Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia.

Patients with schizophrenia show decreased processing speed on neuropsychological testing and decreased white matter integrity as measured by diffusion tensor imaging, two traits shown to be both heritable and genetically associated indicating that there may be genes that influence both traits as well as schizophrenia disease risk. The potassium channel gene family is a reasonable candidate to harbor such a gene given the prominent role potassium channels play in the central nervous system in signal transduction, particularly in myelinated axons. We genotyped members of the large potassium channel gene family focusing on putatively functional single nucleotide polymorphisms (SNPs) in a population of 363 controls, 194 patients with schizophrenia spectrum disorder (SSD) and 28 patients with affective disorders with psychotic features who completed imaging and neuropsychological testing. We then performed three association analyses using three phenotypes - processing speed, whole-brain white matter fractional anisotropy (FA) and schizophrenia spectrum diagnosis. We extracted SNPs showing an association at a nominal P value of <0.05 with all three phenotypes in the expected direction: decreased processing speed, decreased FA and increased risk of SSD. A single SNP, rs8234, in the 3' untranslated region of voltage-gated potassium channel subfamily Q member 1 (KCNQ1) was identified. Rs8234 has been shown to affect KCNQ1 expression levels, and KCNQ1 levels have been shown to affect neuronal action potentials. This exploratory analysis provides preliminary data suggesting that KCNQ1 may contribute to the shared risk for diminished processing speed, diminished white mater integrity and increased risk of schizophrenia.

Sustainability of an enhanced recovery after surgery program (ERAS) in colonic surgery.

BACKGROUND: Between 2006 and 2008 the enhanced recovery after surgery (ERAS) program was implemented in colonic surgery in one-third of all hospitals in the Netherlands (n = 33). This resulted in enhanced recovery and a decrease in hospital length of stay (LOS) from a median of 9 days at baseline to 6 days at one-year follow-up. The present study assessed the sustainability of the ERAS program 3-5 years after its implementation. MATERIALS AND METHODS: From the 33 ERAS hospitals, 10 initially successful hospitals were selected, with success defined as a median LOS of 6 days or lower and protocol adherence rates above 70 %. In 2012 a retrospective audit of 30 consecutive patients was performed in each of these hospitals. Sustainability of the ERAS program was assessed on hospital level, using median hospital LOS, protocol adherence rates and time to functional recovery. Data were compared with the implementation phase data. RESULTS: Overall median LOS in the selected hospitals increased from 5.25 days (interquartile range [IQR] 4.75-6.00; min, 4.00-max, 6.00) to 6 days (IQR 5.00-7.00; min, 5.00-max, 8.00), but this change was not significant (p = 0.052). Time to functional recovery was equal in both phases: median 3.00 days (p = 0.26). Protocol adherence decreased from 75 to 67 % (p = 0.32). Especially adherence to postoperative care elements dropped considerably. CONCLUSIONS: Despite a slight decrease in protocol adherence, the ERAS program was sustained reasonably well in the 10 selected hospitals, although there was quite some variation between the hospitals.

Sustainability of short stay after breast cancer surgery in early adopter hospitals.

Between 2005 and 2007 a short stay programme for breast cancer surgery was successfully implemented in early adopter hospitals. The current study evaluates the sustainability of this success five years following implementation. A retrospective audit of 160 consecutive patients undergoing breast cancer surgery was performed five years following implementation of short stay. The total proportion of patients treated in short stay was 82% (hospital 1 83%, hospital 2 78%, hospital 3 87%, hospital 4 80%) after five years follow-up, which was comparable to the proportion in short stay directly after implementation (p = 0.938). Overall compliance to the key recommendations to facilitate short stay after breast cancer surgery increased from 65% directly after implementation to 78% five years after implementation. This study shows that short stay after breast cancer surgery was successfully sustained in early adopter hospitals five years following implementation.

Brain gene expression changes elicited by peripheral vitellogenin knockdown in the honey bee.

Vitellogenin (Vg) is best known as a yolk protein precursor. Vg also functions to regulate behavioural maturation in adult honey bee workers, but the underlying molecular mechanisms by which it exerts this novel effect are largely unknown. We used abdominal vitellogenin (vg) knockdown with RNA interference (RNAi) and brain transcriptomic profiling to gain insights into how Vg influences honey bee behavioural maturation. We found that vg knockdown caused extensive gene expression changes in the bee brain, with much of this transcriptional response involving changes in central biological functions such as energy metabolism. vg knockdown targeted many of the same genes that show natural, maturation-related differences, but the direction of change for the genes in these two contrasts was not correlated. By contrast, vg knockdown targeted many of the same genes that are regulated by juvenile hormone (JH) and there was a significant correlation for the direction of change for the genes in these two contrasts. These results indicate that the tight coregulatory relationship that exists between JH and Vg in the regulation of honey bee behavioural maturation is manifest at the genomic level and suggest that these two physiological factors act through common pathways to regulate brain gene expression and behaviour.

PET lung ventilation/perfusion imaging using (68)Ga aerosol (Galligas) and (68)Ga-labeled macroaggregated albumin.

Pulmonary imaging using ventilation/perfusion (V/P) single-photon emission tomography (V/P scan) with Tc-99m-labeled radiotracers is a well-established diagnostic tool for clinically suspected pulmonary embolism (PE). Ga-68 aerosol (Galligas) and Ga-68-labeled macroaggregated albumin (MAA) are potential tracers for positron emission tomography (PET) lung V/P imaging and could display an advantage over conventional V/P scans in terms of sensitivity and specificity. After radiochemical and animal studies, the clinical applicability of Ga-68 aerosol (Galligas) and Ga-68-labeled MAA was investigated in an exploratory study in patients with clinical suspicion of PE. PET scans were acquired using a 16-slice Gemini TF positron emission tomography/computed tomography (PET/CT) scanner. The acquisition protocol included low-dose computed tomography (CT) for attenuation correction (AC). Dosimetry calculations and continuative phantom measurements were performed. Structural analyses showed no modification of the particles due to the labeling process. In addition, in vitro experiments showed stability of Ga-68 MAA in various media. As expected, Ga-68-labeled human serum albumin microspheres (HSAM) were completely retained in the lung of the animals. In clinical use, PET lung ventilation and perfusion imaging using Ga-68 aerosol (Galligas) and Ga-68-labeled MAA was successful in all cases. In one case a clinically suspected PE could be detected and verified. The administered activity of Ga-68 aerosol (Galligas) and Ga-68-labeled MAA may be reduced by more than 50%, resulting in comparable radiation exposure to conventional V/P scans. In conclusion, Ga-68 aerosol (Galligas) and Ga-68-labeled MAA are efficient substitutes for clinical use and could be an interesting alternative with high accuracy for lung V/P imaging with Tc-99m-labeled radiotracers, especially in times of Mo-99 shortages and increasing use and spread of PET/CT scanners and Ga-68 generators, respectively.

Behavioral plasticity in honey bees is associated with differences in brain microRNA transcriptome.

Small, non-coding microRNAs (miRNAs) have been implicated in many biological processes, including the development of the nervous system. However, the roles of miRNAs in natural behavioral and neuronal plasticity are not well understood. To help address this we characterized the microRNA transcriptome in the adult worker honey bee head and investigated whether changes in microRNA expression levels in the brain are associated with division of labor among honey bees, a well-established model for socially regulated behavior. We determined that several miRNAs were downregulated in bees that specialize on brood care (nurses) relative to foragers. Additional experiments showed that this downregulation is dependent upon social context; it only occurred when nurse bees were in colonies that also contained foragers. Analyses of conservation patterns of brain-expressed miRNAs across Hymenoptera suggest a role for certain miRNAs in the evolution of the Aculeata, which includes all the eusocial hymenopteran species. Our results support the intriguing hypothesis that miRNAs are important regulators of social behavior at both developmental and evolutionary time scales.

Application of local anesthesia inhibits effects of low-energy extracorporeal shock wave treatment (ESWT) on nociceptors.

OBJECTIVE: Clinical studies of extracorporeal shock wave therapy (ESWT) provided conflicting results depending on the use of local anesthesia (LA). DESIGN: The present study investigated whether the biological effects of ESWT differ between application with and without LA. SETTING AND PATIENTS: In 20 healthy subjects, ESWT was applied to the ventral surface of forearm skin, either after topical lidocaine pretreatment or without on the corresponding contralateral side. MEASURES: During and after ESWT ongoing pain, axon-reflex vasodilation (laser Doppler imaging), thresholds for pinprick, and blunt pressure were recorded. RESULTS: The results indicate that increasing ESWT energy flux density led to increasing pain (P < 0.001). LA reduced ESWT-related pain (P < 0.02) and in parallel inhibited local axon-reflex vasodilation (P < 0.001). In addition, LA prevented ESWT-related drop in pressure pain threshold (P < 0.001). CONCLUSION: This study provided evidence that ESWT dose-dependently activates and sensitizes primary afferent nociceptive C-fibers, and that both activation and sensitization were prevented if LA was applied locally. These results suggest that LA substantially alters the biological responses of ESWT.

Neuropeptide Y-like signalling and nutritionally mediated gene expression and behaviour in the honey bee.

Previous research has led to the idea that derived traits can arise through the evolution of novel roles for conserved genes. We explored whether neuropeptide Y (NPY)-like signalling, a conserved pathway that regulates food-related behaviour, is involved in a derived, nutritionally-related trait, the division of labour in worker honey bees. Transcripts encoding two NPY-like peptides were expressed in separate populations of brain neurosecretory cells, consistent with endocrine functions. NPY-related genes were upregulated in the brains of older foragers compared with younger bees performing brood care ('nurses'). A subset of these changes can be attributed to nutrition, but neuropeptide F peptide treatments did not influence sugar intake. These results contrast with recent reports of more robust associations between division of labour and the related insulin-signalling pathway and suggest that some elements of molecular pathways associated with feeding behaviour may be more evolutionarily labile than others.

Carbohydrate metabolism genes and pathways in insects: insights from the honey bee genome.

Carbohydrate-metabolizing enzymes may have particularly interesting roles in the honey bee, Apis mellifera, because this social insect has an extremely carbohydrate-rich diet, and nutrition plays important roles in caste determination and socially mediated behavioural plasticity. We annotated a total of 174 genes encoding carbohydrate-metabolizing enzymes and 28 genes encoding lipid-metabolizing enzymes, based on orthology to their counterparts in the fly, Drosophila melanogaster, and the mosquito, Anopheles gambiae. We found that the number of genes for carbohydrate metabolism appears to be more evolutionarily labile than for lipid metabolism. In particular, we identified striking changes in gene number or genomic organization for genes encoding glycolytic enzymes, cellulase, glucose oxidase and glucose dehydrogenases, glucose-methanol-choline (GMC) oxidoreductases, fucosyltransferases, and lysozymes.