LED Zappelin': An open source LED controller for arbitrary spectrum visual stimulation and optogenetics during 2-photon imaging.

Two-photon (2P) microscopy is a cornerstone technique in neuroscience research. However, combining 2P imaging with spectrally arbitrary light stimulation can be challenging due to crosstalk between stimulation light and fluorescence detection. To overcome this limitation, we present a simple and low-cost electronic solution based on an ESP32 microcontroller and a TLC5947 LED driver to rapidly time-interleave stimulation and detection epochs during scans. Implemented for less than $100, our design can independently drive up to 24 arbitrary spectrum LEDs to meet user requirements. We demonstrate the utility of our stimulator for colour vision experiments on the in vivo tetrachromatic zebrafish retina and for optogenetic circuit mapping in Drosophila.

Modelling the effects of glucagon during glucose tolerance testing.

BACKGROUND: Glucose tolerance testing is a tool used to estimate glucose effectiveness and insulin sensitivity in diabetic patients. The importance of such tests has prompted the development and utilisation of mathematical models that describe glucose kinetics as a function of insulin activity. The hormone glucagon, also plays a fundamental role in systemic plasma glucose regulation and is secreted reciprocally to insulin, stimulating catabolic glucose utilisation. However, regulation of glucagon secretion by α-cells is impaired in type-1 and type-2 diabetes through pancreatic islet dysfunction. Despite this, inclusion of glucagon activity when modelling the glucose kinetics during glucose tolerance testing is often overlooked. This study presents two mathematical models of a glucose tolerance test that incorporate glucose-insulin-glucagon dynamics. The first model describes a non-linear relationship between glucagon and glucose, whereas the second model assumes a linear relationship. RESULTS: Both models are validated against insulin-modified and glucose infusion intravenous glucose tolerance test (IVGTT) data, as well as insulin infusion data, and are capable of estimating patient glucose effectiveness (sG) and insulin sensitivity (sI). Inclusion of glucagon dynamics proves to provide a more detailed representation of the metabolic portrait, enabling estimation of two new diagnostic parameters: glucagon effectiveness (sE) and glucagon sensitivity (δ). CONCLUSIONS: The models are used to investigate how different degrees of pax'tient glucagon sensitivity and effectiveness affect the concentration of blood glucose and plasma glucagon during IVGTT and insulin infusion tests, providing a platform from which the role of glucagon dynamics during a glucose tolerance test may be investigated and predicted.

A Framework for the Generation of Realistic Synthetic Cardiac Ultrasound and Magnetic Resonance Imaging Sequences From the Same Virtual Patients.

The use of synthetic sequences is one of the most promising tools for advanced in silico evaluation of the quantification of cardiac deformation and strain through 3-D ultrasound (US) and magnetic resonance (MR) imaging. In this paper, we propose the first simulation framework which allows the generation of realistic 3-D synthetic cardiac US and MR (both cine and tagging) image sequences from the same virtual patient. A state-of-the-art electromechanical (E/M) model was exploited for simulating groundtruth cardiac motion fields ranging from healthy to various pathological cases, including both ventricular dyssynchrony and myocardial ischemia. The E/M groundtruth along with template MR/US images and physical simulators were combined in a unified framework for generating synthetic data. We efficiently merged several warping strategies to keep the full control of myocardial deformations while preserving realistic image texture. In total, we generated 18 virtual patients, each with synthetic 3-D US, cine MR, and tagged MR sequences. The simulated images were evaluated both qualitatively by showing realistic textures and quantitatively by observing myocardial intensity distributions similar to real data. In particular, the US simulation showed a smoother myocardium/background interface than the state-of-the-art. We also assessed the mechanical properties. The pathological subjects were discriminated from the healthy ones by both global indexes (ejection fraction and the global circumferential strain) and regional strain curves. The synthetic database is comprehensive in terms of both pathology and modality, and has a level of realism sufficient for validation purposes. All the 90 sequences are made publicly available to the research community via an open-access database.

A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea.

BACKGROUND: AGI004 is a controlled-release transdermal patch preparation of mecamylamine. We conducted a randomised placebo-controlled phase II study of two dose levels of AGI004 in chemotherapy-induced diarrhoea (CID). METHODS: Adult patients receiving chemotherapy who had experienced diarrhoea (NCI grade 1-2) during previous cycles of chemotherapy were eligible. In all, 64 patients were randomised to receive AGI004 4 mg then 8 mg per 24 h transdermal patch or placebo for two sequential cycles of chemotherapy. Patients' severity of diarrhoea was physician-assessed using NCI grade of diarrhoea and patient-assessed using information recorded in daily diaries of bowel movements. RESULTS: Overall AGI004 doubled the odds of a response to treatment on the first day of chemotherapy based on physician assessment of NCI grade of diarrhoea compared with placebo (odds ratio=2.0, 90% confidence interval: 0.9-4.5) and there was a trend to improved response rates for AGI004 for the full treatment cycle although these results were not statistically significant. There was also evidence of significantly improved response rates based on patient assessment of diarrhoea both overall (P=0.05) and at the 8-mg dose level (P=0.02) compared with placebo. CONCLUSION: AGI004 demonstrated effectiveness in reducing chemotherapy-associated diarrhoea, with results suggesting response across multiple measurements of diarrhoea. Treatment was well tolerated with no drug-related adverse events. Further evaluation of this agent in the management of CID is warranted.

The role of contrast enhanced ultrasound in the assessment of superficial lymph nodes.

Evaluation of superficial lymphadenopathy is important for patients with pathologies like head and neck cancers or breast cancer, as it helps the assessment of patient prognosis and the selection of treatment method. Cervical lymph nodes are also common sites of involvement in lymphoma. Lymphomatous nodes are usually difficult to differentiate from metastatic nodes in clinical examinations. As the treatment for lymphoma and metastases is different, accurate differential diagnosis between the two conditions is important. Ultrasound is a useful imaging modality in evaluation of superficial lymphadenopathy because of its high sensitivity and specificity, especially when combined histopathology. With the use of power Doppler sonography, the vasculature of the lymph nodes can also be evaluated, which provides additional information in the sonographic examination of superficial lymph nodes. But there are still nodes that cannot be examined by Doppler or their vasculature cannot be visualized. So, in the last decade, contrast-enhanced ultrasound was more and more discussed as a non-invasive method for a more accurate differential diagnosis of cervical lymphadenopathy.

[Oral health: social determinants of a health inequality]. / Santé buccale: déterminants sociaux d'un terrain majeur des inégalités.

The oral health of disadvantaged social groups is worse at all the ages than that of the favored groups. If tooth decay prevalence decreases, this disease is still unequally distributed: 20% of the children, those with the weakest socio-economic statute (SES), concentrate 60% of the decays. Edentulism strikes significantly more people with weak SES. The inequalities of oral health reflect those of general health. Evidence of the inequalities in oral health is exposed even in the developed countries. Different models of intervention are presented: risk groups identification and targeting by specific programs; oral health community approach which includes socio-economic and public health measures aiming all the population; insurance approach to be combined with the preceding ones.

Experimental and theoretical modelling of blind-ended vessels within a developing angiogenic plexus.

Angiogenic sprouts at the leading edge of an expanding vascular plexus are recognised as major regulators of the structure of the developing network. Early in sprout development, a vascular lumen is often evident which communicates with the parent vessel while the distal tip is blind-ended. Here we describe the temporal evolution of blind-ended vessels (BEVs) in a small wound made in the panniculus carnosus muscle of a mouse viewed in a dorsal skin-fold window-chamber model with intra-vital microscopy during the most active period of angiogenesis (days 5-8 after injury). Although these structures have been mentioned anecdotally in previous studies, we observed BEVs to be frequent, albeit transient, features of plexus formation. Plasma leakage into the surrounding extracellular matrix occurring from these immature conduits could play an important role in preparing hypoxic tissue for vascular invasion. Although sprout growth is likely to be regulated by its flow environment, the parameters regulating flow into and through BEVs have not been characterised in situ. Longitudinal data from individual animals show that the number of BEVs filled with plasma alone peaks at day 7, when they can exceed 150 microm in length. Additionally, BEVs greater than 40 microm in length are more likely to be filled with stationary erythrocytes than with plasma alone. Using a mathematical model, we show how the flux of 150 kD fluorinated (FITC-) dextran through an individual plasma-filled BEV is related to its geometry being determined primarily by its surface area; by fitting theoretical intensity values to experimental data we assess the permeability of the vessel to FITC-dextran. Plasma skimming provides a mechanistic explanation for the observation that BEVs with larger surface area are more likely to recruit erythrocytes.

Imaging aspects of the lacrimal gland in Sjögren syndrome--case report.

PURPOSE: The study presents a case of bilateral lacrimal gland hypertrophy with secondary glaucoma due to the increased episcleral venous pressure. METHOD: The case was investigated by means of clinical methods associated with ultrasound (A and B-scan, Doppler-ultrasound) and magnetic resonance imaging techniques. RESULTS: The clinical data revealed proptosis, episcleral congestion, and elevated intraocular pressure. An abnormal Schirmer test and xerophthalmia were also present. Ultrasound examination identifies enlarged masses in the bilateral lacrimal fossa, supra-temporal to the globe, mostly on the left side, having a cystic structure. The Doppler ultrasound investigation revealed the vascularisation, and the magnetic resonance imaging completed the dates offered by the ultrasound methods. According to the clinical aspect and the possible visual impairment produced by the secondary glaucoma, the mass lesion was removed on the left side by neurosurgical approach. The histopathological exam confirmed the destruction of the lacrimal gland, and, furthermore, the immunohistochemical study revealed the aspect of Sjögren syndrome lesions. CONCLUSIONS: Sonography is able to provide noninvasively much of the information needed by the clinician. Ultrasound techniques (A-scan, B-scan and color Doppler) and magnetic resonance imaging allow tracking and discrimination of the orbital diseases, such as lacrimal gland lesions. Associated with the clinical features, these methods offer the basis of a correct diagnosis and a proper therapy for lacrimal gland pathology.

Shock formation and non-linear dispersion in a microvascular capillary network.

Temporal and spatial fluctuations are a common feature of blood flow in microvascular networks. Among many possible causes, previous authors have suggested that the non-linear rheological properties of capillary blood flow (notably the Fåhraeus effect, the Fåhraeus-Lindqvist effect and the phase-separation effect at bifurcations) may be sufficient to generate temporal fluctuations even in very simple networks. We have simulated blood flow driven by a fixed pressure drop through a simple arcade network using coupled hyperbolic partial differential equations (PDEs) that incorporate well-established empirical descriptions of these rheological effects, accounting in particular for spatially varying haematocrit distributions; we solved the PDE system using a characteristic-based method. Our computations indicate that, under physiologically realistic conditions, there is a unique steady flow in an arcade network which is linearly stable and that plasma skimming suppresses the oscillatory decay of perturbations. In addition, we find that non-linear perturbations to haematocrit distributions can develop shocks via the Fåhraeus effect, providing a novel mechanism for non-linear dispersion in microvascular networks.

[Is atropine efficient in para-bulbar injections?]. / Este eficienta atropina administrata parabulbar?

Supposing the fact that atropine has antispastic effect on blood vessels, we studied the variation of blood flow in ophthalmic artery, central retinal artery and ciliary arteries, by Doppler ultrasound. We used 1 ml Atropine 1@1000 in parabulbar administration to 17 eyes with neuro-retinal diseases and the arterial flow was registered for 3 times: before the injection, at 15 and respective 30 minutes after administration. The results were processed using t-Student method. The atropine effect seemed to be more intensive 30 minutes after administration on central retinal artery.

Phagocytosis and clearance of apoptotic cells is mediated by MER.

Apoptosis is fundamental to the development and maintenance of animal tissues and the immune system. Rapid clearance of apoptotic cells by macrophages is important to inhibit inflammation and autoimmune responses against intracellular antigens. Here we report a new function for Mer, a member of the Axl/Mer/Tyro3 receptor tyrosine kinase family. mer(kd) mice with a cytoplasmic truncation of Mer had macrophages deficient in the clearance of apoptotic thymocytes. This was corrected in chimaeric mice reconstituted with bone marrow from wild-type animals. Primary macrophages isolated from mer(kd) mice showed that the phagocytic deficiency was restricted to apoptotic cells and was independent of Fc receptor-mediated phagocytosis or ingestion of other particles. The inability to clear apoptotic cells adequately may be linked to an increased number of nuclear autoantibodies in mer(kd) mice. Thus, the Mer receptor tyrosine kinase seems to be critical for the engulfment and efficient clearance of apoptotic cells. This has implications for inflammation and autoimmune diseases such as systemic lupus erythematosus.

[ A new technique for the treatment of varicose veins]. / O tehnica noua de tratament a varicelor.

UNLABELLED: The thoroughgoing study of the venous wall and venous flow using fundamental research and diagnostic techniques allowed us to apply new therapeutic methods in the primary varicose veins of the lower extremities (PVV). The aim of the present study is to present a relatively new method of conservative surgical treatment which combine the external valvuloplasty technique with the technique proposed by Franceschi (TF). MATERIAL AND METHOD: Between 1992-2000 we applied on 25 patients with PVV Mach II, the technique of external muffing of the long saphenous vein from its junction with the common femoral vein retrograde for 6-8 cm, for a venous diameter of 0.5 cm interrupting at the same time the long or the short ebbing (clinical and Doppler criterions). In 5 patients we performed the valvuloplasty using TF. The patients were annually evaluated; in the present we have a group of 10 patients up to 8 years after surgery. RESULTS AND CONCLUSIONS: 1. Conservative methods of external valvuloplasty associate with Franceschi technique have a solid physiopathologic and pathogenic basement. 2. The materials used for the external muffing (Dacron, PTTF, polyamide net) are very well tolerate. 3. Relapses were present in 8 years at 30% and in 5 years at 10% of the patients who undergo the operation.

Clinical and etiopathogenetic profile of heart failure in the First Medical Clinic of Cluj-Napoca. A study of 5 years.

The authors analysed the main etiopathogenetic conditions and the clinical and evolutional profile of 1586 patients with heart failure (HF), admitted to the First Medical Clinic of Cluj-Napoca between 1990 and 1994. Ischemic heart disease was found in 1,236 patients (78%), followed by chronic cor pulmonale, valvulopathies and congenital heart diseases. Among the precipitating and/or aggravating factors of HF, the most important were infections in 434 patients (33.10%), and arrhythmias, especially atrial fibrillation, in 332 patients (25.39%). In decreased order of frequency there were also failure to observe prescribed therapy, uncontrolled arterial hypertension, anemias, dyselectrolytemias, dysproteinemias. HF had a chronic evolution in 1,450 patients (91.40%), and an acute one in 136 (8.6%). In conditions of complex therapy including cardiotonics, diuretics, plus, more recently, conversion enzyme inhibitors, the clinical evolution was favourable in 1,432 patients (90.20%), which had a lower functional class on discharge from hospital.

[Functional dyspepsia in liver cirrhosis]. / Funktionelle Dyspepsie bel Leberzirrhose.

Many patients with liver cirrhosis have dyspeptic complaints. Peptic ulcer, gallstones and oesophagitis are the most common causes of dyspepsia. Functional dyspepsia is infrequently investigated in liver cirrhosis. Sixty-two patients with liver cirrhosis and dyspepsia were submitted to endoscopic and sonographic investigation. In 28 of them no organic finding was detected. These cases were considered as having functional dyspepsia. 36% were of dysmotility-like type, 28% were ulcer- and reflux-like, each, and 7% were of idiopathic type. Aerophagia could not be taken in consideration as functional dyspepsia, due to portal hypertension. In comparison with a group of 30 patients with functional dyspepsia without liver cirrhosis, functional dyspepsia in liver cirrhosis is more frequent in men than in women and occurs about a decade later. In 12 subjects the gastric emptying of a semifluid meal estimated by sonography was normal. Functional dyspepsia is a reality in liver cirrhosis. Gastric emptying seems not to have a major role in the etiopathogenesis of such complaints.

Correlation between fibronectin and cardiothoracic ratio in heart failure treated with angiotensin converting enzyme inhibitors.

A group of 17 patients with ischemic heart disease, significant left ventricular dilatation and congestive heart failure, class III NYHA (9 patients) and class IV NYHA (8 patients) was studied. The patients received angiotensin converting enzyme inhibitor--captopril 75 mg/day or perindopril 4 mg/day--added to diuretics, digitalis and nitrates. The plasmatic level of fibronectin was investigated, by radial immunodiffusion, before and one month after the beginning of the treatment with angiotensin converting enzyme (ACE) inhibitor. The plasmatic level of fibronectin is increased significantly (p < 0.001) while the cardiothoracic ratio is decreased significantly (p < 0.02) after one month of ACE inhibitors treatment. A positive correlation between the increase of the plasmatic level of fibronectin and the decrease of cardiothoracic ratio is found (r = 0.62; p < 0.01). The increased fibronectin plasmatic level can be a marker of the favorable effect of ACE inhibitor on the myocardium interstitium.

Homozygous or compound heterozygous qualitative antithrombin III deficiency.

A male patient of 24 years who had experienced thrombotic episodes since the age of 15 displayed an unusually low antithrombin III (AT III) activity measured as heparin cofactor (13% of the normal), while a similarly decreased value (16% of normal) was found in a 26 year old brother who had suffered from thrombotic events since the age of 12 years. AT III heparin cofactor activities were close to 50% of normal in the father, mother, another brother and a sister, none of whom had experienced thrombotic episodes. Since all available members of the family, including the patient, displayed near normal AT III antigen levels (73-85%) normal total progressive antithrombin activities (92-110%) as assessed by the thrombin agarose diffusion technique and normal total progressive anti-Xa activities, the propositus and his brother could be considered to be homozygotes or compound heterozygotes for a qualitative familial AT III deficiency probably caused by an abnormality of the heparin binding site. Molecular techniques would be required to elucidate the precise mutation giving rise to the deficiency.

Antithrombin III deficiency.

Data on clinical features and laboratory diagnosis of familial antithrombin deficiency, a rather heterogeneous group of disorders, are illustrated by observations on two Romanian kindreds afflicted by recurrent thrombotic episodes. In a first family, both plasma antithrombin III antigen and activity were reduced to 50% of normal, a condition characteristic for a heterozygous type I (quantitative) familial antithrombin III deficiency. In a second kindred, the two brothers who had experienced thrombotic events since they were teenagers, displayed exceedingly low AT III heparin cofactor activity (13% and 16% of the normal, respectively) while values around 50% of the normal were recorded in their parents who had not experienced thrombotic episodes. Since plasma antithrombin III antigen and total progressive antithrombin III activity were within normal limits in all the investigated members of this family it was considered that the two brothers were homozygotes or compound heterozygotes and the parents were heterozygotes for a qualitative-antithrombin III deficiency caused by an abnormality of the heparin binding site.

Influence of Reconstitution on Isolation and Enumeration of Listeria monocytogenes from Milk Powder Used for Reference Samples.

To test the performance of the Listeria isolation methods, reference samples consisting of gelatin capsules filled with spray-dried milk powder containing Listeria have been developed. During the spray-drying process the Listeria cells are exposed to heat stress and are susceptible to osmotic stress during the reconstitution procedure. To limit the effect of osmotic shock, the milk powder has to be encapsulated in gelatin in order to guarantee slow dissolution. Furthermore, the capsules have to be preen-riched in a nonselective medium. The practical consequences of these findings are discussed.