Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients.

PURPOSE: Chemotherapy for operable breast cancer decreases the risk of death. Docetaxel is one of the most active agents in breast cancer, but resistance or incomplete response is frequent. PATIENTS AND METHODS: Core biopsies from 24 patients were obtained before treatment with neoadjuvant docetaxel (four cycles, 100 mg/m(2) every 3 weeks), and response was assessed after chemotherapy. After 3 months of neoadjuvant chemotherapy, surgical specimens (n = 13) were obtained, and laser capture microdissection (LCM; n = 8) was performed to enrich for tumor cells. From each core, surgical, and LCM specimen, sufficient total RNA (3 to 6 microg) was extracted for cDNA array analysis using the Affymetrix HgU95-Av2 GeneChip (Affymetrix, Santa Clara, CA). RESULTS: From the initial core biopsies, differential patterns of expression of 92 genes correlated with docetaxel response (P = .001). However, the molecular patterns of the residual cancers after 3 months of docetaxel treatment were strikingly similar, independent of initial sensitivity or resistance. This relative genetic homogeneity after treatment was observed in both LCM and non-LCM surgical specimens. The residual tumor after treatment in tumors that were initially sensitive indicates selection of a residual and resistant subpopulation of cells. The gene expression pattern was populated by genes involved in cell cycle arrest at G(2)M (eg, mitotic cyclins and cdc2) and survival pathways involving the mammalian target of rapamycin. CONCLUSION: A specific and consistent gene expression pattern was found in residual tumors after docetaxel treatment. These profiles provide therapeutic targets that could lead to improved treatment.     

An update on therapies for the treatment of diabetes-induced osteoporosis

Introduction: Currently, 424 million people aged between 20 and 79 years worldwide are diabetic. More than 25% of adults aged over 65 years in North America have Type 2 diabetes mellitus (DM). Diabetes-induced osteoporosis (DM-OS) is caused by chronic hyperglycemia, advanced glycated end products and oxidative stress. The increase in the prevalence of DM-OS has prompted researchers to develop new biological therapies for the management of DM-OS.

Areas covered: This review covered the current and novel biological agents used in the management of DM-OS. Data were retrieved from PubMed, Scopus, American Diabetes Association and International Osteoporosis Foundation websites, and ClinicalTrials.gov. The keywords for the search included: DM, osteoporosis, and management.

Expert opinion: Several biological molecules have been examined in order to find efficient drugs for the treatment of DM-OS. These biological agents include anti-osteoporosis drugs: net anabolics (parathyroid hormone/analogs, androgens, calcilytics, anti-sclerostin antibody), net anti-resorptive osteoporosis drugs (calcitonin, estrogen, selective estrogen receptor modulators, bisphosphonates, RANKL antibody) and anti-diabetic drugs (alpha glucosidase inhibitors, sulfonylureas, biguanides, meglitinides, thiazolidinediones, GLP-1 receptor agonists, dipeptidylpeptidase-4 inhibitors, sodium glucose co-transporter-2 inhibitors, insulin). Biological medications that effectively decrease hyperglycemia and, at the same time, maintain bone health would be an ideal drug/drug combination for the treatment of DM-OS.     

Subclavian stenting in a hostile aortic arch facilitated by a low-profile brachial artery through-and-through access

Subclavian stenting can be extremely difficult in a hostile type II aortic arch (with acute angulation of the subclavian artery origin) or type III aortic arch. This case illustrates use of a low-profile system to gain through-and-through (flossing) access through the brachial artery to facilitate stenting via the femoral approach. This approach can be useful in patients with small brachial arteries where the risk of complication may be high if a standard vascular sheath was placed for stenting via the brachial approach. This technique also avoids the use of a surgical cut down.     

Recrystallization techniques for the synthesis of ZnO nanorods: an in situ process for carbon doping and enhancing the dispersion concentration of ZnO nanorods

Zinc acetate is recrystallized as lumber-shaped tetragonal rods by a novel recrystallization technique. Subsequently, the recrystallized zinc acetate is converted into ZnO nanorods in a glass vial by the simplest and cheapest method without utilizing any expensive instrumentation. Carbon is doped in ZnO nanorods during the preparation ZnO nanorods without any extra steps, chemicals, or effort. The carbon-doped ZnO nanorods can be dispersed in a solvent at very high concentrations and are also stable for a very long time, which are comparatively higher than those of the other existing ZnO nanoparticles. The higher dispersion concentration and higher stability of ZnO nanoparticles are explained by a scheme that demonstrates the suspending mechanism of the ZnO nanoparticles at higher concentrations with higher stabilities in a solvent through the anchoring groups of carbon. No materials are used for surface modification; no surface coatings, ionic materials, or pH controlling materials are used to increase the dispersion concentration and stability. This is the first observation of the doped carbon playing a significant role in the dispersion of ZnO nanoparticles at higher concentrations by withholding them in the solvent. Therefore, doped carbon at the surface of ZnO nanoparticles prevents the self-aggregation of ZnO nanoparticles in the solution phase by interfacial barrier layers among ZnO nanorods and interfacial interactive layer between ZnO nanorod and solvent.

Dispersed ZnO hexagonal nanorods in ethanol solvent and its interfacial behavior in this liquid phase.     

Association of FcγRIIa Polymorphism with Clinical Outcome of Dengue Infection: First Insight from Pakistan

Dengue illness has been a major health concern in Pakistan during the last decade. Dengue infection can result in a spectrum of clinically distinct outcomes, ranging from asymptomatic infection to potentially life-threatening forms of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). A single-nucleotide polymorphism in FcγRIIa (rs1801274) results in altered affinity of the receptor for different subclasses of immunoglobulin G, and is a key player in determining the susceptibility to or protection from severe clinical infection of dengue. In this study, we analyzed the allelic and genotypic distribution of rs1801274 in subjects of Pakistani origin with subclinical dengue infection (n = 40), dengue fever (DF) (n = 40), and DHF/DSS (n = 30). We found that HH homozygotes and heterozygotes were significantly more likely to develop clinical dengue (odds ratio [OR] = 3.21, 95% confidence interval [CI] = 1.29–7.97, P = 0.009), either DF (OR = 2.82, 95% CI = 1.00–7.97, P = 0.045) or DHF/DSS (OR = 3.90, 95% CI = 1.13–13.07, P = 0.024) than the asymptomatic dengue infection. Results of allelic distribution comparisons and logistic regression analysis also supported the same relationship. The results suggest complex nature of interacting factors in determining the course for severe dengue illness.     

Assessment of knowledge of celiac disease among health care professionals

Objectives:

To assess knowledge of celiac disease among medical professionals (physicians).

Methods:

We conducted a cross-sectional survey of hospital-based medical staff in primary, secondary, and tertiary care public, and private hospitals in Riyadh, Saudi Arabia (KSA). We carried out the study between January 2013 and January 2104 at King Khalid University Hospital, King Saud University, Riyadh, KSA. A pretested questionnaire was distributed to the potential participants. A scoring system was used to classify the level of knowledge of participants into 3 categories: poor, fair, and good.

Results:

A total of 109 physicians completed the survey and of these participants, 86.3% were from public hospitals, and 13.7% from private hospitals; 58.7% were males. Of the physicians, 19.2% had poor knowledge. Interns and residents had fair to good knowledge, but registrars, specialists, and even the consultants were less knowledgeable of celiac disease.

Conclusion:

Knowledge of celiac disease is poor among a significant number of physicians including consultants, which can potentially lead to delays in diagnosis. Educational programs need to be developed to improve awareness of celiac disease in the health care profession.Celiac disease (CD) is an autoimmune disorder that is triggered by ingestion of gluten in genetically susceptible individuals. This leads to small intestinal villous atrophy and its ensuing complications. Celiac disease is a common disorder, and the prevalence seems to be on the rise. The exact prevalence of CD in the Middle East and Saudi Arabia (KSA) is not known, but it affects approximately 0.5-1% of the general population in the West.1 The classical presentation of CD is in early childhood with a mal-absorptive picture leading to diarrhea and failure to thrive. However, many cases now present in adulthood. It can also have a variety of non-intestinal presentations such as anemia, fatigue, bone disease, liver enzyme elevation, and infertility.1,2 Highly sensitive screening tests such as immunoglobulin (Ig)A-tissue transglutaminase antibody are now available to screen for CD. The diagnosis of CD is confirmed with small intestinal biopsies, and treatment consists of a strict gluten-free diet for life.3 Health care professionals need to be aware of both the classical and non-classical (extra-intestinal) manifestations of CD in order to make a timely diagnosis. Delays in diagnosis can lead to potentially serious complications such as osteoporosis and small intestinal lymphoma.4 The purpose of the study was to assess the knowledge of CD among the medical professionals. The information obtained will help to design and conduct educational and training programs on CD.