Comparative analysis of BNT162b2, mRNA-1273 and ChAdOx1 COVID-19 vaccine induced antibody responses and the 3rd BNT162b2 vaccine induced neutralizing antibodies against Delta and Omicron variants

Two COVID-19 mRNA and two adenovirus vector vaccines have been licensed in Europe and various vaccine combinations and dosing strategies have been exploited to maximize the immunity against COVID-19. Here, we show that among health care workers (n=328) two doses of BNT162b2, mRNA-1273, or ChAdOx1 as also a combination of an adenovirus vector and mRNA vaccines induces equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against B.1 and B.1.617.2 when administrated with a long 12-week dose interval. Two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies compared to the long interval. Third mRNA vaccine dose for the short dose interval group increased the antibody levels 4-fold compared to the levels after the second dose. Importantly, sera from all three-times vaccinated neutralized B.1.1.529 (Omicron). The data indicates that a third COVID-19 mRNA vaccine dose efficiently induces cross-protective neutralizing antibodies against multiple variants.

The Effects of Retrieval Practice Across Levels of Thinking and Retention Interval on Reading Comprehension

The present study examined the effect of different types of retrieval practice on reading comprehension across levels of thinking and retention interval in a classroom setting. One hundred undergraduates divided into two retention interval groups (short- and long-retention interval) were asked to read a passage on a topic in Cognitive Psychology and were then required to engage in a retrieval practice learning strategy using the two types of question format (production test and recognition test) and different levels of thinking (lower-order thinking and higher-order thinking). A three-way mixed ANOVA statistical test was used to analyse the data and found no significant differences in reading comprehension across the different types of retrieval practice, suggesting that the performance when using the recognition test is equivalent to when using the production test. The difference in reading comprehension between the different types of retention interval also was not observed, indicating that students in the short-retention interval group retained just as much information as those in the long-retention interval group. Additionally, the present study observed a significant difference in students’ reading comprehension between different levels of thinking, signifying that the students’ performance for the lower-level thinking questions was better than that for the higher-level thinking questions. The present finding contributed to the existing body of knowledge in which it suggested that the performance in reading comprehension when using a recognition test, particularly a well-constructed one, with competitive alternatives was equivalent to when using a production test. Keywords: Levels of thinking, Question format, Reading comprehension, Retention interval, Retrieval practice

Characteristics of the Dynamic Electrocardiogram in the Elderly with Nonvalvular Atrial Fibrillation Combined with Long R-R Intervals

Objective. To investigate the characteristics of dynamic electrocardiogram and their clinical implications in elderly patients with nonvalvular atrial fibrillation combined with long R-R intervals. Methods. Elderly patients diagnosed with nonvalvular atrial fibrillation who were admitted as an inpatient or attended the outpatient department from January 2015 to January 2020 were selected. Patients were divided into two groups based on the presence of a long R-R interval. The characteristics and therapeutic significance of dynamic electrocardiogram between the two groups were compared. Results. A total of 532 patients were included in our analyses. Of these, 399 patients were in the long R-R interval group and 133 in the nonlong R-R interval group. In 399 patients, there were 48,840 long R-R intervals manifested within 24 hours. The average, slowest, and fastest ventricular rates during sleep time were higher than those in nonsleep time, while the number of long R-R intervals in sleep time was significantly smaller than that in nonsleep time ( P < 0.05 ). Clinical parameters including dizziness/syncope, cerebral infarction, ST-segment changes, platelet count, average hematocrit, prothrombin time (PT), left ventricular systolic function, end-diastolic diameter, pulmonary artery pressure, and left ventricular ejection fraction were comparable between the groups ( P > 0.05 ). When compared with the nonlong R-R interval group, the level of C-reactive protein was slightly lower in the long R-R interval group ( P < 0.05 ). In addition, the long R-R interval group had a higher incidence of atrial premature beats but a lower incidence of ventricular premature beats. Furthermore, the probability of long R-R interval combined with paroxysmal atrial tachycardia, transient ventricular arrest, second-degree atrioventricular block, and complete or incomplete right bundle branch block was higher than that of nonlong R-R interval ( P < 0.05 ). In patients with long R-R interval >3 s, the risk of having second-degree atrioventricular block and complete or incomplete right bundle branch block was significantly lower, while the risk of having transient ventricular arrest was higher when compared to patients with long R-R intervals of 2-3 s ( P < 0.05 P). Conclusions. Long R-R interval is a common electrocardiographic phenomenon among the elderly with nonvalvular atrial fibrillation. The long R-R interval mostly occurs in nonsleeping time. The average ventricular rate, slowest ventricular rate, and fastest ventricular rate of sleep time are higher than nonsleeping time. Analysis of the characteristics of the dynamic electrocardiogram of these patients may shed light on the mechanisms for long R-R intervals, including the likelihood of concealed conduction and physiological interference in the atrioventricular node, overspeed inhibition, increased vagus nerve tension, or pathological atrioventricular block.

The Effect of Betamethasone Dosing Interval on Perinatal Outcomes: 12 Hours or 24 Hours Apart

Objective Antenatal steroids are commonly used to stimulate fetal lung maturation, particularly in pregnancies at risk of early preterm labor. This study aimed to compare the effects of administering betamethasone at a 12- versus 24-hour interval on perinatal outcomes. Study Design This retrospective study included 423 early preterm births from 26+0/7 to 33+6/7 weeks of gestation. Patients received betamethasone at either a 12- or 24-hour dosing interval. Results When all patients in each group were evaluated together, there was no statistically significant difference between both groups for complications of prematurity, including respiratory distress syndrome (RDS). When the two groups were divided by gestational age (GA), the 32+0/7 to 33+6/7-week group that received betamethasone at a 24-hour interval had statistically lower 1- and 5-minute APGAR scores (p = 0.06 and p = 0.02, respectively). They also had a greater need for neonatal intensive care unit (NICU), NICU length of stay, RDS, and need for surfactant (p = 0.20, p = 0.09, p = 0.27, and p = 0.23, respectively) than did the infants at 32+0/7 to 33+6/7 weeks, who received betamethasone at a 12-hour interval. In the group with GA between 28+0/7 and 29+6/7 weeks, the 1-minute APGAR score was lower (p = 0.22), and the durations of hospital stay, and mechanical ventilation were longer (p = 0.048, p = 0.21, respectively) in the 24-hour interval group. No statistically significant difference was observed for all parameters in other GA groups. Conclusion A 12-hour dosing interval for betamethasone appears to be more appropriate, as it results in a reduction in some neonatal complications and provides a short dose interval. Key Points

Effect of Interval Time between Corrosive and Abrasive Challenges on a Nanoparticulate Composite Resin

Objective This study aimed to evaluate the effect of interval time after acidic beverage intake and brushing on roughness and hardness of resin composite. Materials and Methods Nanofilled resin composites were tested as per interval time (no interval, 15 or 30 minutes) between aging media (isotonic, sports drink) and brushing. Specimens (n = 9) were subjected to three cycles daily for 5 days with immersion in beverage followed by simulated brushing (585 strokes). The brushing (control) group was submitted only in brushing cycles. Roughness and microhardness were analyzed in the baseline and end of the experiment. Surface morphology was analyzed by using scanning electron microscopy (SEM). Statistical analysis Data were analyzed by one-way ANOVA and Tukey’s honestly significant difference (α = 0.05). Results Roughness was higher in no interval group and lower in 30 minutes and control. The 15 minutes present no statistical difference between control, 30 minutes and no interval. The hardness not present difference between groups. The SEM showed the no interval more roughness than 15 and 30 minutes, control and baseline. Conclusion The interval time between erosive and abrasive challenge is important to preserve the smoothness surface of composite resin.

Delayed interval BNT162b2 mRNA COVID-19 vaccination provides robust immunity

Shortages of COVID-19 vaccines have results in delayed dosing intervals as a strategy to immunize a greater proportion of the population. The effect of this strategy on vaccine immunogenicity is not well studied. Humoral (anti-RBD levels and neutralization) and cellular immune responses were compared in health care workers receiving two doses of BNT162b2 (Pfizer-BioNTech) vaccines at standard (3-6 week) and delayed (8-12 week) intervals. In the delayed group, anti-RBD antibody titres were significantly enhanced compared to the standard interval group. Neutralizing antibody responses were excellent and comparable in both groups. A slight decrease in Spike-specific polyfunctional CD4+ T-cells expressing interferon-γ and IL-2 as well as monofunctional CD4+ T-cells was seen in the delayed group. Both polyfunctional and monofunctional CD8+ T-cell responses were comparable. Our data suggest that the strategy of delayed second dose mRNA vaccination is not overtly detrimental, and specifically may lead to an enhanced humoral immune response.

Impact of dose-dense neoadjuvant chemotherapy on pathologic response and survival for HER2-positive breast cancer patients who receive trastuzumab

To compare outcomes in patients with human epidermal growth factor receptor-2 (HER2)-positive breast cancer who received either dose-dense neoadjuvant chemotherapy (NAC) with trastuzumab or standard-interval chemotherapy with trastuzumab. Patients with HER2-positive breast cancer who received NAC, including epirubicin and cyclophosphamide followed by paclitaxel with trastuzumab were included. Patients were divided into either the dose-dense or standard-interval group. We compared pathologic complete remission (pCR), distant disease-free survival (DDFS), event-free survival (EFS), and breast cancer-specific survival (BCSS) between the two groups. Two hundred (49.6%) patients received dose-dense NAC, and 203 (50.4%) received standard-interval NAC. The pCR rate was 38.4% in the dose-dense group and 29.2% in the standard-interval group (P = 0.052). In patients with lymph node (LN) metastases, the LN pCR rate was 70.9% in the dose-dense group and 56.5% in the standard-interval group (P = 0.037). After a median follow-up of 54.6 months, dose-dense chemotherapy presented an improvement on DDFS (hazard ratio [HR] = 0.49, 95% confidence interval [CI]: 0.19–1.28, EFS (HR = 0.54, 95% CI: 0.24–1.21), and BCSS (HR = 0.41, 95% CI: 0.11–1.51), but the difference was not significant. Compared with standard-interval chemotherapy, dose-dense chemotherapy resulted in a superior 5-year DDFS (100% vs. 75.3%, P = 0.017) and 5-year EFS (96.9% vs. 78.3%, P = 0.022) in patients younger than 40 years. HER2-positive patients can achieve a higher LN pCR rate with dose-dense NAC than with standard-interval NAC with trastuzumab. Better survival may also be achieved with dose-dense chemotherapy with trastuzumab than with standard-interval chemotherapy with trastuzumab among young patients (age ≤ 40 years).

PfSPZ-CVac efficacy against malaria increases from 0% to 75% when administered in the absence of erythrocyte stage parasitemia: A randomized, placebo-controlled trial with controlled human malaria infection

PfSPZ-CVac combines ‘PfSPZ Challenge’, which consists of infectious Plasmodium falciparum sporozoites (PfSPZ), with concurrent antimalarial chemoprophylaxis. In a previously-published PfSPZ-CVac study, three doses of 5.12x104 PfSPZ-CVac given 28 days apart had 100% vaccine efficacy (VE) against controlled human malaria infection (CHMI) 10 weeks after the last immunization, while the same dose given as three injections five days apart had 63% VE. Here, we conducted a dose escalation trial of similarly condensed schedules. Of the groups proceeding to CHMI, the first study group received three direct venous inoculations (DVIs) of a dose of 5.12x104 PfSPZ-CVac seven days apart and the next full dose group received three DVIs of a higher dose of 1.024x105 PfSPZ-CVac five days apart. CHMI (3.2x103 PfSPZ Challenge) was performed by DVI 10 weeks after the last vaccination. In both CHMI groups, transient parasitemia occurred starting seven days after each vaccination. For the seven-day interval group, the second and third vaccinations were therefore administered coincident with parasitemia from the prior vaccination. Parasitemia was associated with systemic symptoms which were severe in 25% of subjects. VE in the seven-day group was 0% (7/7 infected) and in the higher-dose, five-day group was 75% (2/8 infected). Thus, the same dose of PfSPZ-CVac previously associated with 63% VE when given on a five-day schedule in the prior study had zero VE here when given on a seven-day schedule, while a double dose given on a five-day schedule here achieved 75% VE. The relative contributions of the five-day schedule and/or the higher dose to improved VE warrant further investigation. It is notable that administration of PfSPZ-CVac on a schedule where vaccine administration coincided with blood-stage parasitemia was associated with an absence of sterile protective immunity. Clinical trials registration: NCT02773979.

Incidence and survival of Hodgkin lymphoma patients treated at a national cancer center in a middle-income country from 1999-2018: A report of 1,382 cases.

e19523 Background: Hodgkin lymphoma (HL) is classically described as a malignancy with a good prognosis and bimodal pattern. We aim to describe the incidence and survival of HL patients treated at the National Cancer Institute (NCI) in Peru. Methods: We evaluated the database at the NCI Epidemiology Department in Peru from 1999-2018. The international classification of diseases (ICD)-10 codes C810-C813, C817, C819 and ICD for Oncology (version 3) codes 96503-96533, 96573-96593, 96533-96553, 96573, 99903 were used to classify both nodal and extra-nodal HL. The estimate of overall survival (OS) curves was performed by the Kaplan-Meier method, and the difference was computed by the log-rank test. Results: During the study period 12,092 patients with lymphoma were found, of which 1,382 (11.4%) were HL. The median age was 24 years (range 2-88). Male patients were 62.4%. Patients of ≤14 years were 32.9%, with the most frequent 5-year interval group those aged 5-9 years-old representing 16.7% of patients. The adolescent and young adults (AYA) (15-39 years) group represented 38.4%. A total of 1,360 (98.4%) were classified as nodal HL. The classification according to the subtypes was as follows: 1,148 (83.1%) were one of the five subtypes [classical HL (cHL) and nodular lymphocyte-predominant HL (NLPHL)], 196 (14.2%) were HL, not otherwise specified, and 38 (2.7%) were HL without pathological confirmation. The classifiable 1,148 patients were categorized as follows: 1,107 patients (96.4%) were cHL and 41 (3.6%) were NLPHL. The cHL patients were classified as mixed cellularity HL (MCHL) in 52.3%, nodular sclerosis HL (NSHL) in 36.7%, lymphocyte-rich HL (LRHL) in 8.1%, and lymphocyte-depleted HL (LDHL) in 2.9%. The whole classifiable cohort (n = 1,148) showed a trimodal pattern. The MCHL subtype was most frequent in the 5-9 years group and in the 60-64 years group. The NSHL subtype was most frequent in the 20-24 years group. The median 5-year OS of the entire cohort (n = 1,382) was 86.3% (95%CI, 83.9-88.5). The OS according to the interval age groups were as follows: for the 0-14 years group the 5-yr OS was 94.9% (95%CI, 91.8-96.8), for the 15-39 years was 84% (95%CI, 79.5-87.68), for the 40-64 years group was 82.5% (95%CI, 75.2-87.8), and for the ≥65 years group was 58.6% (95%CI, 43.4-71.1). The OS according to age range showed a statistically significant difference p < 0.01. Conclusions: In our study, patients with HL are younger compared to those in developed countries. The most frequent 5-year interval group is the 5-9 years group. HL incidence had a trimodal pattern. Extra-nodal presentation was extremely rare. NLPHL was also rare. The most frequent subtype was MCHL, however, in AYA patients the most frequent subtype was NSHL. Better OS was seen in the 0-14 year group, this being statistically significant compared to the older groups. Worse OS was observed in patients aged 65 and older.

Changes in brain and behavior during food-based decision-making following treatment of anorexia nervosa

Background Anorexia nervosa is a severe illness with a high mortality rate, driven in large part by severe and persistent restriction of food intake. A critical challenge is to identify brain mechanisms associated with maladaptive eating behavior and whether they change with treatment. This study tested whether food choice-related caudate activation in anorexia nervosa changes with treatment. Methods Healthy women (n = 29) and women hospitalized with anorexia nervosa (n = 24), ages 18 to 40 years, completed a Food Choice Task during fMRI scanning at two timepoints. Among patients, procedures occurred upon hospital admission (Time 1) and again after patients had gained to normal weight (Time 2). Healthy controls were tested twice at an interval group-matched to patients. Choice-related caudate activation was assessed at each timepoint, using parametric analyses in an a priori region of interest. Results Among patients, the proportion of high-fat foods selected did not change over time (p’s > 0.47), but decreased neural activity in the caudate after treatment was associated with increased selection of high-fat foods (r23 = − 0.43, p = 0.037). Choice-related caudate activation differed among women with anorexia nervosa vs healthy control women at Time 1 (healthy control: M = 0.15 ± 0.87, anorexia nervosa: M = 0.70 ± 1.1, t51 = − 2.05, p = 0.045), but not at Time 2 (healthy control: M = 0.18 ± 1.0, anorexia nervosa: M = 0.37 ± 0.99, t51 = − 0.694, p = 0.49). Conclusions Caudate activity was more strongly associated with decisions about food among individuals with anorexia nervosa relative to healthy comparison individuals prior to treatment, and decreases in caudate engagement among individuals with anorexia nervosa undergoing treatment were associated with increases in high-fat food choices. The findings underscore the need for treatment development that more successfully alters both eating behavior and the neural mechanisms that guide it.