Early life malnutrition and fluctuating asymmetry in the rat bony labyrinth

Maternal malnutrition during gestation and lactation is known to have adverse effects on offspring. We evaluate the impact of maternal diet on offspring bony labyrinth morphology. The bony labyrinth develops early and is thought to be stable to protect vital sensory organs within. For these reasons, bony labyrinth morphology has been used extensively to assess locomotion, hearing function, and phylogeny in primates and numerous other taxa. While variation related to these parameters has been documented, there is still a component of intraspecific variation that is unexplained. Although the labyrinthine developmental window is small, it may provide the opportunity for developmental instability to produce corresponding shape differences, as measured by fluctuating asymmetry (FA). We hypothesized that (a) offspring with poor maternal diet would exhibit increased FA, but (b) no unilateral shape difference. To test these hypotheses, we used two groups of rats (Rattus norvegicus; Crl:WI[Han] strain), one control group and one group exposed to a isocaloric, protein-restricted maternal diet during gestation and suckling. Individuals were sampled at weaning, sexual maturity, and old age. A Procrustes analysis of variance identified statistically significant FA in all diet-age subgroups. No differences in level of FA were identified among the subgroups, rejecting our first hypothesis. A principal components analysis identified no unilateral shape differences, supporting our second hypothesis. These results indicate that bony labyrinth morphology is remarkably stable and likely protected from a poor maternal diet during development. In light of this result, other factors must be explored to explain intraspecific variation in labyrinthine shape.     

Saturation recovery-prepared magnetic resonance angiography for assessment of left atrial and esophageal anatomy

Objectives:Magnetic resonance angiography (MRA) has been established as an important imaging method in cardiac ablation procedures. In pulmonary vein (PV) isolation procedures, MRA has the potential to minimize the risk of severe complications, such as atrio-esophageal fistula, by providing detailed information on esophageal position relatively to cardiac structures. However, traditional non-gated, first-pass (FP) MRA approaches have several limitations, such as long breath-holds, non-uniform signal intensity throughout the left atrium (LA), and poor esophageal visualization. The aim of this observational study was to validate a respiratory-navigated, ECG-gated (EC), saturation recovery-prepared MRA technique for simultaneous imaging of LA, LA appendage, PVs, esophagus, and adjacent anatomical structures.Methods:Before PVI, 106 consecutive patients with a history of AF underwent either conventional FP-MRA (n = 53 patients) or our new EC-MRA (n = 53 patients). Five quality scores (QS) of LA and esophagus visibility were assessed by two experienced readers. The non-parametric Mann–Whitney U-test was used to compare QS between FP-MRA and EC-MRA groups, and linear regression was applied to assess clinical contributors to image quality.Results:EC-MRA demonstrated significantly better image quality than FP-MRA in every quality category. Esophageal visibility using the new MRA technique was markedly better than with the conventional FP-MRA technique (median 3.5 [IQR 1] vs median 1.0, p < 0.001). In contrast to FP-MRA, overall image quality of EC-MRA was not influenced by heart rate.Conclusion:Our ECG-gated, respiratory-navigated, saturation recovery-prepared MRA technique provides significantly better image quality and esophageal visibility than the established non-gated, breath-holding FP-MRA. Image quality of EC-MRA technique has the additional advantage of being unaffected by heart rate.Advances in knowledge:Detailed information of cardiac anatomy has the potential to minimize the risk of severe complications and improve success rates in invasive electrophysiological studies. Our novel ECG-gated, respiratory-navigated, saturation recovery-prepared MRA technique provides significantly better image quality of LA and esophageal structures than the traditional first-pass algorithm. This new MRA technique is robust to arrhythmia (tachycardic, irregular heart rates) frequently observed in AF patients.     

Intra-amygdala infusion of the NPY Y1 receptor antagonist BIBP 3226 attenuates operant ethanol self-administration

BACKGROUND: Neuropeptide Y (NPY) is the most abundant and widely distributed peptide in the mammalian central nervous system. Evidence suggests that NPY transmission at Y1 receptors may regulate alcohol self-administration in rodent models. The purpose of the present study was to test the involvement of NPY Y1 receptors in the amygdala in the reinforcing effects of alcohol. METHODS: Long-Evans rats were trained to self-administer ethanol (10% v/v) vs. water on a concurrent FR-1 schedule of reinforcement using a sucrose fading procedure. After a 1 month baseline period, bilateral injector cannulae were surgically implanted to terminate 1 mm dorsal to the central nucleus of the amygdala. Daily (Monday through Friday) operant self-administration sessions were conducted for 6 months after surgery. Then, the effects of intra-amygdala infusion of the high-affinity nonpeptide NPY Y1 receptor antagonist BIBP 3226 (1, 10, or 20 microMg) were determined on parameters of operant alcohol self-administration. RESULTS: Intra-amygdala administration of 10 microM or 20 microM BIBP 3226 decreased total alcohol-reinforced responding and dose of self-administered ethanol (g/kg) without significantly altering total water responses or intake compared with vehicle control. Response onset was unaffected. Analysis of the temporal pattern of ethanol- and water-reinforced responding showed that BIBP 3226 decreased cumulative ethanol-reinforced responding during the 30 to 60 min period of the sessions. Water-reinforced responses were increased by the low dose of BIBP 3226 (1 microM) during the 50 to 60 min period. CONCLUSIONS: Results from this study indicate that alcohol-reinforced responding is reduced by acute blockade of NPY Y1 receptors in the amygdala of rats with a long-term history of alcohol self-administration. These data are consistent with the hypothesis that alcohol self-administration is maintained by NPY neurotransmission at Y1 receptors in the central nucleus of the amygdala.     

Bedside Coagulometry During Intravenous Heparin Therapy after Coronary Angioplasty

In order to assess the applicability of a bedside coagulometer for measurement of b-APTT, serial blood samples were obtained from 20 patients receiving intravenous heparin treatment following PTCA, and from 5 healthy volunteers. B-APTT was analysed bedside on the Hemochron® coagulometer; p-APTT and p-heparin, measured asfactor anti-Xa activity, were analysed ex-vivo in the laboratory. B-APTT values, determined by the Hemochron coagulometer, were closely correlated to p-heparin (r=0.83, p<0.001, SD=52 seconds (sec), n=89), and duplicate determinations of b-APTT on the Hemochron coagulometer showed an acceptable repeatability. However, an APTT ratio of 1.5–2.5 was not related to a therapeutic p-heparin level, neither as measured by the Hemochron device nor in the laboratory. Abstract. Background: When administering intravenous heparin during angioplasty procedures, a quick and reliable method for safe and effective monitoring of anticoagulation is necessary. Objective: To assess the applicability of a bedside coagulometer, measuring the activated partial thromboplastin time (APTT) in patients receiving intravenous heparin treatment after percutaneous transluminal coronary angioplasty (PTCA). Methods: In patients with stable angina pectoris, receiving intravenous heparin treatment following PTCA, serial blood samples were obtained by venipuncture and from the arterial sheath for analysis of whole blood APTT (b-APTT), and plasma heparin concentration (p-heparin). Additionally, in healthy volunteers blood samples were obtained after a single bolus injection of heparin. B-APTT was analysed bedside on the Hemochron® coagulometer; p-APTT and p-heparin, measured as factor anti-Xa activity, were analysed ex-vivo in the laboratory using conventional analytical methods. Results: In 20 patients a total of 94 venous and 69 arterial blood samples were analysed, and in five healthy volunteers analyses were performed in 20 venous blood samples. B-APTT values, determined by the Hemochron coagulometer, were closely correlated to p-heparin (r=0.83, p<0.001, SD=52 seconds (sec), n=89). An APTT ratio of 1.5–2.5 was not related to a therapeutic p-heparin level, however, neither when using APTT assessed by the Hemochron device nor APTT measured in the laboratory. Duplicate determinations of b-APTT on the Hemochron coagulometer showed an acceptable repeatability; the mean difference between duplicate measurements was 4[emsp4 ] sec (coefficient of variation (c.v.)=6%, p<0.05, n=163). Conclusions: In patients receiving intravenous heparin after PTCA treatment, b-APTT values measured by the Hemochron method showed an acceptable repeatability and were significantly correlated to p-heparin.     

Preventable Major Cardiovascular Events Associated With Uncontrolled Glucose,Blood Pressure,and Lipids and Active Smoking in Adults With Diabetes With and Without Cardiovascular Disease: A Contemporary Analysis

OBJECTIVEThe objective of this study was to assess the incidence of major cardiovascular (CV) hospitalization events and all-cause deaths among adults with diabetes with or without CV disease (CVD) associated with inadequately controlled glycated hemoglobin (A1C), high LDL cholesterol (LDL-C), high blood pressure (BP), and current smoking.RESULTSMean (SD) age at baseline was 59 (14) years; 48% of subjects were female, 45% were white, and 31% had CVD. Mean follow-up was 59 months. Event rates per 100 person-years for adults with diabetes and CVD versus those without CVD were 6.0 vs. 1.7 for MI/ACS, 5.3 vs. 1.5 for stroke, 8.4 vs. 1.2 for HF, 18.1 vs. 40 for all CV events, and 23.5 vs. 5.0 for all-cause mortality. The percentages of CV events and deaths associated with inadequate risk factor control were 11% and 3%, respectively, for those with CVD and 34% and 7%, respectively, for those without CVD.CONCLUSIONSAdditional attention to traditional CV risk factors could yield further substantive reductions in CV events and mortality in adults with diabetes.     

Tumor suppression by cell competition through regulation of the Hippo pathway

Homeostatic mechanisms can eliminate abnormal cells to prevent diseases such as cancer. However, the underlying mechanisms of this surveillance are poorly understood. Here we investigated how clones of cells mutant for the neoplastic tumor suppressor gene scribble (scrib) are eliminated from Drosophila imaginal discs. When all cells in imaginal discs are mutant for scrib, they hyperactivate the Hippo pathway effector Yorkie (Yki), which drives growth of the discs into large neoplastic masses. Strikingly, when discs also contain normal cells, the scrib(-) cells do not overproliferate and eventually undergo apoptosis through JNK-dependent mechanisms. However, induction of apoptosis does not explain how scrib(-) cells are prevented from overproliferating. We report that cell competition between scrib(-) and wild-type cells prevents hyperproliferation by suppressing Yki activity in scrib(-) cells. Suppressing Yki activation is critical for scrib(-) clone elimination by cell competition, and experimental elevation of Yki activity in scrib(-) cells is sufficient to fuel their neoplastic growth. Thus, cell competition acts as a tumor-suppressing mechanism by regulating the Hippo pathway in scrib(-) cells.     

The initial health-system response to the earthquake in Christchurch, New Zealand, in February, 2011

At 1251 h on Feb 22, 2011, an earthquake struck Christchurch, New Zealand, causing widespread destruction. The only regional acute hospital was compromised but was able to continue to provide care, supported by other hospitals and primary care facilities in the city. 6659 people were injured and 182 died in the initial 24 h. The massive peak ground accelerations, the time of the day, and the collapse of major buildings contributed to injuries, but the proximity of the hospital to the central business district, which was the most affected, and the provision of good medical care based on careful preparation helped reduce mortality and the burden of injury. Lessons learned from the health response to this earthquake include the need for emergency departments to prepare for: patients arriving by unusual means without prehospital care, manual registration and tracking of patients, patient reluctance to come into hospital buildings, complete loss of electrical power, management of the many willing helpers, alternative communication methods, control of the media, and teamwork with clear leadership. Additionally, atypical providers of acute injury care need to be integrated into response plans.