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In this issue, Kresovich and colleagues [1] have published a hallmark paper in Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology. The authors created a new methylation-based breast cancer risk score (mBCRS) based on blood DNA methylation that could be as powerful as the current best polygenic risk score (PRS) in differentiating women of the same age in terms of their breast cancer risk.Epigenetic alterations are a hallmark of aging and age-related diseases. Computational models using DNA methylation data can create "epigenetic clocks" which are proposed to reflect "biological" aging. Thus, it is important to understand the relationship between predictive clock sites and aging biology. To do this, we examined over 450,000 methylation sites from 9,699 samples. We found ~20% of the measured genomic cytosines can be used to make many different epigenetic clocks whose age prediction performance surpasses that of telomere length. Of these predictive sites, the average methylation change over a lifetime was small (~1.5%) and these sites were under-represented in canonical regions of epigenetic regulation. There was only a weak association between "accelerated" epigenetic aging and disease. We also compare tissue-specific and pan-tissue clock performance. This is critical to applying clocks both to new sample sets in basic research, as well as understanding if clinically available tissues will be feasible samples to evaluate "epigenetic aging" in unavailable tissues (e.g., brain). Despite the reproducible and accurate age predictions from DNA methylation data, these findings suggest they may have limited utility as currently designed in understanding the molecular biology of aging and may not be suitable as surrogate endpoints in studies of anti-aging interventions. Purpose-built clocks for specific tissues age ranges or phenotypes may perform better for their specific purpose. However, if purpose-built clocks are necessary for meaningful predictions, then the utility of clocks and their application in the field needs to be considered in that context.

Delays in seeking healthcare for dengue are associated with poor health outcomes. Despite this, the factors influencing such delays remain unclear, rendering interventions to improve healthcare seeking for dengue ineffective. This systematic review aimed to synthesise the factors influencing healthcare seeking of patients with dengue and form a comprehensive framework.

This review included both qualitative and quantitative studies. Studies were obtained by searching five databases, contacting field experts and performing backward reference searches. The best-fit meta-synthesis approach was used during data synthesis, where extracted data were fitted into the social-ecological model. Sub-analyses were conducted to identify the commonly reported factors and their level of statistical significance.

Twenty studies were selected for meta-synthesis. Eighteen factors influencing healthcare seeking in dengue were identified and categorised under four domains individual (11 factors), interpersonal (one factor), o improve dengue healthcare-seeking behaviour.In the area of illicit drugs, forensic case data has proven effective at detecting links between seizures and providing greater insights into illicit drug markets. This research explored the application of mathematical and statistical techniques to several chemical profiles of Australian methylamphetamine seizures. The main aim was to create and deliver a method that would expand the use of illicit drug profiling for strategic intelligence purposes, contributing to the fight against illicit drug trafficking. The use of comparison metrics and clustering analysis to determine links between existing illicit drug specimens and subsequent new specimens was evaluated and automated. Relational, temporal and spatial analyses were subsequently used to gain an insight into illicit drug markets. Relational analysis identified clusters of seizures central to the network. Temporal analysis then provided insights into the behaviour of distribution markets, specifically the emergence and extinction of certain clusters of seizures over time. Spatial analysis aided the understanding of the inter-jurisdictional nature of illicit drug markets. These analyses allowed for the generation of strategic intelligence relating to when and where the Australian methylamphetamine illicit drug market was the most active. Additionally, the strategic level trends identified clusters of seizures which were worth investigating further. These clusters were explored through a case study, which exploited additional chemical profiling data to provide drug market knowledge at an operational level. In turn, the intelligence produced at various levels could allow relevant law enforcement agencies to take necessary measures in disrupting markets.Programmed cell death protein 1 (PD-1)/its ligand PD-L1, concomitant with T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3)/its ligand galectin 9 (Gal-9) and the forkhead box protein P3 (Foxp3) might be involved in tolerance after liver transplantation (LT). Liver biopsies from 38 tolerant, 19 nontolerant (including 16 samples that triggered reintroduction of immunosuppression (IS) and 19 samples after IS reintroduction) and 38 control LT patients were studied. The expressions of PD-1, PD-L1, Gal-9, and Foxp3 were determined by immunohistochemical and immunofluorescence (IF) staining. The success period of IS withdrawal was calculated using Kaplan-Meier analysis. Tolerant and control patients exhibited higher PD-L1, higher Gal-9, and higher Foxp3 levels than nontolerant patients at the moment of triggering IS reintroduction. High expression of PD-L1 and Gal-9 was associated with prolonged success of tolerance (83.3% vs. 36.7%, p less then 0.01; 73.1% vs. 42.9%, p=0.03). A strong correlation between PD-L1 and Gal-9 expression levels was detected (Spearman r=0.73, p= less then 0.0001) and IF demonstrated colocalization of PD-L1 and Gal-9 in the cytoplasm of hepatocytes. FB23-2 In conclusion, the present study demonstrated that an increased expression of PD-L1 and Gal-9 was associated with sustained tolerance after IS withdrawal in pediatric liver transplantation.

Serum lactate dehydrogenase has been extensively studied in hypertensive disorders of pregnancy. However, to date, its clinical usefulness in the field remains unknown. The present meta-analysis has been designed to evaluate differences in serum LDH values among patients with hypertensive disorders of pregnancy and to help determine its diagnostic accuracy as well its predictive accuracy in determining adverse pregnancy outcomes.

We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases from their inception till 18 March 2021. Observational studies that assessed differences in serum LDH levels among women with hypertensive disorders of pregnancy and healthy controls were included. Meta-analysis was performed using Rstudio. Pooled mean differences (MD) were calculated with the Hartung-Knapp-Sidik-Jonkman. Meta-regression analyses, publication bias assessment and Trim and Fill function were also performed. The adequacy of the clinical practice; hence, research should expand in this direction to evaluate its clinical utility.

Despite the extensive research in the field of hypertensive disorders of pregnancy, there is still lack of evidence concerning the diagnostic performance of serum LDH in clinical practice; hence, research should expand in this direction to evaluate its clinical utility.Since the outbreak of African swine fever (ASF) in Shengyang, it has continued spreading in China. In the early stage of the epidemic, multi-point and concentrated outbreaks were mainly in the swill feeding areas. In this paper, we developed compartmental models to investigate the transmission of ASF in several raising units including Guquan, Jinba and Liancheng. Using the data collected from these three infected premises, we calibrated the models to estimate that the average incubation period was between 8 and 11 days, the onset period was about 2-3 days and the basic reproductive number was about 4.83-11.90. We also estimated the infection on the day before culling to be 45.24% (Guquan), 89.20% (Jinba) and 16.35% (Liancheng), respectively. The infection rate of Guquan could reach about 74.8% if culling were postponed by 2 days. We found that the infection was significantly higher than the morbidities (22.11% (Guquan), 49.35% (Jinba) and 12.94% (Liancheng)) calculated by actual statistical data. Besides, we simulated and compared the control effect of stopping transport, disinfecting, stopping swill and culling. Our findings suggest that any single measure was not enough to prevent the spread of ASF on a regional level but the combined measures is the key. Under the current situation, fully culling was recognized as most effective in controlling the epidemic, despite the culling of uninfected pigs.

Children with dyskinetic cerebral palsy (CP) are often severely affected and effective treatment is difficult, due to different underlying disease mechanisms. Comprehensive systematic movement disorder evaluations were carried out on patients with this disorder.

Patients born from1995-2007 were identified from the Danish Cerebral Palsy Register and referrals to the neuropaediatric centre, Rigshospitalet, Copenhagen. They were classified by gross motor function, manual functional ability, communication ability, dystonia and spasticity. Electromyography was carried out on the upper and lower limbs. Magnetic resonance imaging scans were revised and aetiological searches for underlying genetic disorders were performed.

We investigated 25 patients with dyskinetic CP at a mean age of 11.7 years. Dystonia, spasticity and rigidity were found in the upper limbs of 21, four and six children, respectively, and in the lower limbs of 18, 18 and three children. The mean total Burke Fahn Marsden score for dystonia was 45.02 and the mean Disability Impairment Scale level was 38% for dystonia and 13% for choreoathetosis. Sustained electromyography activity was observed in 20/25 children. Stretching increased electromyography activity more in children with spasticity. There were 10 reclassifications.

The children had heterogenic characteristics and 40% were reclassified after systematic movement disorder evaluation.

The children had heterogenic characteristics and 40% were reclassified after systematic movement disorder evaluation.

Alexithymia is a multifaceted personality construct described as "a lack of words to express emotions" that includes difficulty identifying feelings, difficulty describing feelings and a concrete, externally oriented cognitive style. Among patients with food allergy (FA) alexithymia has been found higher than in general population and associated with dysfunctional coping strategies. Childhood traumatic experiences and/or dysfunctional parent-child relationship can contribute to alexithymia. The study aimed to explore possible associations between child alexithymia and mother alexithymia and anxiety, as well as previous anaphylaxis.

Sixty-five mother-child pairs have been recruited. Children had a medical diagnosis of FA. The Toronto Alexithymia Scale-20 was used to assess alexithymia in participants. The State-Trait Anxiety Inventory was used to assess trait anxiety in mothers. Statistical analysis was performed to investigate the influence of variables sex, previous anaphylaxis, and adrenaline auto-injector prescription on child and mother's alexithymia and to explore possible association between maternal and child alexithymia.