Objective: To examine dose-response relationships between the cumulative number of months women lactated and postmenopausal risk factors for cardiovascular disease. Methods: We examined data from 139,681 postmenopausal women (median age 63 years) who reported at least 1 live birth upon enrolling in the Women's Health Initiative (WHI) observational study or controlled trials. Multivariable models were used to control for sociodemographic (age, parity, race, education, income, age at menopause), lifestyle, and family history variables when examining the impact of duration of lactation on risk factors for cardiovascular disease, including obesity (body mass index(BMI) at or above 30), hypertension, self-reported diabetes, hyperlipidemia, prevalent and incident cardiovascular disease. Results: Dose-response relationships were observed; in fully-adjusted models, women who reported a lifetime history of more than 12 months of lactation were less likely to have hypertension (OR=0.88, p<0.001), diabetes (OR= 0.80, p<0.001), hyperlipidemia (OR=0.81, p<0.001) or cardiovascular disease (OR= 0.91, p=0.008) than women who never breastfed, but they were not less likely to be obese. In models adjusted for all above variables and BMI, similar relationships were seen. Over an average of 7.9 years of postmenopausal participation in the WHI, women with a single live birth who breastfed for 7-12 months were significantly less likely to develop cardiovascular disease (HR 0.72 (0.53 to 0.97)) than women who never breastfed.
Rheumatoid Arthritis (RA) is a chronic autoimmune disease associated with inflammation and joint remodeling. Adenosine deaminase (ADA), a risk factor in RA, degrades adenosine, an anti-inflammatory molecule, resulting in an inflammatory bias. We present an integrative analysis of clinical data, cytokines, serum metabolomics in RA patients and mechanistic studies on ADA-mediated effects on in vitro cell culture models. ADA activity differentiated patients into low and high ADA sets. The levels of the cytokines TNFα, IFNγ, IL-10, TGFβ and sRANKL were elevated in RA and more pronounced in high ADA sets. Serum metabolomic analysis shows altered metabolic pathways in RA which were distinct between low and high ADA sets. Comparative analysis with previous studies shows similar pathways are modulated by DMARDs and biologics. Random forest analysis distinguished RA from control by methyl-histidine and hydroxyisocaproic acid, while hexose-phosphate and fructose-6-phosphate distinguished high ADA from low ADA. The deregulated metabolic pathways of High ADA datasets significantly overlapped with high ADA expressing PBMCs GEO transcriptomics dataset. ADA induced the death of chondrocytes, synoviocyte proliferation, both inflammation in macrophages and their differentiation into osteoclasts and impaired differentiation of mesenchymal stem cells to osteoblasts and mineralization. PBMCs expressing elevated ADA had increased expression of cytokines and P2 receptors compared to synovial macrophages which has low expression of ADA. Our data demonstrates increased cytokine levels and distinct metabolic signatures of RA based on the ADA activity, suggests an important role for ADA in the pathophysiology of RA joints and as a potential marker and therapeutic target in RA patients.
A 68-year-old man, a known case of hypertension, coronary artery disease and old cardiovascular accident with right-sided hemiplegia, came with the chief complaints of a large cauliflower like growth with pus discharge on the left heel since 15 years. The patient had sustained a penetrating injury by a thorn on the left heel region few days before the lesion appeared. Dermatological examination revealed a single verrucous lesion measuring 7 × 7 cm on the left heel region associated with discharge of foul smelling cheesy material. There was also a enlarged right inguinal lymph node which was non-tender, firm, measuring 2 cm in diameter with normal overlying skin. X-ray left ankle was done which showed some soft tissue swelling. A skin biopsy showed hyperkeratosis, acanthosis and parakeratosis. Elongated rete ridges with keratinocyte hyperplasia, forming a large mass pressing on the underlying dermis were seen. There was formation of multiple large keratin filled invaginations and crypts. No atypical cells were seen. Based on history, clinical examination and investigations, a diagnosis of epithelium cuniculatum type of verrucous squamous cell carcinoma was made. A wide excision with a flap cover was performed in consultation with the oncosurgeon and the excision sample was sent for histopathological re-examination, which confirmed the diagnosis of epithelioma cuniculatum.
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