Paediatric chronic pain prevalence in low- and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: Chronic pain is a leading cause of morbidity in children and adolescents globally, with a significant impact on quality of life. This is the first systematic review and meta-analysis on paediatric chronic pain in low- and middle-income countries (LMICs). METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched MEDLINE (via PubMed), Embase, CINAHL, PsycINFO, Web of Science, Cochrane Database of Systematic Reviews, and the WHO Global Index Medicus for all studies published prior to January 7, 2022. Articles published in all languages that included populations age 19 years and under living in LMICs were considered. Chronic pain was defined as persistent or recurrent pain that is present for ≥3 months, per the International Classification of Diseases (ICD-11) definition. Summary data were extracted from published reports and evaluated with mixed-effects regression analysis. PROSPERO Record ID: CRD42021227967. FINDINGS: Of the 2875 studies identified, 70 articles were reviewed, with 27 studies representing 20 LMICs eligible for analysis. The average prevalence for each pain type reported with 95% confidence interval is as follows: general/multi-site/any 20% (16-25), musculoskeletal (MSK) pain 9% (7-13), abdominal pain 7% (5-10), headache 4% (2-10), and fibromyalgia per American College of Rheumatology or Yunus and Masi criteria 3% (1-10). Overall, a pooled mean of 8% chronic pain was estimated across all studies. A significantly high level of heterogeneity was found across all studies (I2  >90%). Chronic headache (OR=1·65, 95% CI 1·39-1·96), abdominal pain (OR=1·36, 95% CI 1·22-1·51), and generalized/multi-site pain (OR=1·54, 95% CI 1·31-1·81) were significantly more prevalent in females than males. INTERPRETATION: The characterization of paediatric chronic pain in low- and middle-income countries suffers from a paucity of data and significant heterogeneity in the assessment methods. Understanding the global burden of chronic pain in this group should be prioritized. FUNDING: None.

The Mechanism of Decreased IgG/IgE-Binding of Ovalbumin by Preheating Treatment Combined with Glycation Identified by Liquid Chromatography and High-Resolution Mass Spectrometry.

Ovalbumin is one of the most important sensitizing ingredients in allergens of egg albumin, which restricts the application of egg in the field of food processing. Previous research has indicated that glycation could cause the protein to partially expand, which may bring about the destruction of the structural IgG and IgE epitopes and induce the decline of the IgG- and IgE-binding ability of ovalbumin. In this research, the effect of a preheating treatment integrated with glycation on the IgG- and IgE-binding capability and the conformation changes of ovalbumin was studied by detecting the glycated sites and the values of degree of substitution per peptide (DSP) by liquid chromatography and high-resolution mass spectrometry (LC-HRMS). Interestingly, we found that a glycation site (K227) attached by two ribose molecules was detected in glycated ovalbumin with preheating treatment. In addition, a new glycation site (K323) appeared in G-60. The results displayed that preheating treament could strengthen the changes in the secondary and tertiary structure of ovalbumin by enhancing glycation and further reduce the IgG/IgE-binding ability by integrating with glycation because of the cover of IgG and IgE epitopes. Therefore, preheating treatment integrated with glycation may offer a way for ovalbumin to reduce sensitization.

LC-Orbitrap MS analysis of the glycation modification effects of ovalbumin during freeze-drying with three reducing sugar additives.

In general, the reducing sugars were extensively utilized as additives to prevent denaturation and inactivation during the freeze-drying process. However, different additives have unequal protective effects on the protein conformation. To evaluate the mechanism of protection the protein structure using different additives in the freeze-drying process, the glycated sites and degree of substitution per peptide (DSP) of each site were investigated by LC-Orbitrap MS. We found that the ovalbumin that was supplemented with ribose and then lyophilized (R-oval) have the highest extent of glycation modification. K227 was the most reactive glycated site in R-Oval, with a DSP of 0.83. The ovalbumin that was supplemented with lactose and then lyophilized (L-Oval) have the lowest degree of glycation, and K227 did not undergo the glycation reaction. It was hypothesized that the order impact of different additives on protection of the protein conformation were lactose > galactose > ribose during the freeze-drying process.

Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.

The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease.

Risk of second gonadal cancers in women and children with germ cell tumors.

BACKGROUND: Men with testicular cancer have an increased risk of developing cancer in the contralateral testis, but the risks of second gonadal cancers (SGCs) in women and children treated for germ cell tumors (GCTs) have not previously been quantified. METHODS: The incidence of SGCs was ascertained in patients who had survived for at least 1 year after GCT diagnosis using data from the Surveillance, Epidemiology, and End Results SEER 9 registries (1980-2012). Relative risks of SGCs were estimated separately for boys, women, and girls compared with men based on Poisson regression analysis. RESULTS: The cohort included 21,546 individuals (1116 boys, 827 women, 622 girls, and 18,981 men). A total of 25 SGCs were identified in boys, 1 in women, and 2 in girls compared with 254 in men. The risk of SGC in postpubertal boys (aged ≥10 years) was comparable to that of adult men (boys: standardized incidence ratio, 15.90; 95% confidence interval, 10.29-23.47; men: standardized incidence ratio, 10.88; 95% confidence interval, 9.58-12.30). However, no SGCs were observed in boys who were diagnosed with a testicular GCT before age 10 years (N = 179). An elevated risk of SGC was also not observed for women or girls. CONCLUSIONS: The apparent lack of an SGC in prepubertal boys suggests that susceptibility is either age-dependent and/or histology-dependent. The sex differences in the risk of SGC suggest differences in the etiology of ovarian versus testicular GCT. The finding that the risk of SGCs in postpubertal boys is similar to that observed in men indicates that long-term follow-up for SGC is warranted in postpubertal boys. Cancer 2016;122:2076-82. © 2016 American Cancer Society.