Use of the Burden of Diabetes Mellitus Score for Cardiovascular Disease Risk Assessment.

Uncontrolled type II diabetes mellitus (DM) using single point hemoglobin A1c levels has been associated with poor cardiovascular outcomes. However, methods to quantify the effect of uncontrolled DM over time have been inconsistent. To quantify hyperglycemia over time and assess its cardiovascular effects we developed and tested a DM burden score which accounts for time in years prior to DM diagnosis, diagnostic HbA1c, and aggregate HbA1c levels thereafter. A retrospective cohort study was performed with patients (n = 188) from a single academic center with type II DM and no prior cardiac disease history. Patient scores were calculated from diagnosis until the year 2015 and were grouped into low (<5.3%; n = 55), moderate (5.3% to 5.5%; n = 80), and high (>5.5%; n = 53) DM burden score cohorts. At 48 months, the cohort with high DM burden scores correlated with significantly worse major adverse cardiovascular events (hazard ratio [HR] 3.07, p = 0.012), myocardial infarction (HR 12.78, p = 0.015), coronary revascularization (HR 4.53, p = 0.019), cardiovascular hospitalizations (HR 4.20, p = 0.005), and all-cause hospitalizations (HR 2.57, p = 0.01). Cardiovascular and all-cause mortality showed significant difference between groups in log-rank testing. Also, a multivariate regression model showed DM burden score (p = 0.045) to be an independent predictor of major adverse cardiovascular events (HR 9.38, p = 0.045). In conclusion, this study provides evidence that DM control over time impacts cardiovascular outcomes.

Breast Cancer Development in a Transgender Male Receiving Testosterone Therapy.

CONTEXT: To describe a case of invasive ductal carcinoma of the breast in a transgender male receiving testosterone therapy for gender-affirming treatment. CASE DESCRIPTION: A 28-year-old transgender male receiving intramuscular testosterone was found to have a breast mass on ultrasound after self-exam revealed a palpable breast lump. Ultrasound-guided breast biopsy revealed estrogen receptor/progesterone receptor (ER/PR) negative, human epidermal growth factor receptor-2 (HER-2) positive, invasive ductal carcinoma of the left breast. He underwent neoadjuvant and adjuvant chemotherapy along with bilateral mastectomy. At patient request, his testosterone injections were permanently discontinued. CONCLUSION: Fewer than 20 cases of breast cancer in transgender male patients have been reported in medical literature. While studies have shown increased risk of breast cancer in postmenopausal women with higher testosterone levels, data regarding premenopausal women is conflicting and little is known about breast cancer risk in transgender individuals receiving gender-affirming hormone therapy (GAHT), with inconclusive results regarding correlation between testosterone therapy and breast cancer. More research is required to evaluate whether a possible increased risk of breast cancer exists for transgender men receiving gender-affirming therapy.

Ascorbic acid deficiency in arabidopsis induces constitutive priming that is dependent on hydrogen peroxide, salicylic acid, and the NPR1 gene.

The ascorbic acid (AA)-deficient Arabidopsis thaliana vtc1-1 mutant exhibits increased resistance to the virulent bacterial pathogen Pseudomonas syringae. This response correlates with heightened levels of salicylic acid (SA), which induces antimicrobial pathogenesis-related (PR) proteins. To determine if SA-mediated, enhanced disease resistance is a general phenomenon of AA deficiency, to elucidate the signal that stimulates SA synthesis, and to identify the biosynthetic pathway through which SA accumulates, we studied the four AA-deficient vtc1-1, vtc2-1, vtc3-1, and vtc4-1 mutants. We also studied double mutants defective in the AA-biosynthetic gene VTC1 and the SA signaling pathway genes PAD4, EDS5, and NPR1, respectively. All vtc mutants were more resistant to P. syringae than the wild type. With the exception of vtc4-1, this correlated with constitutively upregulated H(2)O(2), SA, and messenger RNA levels of PR genes. Double mutants exhibited decreased SA levels and enhanced susceptibility to P. syringae compared with the wild type, suggesting that vtc1-1 requires functional PAD4, EDS5, and NPR1 for SA biosynthesis and pathogen resistance. We suggest that AA deficiency causes constitutive priming through a buildup of H(2)O(2) that stimulates SA accumulation, conferring enhanced disease resistance in vtc1-1, vtc2-1, and vtc3-1, whereas vtc4-1 might be sensitized to H(2)O(2) and SA production after infection.