Τετάρτη 1 Φεβρουαρίου 2023

Emerging Omicron subvariants evade neutralizing immunity elicited by vaccine or BA.1/BA.2 infection

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Abstract

The newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2.75 and BA.2.76 subvariants contained 35 and 29 additional mutations in its spike (S) protein compared to the reference SARS-CoV-2 genome, respectively. Here, we measured the evasion degree of the BA.1, BA.2, BA.4, BA.5, BA.2.75, and BA.2.76 subvariants from neutralizing immunity in people previously infected with the Omicron BA.1 and BA.2, determined the effect of vaccination on immune evasion, and compared the titers of neutralizing antibodies in serums between acute infection and convalescence. Results showed that the neutralization effect of serums from patients with different vaccination statuses and BA.1/BA.2 breakthrough infection decreased with the Omicron evolution from BA.1 to BA.2, BA.4, BA.5, BA.2.75, and BA.2.76. This study also indicated that the existing vaccines could no longer provide effective protection, especially for the emerging BA.2.75 and BA.2.76 subvariants. Therefo re, vaccines against emerging epidemic strains should be designed specifically. In the future, we can not only focus on the current strains, but also predict and design new vaccines against potential mutant strains. At the same time, we can combine the virus strains' infection characteristics to develop protective measures for virus colonization areas, such as nasal protection spray. Besides, further studies on the Y248N mutation of BA.2.76 subvariant were also necessary to explore its contribution to the enhanced immune evasion ability.

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Clostridioides difficile near patient testing versus centralized testing: A pragmatic cluster randomized cross-over trial

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Abstract
Background
Management of suspected C. difficile infections (CDI) in the hospital setting typically results in patient isolation, laboratory testing, infection control, and presumptive treatment. We investigated whether implementation of rapid near patient testing (NPT) reduced patient isolation time, hospital length of stay, antibiotic usage, and cost.
Methods
A two-period pragmatic cluster randomized crossover trial was conducted. 39 wards were randomized into two study arms. The primary outcome measure was effect of NPT on patient isolation time using a mixed effect generalized linear regression model. Secondary outcomes examined included hospital length of stay and antibiotic therapy based on a negative binomial regression model. Natural experiment (NE), intention-to-treat (ITT), and per protocol (PP) analyses was conducted.
Results
During the entire study period, a total of 656 patients received NPT for CDI and 166 7 received SOC testing. For the primary outcome, a significant decrease of patient isolation time with NPT was observed (NE 9.4 hours [p<0.01], ITT 2.3 [p<0.05], PP 6.7[p<0.1]). A significant reduction in hospital length of stay was observed with NPT for short stay (NE 47.4% [p<0.01], ITT 18.4% [p<0.01] and ITT 34.2% [p<0.01]). Each additional hour delay for a negative result increased metronidazole use (24 DDD per 1000 patients, p<0.05) and non-CDI treating antibiotics by 70.13 mg (p<0.01). NPT testing was found to save USD25.48 per patient when including test cost and patient isolation.
Conclusions
The cluster randomized cross-over trial demonstrated that implementation of CDI NPT can contribute to significant reductions in isolation time, hospital length of stay, antibiotic usage, and health care cost.
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A lifestyle pattern characterized by high consumption of sweet and salty snacks, sugar sweetened beverages and sedentary time is associated with blood pressure in families at risk for type 2 diabetes mellitus in Europe. The Feel4Diabetes Study.

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Abstract

Objective

Individuals from families at high-risk for type 2 diabetes mellitus (T2DM) are also in high risk for hypertension and cardiovascular disease. Studies identifying lifestyle patterns combining dietary, physical activity or sedentary variables and examining their possible role to developing blood pressure (BP) are limited. This study aimed to examine the association of different lifestyle patterns (LPs) with BP levels in families at high risk for T2DM in Europe.

Research Methods & Procedures

1844 adults (31.6% males) at high-risk for T2DM across 6 European countries were included in this cross-sectional study using data from the baseline assessment of the Feel4Diabetes Study. BP measurements, dietary and physical activity assessments were conducted, and screen times was surveyed. Lifestyle patterns were revealed with Principal Component Analysis (PCA) of various data regarding diet, physical activity, screen time and smoking.

Results

3 LPs were identified, LP3 (high consumption of sweet & salty snacks, sugar sweetened soft drinks and juices and high amount of screen time) was positively associated with diastolic BP [B, 0.52 95%CI (0.05-0.99)] and existence of hypertension [OR,1.12 95%CI (1.00-1.25)]. Participants in the highest tertile of LP3 spent mean 3 hours of screen time, consumed 1.5 portions of sweet and/or salty snacks and 1 liter of soft drinks on a daily basis, were associated with 12% higher risk of hypertension.

Conclusion

Focusing on the combination of eating and lifestyle behaviors may more accurately identify, and therefore guide preventive measures tailored to the specific needs of high-risk populations.

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Effect of finish line location and saliva contamination on the accuracy of crown finish line scanning

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Abstract

Purpose

Intraoral scanners are used widely as an alternative to conventional impressions, but studies on the influence of finish line location and saliva contamination on scanning trueness are lacking. The purpose of this in vitro study was to evaluate the influence of finish line location and saliva contamination on the scanning trueness of crown finish lines.

Materials and Methods

Three ivorine teeth were prepared for all-ceramic crowns with finish lines placed equigingivally, 0.5 mm subgingivally, and 1.0 mm subgingivally. A single-cord technique was used for gingival retraction and a total of 180 intraoral scans were made using two intraoral scanners (Emerald; Planmeca USA Inc., Hoffman Estates, IL & Trios3; 3Shape A/S, Copenhagen, Denmark). The prepared teeth were separated from the dentoform and scanned using the same intraoral scanners to create reference scans. All scans were imported to the design software (Dental System 2019; 3Shape A/S, Copenhagen, Denmark). After marking the finish lines of prepared teeth, intraoral scans were aligned to the reference scans for comparisons. Vertical and horizontal marginal discrepancies were measured at 4 different measuring points (buccal, lingual, mesial, and distal) and analyzed. Two-way ANOVA and Tukey HSD tests were used for statistical analysis (α = 0.05).

Results

The average vertical and horizontal discrepancies from various groups ranged from -33μm to 440μm. For both intraoral scanners, subgingival finish line groups showed greater vertical and horizontal discrepancies compared with equigingival finish line groups. Saliva contamination significantly increased both vertical and horizontal discrepancies for all finish line locations. The discrepancy increases due to saliva contamination were greater for the subgingival groups.

Conclusions

Subgingival finish lines were not accurately captured using the intraoral scanners. The presence of saliva significantly reduced scanning trueness and this was amplified when the finish lines were located subgingivally.

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Short-term Air Pollution Levels and Blood Pressure in Older Women

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imageBackground: Evidence of associations between daily variation in air pollution and blood pressure (BP) is varied and few prior longitudinal studies adjusted for calendar time. Methods: We studied 143,658 postmenopausal women 50 to 79 years of age from the Women's Health Initiative (1993–2005). We estimated daily atmospheric particulate matter (PM) (in three size fractions: PM2.5, PM2.5-10, and PM10) and nitrogen dioxide (NO2) concentrations at participants' residential addresses using validated lognormal kriging models. We used linear mixed-effects models to estimate the association between air pollution concentrations and repeated measures of systolic and diastolic BP (SBP, DBP) adjusting for confounders and calendar time. Results: Short-term PM2.5 and NO2 were each positively associated with DBP {0.10 mmHg [95% confidence interval (CI): 0.04, 0.15]; 0.13 mmHg (95% CI: 0.09, 0.18), respectively} for interquartile range changes in lag 3-5 day PM2.5 and NO2. Short-term NO2 was negatively associated with SBP [−0.21 mmHg (95%CI: −0.30, −0.13)]. In two-pollutant models, the NO2–DBP association was slightly stronger, but for PM2.5 was attenuated to null, compared with single-pollutant models. Associations between short-term NO2 and DBP were more pronounced among those with higher body mass index, lower neighborhood socioeconomic position, and diabetes. When long-term (annual) and lag 3-5 day PM2.5 were in the same model, associations with long-term PM2.5 were stronger than for lag 3-5 day. Conclusions: We observed that short-term PM2.5 and NO2 levels were associated with increased DBP, although two-pollutant model results suggest NO2 was more likely responsible for observed associations. Long-term PM2.5 effects were larger than short-term.
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Τρίτη 31 Ιανουαρίου 2023

Detect and suppress future zoonotic‐derived outbreaks: A lesson from last two decades

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Abstract

COVID-19 pandemic has revealed how vulnerable and inexperienced we are when dealing with an unprecedented global infectious threat. Looking back on the last few decades, there has been a surge in zoonotic-derived viruses globally. Notably, these outbreaks emerged as harmless zoonotic diseases within a favorable environment, then spilled over to humans and widely spread to become outbreaks. Most of these are respiratory viruses (particularly Orthomyxoviridae Orthomyxoviridae or Coronaviridae Coronaviridae family), with high transmissibility and can be easily spread. Low- and middle-income countries, particularly those with tropical climates, provide ideal environments for the growth and evolution of these zoonotic viruses. Nevertheless, a lot of our advanced centers for infectious diseases are located in high-income countries (HIC) and focus on human pathogens only (e.g., influenza, RSV, adenovirus). We should critically think about reallocating health resources in th e near-term. It is an urge for a few surveillance centers aim to detect surges in cases of respiratory pathogens or any spikes in cases, and suppress the transmission chain from an early stage. In this article, we digest lessons learned from the previous spillover pandemics and suggest actionable tactics to deal with future pandemics properly.

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Genetic characteristics and treatment outcome in infants with KMT2A germline B‐cell precursor acute lymphoblastic leukemia: Results of MLL‐Baby protocol

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Abstract

The aim of this study was to present the diagnostic and outcome characteristics of infants with germline status of KMT2A gene (KMT2A-g) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treated consistently according to the MLL-Baby protocol, a moderate-intensity protocol. Of the 139 patients enrolled in the MLL-Baby study, 100 (71.9%) carried different types of rearranged KMT2A (KMT2A-r), while the remaining 39 infants (28.1%) had KMT2A-g. KMT2A-g patients were generally older (77% older than 6 months), less likely to have a very high white blood cell count (greater than 100 × 109/L), less likely to be central nervous system (CNS)-positive, and more likely to be CD10-positive. The 6-year event-free survival and overall survival rates for all 39 patients were 0.74 (standard error [SE] 0.07) and 0.80 (SE 0.07), respectively. Relapse was the most common adverse event (n = 5), with a cumulativ e incidence of relapse (CIR) of 0.13 (SE 0.06), while the incidence of a second malignancy (n = 1) and death in remission (n = 3) was 0.03 (SE 0.04) and 0.08 (SE 0.04), respectively. None of the initial parameters, including genetics and the presence of recently described fusions of NUTM1 and PAX5 genes, was able to distinguish patients with different outcomes. Only rapidity of response, measured as minimal residual disease (MRD) by flow cytometry, showed a statistically significant impact. Moderate-intensity therapy, as used in the MLL-Baby protocol in infants with KMT2A-g BCP-ALL, yields results comparable to other infant studies. Patients with a slow multicolor flow cytometry (MFC)-MRD response should be subjected to advanced therapies, such as targeted or immunotherapies.

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