Vagus nerve stimulation ameliorated deficits in one-way active avoidance learning and stimulated hippocampal neurogenesis in bulbectomized rats

BackgroundVagus nerve stimulation (VNS) has been introduced as a therapeutic option for treatment-resistant depression. The neural and chemical mechanisms responsible for the effects of VNS are largely unclear.MethodsBilateral removal of the olfactory bulbs (OBX) is a validated animal model in depression research. We studied the effects of vagus nerve stimulation (VNS) on disturbed one-way active avoidance learning and neurogenesis in the hippocampal dentate gyrus of rats.ResultsAfter a stimulation period of 3 weeks, OBX rats acquired the learning task as controls. In addition, the OBX-related decrease of neuronal differentiated BrdU positive cells in the dentate gyrus was prevented by VNS.ConclusionsThis suggests that chronic VNS and changes in hippocampal neurogenesis induced by VNS may also account for the amelioration of behavioral deficits in OBX rats. To the best of our knowledge, this is the first report on the restorative effects of VNS on behavioral function in an animal model of depression that can be compared with the effects of antidepressants.     

Pregnancy related issues in inflammatory bowel disease: evidence base and patients' perspective

Inflammatory bowel disease (IBD) affects women of childbearing age and can influence fertility, pregnancy and decisions regarding breastfeeding. Women with IBD need to consider the possible course of disease during pregnancy, the benefits and risks associated with medications required for disease management during pregnancy and breastfeeding and the effects of mode of delivery on their disease. When indicated, aminosalicylates and thiopurines can be safely used during pregnancy. Infliximab and Adalimumab are considered probably safe during the first two trimesters. During the third trimester the placenta can be crossed and caution should be applied. Methotrexate is associated with severe teratogenicity due to its folate antagonism and is strictly contraindicated. Women with IBD tend to deliver earlier than healthy women, but can have a vaginal delivery in most cases. Caesarean sections are generally recommended for women with active perianal disease or after ileo-anal pouch surgery.While the impact of disease activity and medication has been addressed in several studies, there are minimal studies evaluating patients' perspective on these issues. Women's attitudes may influence their decision to have children and can positively or negatively influence the chance of conceiving, and their beliefs regarding therapies may impact on the course of their disease during pregnancy and/or breastfeeding. This review article outlines the impact of IBD and its treatment on pregnancy, and examines the available data on patients' views on this subject.     

Mortality from inflammatory bowel diseases

Ulcerative colitis (UC) and Crohn's disease (CD) may directly result in morbidity and rarely mortality from complications such as colorectal cancer or sepsis. Mortality rates compared with the matched general population, measured by standardized mortality ratio, may therefore be increased. This review examines the evidence derived from cohort- and population-based mortality studies. In CD the majority of studies and two meta-analyses demonstrated increased standardized mortality ratios of ≈ 1.5-fold, especially for those diagnosed at younger ages and requiring extensive or multiple resection surgery. In UC mortality rates are similar to those of the general population in most studies and a meta-analysis. Proctocolectomy removes the inflammatory burden of UC and can manage colorectal dysplasia but may result in perioperative complications. There is no clear temporal trend of improvement in survival for either CD or UC. Few data are available from countries outside Europe and North America, so geographical influences remain largely unknown.     

Opposing roles of sensory and parietal cortices in awareness in a bistable motion illusion

Motion-induced blindness (MIB) is a bistable visual phenomenon in which stationary disks surrounded by a moving pattern intermittently disappear from the viewer's awareness. We explored the cortical network that subserves the MIB phenomenon by targeting its constituent parts with disruptive transcranial magnetic stimulation (TMS), in the form of continuous theta burst stimulation (cTBS). Previous neuroimaging and TMS studies have implicated the right posterior parietal cortex (rPPC) in perceptual transitions such as binocular rivalry, while the visual area V5/MT has been suggested to play a key role in MIB. In this study, we found that cTBS applied to the rPPC lengthened the duration of disappearance in MIB, while cTBS applied to V5/MT shortened the duration of disappearance and decreased the frequency of disappearance in MIB. These results demonstrate a causal role for both the rPPC and V5/MT in MIB, and suggest that the rPPC is involved in shifting resources between competing functional areas, while V5/MT processing initiates and maintains MIB.     

An in situ study investigating dentine tubule occlusion of dentifrices following acid challenge

Objectives

To investigate the dentine occlusion and acid resistance of dentifrices developed to treat dentine hypersensitivity.

Methods

This was a single centre, single blind, randomised, split mouth, four treatments, two period crossover, in situ study in healthy subjects. Subjects wore buccal intra-oral appliances each fitted with four dentine samples over four consecutive days with one study product applied per appliance; 8% strontium acetate in silica base, 1040 ppm sodium fluoride (Sensodyne^® Rapid Relief), 8% arginine, calcium carbonate, 1450 ppm sodium monofluorophosphate (Colgate Sensitive Pro-Relief^®), 1450 ppm sodium fluoride (control paste) and water. On days 3 and 4, two agitated grapefruit juice challenges (ex vivo) occurred for 1 min. At the end of each treatment day 1 dentine sample was removed from each appliance for scanning electron microscopy (SEM). The extent of tubule occlusion was measured using an examiner-based visual scoring index (three trained examiners).

Results

In total, 28 subjects ((12 males and 16 females with a mean age of 34.7 years (SD 8.41 years)) completed the study. On day 2, both test dentifrices demonstrated significantly better dentine tubule occlusion than water (p < 0.0001) and control paste (8% strontium p = 0.0003 and 8% arginine p = 0.0019). After 3 and 4 days of twice daily brushing with acid challenges on days 3 and 4 the strontium-based dentifrice demonstrated significantly better dentine occlusion than all other treatments (p < 0.0001).

Conclusions

Strontium acetate and arginine-based dentifrice result in statistically significant dentine tubular occlusion compared to controls, but the arginine-based dentifrice is more susceptible to acid challenge.

Clinical significance

Erosive beverages are an important aetiology in DH by exposing dentine tubules. Their consumption has increased significantly over the past decade in the UK. This 4-day in situ study investigated the properties of commercially available dentifrices designed to occlude dentine tubules and their resistance to an agitated acid challenge.     

Current knowledge on the sensitivity of the <Superscript>68</Superscript>Ga-somatostatin receptor positron emission tomography and the SUV<Subscript>max</Subscript> reference range for management of pancreatic neuroendocrine tumours

Physiologically increased pancreatic uptake at the head/uncinate process is observed in more than one-third of patients after injection of one of the three ⁶⁸Ga-labelled octreotide-based peptides used for somatostatin (sst) receptor (r) imaging. There are minor differences between these ⁶⁸Ga-sstr-binding peptides in the imaging setting. On ⁶⁸Ga-sstr-imaging the physiological uptake can be diffuse or focal and usually remains stable over time. Differences in the maximal standardised uptake values (SUV_max) reported for the normal pancreas as well as for pancreatic neuroendocrine tumour (PNET) lesions may be related to several factors, including (a) differences in the peptide binding affinities as well as differences in sstr subtype expression of pancreatic α- and β-cells, and heterogeneity / density of tumour cells, (b) differences in scanner resolution, image reconstruction techniques and acquisition protocols, (c) mostly retrospective study designs, (d) mixed patient populations, or (e) interference with medications such as treatment with long-acting sst analogues. The major limitation in most of the studies lies in the lack of histopathological confirmation of abnormal findings. There is a significant overlap between the calculated SUV_max-values for physiological pancreas and PNET-lesions of the head/uncinate process that do not favour the use of quantitative parameters in the clinical setting. Anecdotal long-term follow-up studies have even indicated that increased uptake in the head/uncinate process still can turn out to be malignant over years of follow up. SUV_max-data for the pancreatic body and tail are limited. Therefore, any visible focal tracer uptake in the pancreas must be considered as suspicious for malignancy irrespective of quantitative parameters. In general, sstr-PET/CT has significant implications for the management of NET patients leading to a change in treatment decision in about one-third of patients. Therefore, follow-up with ⁶⁸Ga-sstr-PET/CT is mandatory in the clinical setting if uptake in the head/uncinate process is observed.