survival and overall survival were 3.0 months and 5·8 months, respectively. The most commonly observed grade 3 or greater treatment-related adverse events were hypertension, hand-foot syndrome, increased L-gamma-glutamyltransferase. CONCLUSIONS: Apatinib exhibited efficacy and an acceptable safety profile in previously heavily-treated ES-SCLC patients. Further exploration of apatinib in phase III trials is warranted. TRIAL REGISTRATION: NCT02945852.

Genistein Inhibited Estradiol-Induced Vascular Endothelial Cell Injury by Downregulating the FAK/Focal Adhesion Pathway.

BACKGROUND/AIMS: In this study, we aimed to investigate the effects of genistein on the focal adhesion signaling pathway through its regulation of FAK. Genistein ultimately restored and alleviated estradiol-induced vascular endothelial injury. METHODS: Microarray analysis was used to select differentially expressed genes. MTT assay was performed to detect the cell activity, and ROS test and NO test were performed to detect the degree of damage to HUVECs (human umbilical vein endothelial cells). The relative mRNA expression levels and protein expression levels of FAK were tested by western blot and qRT-PCR. GO functional analysis and KEGG pathway analysis were applied to predict the possible relationship between functions and related pathways, and transwell assay was used to detect cell invasion and migration. RESULTS: FAK was highly expressed in the HUVECs treated with estradiol (HU-ESTs). Cell viability and NO level decreased, whereas ROS level increased in the HU-ESTs. Effective knockdown of FAK in HU-ESTs elevated cell viability and NO levels while suppressing ROS levels. In addition, inhibition of FAK greatly decreased cell invasion and migration, while the overexpression of FAK enhanced cell invasion and migration. KEGG further indicated focal adhesion pathways were activated. Genistein elevated HU-EST viability, and NO and ROS level increased in a concentration dependent manner. Transwell and western blot assays revealed that genistein could reduce the FAK expression levels and alleviate the damage to the HU-ESTs. CONCLUSION: FAK overexpression promoted invasion and migration of the HU-ESTs. However, genistein greatly suppressed FAK and estradiol-induced vascular endothelial cell injury.

[Exercise-sensitive Indices Screening from Electrocardiogram Based on Rest-workload Alternating Pattern].

Heart rate is the most common index to directly monitor the level of physical stress by comparing the subject's heart rate with an appropriate "target heart rate" during exercise. However, heart rate only reveals the cardiac rhythm of the complex cardiovascular changes that take place during exercise. It is essential to get the dynamic response of the heart to exercise with various indices instead of only one single measurement. Based on the rest-workload alternating pattern, this paper screens the sensitive indices of exercise load from electrocardiogram (ECG) rhythm and waveform, including 4 time domain indices and 4 frequency domain indices of heart rate variability (HRV), 3 indices of waveform similarity and 2 indices of high frequency noise. In conclusion, RR interval (heart rate) is a reliable index for the realtime monitoring of exercise intensity, which has strong linear correlation with load intensity. The ECG waveform similarity and HRV indices are useful for the evaluation of exercise load.

Aortic valve perivascular adipose tissue computed tomography attenuation in patients with aortic stenosis.

OBJECTIVE: Aortic stenosis (AS) shares pathophysiological similarities with atherosclerosis including active inflammation. CT attenuation of perivascular adipose tissue provides a measure of vascular inflammation that is linked to prognosis and has the potential to be applied to the aortic valve. We investigated perivascular adipose tissue attenuation around the aortic valve in patients with AS. METHODS: CT attenuation was measured in the perivascular adipose tissue extending 3 mm radially and 10 mm longitudinally around the aortic valve in patients with and without AS. Associations between perivascular adipose tissue attenuation and AS disease severity, activity and progression were investigated. RESULTS: Perivascular adipose tissue attenuation around the aortic valve demonstrated good intraobserver and interobserver repeatability (interobserver: intraclass correlation coefficient 0.977 (95% CI: 0.94, 0.99)) but was similar between patients with AS (n=120) and control subjects (n=80) (-62.4 (-68.7, -56.5) Hounsfield units (HU) vs -61.2 (-65.3, -55.6) HU, p=0.099). There were no differences between perivascular adipose tissue attenuation in patients with mild (-60.2 (-66.9, -55.1) HU), moderate (-62.8 (-69.6, -56.80) HU) or severe (-62.3 (-69.3, -55.4) HU) AS (all p>0.05), and perivascular adipose tissue attenuation did not demonstrate an association with AS severity as assessed by echocardiography or CT calcium scoring, nor with disease activity assessed by 18F-sodium fluoride positron emission tomography. Moreover, there was no association between baseline aortic valve perivascular adipose tissue attenuation and subsequent AS progression (annualised change in peak velocity: r=0.072, p=0.458). Similar results were found using five other image analysis methods. CONCLUSIONS: CT-derived aortic valve perivascular adipose tissue attenuation is not associated with AS disease severity, activity or progression suggesting that it has no value in the investigation and management of patients with AS.

Abnormal activation of brain regions in idiopathic trigeminal neuralgia patients by fMRI: An activation likelihood estimation meta-analysis.

BACKGROUND: Idiopathic trigeminal neuralgia (ITN) is one of the most common types of neuropathic pain, severely affecting the physiological and psychological wellbeing of patients. Recently, fMRI has been used to examine abnormal activation of brain regions in patients with ITN. However, sample sizes have been small in these few studies, and the abnormally activated brain regions remain unclear. Therefore, in the present study, we retrieved and analyzed literature on the brain areas with abnormal or reduced activation in ITN patients, with the aim of providing insight into the neuropathological basis of the disease and to provide new targets for treatment. METHODS: We retrieved resting state fMRI studies on trigeminal neuralgia patients from PubMed, the Web of Science and Scopus databases until November 2022, and we extracted the coordinates of the sites with increased or decreased activation. We used activation likelihood estimation (ALE) meta-analysis to identify regions of abnormal activation in ITN patients. RESULTS: ALE meta-analysis revealed that the left caudate nucleus and right anterior ventral nucleus of the thalamus are abnormally hyperactivated in ITN patients. Moreover, ITN patients showed reduced activation in the left precuneus, middle temporal gyrus, lingual gyrus, and medial frontal gyrus. CONCLUSION: ALE meta-analysis identified several brain regions with abnormally high or decreased activation in ITN patients. Sites with altered activation may be potential targets for non-invasive brain stimulation as adjunct therapy for ITN.

Moringa oleifera Lam.: a comprehensive review on active components, health benefits and application.

Moringa oleifera Lam. is an edible therapeutic plant that is native to India and widely cultivated in tropical countries. In this paper, the current application of M. oleifera was discussed by summarizing its medicinal parts, active components and potential mechanism. The emerging products of various formats such as drug preparation and product application reported in the last years were also clarified. Based on literature reports, the unique components and biological activities of M. oleifera need to be further studied. In the future, a variety of new technologies should be applied to the development of M. oleifera products, to enrich the varieties of dosage forms, improve the bitter taste masking technology, and make it better for use in the fields of food and medicine.

Serum lipoprotein(a) and bioprosthetic aortic valve degeneration.

AIMS: Bioprosthetic aortic valve degeneration demonstrates pathological similarities to aortic stenosis. Lipoprotein(a) [Lp(a)] is a well-recognized risk factor for incident aortic stenosis and disease progression. The aim of this study is to investigate whether serum Lp(a) concentrations are associated with bioprosthetic aortic valve degeneration. METHODS AND RESULTS: In a post hoc analysis of a prospective multimodality imaging study (NCT02304276), serum Lp(a) concentrations, echocardiography, contrast-enhanced computed tomography (CT) angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) were assessed in patients with bioprosthetic aortic valves. Patients were also followed up for 2 years with serial echocardiography. Serum Lp(a) concentrations [median 19.9 (8.4-76.4) mg/dL] were available in 97 participants (mean age 75 ± 7 years, 54% men). There were no baseline differences across the tertiles of serum Lp(a) concentrations for disease severity assessed by echocardiography [median peak aortic valve velocity: highest tertile 2.5 (2.3-2.9) m/s vs. lower tertiles 2.7 (2.4-3.0) m/s, P = 0.204], or valve degeneration on CT angiography (highest tertile n = 8 vs. lower tertiles n = 12, P = 0.552) and 18F-NaF PET (median tissue-to-background ratio: highest tertile 1.13 (1.05-1.41) vs. lower tertiles 1.17 (1.06-1.53), P = 0.889]. After 2 years of follow-up, there were no differences in annualized change in bioprosthetic hemodynamic progression [change in peak aortic valve velocity: highest tertile [0.0 (-0.1-0.2) m/s/year vs. lower tertiles 0.1 (0.0-0.2) m/s/year, P = 0.528] or the development of structural valve degeneration. CONCLUSION: Serum lipoprotein(a) concentrations do not appear to be a major determinant or mediator of bioprosthetic aortic valve degeneration.

Myocardial ischemia analysis based on electrocardiogram QRS complex.

Electrocardiogram (ECG) is an economic, convenient, and non-invasive detecting tool in myocardial ischemia (MI), and its clinical appearance is mainly exhibited by the changes in ST-T complex. Recently, QRS complex characters were proposed to analyze MI by more and more researchers. In this paper, various QRS complex characters were extracted in ECG signals, and their relationship was analyzed systematically. As a result, these characters were divided into two groups, and there existed good relationship among them for each group, while the poor relationship between the groups. Then these QRS complex characters were applied for statistical analysis on MI, and five characters had significant differences after ECG recording verification, which were: QRS upward and downward slopes, transient heart rate, angle R and angle Q. On the other hand, these QRS complex characters were analyzed in frequency domain. Experimental results showed that the frequency features of RR interval series (Heart Rate Variability, HRV), and QRS barycenter sequence had significant differences between MI states and normal states. Moreover, QRS barycenter sequence performed better.

Corrigendum: The Pathophysiology of Degenerative Cervical Myelopathy and the Physiology of Recovery Following Decompression.

[This corrects the article DOI: 10.3389/fnins.2020.00138.].

The Pathophysiology of Degenerative Cervical Myelopathy and the Physiology of Recovery Following Decompression.

Background: Degenerative cervical myelopathy (DCM), also known as cervical spondylotic myelopathy is the leading cause of spinal cord compression in adults. The mainstay of treatment is surgical decompression, which leads to partial recovery of symptoms, however, long term prognosis of the condition remains poor. Despite advances in treatment methods, the underlying pathobiology is not well-known. A better understanding of the disease is therefore required for the development of treatments to improve outcomes following surgery. Objective: To systematically evaluate the pathophysiology of DCM and the mechanism underlying recovery following decompression. Methods: A total of 13,808 published articles were identified in our systematic search of electronic databases (PUBMED, WEB OF SCIENCE). A total of 51 studies investigating the secondary injury mechanisms of DCM or physiology of recovery in animal models of disease underwent comprehensive review. Results: Forty-seven studies addressed the pathophysiology of DCM. Majority of the studies demonstrated evidence of neuronal loss following spinal cord compression. A number of studies provided further details of structural changes in neurons such as myelin damage and axon degeneration. The mechanisms of injury to cells included direct apoptosis and increased inflammation. Only four papers investigated the pathobiological changes that occur in spinal cords following decompression. One study demonstrated evidence of axonal plasticity following decompressive surgery. Another study demonstrated ischaemic-reperfusion injury following decompression, however this phenomenon was worse when decompression was delayed. Conclusions: In preclinical studies, the pathophysiology of DCM has been poorly studied and a number of questions remain unanswered. The physiological changes seen in the decompressed spinal cord has not been widely investigated and it is paramount that researchers investigate the decompressed spinal cord further to enable the development of therapeutic tools, to enhance recovery following surgery.

The sequence and de novo assembly of hog deer genome.

Hog deer (Axis porcinus) is a small deer species in family Cervidae and has been undergoing a serious and global decline during the past decades. Chengdu Zoo currently holds a captive population of hog deer with sufficient genetic diversity in China. We sequenced and de novo assembled its genome sequence in the present study. A total of six different insert-size libraries were sequenced and generated 395 Gb of clean data in total. With aid of the linked reads of 10X Genomics, genome sequence was assembled to 2.72 Gb in length (contig N50, 66.04 Kb; scaffold N50, 20.55 Mb), in which 94.5% of expected genes were detected. We comprehensively annotated 22,473 protein-coding genes, 37,019 tRNAs, and 1,058 Mb repeated sequences. The newly generated reference genome is expected to significantly contribute to comparative analysis of genome biology and evolution within family Cervidae.

Protective effect of KLF15 on vascular endothelial dysfunction induced by TNF­α.

Atherosclerosis (AS) is a cardiovascular disease with a relatively high incidence rate. Krüppel­like factor 15 (KLF15) has a role in numerous pathological processes, including nephropathy, abnormal glucose metabolism and myocardial injury. The aim of the present study was to investigate the function of KLF15 in vascular endothelial dysfunction. MTT analyses, nitric oxide (NO) detection and cell adhesion detection kits were used to investigate the viability and adhesion of, and quantity of NO released by Eahy926 cells induced by tumor necrosis factor (TNF)­α, respectively. Reverse transcription­quantitative polymerase chain reaction and western blot analyses were performed to determine the expression levels of KLF15, endothelial nitric oxide synthase, monocyte chemoattractant protein­1 (MCP­1), intercellular adhesion molecule­1 (ICAM­1), transforming growth factor­ß1 (TGF­ß1), phosphorylated (p­)transcription factor p65 (p65) and nuclear factor erythroid 2­related factor 2 (Nrf2). The results of the present study demonstrated that TNF­α was able to induce vascular endothelial dysfunction in Eahy926 cells at an optimum concentration of 10 ng/ml. Overexpression of KLF15 markedly enhanced cell viability in addition to the quantity of released NO of TNF­α­induced Eahy926 cells, and increased the expression levels of eNOS and Nrf2. Furthermore, overexpression of KLF15 markedly suppressed the rate of cellular adhesion, and downregulated levels of MCP­1, ICAM­1, TGF­ß1 and p­p65 in TNF­α induced Eahy926 cells. In conclusion, the results of the present study suggested that overexpression of KLF15 in Eahy926 cells exhibited a protective effect against TNF­α induced dysfunction via activation of Nrf2 signaling and inhibition of nuclear factor κB signaling.

Correlation between microtubule-associated gene expression and chemosensitivity of patients with stage II non-small cell lung cancer.

The aim of this study was to explore the correlation between mRNA expression of ß-tubulin-III and stathmin in patients with stage II non-small cell lung cancer (NSCLC) and the chemosensitivity to Navelbine plus cisplatin (NP), as well as to provide a basis for personalized treatment. A single-gene quantitative test was performed to detect the mRNA expression of ß-tubulin-III and stathmin in the tumor tissue of patients with stage II NSCLC. All the patients underwent NP treatment following surgery and were followed-up to record their disease-free survival (DFS) and overall survival (OS). Statistical analyses were conducted to investigate the correlation between ß-tubulin-III and stathmin mRNA expression and DFS and OS in the patients. ß-tubulin-III mRNA expression was associated with OS in the 73 patients (P=0.003) and DFS was correlated with ß-tubulin-III mRNA expression and lymphatic metastasis (P<0.01). Stathmin mRNA expression was not correlated with OS or DFS (P>0.05). OS and DFS were longer in the patients with low ß-tubulin-III mRNA expression than in those with high ß-tubulin-III mRNA expression (P<0.01); there was no significant change in OS and DFS between the patients with high and low mRNA expression of stathmin (P>0.05). The mRNA expression levels of ß-tubulin-III in the tumor tissue of patients with stage II NSCLC may be considered as an index of prognosis and chemosensitivity, as well as a reference for personalized chemotherapeutic applications in patients.

[Expression of hMLH1 in rectal intraepithelial neoplasm and early rectal carcinoma].

OBJECTIVE: To explore whether the abnormality of hMLH1 gene may be an early event of carcinogenesis in rectal carcinoma, and to evaluate the diagnostic value in differentiation between intraepithelial neoplasm and early stage of colorectal carcinoma. METHODS: The expression of hMLH1 protein in 28 cases with early invasive rectal carcinoma(EIRC), 36 cases with rectal intraepithelial neoplasm(RIEN), and 30 cases with normal rectal mucosa(NRM) which were collected through surgical operations were detected by PV-9000 immunohistochemical method. RESULTS: The positive expression rates of hMLH1 protein were 100%(30/30), 77.8%(28/36), and 39.3%(11/28) in NRM, RIEN, and EIRC respectively. The difference was statistically significant between RIEN and EIRC(P=0.002), and the difference was also statistically significant between RIEN and NRM(P=0.006). The positive expression of hMLH1 was not related to age, gender, tumor maximum diameter, dysplasia, tumor types, and distance from the anal verge in RIEV group(P>0.05). In EIRC group, hMLH1 was associated with tumor differentiation(P<0.05). CONCLUSION: hMLH1 gene deletion may be an early event during carcinogenesis of rectal carcinoma, which may be useful in differentiation of intraepithelial neoplasm from early rectal carcinoma.

[Safety and efficacy of prophylactic single antibiotics administration in selective open colorectal surgery].

OBJECTIVE: To investigate the safety and efficacy of prophylactic single antibiotic administration in selective open colorectal surgery. METHODS: Two hundred and seventy-five patients undergoing selective open colorectal surgery in the Peking Union Medical College Hospital from October 2009 to October 2011 were retrospectively reviewed. Prophylatic single antibiotic administration was used by intravenous infusion 30-60 min before incision. No antibiotics would be given after operation if there was no surgical site infection(SSI). According to the incidence of postoperative SSI, unexplained use of antibiotics, anastomotic leakage and distant-site infection, the clinical outcome was assessed to be prophylactic success, prophylactic failure or distant-site infection, respectively. RESULTS: There was no intraoperative or postoperative antibiotics related drug anaphylaxis in all the 275 patients. By prophylactic single antibiotic administration, there were prophylactic success in 243 patients(88.4%,243/275), prophylactic failure in 23(8.4%,23/275), distant-site infection in 9(3.3%,9/275). In the 23 patients with failed prophylaxis, there were SSI in 13(4.7%,13/275) patients, postoperative use of broad-spectrum antibiotics for unexplained fever in 2(0.7%,2/275), postoperative anastomotic leakage in 8(3.6%,8/222). CONCLUSION: Prophylactic single antibiotic administration in selective open colorectal surgery is safe and effective.