Animal models for COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (first detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the findings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19.

Two-dose schedules for human papillomavirus vaccine: Systematic review and meta-analysis.

Simpler schedules for human papillomavirus (HPV) vaccine delivery could improve vaccine coverage and the effectiveness of cervical cancer prevention. The objective of this study was to systematically review evidence about the effects of two-dose compared with three-dose schedules for human papillomavirus (HPV) vaccine and to describe the uptake of two-dose HPV vaccination schedules globally. We searched PubMed, the Cochrane Central Registry of Controlled Trials, trials registers, and manufacturers' databases from their earliest date to February 2016. We selected randomised controlled trials and controlled clinical trials that directly compared HPV vaccine schedules with two or three doses. We extracted data on immunological and clinical outcomes and used meta-analysis where appropriate. We also described the use of two-dose HPV vaccine schedules globally. We screened 1464 items and included seven eligible noninferiority trials in 11 countries. In randomised comparisons amongst adolescent girls (three trials), geometric mean concentrations (GMC) of antibodies against HPV16 and HPV18 were non-inferior or inconclusive, up to 24months after a two-dose compared with a three-dose schedule. One trial with a clinical outcome found no persistent HPV infections occurred after either two or three doses. In non-randomised comparisons, GMC were non-inferior or superior in adolescent girls receiving the two-dose schedule compared with women receiving the three-dose schedule for at least 21months after vaccination. By February 2017, 23 low and middle income and 25 high income countries had adopted a two-dose HPV vaccination schedule. A two-dose HPV vaccine schedule provides satisfactory immunological outcomes in adolescent girls, but uptake globally is limited, particularly in countries with the highest burden of cervical cancer.

A randomized, controlled trial of an aerosolized vaccine against measles.

BACKGROUND: Aerosolized vaccine can be used as a needle-free method of immunization against measles, a disease that remains a major cause of illness and death. Data on the immunogenicity of aerosolized vaccine against measles in children are inconsistent. METHODS: We conducted an open-label noninferiority trial involving children 9.0 to 11.9 months of age in India who were eligible to receive a first dose of measles vaccine. Children were randomly assigned to receive a single dose of vaccine by means of either aerosol inhalation or a subcutaneous injection. The primary end points were seropositivity for antibodies against measles and adverse events 91 days after vaccination. The noninferiority margin was 5 percentage points. RESULTS: A total of 1001 children were assigned to receive aerosolized vaccine, and 1003 children were assigned to receive subcutaneous vaccine; 1956 of all the children (97.6%) were followed to day 91, but outcome data were missing for 331 children because of thawed specimens. In the per-protocol population, data on 1560 of 2004 children (77.8%) could be evaluated. At day 91, a total of 662 of 775 children (85.4%; 95% confidence interval [CI], 82.5 to 88.0) in the aerosol group, as compared with 743 of 785 children (94.6%; 95% CI, 92.7 to 96.1) in the subcutaneous group, were seropositive, a difference of -9.2 percentage points (95% CI, -12.2 to -6.3). Findings were similar in the full-analysis set (673 of 788 children in the aerosol group [85.4%] and 754 of 796 children in the subcutaneous group [94.7%] were seropositive at day 91, a difference of -9.3 percentage points [95% CI, -12.3 to -6.4]) and after multiple imputation of missing results. No serious adverse events were attributable to measles vaccination. Adverse-event profiles were similar in the two groups. CONCLUSIONS: Aerosolized vaccine against measles was immunogenic, but, at the prespecified margin, the aerosolized vaccine was inferior to the subcutaneous vaccine with respect to the rate of seropositivity. (Funded by the Bill and Melinda Gates Foundation; Measles Aerosol Vaccine Project Clinical Trials Registry-India number, CTRI/2009/091/000673.).

Prognostic value of oncoprotein expressions in thyroid papillary carcinoma.

The aim of this study was to evaluate the expressions of oncoproteins and to correlate the results with clinicopathologic parameters in papillary thyroid carcinoma (PTC). Papillary thyroid cancer (PTC) is the most common form and accounts for about 80% of all thyroid cancers. Although PTC generally has a good prognosis, some patients suffer from local recurrence and/or distant metastasis. Oncogenes have reported to be related not only in carcinogenesis but also in tumor prognosis, tumor type, differentiation and site of tumor in epithelial malignant tumors such as thyroid, breast, ovarian, and stomach cancer. This study was planned retrospectively and was performed in 87 patients (47 PTC, 40 benign lesions). The data of clinicopathologic parameters and tissue samples were collected from the archives. Sections stained with H&E were evaluated for each case and after confirming the diagnosis of PTC, oncoprotein expressions were determined by immunohistochemical analysis. The differences of oncoprotein expressions in PTC compared with control group were statistically significant. Cyclin D1 and p53 expressions were significantly increased in PTC. The expressions of bcl-2 and c-erbB-2 in PTC were found as increased, but the correlation between these proteins and poor prognostic parameters were not significant. We suggest that increased expressions of cyclin D1 and p53 could be used as prognostic factors in patients with PTC.

Constipation as a defecation disorders: what do we expect from the physiologic tests?

BACKGROUND: Constipation is often associated with some clinical signs as hard stool, incomplete defecation, chronic straining, and abdominal pain and long stays in bathroom. Some diagnostic uncertainties came from functional and structural variations of the anorectum and the assessment from few imaging procedures, which were thought as the best but could not always give the expected result. Then physiologic tests were required to be used. The aim was to study which physiologic test correlated to the clinical symptoms, was valuable and have to be performed in the patients with chronic constipation in this series. METHODS: One hundred twenty-seven patients (56.3 % females; mean age, 56.7) with chronic constipation according to the Rome II criteria were initially treated by dietary change and increased physical activation. The unresponsive (80) patients were instructed to be evaluated by the physiologic tests (anal manometry, defecography, colonic transit time-CTT) and clinical symptoms. The assessments from physiologic tests, which were originated from 4 distinctive categories, were investigated by factor analysis. ROC curve analysis was used to take involved assessments, which had a big impact on the constipation status. RESULTS: 80 patients, mostly female (89 %), had experienced several symptoms in 11.9 years. The CCT, scoring system, evacuation problem, hard stool, habitual laxative use and digital assist for defecation were significantly different in 17 factors originated from different categories. We analyzed the extracted factor, which had an important effect on the constipation and consequently considered the necessary physiologic test and other related symptoms. CONCLUSIONS: Scoring system, CTT, anal manometry and other physiologic tests are important to establish a true diagnosis of the etiology of the constipation. However, defecography and clinical symptoms are the factors, which has a great impact on the diagnosis of constipation (Tab. 7, Ref. 25).

Randomized study comparing omeprazole with ranitidine as anti-secretory agents combined in quadruple second-line Helicobacter pylori eradication regimens.

BACKGROUND: Few data are available on the efficacy of second-line H. pylori eradication regimens. AIM: To compare the efficacy of either omeprazole or ranitidine in a second-line quadruple regimen in patients with duodenal ulcer or erosive duodenitis. PATIENTS AND METHODS: A total of 37 patients with erosive duodenitis and 119 with duodenal ulcer who have failed eradication of H. pylori with double or triple regimens, without metronidazole, were randomly assigned to receive tripotassium dicitrato bismuthate 600 mg t.d.s. + metronidazole 500 mg t.d.s. + tetracycline hydrochloride 500 mg t.d. s. combined with either omeprazole 20 mg b.d. (group O, 78 patients) or ranitidine 300 mg b.d. (group R, 78 patients) for 14 days. H. pylori eradication was verified by histology, rapid urease test and 13C-urea breath test. STATISTICS: t-test, chi2-test. RESULTS: A total of 143 patients had a post-treatment endoscopy. Eradication rates were: intention-to-treat: group O 77% (67-87), group R 76% (66-85), P=0.85; per protocol analysis: group O 86% (77-95), group R 82 (71-93), P=0.58. Side-effects were frequent but mild. CONCLUSIONS: Omeprazole 20 mg b.d. and ranitidine 300 mg b.d. were equally effective as antisecretory agents combined in a second-line quadruple eradication regimen.