Duration of type 2 diabetes mellitus and pulmonary function tests: a correlative study

International Journal of Diabetes in Developing Countries - Diabetes mellitus (DM) encompasses a group of metabolic disorders characterized by elevated levels of plasma glucose leading to macro-...     

Pharmacogenetics and outcome with antipsychotic drugs

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h²~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.     

Axonal dysfunction,dysmyelination, and conduction failure in hereditary neuropathy with liability to pressure palsies

Introduction: Patients with hereditary neuropathy with liability to pressure palsies (HNPP) manifest with episodes of focal paresis when exposed to mechanical stress, although the basis for vulnerability to conduction block remains relatively unexplained. Methods: Axonal excitability techniques were utilized to provide insights into pathophysiological mechanisms in 13 HNPP patients, stimulating median motor and sensory axons at the wrist. Results: In HNPP, distal latencies were prolonged, and motor and sensory amplitudes were reduced. Threshold was increased. Depolarizing and hyperpolarizing electrotonus was greater, and resting current–threshold slope was reduced. There were greater threshold changes in superexcitability, and refractoriness was decreased. Conclusions: Taken together, excitability testing in patients with HNPP established axonal hyperpolarization in both motor and sensory axons that may be attributable to changes in nerve architecture. In turn, the hyperpolarized resting membrane potential in HNPP may be a major predisposing factor for development of conduction block with mechanical stresses. Muscle Nerve 49 : 858–865, 2014     

Primary intra osseous venous malformation of nasal bone: A rare case report

Primary intra osseous venous malformation with involvement of nasal bone is a rare phenomenon. Nasal bone intraosseous venous malformation on a back ground of port wine stain of face has not been reported in the available literature. We report the very rare case of intraosseous venous malformation of left nasal bone developing on a background of port wine stain of face, its diagnosis, pathology, management and review of literature.KEY WORDS: Intraosseous venous malformation, nasal bone, port wine stain, sun burst appearance     

Insulin Resistance and Bone Strength: Findings From the Study of Midlife in the United States

Although several studies have noted increased fracture risk in individuals with type 2 diabetes mellitus (T2DM), the pathophysiologic mechanisms underlying this association are not known. We hypothesize that insulin resistance (the key pathology in T2DM) negatively influences bone remodeling and leads to reduced bone strength. Data for this study came from 717 participants in the Biomarker Project of the Midlife in the United States Study (MIDUS II). The homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated from fasting morning blood glucose and insulin levels. Projected 2D (areal) bone mineral density (BMD) was measured in the lumbar spine and left hip using dual‐energy X‐ray absorptiometry (DXA). Femoral neck axis length and width were measured from the hip DXA scans, and combined with BMD and body weight and height to create composite indices of femoral neck strength relative to load in three different failure modes: compression, bending, and impact. We used multiple linear regressions to examine the relationship between HOMA‐IR and bone strength, adjusted for age, gender, race/ethnicity, menopausal transition stage (in women), and study site. Greater HOMA‐IR was associated with lower values of all three composite indices of femoral neck strength relative to load, but was not associated with BMD in the femoral neck. Every doubling of HOMA‐IR was associated with a 0.34 to 0.40 SD decrement in the strength indices (p < 0.001). On their own, higher levels of fasting insulin (but not of glucose) were independently associated with lower bone strength. Our study confirms that greater insulin resistance is related to lower femoral neck strength relative to load. Further, we note that hyperinsulinemia, rather than hyperglycemia, underlies this relationship. Although cross‐sectional associations do not prove causality, our findings do suggest that insulin resistance and in particular, hyperinsulinemia, may negatively affect bone strength relative to load. © 2014 American Society for Bone and Mineral Research.     

Reclassification of predictions for uncovering subgroup specific improvement

Risk prediction models play an important role in prevention and treatment of several diseases. Models that are in clinical use are often refined and improved. In many instances, the most efficient way to improve a successful model is to identify subgroups for which there is a specific biological rationale for improvement and tailor the improved model to individuals in these subgroups, an approach especially in line with personalized medicine. At present, we lack statistical tools to evaluate improvements targeted to specific subgroups. Here, we propose simple tools to fill this gap. First, we extend a recently proposed measure, the Integrated Discrimination Improvement, using a linear model with covariates representing the subgroups. Next, we develop graphical and numerical tools that compare reclassification of two models, focusing only on those subjects for whom the two models reclassify differently. We apply these approaches to BRCAPRO, a genetic risk prediction model for breast and ovarian cancer, using data from MD Anderson Cancer Center. We also conduct a simulation study to investigate properties of the new reclassification measure and compare it with currently used measures. Our results show that the proposed tools can successfully uncover subgroup specific model improvements. Copyright © 2013 John Wiley & Sons, Ltd.     

The promotion of functional urinary bladder regeneration using anti-inflammatory nanofibers

Current attempts at tissue regeneration utilizing synthetic and decellularized biologic-based materials have typically been met in part by innate immune responses in the form of a robust inflammatory reaction at the site of implantation or grafting. This can ultimately lead to tissue fibrosis with direct negative impact on tissue growth, development, and function. In order to temper the innate inflammatory response, anti-inflammatory signals were incorporated through display on self-assembling peptide nanofibers to promote tissue healing and subsequent graft compliance throughout the regenerative process. Utilizing an established urinary bladder augmentation model, the highly pro-inflammatory biologic scaffold (decellularized small intestinal submucosa) was treated with anti-inflammatory peptide amphiphiles (AIF-PAs) or control peptide amphiphiles and used for augmentation. Significant regenerative advantages of the AIF-PAs were observed including potent angiogenic responses, limited tissue collagen accumulation, and the modulation of macrophage and neutrophil responses in regenerated bladder tissue. Upon further characterization, a reduction in the levels of M2 macrophages was observed, but not in M1 macrophages in control groups, while treatment groups exhibited decreased levels of M1 macrophages and stabilized levels of M2 macrophages. Pro-inflammatory cytokine production was decreased while anti-inflammatory cytokines were up-regulated in treatment groups. This resulted in far fewer incidences of tissue granuloma and bladder stone formation. Finally, functional urinary bladder testing revealed greater bladder compliance and similar capacities in groups treated with AIF-PAs. Data demonstrate that AIF-PAs can alleviate galvanic innate immune responses and provide a highly conducive regenerative milieu that may be applicable in a variety of clinical settings.