Glycosylated hemoglobin and functional decline in community-dwelling nursing home-eligible elderly adults with diabetes mellitus

Objectives

To determine whether glycosylated hemoglobin (HbA1c) levels predict functional decline in older adults.

Design

Longitudinal cohort study.

Participants

Community‐dwelling, nursing home (NH)‐eligible individuals with diabetes mellitus enrolled at On Lok between October 2002 and December 2008 (367 participants, 1,579 HbA1c measurements).

Setting

On Lok Lifeways, the original model for Programs of All‐Inclusive Care for the Elderly.

Measurements

The outcomes were functional decline or death at 2 years. The primary predictor was HbA1c. Age, sex, race and ethnicity, baseline function, comorbid conditions, length of time enrolled at On Lok, insulin use, and clustering of HbA1c within participants were adjusted for with mixed‐effects Poisson regression.

Results

Mean age was 80, and 185 participants (50%) were taking insulin. Sixty‐three percent of participants experienced functional decline, and 75% experienced death or functional decline during the study period. At 2 years, higher HbA1c was associated with less functional decline or death (P for trend = .006). Accounting for clustering and confounding factors, HbA1c of 8.0% to 8.9% was associated with a lower likelihood (relative risk = 0.88, 95% confidence interval = 0.79–0.99) of functional decline or death than HbA1c of 7.0% to 7.9%.

Conclusion

In community‐dwelling, NH‐eligible individuals with diabetes mellitus, HbA1c of 8.0% to 8.9% is associated with better functional outcomes at 2 years than HbA1c of 7.0% to 7.9%, suggesting that the current American Geriatrics Society guideline recommending a HbA1c target of 8.0% or less for older adults with limited life expectancy may be lower than necessary to maintain function.     

The role of stem cells in the treatment of diabetic foot ulcers

Metformin is a cornerstone in the treatment of type 2 diabetes. Although its mechanism of action is not well understood, there is new evidence about its possible role in cancer. A Pubmed search from 1990 to 2011 was done using the terms metformin, cancer, mechanism of action, diabetes treatment and prevention. We found more than one thousand articles and reviewed studies that had assessed the efficacy of metformin in treatment and prevention of type 2 diabetes and its mechanisms of actions, as well as articles on its antitumoral effects. We found that the United Kingdom Prospective Diabetes Study and the Diabetes Prevention Program have demonstrated the efficacy of metformin in terms of treatment and prevention of type 2 diabetes; metformin is safe, cost effective and remains the first line of diabetes therapy with diet and exercise. The mechanisms of action include a decrease of hepatic insulin resistance, change in bile acids metabolism, incretins release and decreased amyloid deposits. The AMP-activated protein kinase seems to be an important target for these effects. Epidemiological retrospective studies point out a possible association between metformin and decreased cancer risk, data supported by in vitro and animal studies. These data should trigger randomized controlled trials to prove or disprove this additional benefit of metformin.     

Fatigue of dental ceramics

Objectives

Clinical data on survival rates reveal that all-ceramic dental prostheses are susceptible to fracture from repetitive occlusal loading. The objective of this review is to examine the underlying mechanisms of fatigue in current and future dental ceramics.

Data/sources

The nature of various fatigue modes is elucidated using fracture test data on ceramic layer specimens from the dental and biomechanics literature.

Conclusions

Failure modes can change over a lifetime, depending on restoration geometry, loading conditions and material properties. Modes that operate in single-cycle loading may be dominated by alternative modes in multi-cycle loading. While post-mortem examination of failed prostheses can determine the sources of certain fractures, the evolution of these fractures en route to failure remains poorly understood. Whereas it is commonly held that loss of load-bearing capacity of dental ceramics in repetitive loading is attributable to chemically assisted ‘slow crack growth’ in the presence of water, we demonstrate the existence of more deleterious fatigue mechanisms, mechanical rather than chemical in nature. Neglecting to account for mechanical fatigue can lead to gross overestimates in predicted survival rates.

Clinical significance

Strategies for prolonging the clinical lifetimes of ceramic restorations are proposed based on a crack-containment philosophy.     

Glucans from the edible mushroom Pleurotus pulmonarius inhibit colitis-associated colon carcinogenesis in mice

Background

We have recently demonstrated that polysaccharides from fruiting body extract (FBE) or mycelia extract (ME) of the edible mushroom Pleurotus pulmonarius exert antiproliferative effects in intestinal cells and an anti-inflammatory effect in a dextran sulfate sodium (DSS) mouse model of acute colitis. The aim of this study was to assess the role of fungal FBE and ME in colon carcinogenesis.

Methods

In vitro, human colorectal cancer cells were treated with FBE and ME and analyzed for inflammation response, for markers of apoptosis, and for cell-cycle progression. In vivo, FBE and ME were tested in a mouse model of colitis-associated colorectal carcinogenesis induced by cyclic treatments with DSS and azoxymethane. Treated mice were fed a daily diet containing 2 or 20?mg FBE or ME per mouse for 80?days.

Results

In vitro, FBE and ME induced apoptosis in a dose-responsive manner and modulated the expression of Bcl-2, Bax, and cytochrome c, and blocked tumor necrosis factor (TNF)-α-induced inhibitor of nuclear factor (NF) (Iκ)-Bα degradation and NF-κB nuclear translocation. In vivo, dietary administration of FBE and ME significantly reduced the formation of aberrant crypt foci, which precedes colorectal cancer, and of microadenomas. The treatments significantly lowered the expression of proliferating cell nuclear antigen and increased the number of cells undergoing apoptosis in the colon. Additionally, FBE and ME inhibited the expression of the proinflammatory cytokine TNF-α in colonic tissue.

Conclusions

We conclude that P. pulmonarius FBE and ME inhibit colitis-associated colon carcinogenesis induced in mice through the modulation of cell proliferation, induction of apoptosis, and inhibition of inflammation.     

Reasons for enhanced activity of doxorubicin on co-delivery with octa(3-aminopropyl)silsesquioxane

This paper presents results of spectroscopic (NMR, FTIR, fluorescence), Q-TOF mass spectrometry and Z-potential analyses of interactions between octa(3-aminopropyl)silsesquioxane hydrochloride (POSS-NH₂·HCl) and anticancer drug – doxorubicin hydrochloride. These studies aimed at explanation of the enhanced activity of doxorubicin on co-delivery with POSS-NH₂. The results point to the formation of active complexes via ionic interactions between the ammonium chloride groups of silsesquioxane and the drug, and not, as suggested earlier, via NH⋯N hydrogen bonding. It has also been shown that the main driving force for the formation of the complexes can be strengthened by π–π stacking and hydrogen bonds. The experimental results are supported by quantum mechanical calculations. This work has proven that co-delivery with POSS offers a potentially advantageous and simple approach for improved efficacy in chemotherapy, avoiding often complicated synthesis of conjugates, involving covalent bonding between drug, nanocarrier and targeting agents.

The interaction between polyhedral oligomeric silsesquioxane (POSS) and doxorubicin, leading to formation of active complexes involving POSS functional aminopropyl groups and anthracycline functional groups.     

Laparoendoscopic single-site (LESS) varicocelectomy with reusable components: comparison with the conventional laparoscopic technique

Background

This study aimed to compare laparoendoscopic single-site varicocelectomy (LESSV) with multiport laparoscopic varicocelectomy (MLV) in terms of intraoperative parameters and postoperative outcomes.

Methods

A retrospective case–control study investigated 10 male adolescents and 89 adults who underwent either LESSV or MLV at the authors’ center. The reusable X-Cone single port was inserted transumbilically. A 5-mm 30° telescope was used together with a straight and a prebent laparoscopic instrument. The MLV procedure was performed using two 5-mm ports and one 10-mm port.

Results

Between January 2009 and November 2012, 20 patients underwent LESSV and 79 patients underwent MLV. The demographic data were comparable between the two groups. The mean operating time was 59.1 ± 15.5 min for LESSV and 51.2 ± 14.4 min for MLV (P = 0.04). In the LESSV group, no conversion to MLV was necessary. The hospital stay was 1.6 ± 0.7 days in the LESSV group versus 1.8 ± 0.5 days in the MLV group (P = 0.17). The postoperative pain scores did differ between the two groups. By day 2, significantly more patients in the LESSV group than in the MLV group fully recovered their normal physical activity (P = 0.02). Comparison of pre- and postoperative values showed relief of testicular pain and improvement of semen parameters for the majority of the patients. The overall incidence of complications was distributed equally between the two groups as follows: paresthesia of the upper thigh (8 %), wound infection (5 %), epididymitis (3 %) and hydrocele (4 %). All the patients in the LESSV group were fully satisfied with their cosmetic results compared with only 76 % of the patients in the MLV group (P = 0.01).

Conclusions

The LESSV procedure performed with the reusable X-Cone is as safe and efficient as MLV. After LESSV, the parameters measuring postoperative patient satisfaction are significantly improved. Given its reusable components, including prebent laparoscopic instruments, the X-Cone platform is a cost-effective alternative to disposable or homemade single ports.