Background Human milk is thought to reduce infant atopy risk. The biologic mechanism for this protective effect is not fully understood. Objectives We tested the hypothesis that infant consumption of four microRNAs (miR-146b-5p, miR-148b-3p, miR-21–5p, and miR-375–3p) in human milk would be associated with reduced atopy risk. Design The Breast Milk IMPACT Study involved a cohort of mother-infant dyads who planned to breastfeed beyond four months. Infant consumption of the four human milk microRNAs in the first six months was calculated as the product of milk microRNA concentration and the number of human milk feeds, across three lactation stages: early milk (0–4 weeks), transitional milk (4–16 weeks), and mature milk (16–24 weeks). The primary outcome was infant atopy in the first year, defined as atopic dermatitis, food allergies, or wheezing. The final analysis included 432 human milk samples and 7,824 weeks of longitudinal health data from 163 dyads. Results Seventy-three infants developed atopy. Forty-one were diagnosed with atopic dermatitis (25%), 33 developed food allergy (20%), and 10 had wheezing (6%). Eleven developed > 1 condition (7%). Infants who did not develop atopy consumed higher levels of miR-375–3p (d = 0.18, P = 0.022, adj P = 0.044) and miR-148b-3p (d = 0.23, P = 0.007, adj P = 0.028). Consumption of miR-375–3p (X2 = 5.7, P = 0.017, OR = 0.92, 95% CI = 0.86, 0.99) was associated with reduced atopy risk. Levels of miR-375–3p increased throughout lactation (r = 0.46, F = 132.3, P = 8.4 × 10−34) and were inversely associated with maternal body mass (r = -0.11, t = -2.1, P = 0.032). Conclusions This study provides evidence that infant consumption of miR-375–3p may reduce atopy risk.
Atopic dermatitis (AD) is a chronic inflammatory skin condition impacting approximately 15% of children worldwide. 1 The incidence of AD has increased over the last 50 years, with approximately 60% of individuals developing symptoms in the first 12 months of life. 2 Predisposition to AD may be influenced by medical and demographic traits, environmental factors, and underlying immunologic phenotypes.Epidermal barrier breakdown is a key driver of AD. 3 Causes of epidermal breakdown are multifactorial, resulting from genetic,
The spine is one of the most common sites to which metastatic cancer is likely to spread and is one of the leading causes of morbidity and mortality in cancer patients. While no medical treatments have been definitively shown to extend the life expectancy of patients with spinal metastasis, interventional options may be the only viable option in improving outcomes. Currently, two main options exist: surgical resection and radiotherapy, with radiotherapy being the primary treatment modality. In this review, we discuss the research comparing the efficacy and outcomes of radiotherapy and surgical resection in treating spinal metastasis. We conclude that while radiosurgery will continue to remain a major treatment modality, surgical intervention has proven to have equal to or superior outcomes at improving function, symptoms, and life expectancy for patients with metastatic spinal disease and should be considered a primary modality in an expanding subset of patients.
Mycoplasma pneumoniae primarily causes atypical pneumonia in children and young adults. 7%-8% of patients with M. pneumoniae infections may experience extra-pulmonary manifestations, including M. pneumoniae-associated Stevens-Johnson Syndrome (SJS), also known as atypical SJS. In recent literature, there have been a few reports of isolated mucositis in children with M. pneumoniae infections. Due to significant overlap with several diseases, including autoimmune disease and infections, atypical mucositis associated with M. pneumoniae is often a diagnostic challenge. In addition, due to limited cases of M. pneumoniae-associated SJS, there is no established standardized treatment guideline that has been shown to reduce hospitalization duration and/or disease progression associated with M. pneumoniae-associated SJS. We report a case of isolated mucositis in the absence of cutaneous involvement in a 10-year-old patient with an acute M. pneumoniae infection. Examination revealed erythematous ulcerations of his lips and pharynx with patchy exudates and bilateral submandibular lymphadenopathy. Laboratory investigation revealed a negative respiratory polymerase chain reaction (PCR) panel, which included M. pneumoniae. Further testing revealed a positive M. pneumoniae immunoglobulin M (IgM) titer on enzyme immunoassay. The diagnosis of atypical SJS was made secondary to M. pneumoniae. Treatment was initiated with systemic steroids and oral antibiotics. Limitations in diagnostic testing for M. pneumoniae in combination with non-specific clinical presentation make for challenges in confirming this pattern of SJS due to a primary M. pneumoniae infection. In this case, serological testing confirmed our suspected diagnosis, which guided treatment and helped reveal some of the difficulties in diagnosing and managing M. pneumoniae-associated SJS.
Food reactions (FR) are multifactorial and impacted by medical, demographic, environmental, and immunologic factors. We hypothesized that multi-omic analyses of host-microbial factors in saliva would enhance our understanding of FR development. This longitudinal cohort study included 164 infants followed from birth through two years. The infants were identified as FR (n = 34) or non-FR (n = 130) using the Infant Feeding Practice II survey and medical record confirmation. Saliva was collected at six months for the multi-omic assessment of cytokines, mRNAs, microRNAs, and the microbiome/virome. The levels of one miRNA (miR-203b-3p, adj. p = 0.043, V = 2913) and one viral phage (Proteus virus PM135, adj. p = 0.027, V = 2955) were lower among infants that developed FRs. The levels of one bacterial phylum (Cyanobacteria, adj. p = 0.048, V = 1515) were higher among infants that developed FR. Logistical regression models revealed that the addition of multi-omic features (miR-203b-3p, Cyanobacteria, and Proteus virus PM135) improved predictiveness for future FRs in infants (p = 0.005, X2 = 12.9), predicting FRs with 72% accuracy (AUC = 0.81, sensitivity = 72%, specificity = 72%). The multi-omic analysis of saliva may enhance the accurate identification of infants at risk of FRs and provide insights into the host/microbiome interactions that predispose certain infants to FRs.
Susceptibility to upper respiratory infections (URIs) may be influenced by host, microbial, and environmental factors. We hypothesized that multi-omic analyses of molecular factors in infant saliva would identify complex host-environment interactions associated with URI frequency. A cohort study involving 146 infants was used to assess URI frequency in the first year of life. Saliva was collected at 6 months for high-throughput multi-omic measurement of cytokines, microRNAs, transcripts, and microbial RNA. Regression analysis identified environmental (daycare attendance, atmospheric pollution, breastfeeding duration), microbial (Verrucomicrobia, Streptococcus phage), and host factors (miR-22-5p) associated with URI frequency (p < 0.05). These results provide pathophysiologic clues about molecular factors that influence URI susceptibility. Validation of these findings in a larger cohort could one day yield novel approaches to detecting and managing URI susceptibility in infants.
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