Importing genetically altered animals: ensuring quality.

The reproducibility of research using laboratory animals requires reliable management of their quality, in particular of their genetics, health and environment, all of which contribute to their phenotypes. The point at which these biological materials are transferred between researchers is particularly sensitive, as it may result in a loss of integrity of the animals and/or their documentation. Here, we describe the various aspects of laboratory animal quality that should be confirmed when sharing rodent research models. We also discuss how repositories of biological materials support the scientific community to ensure the continuity of the quality of laboratory animals. Both the concept of quality and the role of repositories themselves extend to all exchanges of biological materials and all networks that support the sharing of these reagents.

Genome Wide Conditional Mouse Knockout Resources.

The International Knockout Mouse Consortium (IKMC) developed high throughput gene trapping and gene targeting pipelines that produced mostly conditional mutations of more than 18,500 genes in C57BL/6N mouse embryonic stem (ES) cells which have been archived and are freely available to the research community as a frozen resource. From this unprecedented resource more than 6,000 mutant mouse strains have been produced by the IKMC and mostly the International Mouse Phenotyping Consortium (IMPC). In addition, a cre-driver resource was established including 250 inducible cre-driver mouse strains in a C57BL/6 background. Complementing the cre-driver resource, a collection of comprising 27 cre-driver rAAVs has also been produced. The resources can be easily accessed at the IKMC/IMPC web portal (www.mousephenotype.org). The IKMC/IMPC resource is a standardized reference library of mouse models with defined genetic backgrounds that enables the analysis of gene-disease associations in mice of different genetic makeup and should therefore have a major impact on biomedical research.

Peri-operative massive pulmonary embolism management: is veno-arterial ECMO a therapeutic option?

Pulmonary embolism remains an important clinical problem with a high mortality rate. The potential for sudden and fatal hemodynamic deterioration highlights the need for a prompt diagnosis and appropriate intervention. The purpose of the present case report is to describe a successful peri-operative veno-arterial extra corporeal membrane oxygenation (VA-ECMO) implantation for assumed massive pulmonary embolism associated with high hemodynamic instability and severe hypoxemia. A 52-year-old female victim of a motorcycle accident had been operated on for unstable fractures that required optimal repair. Despite subcutaneous administration of 40 mg enoxaparin on day 0 and day 1, the patient developed a massive pulmonary embolism leading to peri-operative pulseless activity. As intravenous thrombolysis was strictly contraindicated, a VA-ECMO was successfully implanted and permitted to stabilize the patient's hemodynamics. The hemodynamic and respiratory status improved by day 3, and the ECMO was removed. A vena cava filter was implanted before successful and definitive stabilization of the femoral fracture and the L2 fracture on days 4 and 5. The patient was able to be mobilized 2 days after the surgery and was transferred to a rehabilitation ward on day 15. At that time, her cognitive functions had fully recovered. ECMO can provide lifesaving hemodynamic and respiratory support in patients with massive pulmonary embolism who are too unstable to tolerate other interventions, who have failed other therapies or for whom other therapies are contraindicated.

Maximum likelihood parametric blur identification based on a continuous spatial domain model.

A formulation for maximum-likelihood (ML) blur identification based on parametric modeling of the blur in the continuous spatial coordinates is proposed. Unlike previous ML blur identification methods based on discrete spatial domain blur models, this formulation makes it possible to find the ML estimate of the extent, as well as other parameters, of arbitrary point spread functions that admit a closed-form parametric description in the continuous coordinates. Experimental results are presented for the cases of 1-D uniform motion blur, 2-D out-of-focus blur, and 2-D truncated Gaussian blur at different signal-to-noise ratios.

3-

The title compound, C(18)H(13)NO(3), exists as a ketoamino tautomer implying a fairly short N-H.O intramolecular hydrogen bond between the 2-naphthalenone and amino moieties [N.O 2.531 (3) A] which is enhanced by the pi-electron delocalization effect. The naphthaldimine and 3-carboxyphenyl fragments are inclined at an angle of 4.41 (7) degrees, so the molecule is almost planar. The molecules are connected by intermolecular O-H.O hydrogen bonds between the carboxy and keto O atoms, forming infinite chains around the twofold screw axes parallel to b.

Which factors have an impact on occurrence, clinical and echocardiographic characteristics of idiopathic chordae rupture?

BACKGROUND: The aim of this study was to determine which risk factors have an influence on occurrence, clinical and echocardiographic characteristics of patients with idiopathic rupture of the chordae tendineae (RCT). METHODS: The study included 149 patients with diagnosed RCT by transthoracic echocardiography: 90 (60.4%) patients with the idiopathic RCT and 59 (39.6%) subjects with a secondary RCT. Clinical and echocardiographic data were collected for each patient. RESULTS: The univariate logistic regression analysis showed that age > or = 65 (OR 3.76, 95% CI; 1.94-6.18), arterial hypertension (HTA) (OR 7.7, 95% CI: 3.43-16.84), duration > or = 15 (OR 1.14, 95%: 1.04-1.24), uncontrolled HTA (OR 4.72, 95% CI: 2.03-7.39), diabetes (OR 3.22, 95%CI: 1.4-7.37), hypercholesterolemia (OR 1.52, 95% CI: 1.05-2.2), hypertriglyceridaemia (OR 1.99, 95% CI: 1.2-3.28), coronary (OR 5.11, 95% CI: 2.34-9.01) and carotid artery disease (OR 4.35, 95% CI: 1.87-6.89), renal failure (OR 7.25, 95% CI: 1.01-15.23), thickness of interventricular septum (OR 3.25, 95% CI: 1.44-7.58), posterior wall (OR 4.67, 95% CI: 2.21-9.13), and relative wall thickness (OR 2.87, 95% CI: 1.65-4.21) correlated with idiopathic RCT. The multiple logistic regression revealed age > or = 65 (OR 1.06, p < 0.001), HTA (OR 4.93, p = 0.001), HTA > or = 15 years (OR 1.35, p = 0.021), uncontrolled HTA (OR 2.28, p=0.007), coronary artery disease (OR 2.78, p = 0.004), and relative wall thickness (OR 3.45, p = 0.005) as independent predictors of idiopathic RCT. CONCLUSION: Independent predictors of idiopathic RCT are advanced age, HTA, its duration, uncontrolled HTA, coronary artery disease, and relative wall thickness.

Proposal for a mesoscopic optical berry-phase interferometer.

We propose a novel spin-optronic device based on the interference of polaritonic waves traveling in opposite directions and gaining topological Berry phase. It is governed by the ratio of the TE-TM and Zeeman splittings, which can be used to control the output intensity. Because of the peculiar orientation of the TE-TM effective magnetic field for polaritons, there is no analogue of the Aharonov-Casher phase shift existing for electrons.

Entangled photon pairs produced by a quantum dot strongly coupled to a microcavity.

We show theoretically that entangled photon pairs can be produced on demand through the biexciton decay of a quantum dot strongly coupled to the modes of a photonic crystal. The strong coupling allows us to tune the energy of the mixed exciton-photon (polariton) eigenmodes and to overcome the natural splitting existing between the exciton states coupled with different linear polarizations of light. Polariton states are moreover well protected against dephasing due to their lifetime of ten to a hundred times shorter than that of a bare exciton. Our analysis shows that the scheme proposed is achievable with the present technology.

[Determination of calcium content in dentine after application of ZOE paste]. / Odredivanje sadrzaja kalcijuma u dentinu posle aplikovanja ZOE paste.

The calcium in dentine after the application of zinc oxide/eugenol paste (ZOE) was determined. The results were compared with the values valid for normal dentine calcium content in order to check some hypothesis suggesting that the effects of ZOE paste on dentine could reduce the calcium content and cause demineralization of dentine. The results obtained for calcium content in various layers of dentine have shown that only the layer of dentine-enamel junction (which should be removed before the application of ZOE paste) contained the increased concentration of calcium in comparison to anatomically deeper layers. The average calcium content in deeper dentine layers are very similar, especially in dentine layers directly exposed to action of ZOE paste, as well as in the layer on which ZOE paste was not applied.

[Determination of content and type of zinc binding in dentine after application of ZOE paste]. / Okredivanje sadrzaja i nacina vezivanja cinka u dentinu posle aplikovanja ZOE paste.

The article deals with the determination of zinc content in dentine after ZOE paste application as well as the investigation of the morphology ant morphological dentine changes caused by the paste action. The obtained data for the content of zinc in various dentine layers have shown that a marked zinc content elevation comparing to the natural content occurred only in the layers of which ZOE paste was directly applied. In anatomically deeper dentine layers (under ZOE paste), the content of zinc corresponded to the natural dentine level. On the basis of data obtained, it was concluded that during ZOE paste application no concomitant zinc diffusion occurred through the tooth tissue, but only zinc content was elevated in the dentine contact layer. However, on the basis of these data it was not possible to conclude weather chemical changes in the contact paste-dentine layer occurred or it made only a strong mechanical effect of paste on dentine adhesion. The investigation of dentine morphology which was removed by grinding (by mean used in dentistry practice) showed that this way of preparing the specimens caused the natural dentine structural alterations. By grinding dentine topography was completely affected. Very deep lesions and visible augmentation of the contact dentine surface that facilitated ZOE paste adhesion, occurred. Thus the permanent ZOE paste attachment to dentine occurred and dentine free energy decreased. In this way permanent adhesion of cement for dentine was impossible with negative consequences for the final therapy.

[SEM/EDAX determination of zinc levels in dentin after administration of zinc oxide-eugenol paste]. / SEM/EDAX odredivanje sadrzaja cinka u dentinu posle delovanja ZOE paste.

The quantitative EDAX analysis of zinc contents was performed in the dentin samples of markedly different morphology after the use of ZOE paste in various time intervals. EDAX analysis has shown that samples of the ground dentin have high zinc content. The mean value of zinc content was 5.42% ten days after the use of ZOE paste and 19.16% after 30 days. Zinc content in samples of the polished dentin determined by EDAX analysis was significantly lower compared to that of the ground dentin. The presence of paste was not found on samples of the polished dentin ten days after the use of ZOE paste while after a 30-day treatment zinc content was only 1.29%.

[Anticardiolipin antibodies in patients with ischemic brain disease]. / Antikardiolipinska antitela kod bolesnika sa ishemijskom bolescu mozga.

Anticardiolipin antibodies are best defined antiphospholipid antibodies and a recently described marker of increased risk for ischemic brain disease. Investigations were performed in 151 patients with ischemic brain disease in order to determine the occurrence of anticardiolipin antibodies and define the clinical characteristics of patients with an increased titer of anticardiolipin antibodies. Measurement of anticardiolipin antibody titer was performed by immunoenzyme method. Besides, analyses of certain tests indicative for blood coagulative properties were also done. In addition, the occurrence of anticardiolipin antibodies was investigated in 49 patients with other non-immune neurological diseases and disorders. Control sera were obtained from 50 healthy subjects and 6 patients with senile cataract. Investigation showed the increase of anticardiolipin antibody titer in 22.8% of the patients with ischemic brain disease (30% with transient ischemic attacks, 19% with brain infarction) and in 4% of the patients with other neurological disorders of non-immunological genesis. The patients with increased titer of anticardiolipin antibodies suffered more frequently from recurrent forms of ischemic brain disease, all of them were below 50, and they had less risk factors for atherosclerosis and ischemic brain disease. It was concluded that the presence of increased titer of anticardiolipin antibodies in younger patients with recurrent forms of ischemic brain disease and less risk factors could be the marker of the increased risk for ischemic brain disease.

[Aneurysms of the subclavian artery]. / Aneurizme potkljucne arterije.

INTRODUCTION: The Subclavian artery aneurysms are not a commonly seen peripheral aneurysm [1-5]-. We present the experience of the Institute of Cardiovascular Diseases of the Serbian Clinical Centre, Belgrade. PATIENTS AND METHODS: Eight cases of subclavian artery aneurysms are presented. There were 3 male and 5 female patients, average age 51 (32-65) years. Of them 3 aneurysms were of atherosclerotic origin, 4 developed due to thoracic outlet syndrome (TOS), and one developed after intra-arterial drug injection. More details about our cases are presented in Table 1. One of our patients had intra-thoracal aneurysm (Case 3), and 7 had extra-thoracal aneurysm (Figure 1). Two aneurysms appeared as an asymptomatic pulsatile mass in supraclavicular space, and two with compression in the brachial plexus (Figure 2). Our patient 3 manifested skin necrosis and haemorrhage in supraclavicular region (Figure 3). The other 3 patients manifested acute hand ischaemia due to partial aneurysmal thrombosis and distal embolization. In these patients all distal arterial pulses were absent (Figures 4 and 5). In patient 8, besides hand ischaemia, transitory ischaemic attack (TIA) with contralateral hemiparesis also occurred. The reason was microembolization of ipsilateral carotid artery due to retrograde thrombo propagation. The diagnosis was established by selective angiography of the subclavian artery, and in 4 patients Duplex ultrasonography was also used. All patients were treated surgically. In 7 patients supraclavicular approach to subclavian artery was used, and in case 3 we used a combined trans-sternal and supraclavicular approach. In 7 patients a complete aneurysmal resection was performed, and in patient 5 due to infection aneurysm was excluded by proximal and distal arterial ligations. In this case arterial flow was reestablished by extra-atomic carotid axillary bypass with saphenous vein graft. In three patients with TOS, after aneurysmal resections, end-to-end anastomosis was performed. In patient 2 in whom aneurysm was also caused by TOS, saphenous vein graft was used for reconstruction. In all 4 patients with TOS, some kind of decompressive procedure at the thoracic outlet was also performed (two cervical and two first-rib resections using supraclavicular approach). In 3 patients with atherosclerotic subclavian artery aneurysms, PTFE graft was used for reconstruction (Figures 6 and 7). RESULTS: One early postoperative complication occurred. It was embolism of the brachial artery which has been successfully treated by transbrachial embolectomy. The early patency rate was 88%. The patients were controlled using physical and Doppler ultrasonographic examinations 1, 3, 6, 12 months, and then every year postoperatively. The mean follow-up period was 3.6 (1-8) years. In that period one (13%) late complication was observed. It was thrombosis of the saphenous vein graft true aneurysm in our patient 2. This aneurysm was resected and replaced with PTFE graft. Postoperative histological examination showed connective tissue disorder of the vein wall. The long-term patency rate was 88%. DISCUSSION: In most cases the true subclavian artery aneurysms are of atherosclerotic origin [1-4, 6, 7, 12]. We had 3 such cases. TOS is also often caused by subclavian artery true aneurysms [5, 13-17]. We had 4 such cases. Fibromuscular dysplasia [1, 18], cystic idiopathic medionecrosis [1, 19, 20], infection [1, 21, 22] and congenital disorders [23, 24], are rare causes of subclavian artery true aneurysms. Subclavian artery pseudoaneurysms can develop after different reconstructive vascular procedures [5, 28-41]. Subclavian artery aneurysms can rupture, thrombosis, embolize, or cause symptoms by local compression [6, 12, 41]. We had two cases with compression on brachial plexus. The compression on the trachea, oesophagus, laryngeal nerve, ganglion stellatum were also described [6, 12, 25, 42, 43]. Most subclavian artery aneurysms present ischaemic symptoms of

Diiodo(3,4,5,6-tetrahydropyrimidinium-2-thiolato-S)mercury(II).

The reaction of 3,4,5,6-tetrahydropyrimidine-2-thione (H(4)pymtH) with mercury(II) iodide in methanol in a 1:1 molar ratio resulted in the formation of single crystals of the title compound, [Hg(C(4)H(8)N(2)S)I(2)]. The Hg atom is coordinated by one S atom from H(4)pymtH at 2.456 (2) A and by two I atoms at distances of 2.6872 (7) and 2.7044 (6) A, and has a characteristic deformed trigonal coordination geometry. The molecule has crystallographic m symmetry but the Hg atom is disordered above and below the mirror plane.

[The antiphospholipid syndrome in systemic connective tissue diseases]. / Antifosfolipidni sindrom u sistemskim bolestima vezivnog tkiva.

The aim of the study was to prove the incidence of antiphospholipid syndrome (APS) in systemic connective tissue disease (SCTD), especially in systemic lupus erythematosus (SLE) and to find out serologic markers of APS. Of 94 patients with SCTD followed up in the last three years 80 had SLE, 7 Sjogren's syndrome, 3 systemic vasculitis, 2 combined systemic connective tissue disease, 1 rheumatoid arthritis, 1 Sjogren's syndrome with vasculitis. Antiphospholipid antibodies (ApSt) were determined by ELISA method. In 31 of 80 patients with SLE (38.07%) antiphospholipid antibodies were proved. In lo of 31 (32.26%) signs of systemic lupus or the presence of APS markers have not been found, while 21 of 31 (67.74%) had some of clinical manifestations of APS (most commonly thrombocytopenia or vascular thrombosis) with evolution of the basic disease. Among our patients with SLE the most common finding was IgG antibody isotype-in 14 or 66.66% of cases. In 5 of 7 patients with Sjogren's syndrome ApAt were proved without clinical evolution of the basic disease and APS. Only 2 of 7 patients of this group showed, together with more increased ApAt, mild evolution of the basic disease and manifestation of APS (livado reticularis and recurrent venous thrombosis).

[The popliteal artery entrapment syndrome]. / Sindrom ukljestenja poplitealne arterije.

The authors are presenting 8 patients with 9 cases of popliteal artery entrapment syndrome. There were one female, and 7 male patients with average age of 36.4 (25-54) years. Six cases were manifested with acute, 2 with chronic foot ischemia, while one case was asymptomatic. For diagnosis a combination of Doppler sonography and transfemoral angiography, was used. Eight cases were operated using posterior, while in one medial approach to the popliteal artery. The types I and IV of the popliteal artery entrapment syndrome were found in one case, type II in two cases, type III in 4 cases, while in one case a type of syndrome had not to be identified. During the operation the resection of the anomalous muscle and reconstruction of the popliteal artery, were done in 8 cases. In one case muscle resection or arterial reconstruction, were not necessary. The early potency rate and limb salvage, were 100%, while long term potency rate after mean follow up period of 6.3 years was 83.5%. The acute or chronic foot ischemia in health, young persons without typical atherosclerotical risk factors, suggests on popliteal artery entrapment syndrome.

[Dacron and polytetrafluoroethylene aorto-bifemoral grafts]. / Dakronski i politetrafluoretilenski aorto-bifemoralni graftovi.

INTRODUCTION: In reconstructive procedures of the abdominal aorta synthetic grafts are today mostly used. There are two types of bifurcated synthetic grafts: Dacron and polytetrafluorethilene (PTFE). In many papers these grafts are compared in aortobifemoral position. Karner 1988, and Lord 1988, found no significant difference between them after aortobifemoral reconstructions. In 1955. Paaske wrote about a new "stretch" bifurcated PTFE graft in aortobifemoral position. Comparing this material with standard Dacron graft, he only found a shorter operating time. The aim of this paper is to compare Dacron and PTFE bifurcated grafts in aortobifemoral position in patients with aortoiliac occlusive diseases. MATERIAL AND METHODS: This prospective study included 283 aortobifemoral reconstructions due to aortoiliac occlusive diseases operated between January 1st, 1984 and December 31st, 1992 at the Institute for Cardiovascular Diseases of the Serbian Clinical Centre in Belgrade. Bifurcated PTFE grafts were used in 136 patients, and nonimpregnated knitted Dacron grafts in 147 subjects. There were 25 (8.8%) female and 258 (91.2%) male patients, average age 56.88 years. Ninety one (32.2%) patients had a claudication discomfort (Fonten stadium II), 91 (32.2%) disabling claudication discomfort (Fonten stadium IIB), 45 (15.9%) rest pain (Fonten stadium III), and 56 (19.8%) gangrene (Fonten stadium IV). In 45 (15.9%) patients previous vascular procedures were performed. Prior to operation, Doppler ultrasonography and translumbar aortography were carried out (Figure 1). Transperitoneal approach to abdominal aorta, and standard inguinal approach to femoral arteries were used. In 154 (54.4%) patients proximal anastomosis had an end to side (TL), and in 129 (45.6%) end to end (TT) form. In 152 (26.88%) cases distal anastomosis was done in the common femoral (AFC) artery, and in 414 (73.2%) cases in the deep femoral (APF) artery. In 7 patients the aorto-femoro-popliteal "jumping" bypass was done, and in 29 patients simultaneous sequential femoro-popliteal bypass graft. The patients were following-up over the period from one, six and twelve months after operation, and later once a year, using physical examination and Doppler ultrasonography. In patients with suspected graft occlusion, anastomotic stenosis, pseudoaneurysms, progression of distal arterial diseases, Duplex ultrasonography and angiography were also used, and leukoscintigraphy in patients with suspected infection. Statistical analysis was performed using Long Rank and Student t-test. RESULTS: Inhospital mortality rate was 11 (7%). Distal reconstructions significantly increased the mortality rate when simultaneously performed with aortobifemoral bypass graft (p < 0.01). The follow-up period was from 2 months to 9.5 years (mean 3.6 years). The early patency rate was 97% from PTFE and 99.4% for Dacron grafts, while the late patency rate was 94.9% for PTFE and 96.6% for Dacron grafts. The type of the graft had no statistical influence on the early and late graft patency (p > 0.05) (Graphs 1, 2, 3). Six (2.1%) early unilateral limb occlusions were observed. Five patients had the PTFE and one the Dacron graft, without statistically significant difference (p > 0.05). The reasons for early graft occlusion were: stenosis of distal anastomosis in 3 patients, and pure run off in 3 patients. In 5 patients urgent reoperation (limb thrombectomy with profundoplasty or femoro-popliteal bypass graft above the knee) were done with complete recovery of legs. However, in one patient the above knee amputation was done. During the follow-up period, 14 (5.2%) late graft occlusions were recorded. There were 11 unilateral limb occlusions and 3 bilateral. All patients with bilateral occlusions had PTFE grafts but this was not statistically significant (p > 0.05) comparing two types of grafts. Taking into account all late occlusions, there were 7 PTFE and 7 Dacron grafts. There was no statistical difference betwe