Noninsulin-dependent, type II diabetes mellitus-related dermatoses: part II

Cutaneous complications of noninsulin-dependent, type II diabetes mellitus are reviewed, including diabetic dermopathy, necrobiosis lipoidica diabeticorum, diabetic bullae (bullosis diabeticorum), certain acquired perforating dermatoses, diabetic thick skin, scleredema adultorum, Dupuytren's contractures, certain xanthomas, carotenoderma, rubeosis faciei, and acanthosis nigricans.     

Fractal dimensions of breast lesions on cytology smears

In the present study, box-counting fractal dimensions of benign and malignant cells of breast tumors on cytology material were measured and compared. We selected fine-needle aspiration cytology smears of 14 cases of histopathology-proven infiltrating duct carcinomas and 7 cases of fibroadenoma of the breast. Five cells were randomly selected from each case. Box-counting fractal dimensions of all cells were measured with the help of an image cytometer (Leica, Cambridge, UK), using Quantimet 600 software (Leica). In total, 70 malignant cells and 35 benign cells were studied. The mean fractal dimensions of malignant cells and benign cells were 0.9571 +/- 0.1265 and 0.8354 +/- 0.1367, respectively. There was significant difference in the fractal dimension of malignant and benign cells (P = 0.006, Mann-Whitney nonparametric test). The measurement of fractal dimension may be helpful in discriminating malignant from benign cells. This may be another discriminating feature of malignant cells, along with classic image morphometry based on Euclidean geometry.     

Interference from Proteins and Surfactants on Particle Size Distributions Measured by Nanoparticle Tracking Analysis (NTA)

Purpose

Characterization of submicron protein particles continues to be challenging despite active developments in the field. NTA is a submicron particle enumeration technique, which optically tracks the light scattering signal from suspended particles undergoing Brownian motion. The submicron particle size range NTA can monitor in common protein formulations is not well established. We conducted a comprehensive investigation with several protein formulations along with corresponding placebos using NTA to determine submicron particle size distributions and shed light on potential non-particle origin of size distribution in the range of approximately 50–300 nm.

Methods

NTA and DLS are performed on polystyrene size standards as well as protein and placebo formulations.

Results

Protein formulations filtered through a 20 nm filter, with and without polysorbate-80, show NTA particle counts. As such, particle counts above 20 nm are not expected in these solutions. Several other systems including positive and negative controls were studied using NTA and DLS.

Conclusions

These apparent particles measured by NTA are not observed in DLS measurements and may not correspond to real particles. The intent of this article is to raise awareness about the need to interpret particle counts and size distribution from NTA with caution.

     

Dyspareunia: a difficult symptom in gynaecological practice

Dyspareunia is recurrent or persistent genital pain associated with sexual intercourse. It is a symptom that can have a significant impact on women's health, relationships and quality of life. There are multiple different causes for it, including both organic and psychosexual components. Despite the high prevalence of sexual pain, estimated to between 3 and 18% worldwide, few guidelines exist for its evaluation and management. Adequate assessment requires a comprehensive sexual history, a systematic and thorough examination of the lower genital tract to rule out anatomical causes and an exploration of potential psychosexual causes. Further investigations may include swabs and a pelvic ultrasound scan. In some cases a diagnostic laparoscopy may be required if there is evidence of endometriosis or utero-vaginal pathology that does not respond to conservative management. This article considers the diagnosis and investigation of women complaining of dyspareunia.     

Polyubiquitin binding to ABIN1 is required to prevent autoimmunity

The protein ABIN1 possesses a polyubiquitin-binding domain homologous to that present in nuclear factor κB (NF-κB) essential modulator (NEMO), a component of the inhibitor of NF-κB (IκB) kinase (IKK) complex. To address the physiological significance of polyubiquitin binding, we generated knockin mice expressing the ABIN1[D485N] mutant instead of the wild-type (WT) protein. These mice developed all the hallmarks of autoimmunity, including spontaneous formation of germinal centers, isotype switching, and production of autoreactive antibodies. Autoimmunity was suppressed by crossing to MyD88(-/-) mice, demonstrating that toll-like receptor (TLR)-MyD88 signaling pathways are needed for the phenotype to develop. The B cells and myeloid cells of the ABIN1[D485N] mice showed enhanced activation of the protein kinases TAK, IKK-α/β, c-Jun N-terminal kinases, and p38α mitogen-activated protein kinase and produced more IL-6 and IL-12 than WT. The mutant B cells also proliferated more rapidly in response to TLR ligands. Our results indicate that the interaction of ABIN1 with polyubiquitin is required to limit the activation of TLR-MyD88 pathways and prevent autoimmunity.     

Comparison of alternate-day atorvastatin treatment to daily treatment in maintaining LDL-cholesterol targets in patients with variable coronary risk profile

3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity of atorvastatin lasts upto 20-30 hours. This study aimed at comparing the maintenance of National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) goal by the alternate-day therapy to daily treatment. This randomized, open-label trial included 300 patients of dyslipidemia or coronary artery disease on stable doses of atorvastatin. These patients met their respective NCEP-ATPIII cholesterol goals and were randomized to receive the same doses of atorvastatin every day (QD) or every other day (QOD) in a 1:1 ratio for 12 weeks. The efficacy criteria were (1) proportion of patients maintaining the low-density lipoprotein-cholesterol (LDL-C) goal, (2) comparison of changes in the total cholesterol, LDL-C, high-density lipoprotein cholesterol, and triglyceride levels from baseline. The proportions of patients maintaining their LDL-C goals in QD and QOD groups at 6 weeks were 83.9% (60.3-97.5) versus 70.9% (59.3-82.5) (P < 0.01) and at 12 weeks were 84.6% (70.9-98.3) versus 73.8% (63.8-83.8) (P < 0.05). Per-protocol analysis showed 95.5% (80.0-111.0) versus 79.1% (66.2-92.0) (P < 0.001) patients at 6 weeks and 91.9% (82.0-106.8) versus 77.4% (64.8-90) (P < 0.05) patients at 12 weeks had maintained their LDL-C goals in the QD and QOD groups. A significant increase was observed in the levels of total cholesterol, LDL-C, and triglyceride at 6 and 12 weeks compared with baseline values in the QOD group. Alternate-day treatment of atorvastatin was inferior to daily treatment in maintaining the NCEP-ATPIII goal.