β-cell intrinsic dynamics rather than gap junction structure dictates subpopulations in the islet functional network.

Diabetes is caused by the inability of electrically coupled, functionally heterogeneous β-cells within the pancreatic islet to provide adequate insulin secretion. Functional networks have been used to represent synchronized oscillatory [Ca] dynamics and to study β-cell subpopulations, which play an important role in driving islet function. The mechanism by which highly synchronized β-cell subpopulations drive islet function is unclear.

Deconstructing the integrated oscillator model for pancreatic β-cells.

Electrical bursting oscillations in the β-cells of pancreatic islets have been a focus of investigation for more than fifty years. This has been aided by mathematical models, which are descendants of the pioneering Chay-Keizer model. This article describes the key biophysical and mathematical elements of this model, and then describes the path forward from there to the Integrated Oscillator Model (IOM).

Circadian distribution of epileptiform discharges in epilepsy: Candidate mechanisms of variability.

Epilepsy is a serious neurological disorder characterised by a tendency to have recurrent, spontaneous, seizures. Classically, seizures are assumed to occur at random. However, recent research has uncovered underlying rhythms both in seizures and in key signatures of epilepsy-so-called interictal epileptiform activity-with timescales that vary from hours and days through to months.

Pulsatile Basal Insulin Secretion Is Driven by Glycolytic Oscillations.

In fasted and fed states, blood insulin levels are oscillatory. While this phenomenon is well studied at high glucose levels, comparatively little is known about its origin under basal conditions. We propose a possible mechanism for basal insulin oscillations based on oscillations in glycolysis, demonstrated using an established mathematical model.

Oscillations in K(ATP) conductance drive slow calcium oscillations in pancreatic β-cells.

ATP-sensitive K (K(ATP)) channels were first reported in the β-cells of pancreatic islets in 1984, and it was soon established that they are the primary means by which the blood glucose level is transduced to cellular electrical activity and consequently insulin secretion. However, the role that the K(ATP) channels play in driving the bursting electrical activity of islet β-cells, which drives pulsatile insulin secretion, remains unclear. One difficulty is that bursting is abolished when several different ion channel types are blocked pharmacologically or genetically, making it challenging to distinguish causation from correlation.

Slow oscillations persist in pancreatic beta cells lacking phosphofructokinase M.

Pulsatile insulin secretion by pancreatic beta cells is necessary for tight glucose control in the body. Glycolytic oscillations have been proposed as the mechanism for generating the electrical oscillations underlying pulsatile insulin secretion. The glycolytic enzyme 6-phosphofructokinase-1 (PFK) synthesizes fructose-1,6-bisphosphate (FBP) from fructose-6-phosphate.

Symbiosis of Electrical and Metabolic Oscillations in Pancreatic β-Cells.

Insulin is secreted in a pulsatile pattern, with important physiological ramifications. In pancreatic β-cells, which are the cells that synthesize insulin, insulin exocytosis is elicited by pulses of elevated intracellular Ca initiated by bursts of electrical activity. In parallel with these electrical and Ca oscillations are oscillations in metabolism, and the periods of all of these oscillatory processes are similar.

Chronic stimulation induces adaptive potassium channel activity that restores calcium oscillations in pancreatic islets in vitro.

Insulin pulsatility is important to hepatic response in regulating blood glucose. Growing evidence suggests that insulin-secreting pancreatic β-cells can adapt to chronic disruptions of pulsatility to rescue this physiologically important behavior. We determined the time scale for adaptation and examined potential ion channels underlying it.

Transitions between bursting modes in the integrated oscillator model for pancreatic β-cells.

Insulin-secreting β-cells of pancreatic islets of Langerhans produce bursts of electrical impulses, resulting in intracellular Ca oscillations and pulsatile insulin secretion. The mechanism for this bursting activity has been the focus of mathematical modeling for more than three decades, and as new data are acquired old models are modified and new models are developed. Comprehensive models must now account for the various modes of bursting observed in islet β-cells, which include fast bursting, slow bursting, and compound bursting.

Clinical Target Volume in Biliary Carcinoma: A Systematic Review of Pathological Studies.

Background/aim: Radiotherapy is a treatment option for both adjuvant and neo-adjuvant settings for biliary tract cancer. Guidelines on the delineation of the target volume of lymph nodes are lacking; only generic indications are available, without specific recommendations for different primary tumour locations (e.g.

Patient-specific computational modeling of cortical spreading depression via diffusion tensor imaging.

Cortical spreading depression, a depolarization wave originating in the visual cortex and traveling towards the frontal lobe, is commonly accepted as a correlate of migraine visual aura. As of today, little is known about the mechanisms that can trigger or stop such phenomenon. However, the complex and highly individual characteristics of the brain cortex suggest that the geometry might have a significant impact in supporting or contrasting the propagation of cortical spreading depression.

Estimation of age-specific rates of reactivation and immune boosting of the varicella zoster virus.

Studies into the impact of vaccination against the varicella zoster virus (VZV) have increasingly focused on herpes zoster (HZ), which is believed to be increasing in vaccinated populations with decreasing infection pressure. This idea can be traced back to Hope-Simpson's hypothesis, in which a person's immune status determines the likelihood that he/she will develop HZ. Immunity decreases over time, and can be boosted by contact with a person experiencing varicella (exogenous boosting) or by a reactivation attempt of the virus (endogenous boosting).

An overview of international literature from cystic fibrosis registries. Part 4: update 2011.

A total of 53 national cystic fibrosis (CF) patient registry studies published between July 2008 and November 2011 have been reviewed, focusing on the following topics: CF epidemiology, nutrition, microbiology, clinical complications, factors influencing diagnosis and lung disease, effects of socioeconomic status, therapeutic strategy evaluation, clinical trial methodology. The studies describe the clinical characteristics of CF patients, the incidence and prevalence of disease and role of gender gap, as well as the influence of socioeconomic status and environmental factors on clinical outcomes, covering a variety of countries and ethnic groups. Original observations describe patients as they get older, with special reference to the adult presentation of CF and long-term survival.

An overview of international literature from cystic fibrosis registries. Part 3. Disease incidence, genotype/phenotype correlation, microbiology, pregnancy, clinical complications, lung transplantation, and miscellanea.

This is the third article related to a review of the literature based on data from national cystic fibrosis (CF) patient registries up to June 2008 and covering a total of 115 published studies. It focuses on several topics: CF incidence, genotype/phenotype correlation, microbiology, pregnancy/paternity, clinical complications, lung transplantation, and others. Seventy seven papers meeting the inclusion criteria were found to be related to the topics listed above.

An overview of international literature from cystic fibrosis registries 2. Neonatal screening and nutrition/growth.

Background: This is the second article related to a review of the literature based on data from national cystic fibrosis (CF) registries up to June 2008 and covering a total of 115 studies. It focuses on two topics: neonatal screening (NS) and nutritional status, with particular reference to growth.

Methods: Ten papers meeting the inclusion criteria were found on the topic of NS and its impact on the course of the disease, and were analyzed according to a dedicated grid.

An overview of international literature from cystic fibrosis registries: 1. Mortality and survival studies in cystic fibrosis.

Patient registries are organized systems of data collection for scientific, clinical or health strategy purposes. Aims of our review were to document scientific literature based on data and information from cystic fibrosis (CF) registries; to understand which clinical problems have been addressed and for which of these the studies concerned have correctly answered the questions raised (i.e.

Lethal short rib syndrome of the Beemer type without polydactyly.

A new case of Beemer short-rib dwarfism is reported and the clinical and radiological differences between this and Majewski type are discussed. The clinical variability related to the lack or presence of polydactyly is underlined, together with the importance of prenatal diagnosis.

[Mitral valve replacement with porcine bioprosthesis in children. Evaluation of 29 patients during 12 years].

Purpose: To analyze the clinical result of the mitral valve substitution for the porcine bioprostheses, the incidence of dysfunction caused by calcification and its importance related to the durability of bioprostheses and also the patients' survival.

Methods: Twenty-nine children of about seven to sixteen years old were operated on from November 1977 to August 1982 and all of them received porcine bioprostheses of low profile.

Results: There were three (10.

[Partial agenesis of the musculus pectoralis major].

The authors report a rare case of partial agenesia of the pectoralis major muscle with presence of the "pars clavicularis" only. Full range of movement was possible in this case, in accordance with other reports in the literature.

Inactive subretinal neovascularization in age-related macular degeneration.

Inactive subretinal new vessels (SRNVs), showing minimal leakage by fluorescein angiography and little progression, were observed in 15 eyes of 12 patients with age-related macular degeneration. In 8 (57%) of 14 eyes followed for longer than 6 months, the new vessels involuted and produced circumscribed areas of retinal pigment epithelium and choriocapillaris atrophy; 6 (43%) showed a further decrease in the fluorescein leakage during the follow-up period (average, 30.1 months).

T-cell response to anti-CD2 monoclonal antibodies in Down's syndrome.

Peripheral blood mononuclear cells from 10 subjects with cytogenetically documented Down's syndrome (DS) and from 10 age- and sex-matched healthy controls were assayed for their ability to proliferate in response to phytohaemagglutinin, anti-CD3 (OKT3), or anti-CD2 (T11(2) plus T11(3] monoclonal antibodies. Interleukin 2 (IL-2) receptor expression and IL-2 production in mitogen-pulsed lymphocyte cultures was also investigated in parallel. DS cells responded poorly to all the blastogenic stimuli used in this study.

Activation of cord T lymphocytes. I. Evidence for a defective T cell mitogenesis induced through the CD2 molecule.

A study was carried out on cord blood T cell activation via the CD2-mediated pathway. Despite similar percentages of circulating CD3+ and CD2+ cells in adult and cord blood, the proliferation of cord PBMC to the anti-CD3 mAb and cord T cells to anti-CD2 mAb were defective. The T cell CD3-surface structure was normally able to control CD2-mediated activation, as its modulation by a non-mitogenic anti-CD3 mAb blocked cord PBMC proliferation induced by anti-CD2 mAb.

T cell response to anti-CD3 antibody in Down's syndrome.

The non-specific mitogen phytohaemagglutinin (PHA) and an anti-CD3 (OKT3) monoclonal antibody were used to measure the lymphocyte proliferative response in blood samples from 15 subjects with Down's syndrome. Blood from 15 healthy controls closely matched for age and sex was also assayed. The mean blastogenic value in PHA stimulated patient lymphocyte cultures was similar to that calculated in the controls.