The main decision-making competence for willingness-to-pay towards COVID-19 vaccination: a family-based study in Taizhou, China.

PURPOSE: This research aimed to explore individuals' willingness to pay (WTP) and studied the role of family decision makers in WTP for COVID-19 vaccines. METHODS: A self-administered online questionnaire evaluating the willingness of community residents to pay for booster vaccination of COVID-19 vaccine was conducted among families in a community in Taizhou, China. The logistic regression model was performed to identify the factors associated with WTP for the COVID-19 vaccines, and all data were analysed by R software, version 4.1.0. RESULTS: 44.2% and 43.7% of 824 community residents were willing to pay for the first two doses and the booster dose of the COVID-19 vaccine, respectively. Decision-makers were more willing to pay for both the first two doses and the boost dose of the COVID-19 vaccines, with OR (95%CI) being 1.75 (1.25-2.47) and 1.89 (1.34-2.67), respectively. Besides, participants' WTP for COVID-19 vaccines were also associated with their occupation and monthly household income. CONCLUSION: This study found that family decision-makers were more willing to pay for both the first two doses and the booster dose of COVID-19 vaccines in Taizhou, China. To improve the WTP for COVID-19 vaccines, public policy programs need to conduct a comprehensive cost-benefit analysis and focus on the role of family decision makers in vaccination.Key MessagesA study evaluating the willingness of community residents to pay for booster vaccination of COVID-19 vaccine was conducted among families in a community in Taizhou, China.Family decision-makers were more willing to pay for both the first two doses and the booster dose of COVID-19 vaccines.To improve the WTP for COVID-19 vaccines, public policy programs need to conduct a comprehensive cost-benefit analysis and focus on the role of family decision-makers in vaccination.

The effect of mifepristone pretreatment on bleeding and pain during medical management of early pregnancy loss.

OBJECTIVES: To compare participant-reported bleeding and pain with two medication regimens for early pregnancy loss (EPL). STUDY DESIGN: We performed a secondary analysis of a randomized trial in which participants took either mifepristone 200 mg orally followed by misoprostol 800 mcg vaginally 24 hours later or misoprostol alone for medical management of EPL. Participants reported bleeding and pain (Numeric Pain Rating Scale, NPRS, 0-10) with daily paper diaries and at study visits on trial days 3, 8, and 30. We used, Fisher's exact, Pearson chi-square, Wilcoxon rank sum, and Student's t-tests to compare onset, duration, and severity of bleeding and pain symptoms between trial arms after misoprostol administration. RESULTS: Among 291 participants who submitted diary data, 143 received mifepristone pretreatment. A larger proportion of this group reported moderate or heavy bleeding on trial day 2, the day of misoprostol administration, compared with those who did not receive pretreatment (73% vs 47%, p < 0.01). Between days 4 and 8, more mifepristone-pretreatment participants reported mild or no bleeding, compared with the misoprostol-only arm (78% vs 61%, p < 0.01). Average pain score for trial days 2-4 was higher for the pretreatment group compared with the misoprostol-only group (6.9 vs 6.0, p = 0.01), and there was a trend toward shorter total duration of pain (15 vs 19 hours, p = 0.08). These differences remained after controlling for treatment success across arms. CONCLUSIONS: Mifepristone pretreatment increased the severity of pain but not bleeding and resulted in a shorter trajectory of symptoms during medical management of EPL. IMPLICATIONS: Mifepristone pretreatment decreases the duration of heavy bleeding and there was a trend toward decreased duration of pain during medical management of miscarriage, indicating that this medication improves the efficiency, in addition to the efficacy, of this treatment.

Utilization of progesterone and cervical length screening for prevention of recurrent preterm birth.

Objective: To assess utilization of progesterone and cervical length (CL) screening among women with prior spontaneous preterm birth (sPTB).Methods: This is a retrospective cohort study of women with prior sPTB. Primary outcomes were the use of progesterone and CL screening. Secondary outcomes were reasons for failure to utilize interventions and factors associated with use of recommended interventions.Results: 180 women had a prior sPTB. Of 171 women eligible for progesterone, 125 (74%) utilized it. Women who utilized progesterone were more likely to have a prior sPTB <28 weeks (50% vs 26%, OR 2.54 (1.18-5.42) p = .006) and a higher number of prior sPTB (1.5 ± 0.9 vs 1.2 ± 0.5, p = .02), and less likely to have a prior full term delivery (54% vs 72%, OR 0.47 (0.22-0.99), p = .04). Of 176 women eligible for CL screening, 157 (89%) utilized it. Women who utilized CL screening were less likely to have a prior full term delivery (59% vs 84%, OR 0.27 (0.07-0.95, p = .01)). The most frequent reason for lack of progesterone and CL screening was patient declining.Conclusion: Most women with prior sPTB received progesterone and CL screening. Those at highest risk for PTB based on obstetric history are more likely to utilize recommended interventions.

Prior Uterine Evacuation and the Risk of Short Cervical Length: A Retrospective Cohort Study.

OBJECTIVES: To determine whether a prior uterine evacuation procedure is associated with an increased risk of short cervical length (≤20 mm) in women without prior spontaneous preterm birth. METHODS: This work was a retrospective cohort study from January 2012 to December 2014 of singletons without prior spontaneous preterm birth with cervical length screening between 18 weeks and 23 weeks 6 days. Women with a prior miscarriage/abortion were excluded if management (medical, surgical, or expectant) was not specified. Prior uterine evacuation was defined as dilation and curettage or dilation and evacuation of a spontaneous or induced abortion. The primary outcome was the risk of short cervical length (≤20 mm) among women with and without 1 of more prior uterine evacuations at any gestational age, assessed by the odds ratio and adjusted odds ratio for confounders. RESULTS: Of 2672 women included, 714 (27%) had at least 1 prior uterine evacuation. The overall incidence of short cervical length in the cohort was 1% (n = 27). Women with at least 1 prior uterine evacuation were more likely to be African American (64% versus 41%; P < .001), smoke (14% versus 8%; P < .001), have a higher body mass index (mean ± SD, 28.1 ± 7.1 versus 26.8 ± 7.1 kg/m2 ; P < .001), and have had prior full-term delivery (60% versus 41%; P < .001). Women with at least 1 prior uterine evacuation had a significantly higher incidence of short cervical length (2% versus 0.7%; P = .003; odds ratio, 2.99 [95% confidence interval, 1.40-6.40]). After adjustment for confounders, prior uterine evacuation remained a source of increased risk of short cervical length (adjusted odds ratio, 2.63 [95% confidence interval, 1.19-5.80]). CONCLUSIONS: Although the overall incidence of short cervical length is low (1%-2%), women with at least 1 prior uterine evacuation have at least a 2-fold increased risk of a short second-trimester cervical length compared to women without a prior uterine evacuation.

Structure of Vps75 and implications for histone chaperone function.

The vacuolar protein sorting 75 (Vps75) histone chaperone participates in chromatin assembly and disassembly at both active and inactive genes through the preferential binding to histone H3-H4. Vps75 is also one of two histone chaperones, along with antisilencing factor 1, that promotes histone H3-Lys-56 acetylation by the regulation of Ty1 transposition protein 109 (Rtt109) histone acetyltransferase. Here, we report the x-ray crystal structure of Vps75 and carry out biochemical studies to characterize its interaction with Rtt109. We find that the Vps75 structure forms a homodimeric "headphone" architecture that includes an extended helical dimerization domain and earmuff domains at opposite ends and sides of the dimerization domain. Despite the similar overall architecture with the yeast nucleosome assembly protein 1 and human SET/TAF-1beta/INHAT histone chaperones, Vps75 shows several unique features including the relative disposition of the earmuff domains to the dimerization domain, characteristics of the earmuff domains, and a pronounced cleft at the center of the Vps75 dimer. These differences appear to correlate with the unique function of Vps75 to interact with Rtt109 for histone acetylation. Our biochemical studies reveal that two surfaces on the earmuff domain of Vps75 participate in Rtt109 interaction with a stoichiometry of 2:1, thus leaving the pronounced central cleft of the Vps75 dimer largely accessible for histone binding. Taken together, our data provide a structural framework for understanding how Vps75 mediates both nucleosome assembly and histone acetylation by Rtt109.

Fungal Rtt109 histone acetyltransferase is an unexpected structural homolog of metazoan p300/CBP.

Rtt109, also known as KAT11, is a recently characterized fungal-specific histone acetyltransferase (HAT) that modifies histone H3 lysine 56 (H3K56) to promote genome stability. Rtt109 does not show sequence conservation with other known HATs and depends on association with either of two histone chaperones, Asf1 or Vps75, for HAT activity. Here we report the X-ray crystal structure of an Rtt109-acetyl coenzyme A complex and carry out structure-based mutagenesis, combined with in vitro biochemical studies of the Rtt109-Vps75 complex and studies of Rtt109 function in vivo. The Rtt109 structure reveals noteworthy homology to the metazoan p300/CBP HAT domain but exhibits functional divergence, including atypical catalytic properties and mode of cofactor regulation. The structure reveals a buried autoacetylated lysine residue that we show is also acetylated in the Rtt109 protein purified from yeast cells. Implications for understanding histone substrate and chaperone binding by Rtt109 are discussed.

Oxidation and haem loss kinetics of poly(ethylene glycol)-conjugated haemoglobin (MP4): dissociation between in vitro and in vivo oxidation rates.

Haemoglobin-based oxygen carriers can undergo oxidation of ferrous haemoglobin into a non-functional ferric form with enhanced rates of haem loss. A recently developed human haemoglobin conjugated to maleimide-activated poly(ethylene glycol), termed MP4, has unique physicochemical properties (increased molecular radius, high oxygen affinity and low cooperativity) and lacks the typical hypertensive response observed with most cell-free haemoglobin solutions. The rate of in vitro MP4 autoxidation is higher compared with the rate for unmodified SFHb (stroma-free haemoglobin), both at room temperature (20-22 degrees C) and at 37 degrees C (P<0.001). This appears to be attributable to residual catalase activity in SFHb but not MP4. In contrast, MP4 and SFHb showed the same susceptibility to oxidation by reactive oxygen species generated by a xanthine-xanthine oxidase system. Once fully oxidized to methaemoglobin, the rate of in vitro haem loss was five times higher in MP4 compared with SFHb in the fast phase, which we assign to the beta subunits, whereas the slow phase (i.e. haem loss from alpha chains) showed similar rates for the two haemoglobins. Formation of MP4 methaemoglobin in vivo following transfusion in rats and humans was slower than predicted by its first-order in vitro autoxidation rate, and there was no appreciable accumulation of MP4 methaemoglobin in plasma before disappearing from the circulation. These results show that MP4 oxidation and haem loss characteristics observed in vitro provide information regarding the effect of poly(ethylene glycol) conjugation on the stability of the haemoglobin molecule, but do not correspond to the oxidation behaviour of MP4 in vivo.