Is There a Role for Visceral Adiposity in Inducing Type 2 Diabetes Remission in Severely Obese Patients Following Biliopancreatic Diversion with Duodenal Switch Surgery?

Background

Severe obesity is often characterized by ectopic fat deposition, which is related to development of type 2 diabetes (T2D). Thus, resolution of T2D may not be linearly associated with weight loss. The importance of ectopic fat reduction after bariatric surgery and T2D resolution is uncertain.

Objective

The aim of this pilot study is to compare body composition and body fat distribution in severely obese patients with or without T2D after biliopancreatic diversion with duodenal switch (BPD-DS) surgery in relation to diabetes resolution.

Methods

Sixty-two severely obese patients were evaluated at baseline, 6, and 12 months. Of these, 40 patients underwent BPD-DS surgery. Anthropometric measurements and abdominal and mid-thigh computed tomography scans were performed at each visit.

Results

Before BPD-DS surgery, obese patients with T2D had higher weight as well as greater ectopic fat deposition in the abdomen and mid-thigh level than obese patients without T2D (p?<?0.05). Resolution of T2D was 65 and 90 % at 6 and 12 months, respectively. No difference in body composition changes at 6 and 12 months could be found between patients without T2D, patients with T2D resolution, and patients who remained T2D. Resolution of T2D was associated with a greater absolute loss of visceral adipose tissue (VAT) in comparison to patients without T2D (?1175?±?570 cm³ vs. ?729?±?394 cm³ at 6 months and ?1647?±?816 cm³ vs. ?1103?±?422 cm³ at 12 months; all p?≤?0.05).

Conclusion

Ectopic fat mobilization, particularly the absolute loss of VAT, may play a major role in T2D resolution following BPD-DS surgery, regardless of the amount of weight loss.

     

Antibacterial activity and mechanism of action of a novel anilinouracil-fluoroquinolone hybrid compound

The anilinouracils (AUs) such as 6-(3-ethyl-4-methylanilino)uracil (EMAU) are a novel class of gram-positive, selective, bactericidal antibacterials which inhibit pol IIIC, the gram-positive-specific replicative DNA polymerase. We have linked various fluoroquinolones (FQs) to the N-3 position of EMAU to generate a variety of AU-FQ "hybrids" offering the potential for targeting two distinct steps in DNA replication. In this study, the properties of a hybrid, "251D," were compared with those of representative AUs and FQs in a variety of in vitro assays, including pol IIIC and topoisomerase/gyrase enzyme assays, antibacterial, bactericidal, and mammalian cytotoxicity assays. Compound 251D potently inhibited pol IIIC and topoisomerase/gyrase, displayed gram-positive antibacterial potency at least 15 times that of the corresponding AU compound, and as expected, acted selectively on bacterial DNA synthesis. Compound 251D was active against a broad panel of antibiotic-resistant gram-positive pathogens as well as several gram-negative organisms and was also active against both AU- and FQ-resistant gram-positive organisms, demonstrating its capacity for attacking both of its potential targets in the bacterium. 251D also was bactericidal for gram-positive organisms and lacked toxicity in vitro. Although we obtained strains of Staphylococcus aureus resistant to the individual parent compounds, spontaneous resistance to 251D was not observed. We obtained 251D resistance in multiple-passage experiments, but resistance developed at a pace comparable to those for the parent compounds. This class of AU-FQ hybrids provides a promising new pharmacophore with an unusual dual mechanism of action and potent activity against antibiotic-sensitive and -resistant gram-positive pathogens.     

Developing academic writing skills: the PROCESS framework

Academic writing is an important aspect of professional development for students and lecturers. It is one way in which they demonstrate their learning, but it can be a difficult skill to master. This article aims to enable students and professionals to develop their academic writing style using a coherent and effective framework.     

Efficacy of bisphosphonates for the control of alveolar bone loss in periodontitis

Periodontal disease is characterized by periodontal bone loss. For this reason, we conducted a study to test the effect of alendronate (ALN), an inhibitor of bone resorption, on alveolar bone mass. A total of 335 patients with periodontal disease (men = 162, women = 173), aged 30 to 79, were randomized to either placebo or ALN 70 mg once weekly. All patients received prophylaxis at baseline, and at 6, 12, and 18 months. Smokers accounted for 62% of patients, and 71% of the patients had severe periodontal disease. The primary efficacy endpoint was the change in alveolar bone loss (ABL). When all subjects were analyzed, 2 years of treatment with alendronate 70 mg once weekly did not significantly change either ABL or alveolar bone density (ABD) relative to placebo. However, in the subgroup of patients with low mandibular bone mineral density (BMD) at baseline, alendronate significantly reduced bone loss relative to placebo (p < 0.01). No such effect was seen in patients with normal baseline mandibular BMD. The overall and upper gastrointestinal safety and tolerability profile of alendronate after 2 years of treatment was very favorable compared to placebo. No cases of osteonecrosis of the jaw were observed. In summary, in patients with periodontal disease receiving prophylaxis, alendronate 70 mg once weekly was well tolerated, but did not have a detectable effect on alveolar bone loss, except in those patients with low mandibular BMD at baseline.     

Effectiveness and acceptability of a multidisciplinary approach in improving the care of patients with advanced chronic kidney disease: a pilot study

International Urology and Nephrology - This study aimed at determining the feasibility of conducting a large-scale pragmatic effectiveness study on the implementation of multidisciplinary care...     

Secular Trends in Hip Fractures Worldwide: Opposing Trends East Versus West

Despite wide variations in hip rates fractures worldwide, reasons for such differences are not clear. Furthermore, secular trends in the age‐specific hip fracture rates are changing the world map of this devastating disease, with the highest rise projected to occur in developing countries. The aim of our investigation is to systematically characterize secular trends in hip fractures worldwide, examine new data for various ethnic groups in the United States, evidence for divergent temporal patterns, and investigate potential contributing factors for the observed change in their epidemiology. All studies retrieved through a complex Medline Ovid search between 1966 and 2013 were examined. For each selected study, we calculated the percent annual change in age‐standardized hip fracture rates de‐novo. Although occurring at different time points, trend breaks in hip fracture incidence occurred in most Western countries and Oceania. After a steep rise in age‐adjusted rates in these regions, a decrease became evident sometimes between the mid‐seventies and nineties, depending on the country. Conversely, the data is scarce in Asia and South America, with evidence for a continuous rise in hip fracture rates, with the exception of Hong‐Kong and Taiwan that seem to follow Western trends. The etiologies of these secular patterns in both the developed and the developing countries have not been fully elucidated, but the impact of urbanization is at least one plausible explanation. Data presented here show close parallels between rising rates of urbanization and hip fractures across disparate geographic locations and cultures. Once the proportion of the urban population stabilized, hip fracture rates also stabilize or begin to decrease perhaps due to the influence of other factors such as birth cohort effects, changes in bone mineral density and BMI, osteoporosis medication use and/or lifestyle interventions such as smoking cessation, improvement in nutritional status and fall prevention. © 2014 American Society for Bone and Mineral Research.     

Human Respiratory Syncytial Virus Infection in a Human T Cell Line Is Hampered at Multiple Steps

Human respiratory syncytial virus (HRSV) is the most frequent cause of severe respiratory disease in children. The main targets of HRSV infection are epithelial cells of the respiratory tract, and the great majority of the studies regarding HRSV infection are done in respiratory cells. Recently, the interest on respiratory virus infection of lymphoid cells has been growing, but details of the interaction of HRSV with lymphoid cells remain unknown. Therefore, this study was done to assess the relationship of HRSV with A3.01 cells, a human CD4⁺ T cell line. Using flow cytometry and fluorescent focus assay, we found that A3.01 cells are susceptible but virtually not permissive to HRSV infection. Dequenching experiments revealed that the fusion process of HRSV in A3.01 cells was nearly abolished in comparison to HEp-2 cells, an epithelial cell lineage. Quantification of viral RNA by RT-qPCR showed that the replication of HRSV in A3.01 cells was considerably reduced. Western blot and quantitative flow cytometry analyses demonstrated that the production of HRSV proteins in A3.01 was significantly lower than in HEp-2 cells. Additionally, using fluorescence in situ hybridization, we found that the inclusion body-associated granules (IBAGs) were almost absent in HRSV inclusion bodies in A3.01 cells. We also assessed the intracellular trafficking of HRSV proteins and found that HRSV proteins colocalized partially with the secretory pathway in A3.01 cells, but these HRSV proteins and viral filaments were present only scarcely at the plasma membrane. HRSV infection of A3.01 CD4⁺ T cells is virtually unproductive as compared to HEp-2 cells, as a result of defects at several steps of the viral cycle: Fusion, genome replication, formation of inclusion bodies, recruitment of cellular proteins, virus assembly, and budding.