Automated Assessment of Breast Positioning Quality in Screening Mammography.

Screening mammography is a widely used approach for early breast cancer detection, effectively increasing the survival rate of affected patients. According to the Food and Drug Administration's Mammography Quality Standards Act and Program statistics, approximately 39 million mammography procedures are performed in the United States each year. Therefore, breast cancer screening is among the most common radiological tasks. Interpretation of screening mammograms by a specialist radiologist includes primarily the review of breast positioning quality, which is a key factor affecting the sensitivity of mammography and thus the diagnostic performance. Each mammogram with inadequate positioning may lead to a missed cancer or, in case of false positive signal interpretation, to follow-up activities, increased emotional burden and potential over-therapy and must be repeated, requiring the return of the patient. In this study, we have developed deep convolutional neuronal networks to differentiate mammograms with inadequate breast positioning from the adequate ones. The aim of the proposed automated positioning quality evaluation is to assist radiology technologists in detecting poorly positioned mammograms during patient visits, improve mammography performance, and decrease the recall rate. The implemented models have achieved 96.5% accuracy in cranio-caudal view classification and 93.3% accuracy in mediolateral oblique view regarding breast positioning quality. In addition to these results, we developed a software module that allows the study to be applied in practice by presenting the implemented model predictions and informing the technologist about the missing quality criteria.

Combined Hyperglycemia- and Hyperinsulinemia-Induced Insulin Resistance in Adipocytes Is Associated With Dual Signaling Defects Mediated by PKC-ζ.

A hyperglycemic and hyperinsulinemic environment characteristic of type 2 diabetes causes insulin resistance. In adipocytes, defects in both insulin sensitivity and maximum response of glucose transport have been demonstrated. To investigate the molecular mechanisms, freshly isolated rat adipocytes were incubated in control (5.6 mM glucose, no insulin) and high glucose (20 mM)/high insulin (100 nM) (HG/HI) for 18 hours to induce insulin resistance. Insulin-resistant adipocytes manifested decreased sensitivity of glucose uptake associated with defects in insulin receptor substrate (IRS)-1 Tyr phosphorylation, association of p85 subunit of phosphatidylinositol-3-kinase, Akt Ser473 and Thr308 phosphorylation, accompanied by impaired glucose transporter 4 translocation. In contrast, protein kinase C (PKC)-ζ activity was augmented by chronic HG/HI. Inhibition of PKC-ζ with a specific cell-permeable peptide reversed the signaling defects and insulin sensitivity of glucose uptake. Transfection of dominant-negative, kinase-inactive PKC-ζ blocked insulin resistance, whereas constitutively active PKC-ζ recapitulated the defects. The HG/HI incubation was associated with stimulation of IRS-1 Ser318 and Akt Thr34 phosphorylation, targets of PKC-ζ. Transfection of IRS-1 S318A and Akt T34A each partially corrected insulin signaling, whereas combined transfection of both completely normalized insulin signaling. In vivo hyperglycemia/hyperinsulinemia in rats for 48 hours similarly resulted in activation of PKC-ζ and increased phosphorylation of IRS-1 Ser318 and Akt Thr34. These data indicate that impairment of insulin signaling by chronic HG/HI is mediated by dual defects at IRS-1 and Akt mediated by PKC-ζ.

Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia.

STUDY OBJECTIVES: Long-duration (> or = 6 months) polysomnographic studies of insomnia medications are lacking. This study evaluated the long-term efficacy of ramelteon, a selective MT1/MT2 melatonin-receptor agonist used for insomnia treatment. DESIGN: Six-month, randomized, double-blind, placebo-controlled study. SETTING: Forty-six investigative sites in the United States, Europe, Russia, and Australia. PARTICIPANTS: Four hundred fifty-one adults (age > or = 18 years) with chronic primary insomnia. INTERVENTIONS: Ramelteon, 8 mg, or placebo 30 minutes before bedtime nightly for 6 months. MEASUREMENTS: Sleep was evaluated by polysomnography and morning questionnaires on the first 2 nights of Week 1; the last 2 nights of Months 1, 3, 5, and 6; and Nights 1 and 2 of the placebo run-out. Next-morning residual effects as well as adverse effects and vital signs were recorded at each visit. Rebound insomnia and withdrawal effects were evaluated during placebo run-out. RESULTS: Over the 6 months of treatment, ramelteon consistently reduced latency to persistent sleep compared with baseline and with placebo; significant decreases were observed at Week 1 and Months 1, 3, 5, and 6 (P < 0.05). Ramelteon significantly reduced subjective sleep latency relative to placebo at Week 1, Month 1, and Month 5 (P < 0.05), with reductions nearing statistical significance at Months 3 and 6 (P < or = 0.08). No significant next-morning residual effects were detected during ramelteon treatment. No withdrawal symptoms or rebound insomnia were detected after ramelteon discontinuation. Most adverse events were mild or moderate in severity. CONCLUSIONS: In adults with chronic insomnia, long-term ramelteon treatment consistently reduced sleep onset, with no next-morning residual effects or rebound insomnia or withdrawal symptoms upon discontinuation.

A case of catecholamine and glucocorticoid excess syndrome due to a corticotropin-secreting paraganglioma.

We present a case of a 61-year-old female patient with ectopic corticotropin (ACTH) syndrome, hypopituitarism, and catecholamine excess due to a paraganglioma at the inferior pole of the left kidney. In this article we discuss the hormonal findings in the patient and its consequences, the pitfalls of the endocrine workup, and the results of our immunohistological and molecular studies in more detail.

Efficacy and tolerability of lumiracoxib 100 mg once daily in knee osteoarthritis: a 13-week, randomized, double-blind study vs. placebo and celecoxib.

OBJECTIVE: To determine the efficacy and safety of lumiracoxib for knee osteoarthritis (OA). METHODS: This was a 13-week, multicentre, randomized, double-blind, double-dummy, placebo-controlled study. Males or females aged >/= 18 years with primary knee OA received lumiracoxib 100 mg od, lumiracoxib 100 mg od with a loading dose of 200 mg od for the first two weeks, celecoxib 200 mg od, or placebo. MAIN OUTCOME MEASURES: Co-primary variables, assessed at week 13, were OA pain intensity in the target knee, patient's global assessment of disease activity and the WOMAC total score. Other variables included OMERACT-OARSI responder rates and WOMAC subscale scores. Safety and tolerability were evaluated. RESULTS: All active treatments were superior to placebo for all co-primary variables. No significant differences were observed between any active treatments. Mean reductions from baseline to week 13 for lumiracoxib 100mg od, 100mg od with loading dose, celecoxib and placebo, respectively, were: OA pain intensity in the target knee: 26.8, 26.2, 26.6 and 21.4mm (all p < 0.01 vs. placebo); patient's global assessment of disease activity: 25.1, 21.9, 22.9 and 18.9 mm (all p < 0.05 vs. placebo); WOMAC total score: 15.2, 14.8, 14.7 and 11.3 (all p < 0.01 vs. placebo). Lumiracoxib was superior to placebo and similar to celecoxib for OMERACT-OARSI response and WOMAC subscale scores. Lumiracoxib was well tolerated. The incidence of adverse events was similar across groups. CONCLUSIONS: Lumiracoxib 100 mg od provided effective relief from the pain of knee OA, with efficacy similar to celecoxib 200 mg od, and was well tolerated.