Motion detection in insect orientation and navigation.

The visual systems of insects are exquisitely sensitive to motion. Over the past 40 years or so, motion processing in insects has been studied and characterised primarily through the optomotor response. This response, which is a turning response evoked by the apparent movement of the visual environment, serves to stabilise the insect's orientation with respect to the environment. Research over the past decade, however, is beginning to reveal the existence of a variety of other behavioural responses in insects, that use motion information in different ways. Here we review some of the recently characterised behaviours, describe the inferred properties of the underlying movement-detecting processes, and propose modified or new models to account for them.     

Alteration of Na+ currents in dorsal root ganglion neurons from rats with a painful neuropathy.

Increased excitability of primary sensory neurons may be important for the generation of neuropathic pain from nerve injury. The currents underlying the action potentials of these neurons are largely carried by Na+, and changes in Na+ currents have been postulated to contribute to this increased excitability. Using patch clamp in whole-cell mode, we recorded Na+ currents from DRG neurons freshly isolated from rats with a chronic constriction injury (CCI), an animal model of neuropathic pain. We found significant changes in Na+ currents after CCI when cell size and Na+ channel properties were used to segregate DRG neurons. Most changes were concentrated in small neurons (< or = 25 microm diameter) and in the slow TTX-resistant current that is predominant in these cells. CCI produced two principal changes in these cells: it shifted the voltage-dependence of activation of the TTX-resistant current to more negative potentials and it reduced the average density of this current. The decrease in density appears to be primarily due to the decrease in the number of small neurons expressing this current. The net result is a change in both activation and steady-state inactivation properties of the total Na+ current to more negative potentials without a significant change in the density of total Na+ current. The change in activation properties of the TTX-resistant Na+ current are similar to those produced by some hyperalgesic autacoids, and may contribute to the increase in primary afferent excitability and hyperalgesia that occurs after this lesion.     

Correlation of MRI and histopathology in epileptogenic parietal and occipital lobe lesions.

INTRODUCTION: To analyze the diagnostic accuracy of MRI in patients undergoing parietal and occipital lobe epilepsy surgery. METHODS: In a retrospective study, we analyzed MRI scans and neuropathology reports of 42 patients who had undergone resective epilepsy surgery in the parietal and occipital lobe between 1998 and 2003. We evaluated, whether lesions were precisely characterized by MRI and whether lesion characterization allowed to estimate postsurgical seizure outcome. RESULTS: Within the categories epilepsy associated tumors, focal cortical dysplasias, vascular malformations, scarring, and others, MRI was concordant with histopathology in 36 of 42 (86%) lesions. Among the discordant lesions, one lesion was re-classified following MRI-histopathology synopsis, another two lesions represented new tumor entities (angiocentric neuroepithelial tumor, isomorphic astrocytoma) which have been described recently. Seizure freedom (Engel class I) one year following surgery was achieved in 25 patients (60%). Seizure outcome was different for lesion categories (Engel class I: epilepsy associated tumors, 62%; focal cortical dysplasias, 71%; vascular malformations, 75%; scarring, 40%), and was unchanged if no lesion was found on preoperative MRI. CONCLUSION: If MRI and histopathology are discordant, not only the MRI findings may be debatable. MRI lesion detection is important, since chance of seizure freedom is low if no lesion is detected.     

Polycystic ovary syndrome and the risk of gynaecological cancer: a systematic review

The objective of this study was to perform a systematic review of the literature to determine whether there is an association between polycystic ovary syndrome (PCOS) and gynaecological malignancy. Medline and Embase databases (1968–2008) were searched to identify publications on the association between PCOS and gynaecological cancers including breast cancer. Studies were selected that examined the association between PCOS and all types of gynaecological malignancies. A total of 19 studies exploring the association between PCOS and breast, endometrial and ovarian cancer were identified. Of these, only eight could be included after review. The data showed variability in the definition of PCOS. A meta-analysis of the data suggests that women with PCOS are more likely to develop cancer of the endometrium (OR 2.70, 95% CI 1.00–7.29) and ovarian cancer (OR 2.52, 95% CI 1.08–5.89) but not breast cancer (OR 0.88, 95% CI 0.44–1.77). Women with PCOS appear to be three times more likely to develop endometrial cancer but are not at increased risk of breast cancer. There is insufficient evidence to implicate PCOS in the development of vaginal, vulval, cervical or ovarian cancers. The paucity of studies investigating the association between PCOS and gynaecological cancers is likely to affect the reliability of the conclusions     

Independent Metabolic Syndrome Variants Predict New-Onset Coronary Artery Disease

OBJECTIVE

Any combination of metabolic abnormalities may constitute the metabolic syndrome (MetS), conferring coronary artery disease (CAD) risk, but the independent effect of different combinations on CAD onset remains unknown.

RESEARCH DESIGN AND METHODS

Healthy adult siblings (n = 987) of premature CAD (<60 years) case subjects were followed for 9.8 ± 3.8 years. Baseline MetS variables (insulin sensitivity index, waist circumference, systolic blood pressure, HDL cholesterol, and triglycerides) were recombined into five principal components (PC1–5), and risk factor–adjusted proportional hazards for CAD onset of median-dichotomized PCs were estimated.

RESULTS

The significant hazard ratios were as follows: for PC1 (all abnormalities except blood pressure) 1.66 (P = 0.036), PC2 (high blood pressure levels, high HDL cholesterol) 1.71 (P = 0.016), and PC4 (low HDL cholesterol, high insulin sensitivity, low triglycerides) 2.0 (P = 0.001). Traditionally defined MetS had a hazard ratio of 1.32 (P = 0.18).

CONCLUSIONS

Independent MetS variants identified by PC analysis may explain metabolic mechanisms that increase CAD risk better than the presence of traditional MetS.Acommon approach to examining the metabolic syndrome (MetS) uses a simple count without taking into account the correlation structure of dichotomous metabolic abnormalities including increased blood pressure, high triglyceride levels, low HDL cholesterol levels, abdominal obesity, and impaired glucose control (1). The goal of this study was to define the structure of independent patterns of metabolic syndrome variables and determine their ability to predict new-onset coronary artery disease (CAD).     

Adolescent eating in the absence of hunger and relation to discretionary calorie allowance

Eating in the absence of hunger is a risk factor for overeating during childhood. The objective of this study was to examine eating in the absence of hunger in adolescents based on their familial predisposition to obesity and current weight status. Thirty-one subjects (16 male, 15 female), who were 13 years of age and born at low risk or high risk for obesity, consumed lunch to fullness. After lunch, subjects had access to different snacks for 15 minutes. Eating in the absence of hunger referred to energy intake from the snacks. Low-risk females consumed two and a half times more calories from snacks than high-risk females and twice as many calories as low-risk and high-risk males when expressed as an individualized percentage of daily allowance for discretionary calories. Normal-weight females consumed two and a half times more calories from snacks than obese females and normal-weight males. The association between eating in the absence of hunger and weight and obesity risk status depended on adolescents' sex and could reflect emerging developmental differences, such as dieting or social desirability.     

A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis

OBJECTIVE: CD40-CD40 ligand (CD40L) interactions play a significant role in the production of autoantibodies and tissue injury in lupus nephritis. We performed an open-label, multiple-dose study to evaluate the safety, efficacy, and pharmacokinetics of BG9588, a humanized anti-CD40L antibody, in patients with proliferative lupus nephritis. The primary outcome measure was 50% reduction in proteinuria without worsening of renal function. METHODS: Twenty-eight patients with active proliferative lupus nephritis were scheduled to receive 20 mg/kg of BG9588 at biweekly intervals for the first 3 doses and at monthly intervals for 4 additional doses. Safety evaluations were performed on all patients. Eighteen patients receiving at least 3 doses were evaluated for efficacy. RESULTS: The study was terminated prematurely because of thromboembolic events occurring in patients in this and other BG9588 protocols (2 myocardial infarctions in this study). Of the 18 patients for whom efficacy could be evaluated, 2 had a 50% reduction in proteinuria without worsening of renal function. Mean reductions of 38.9% (P < 0.005), 50.1% (P < 0.005), and 25.3% (P < 0.05) in anti-double-stranded DNA (anti-dsDNA) antibody titers were observed at 1, 2, and 3 months, respectively, after the last treatment. There was a significant increase in serum C3 concentrations at 1 month after the last dose (P < 0.005), and hematuria disappeared in all 5 patients with significant hematuria at baseline. There were no statistically significant reductions in lymphocyte count or serum immunoglobulin, anticardiolipin antibody, or rubella IgG antibody concentrations after therapy. CONCLUSION: A short course of BG9588 treatment in patients with proliferative lupus nephritis reduces anti-dsDNA antibodies, increases C3 concentrations, and decreases hematuria, suggesting that the drug has immunomodulatory action. Additional studies will be needed to evaluate its long-term effects.     

Preventing and treating obesity in girls and young women to curb the epidemic

Obesity and its serious comorbidities, type 2 diabetes, coronary heart disease, hypertension, and dyslipidemia, have reached epidemic proportions in adults and children. Female obesity is more prevalent and, thus, has greater epidemiological importance: mothers transmit the disease epigenetically and genetically. Maternal obesity affects maternal health, pregnancy outcome, and fetal, neonatal, childhood, and ultimately adult morbidity and mortality. Obesity is easy to diagnose, as are most of its risk factors, yet very little progress has been made in preventing the disease. During a brief period of rapid early growth, there is imprinting of antecedents of adult obesity and obesity-related disease. Because of the rapidity of this early growth and the relative brevity of the critical period, early recognition and prompt intervention are necessary and possibly sufficient to prevent the development of obesity. Identification of inappropriate rapid weight gain through frequent weighing should trigger immediate adjustment of energy intake, a simple intervention in bottle-fed infants, the ones at greatest risk for becoming obese. This review presents a step-care strategy with fail-safe action levels starting with maternal education and diet, exercise, and behavior modification for mother and child and progressing to drug treatment and, in selected cases, laparoscopic surgery for young women of childbearing age in whom other measures have failed. This approach is predicated on the assumption that careful monitoring and responsive supplementation of potential deficiencies is easier to achieve, more cost-effective, and safer than effectively treating manifest obesity and its comorbidities in adults.