Out-of-field effects: lessons learned from partial body exposure.

Partial body exposure and inhomogeneous dose delivery are features of the majority of medical and occupational exposure situations. However, mounting evidence indicates that the effects of partial body exposure are not limited to the irradiated area but also have systemic effects that are propagated outside the irradiated field. It was the aim of the "Partial body exposure" session within the MELODI workshop 2020 to discuss recent developments and insights into this field by covering clinical, epidemiological, dosimetric as well as mechanistic aspects. Especially the impact of out-of-field effects on dysfunctions of immune cells, cardiovascular diseases and effects on the brain were debated. The presentations at the workshop acknowledged the relevance of out-of-field effects as components of the cellular and organismal radiation response. Furthermore, their importance for the understanding of radiation-induced pathologies, for the discovery of early disease biomarkers and for the identification of high-risk organs after inhomogeneous exposure was emphasized. With the rapid advancement of clinical treatment modalities, including new dose rates and distributions a better understanding of individual health risk is urgently needed. To achieve this, a deeper mechanistic understanding of out-of-field effects in close connection to improved modelling was suggested as priorities for future research. This will support the amelioration of risk models and the personalization of risk assessments for cancer and non-cancer effects after partial body irradiation.

Rapid urbanisation threatens fertile agricultural land and soil carbon in the Nile delta.

Agriculture land in Egypt represents only 3.8% of the total area. The Nile delta provides two thirds of Egypt's agriculture land, but is threatened by urban sprawl. The paper aims to quantify urban expansion over a 45 year period using 6 time points from 1972 to 2017, and its impacts on agricultural potential, soil organic carbon stocks, and implications for water use. The study used multi-temporal satellite data and remote sensing techniques (Maximum Likelihood supervised classification, and NDVI), soil sampling and analysis, data on water irrigation, and agroecological system and ecosystem services model (MicroLEIS, InVEST) to assess the effects of land use change. Urban area increased by a factor of 5, from 452 km2 in 1972 to 2644 km2 in 2017. The greatest losses occurred to the fertile Vertic Torrifluvent soils on the older delta, which lost 1734 km2. Soil organic carbon (0-75 cm depth) lost as a result of soil sealing from urbanisation rose from 25,000 to 141,000 Mg C over the 45 years. As a result of increased pressure on delta land, agriculture expanded into the higher desert areas outside the delta, on marginal land sustained by intensive fertiliser use and irrigation, which in turn puts pressure on water use. Therefore, rapid urban expansion has resulted in a loss of soil carbon and a shift in agriculture from fertile soils to marginal soils, requiring more capital inputs, which is ultimately less sustainable. Modelling suggested that soil management improvement could make better use of fertile soils within the Delta currently affected by high salinity and poor drainage. Future planning should encourage urban expansion on the less fertile soils outside of the delta, while improving suitability of existing agricultural land and minimising land degradation within the delta.

The antioxidant role of paraoxonase 1 and vitamin E in three autoimmune diseases.

PURPOSE OF THE STUDY: To investigate the role of paraoxonase 1 (PON1) and vitamin E in the pathogenesis of some autoimmune diseases, and to correlate their levels with the disease activity. PROCEDURES: This randomized case control study was performed on 60 subjects: 45 patients [suffering from psoriasis, vitiligo and alopecia areata (AA) 15 patients each group] and 15 healthy controls. Venous blood and tissue biopsy were collected from each subject to estimate the levels of vitamin E and PON1. RESULTS: All patients showed significantly lower levels of both PON1 and vitamin E in tissue and serum than the controls (p < 0.001). CONCLUSION: An association between oxidative stress and pathogenesis of these autoimmune diseases is identified. Attenuation of oxidative stress might be a relevant therapeutic approach and it would be useful to recommend additional drugs with antioxidant effects in the treatment of these conditions.

Structural, optical, and cytotoxicity studies of laser irradiated ZnO doped borate bioactive glasses.

Borate glasses (BG) doped with different amounts of ZnO (0-0.6 mol%) were formed by the traditional melt quenching technique. The different glasses so made were characterized using different characterization techniques such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and UV-Vis absorption optical properties. The XRD patterns showed an amorphous structure with one broad peak at 2θ = 29°, while the phonons bands were studied in terms of the FTIR bands. Optical properties of the glasses were studied using UV-Vis absorption spectra in the range 190-1100 nm, in which the prominent band lies at about 261.5 nm of peak position, from which the bandgab (Eg) was calculated from its edge using Tauc's plot, with Eg ~ 3.5 eV. The laser irradiation showed no significant changes in the absorption bands, despite a significant change observed in the amorphous behavior in the XRD pattern. The cell viability was performed for two samples of the BG and 0.6 mol% ZnO doped using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay method. The result showed better cell viability and low toxicity. So, ZnO doped BG can be used in various biomedical applications.

The protective effect of melatonin supplementation against taxol-induced testicular cytotoxicity in adult rats.

The aim of the present investigation was to study the toxic influences of taxol (TXL) on the testes of rats and the protective impact of melatonin (MLT) against such effects. Rats were classified into control, sham, TXL, MLT, and MLT+TXL-treated groups. Histological and ultrastructural changes were observed in testicular tissues of TXL-intoxicated rats including thickening of tunica albuginea and degenerative alterations in spermatogenic, Sertoli, and Leydig cells. A significant increase (P≤0.05) was found in the thickness of tunica albuginea and numbers of tubules without sperm, apoptotic germinal epithelia, and apoptotic Leydig cells, whereas the diameter of tubules and height of germinal epithelia displayed a significant decrease (P≤0.05) compared with the control, sham, and MLT-treated groups. Immunohistochemically, a marked decrease (P≤0.05) in Bcl-2 immunoreactivity and significant elevation (P≤0.05) in P53 and caspase-3 immunoreactivities were recorded. Co-treatment of MLT and TXL modulated such histological, histomorphometrical, and ultrastructural changes induced by TXL. Also, MLT had a protective effect against testicular apoptosis induced by TXL, as shown by the elevated expression of Bcl-2 and decreased expression of P53 and caspase-3. In conclusion, the current investigation proved that MLT had a protective role against TXL-induced testicular cytotoxicity, which may be a result of inhibition of testicular apoptosis.

Hypothermic machine preservation in human liver transplantation: the first clinical series.

Hypothermic machine perfusion (HMP) is widely used to preserve kidneys for transplantation with improved results over cold storage (CS). To date, successful transplantation of livers preserved with HMP has been reported only in animal models. In this, the first prospective liver HMP study, 20 adults received HMP-preserved livers and were compared to a matched group transplanted with CS livers. HMP was performed for 3-7 h using centrifugal perfusion with Vasosol solution at 4-6 degrees C. There were no cases of primary nonfunction in either group. Early allograft dysfunction rates were 5% in the HMP group versus 25% in controls (p = 0.08). At 12 months, there were two deaths in each group, all unrelated to preservation or graft function. There were no vascular complications in HMP livers. Two biliary complications were observed in HMP livers compared with four in the CS group. Serum injury markers were significantly lower in the HMP group. Mean hospital stay was shorter in the HMP group (10.9 +/- 4.7 days vs. 15.3 +/- 4.9 days in the CS group, p = 0.006). HMP of donor livers provided safe and reliable preservation in this pilot case-controlled series. Further multicenter HMP trials are now warranted.

Bacillus cereus induces permeability of an in vitro blood-retina barrier.

Most Bacillus cereus toxin production is controlled by the quorum-sensing-dependent, pleiotropic global regulator plcR, which contributes to the organism's virulence in the eye. The purpose of this study was to analyze the effects of B. cereus infection and plcR-regulated toxins on the barrier function of retinal pigment epithelium (RPE) cells, the primary cells of the blood-retina barrier. Human ARPE-19 cells were apically inoculated with wild-type or quorum-sensing-deficient B. cereus, and cytotoxicity was analyzed. plcR-regulated toxins were not required for B. cereus-induced RPE cytotoxicity, but these toxins did increase the rate of cell death, primarily by necrosis. B. cereus infection of polarized RPE cell monolayers resulted in increased barrier permeability, independent of plcR-regulated toxins. Loss of both occludin and ZO-1 expression occurred by 8 h postinfection, but alterations in tight junctions appeared to precede cytotoxicity. Of the several proinflammatory cytokines analyzed, only interleukin-6 was produced in response to B. cereus infection. These results demonstrate the deleterious effects of B. cereus infection on RPE barrier function and suggest that plcR-regulated toxins may not contribute significantly to RPE barrier permeability during infection.

The multilayered structure of the human corpus spongiosum.

PURPOSE: Urethral reconstruction is performed in patients with urethral strictures or for correction of congenital disorders. In the case of shortage of tissue, engineered tissue may enhance urethral reconstruction. As the corpus spongiosum (CS) is important in supporting the function of the urethra, tissue engineering of the urethra should be combined with reconstruction of a CS. For that purpose, detailed knowledge of the composition of the CS, more specifically its extracellular matrix (ECM) and vascularization is needed for scaffold design. The objective of this study is to analyze the microarchitecture of the CS through (immuno) histology and scanning electron microscopy (SEM). METHODS: The CS including the urethra of patients undergoing male-to-female genital confirming surgery was harvested. This CS was fixed and processed for either (immuno) histology or for SEM. RESULTS: Four layers could be distinguished in the CS; first a transition zone from urethra epithelium to a collagen rich layer, which was highly vascularized, followed by a second, elastin rich layer. The third layer was formed by veins, arteries and vascular spaces and the last layer showed the transition from this vascular rich region to the collagen rich tunica albuginea. In this layer collagen bundles intertwined with elastic fibres. In the CS different components of the ECM were visible and distinguishable. CONCLUSION: This study provides novel and detailed information on the microarchitecture of the CS and the distribution of vascularization, which is important for scaffold design in tissue engineering.

The protective effect of melatonin supplementation against taxol-induced testicular cytotoxicity in adult rats

The aim of the present investigation was to study the toxic influences of taxol (TXL) on the testes of rats and the protective impact of melatonin (MLT) against such effects. Rats were classified into control, sham, TXL, MLT, and MLT+TXL-treated groups. Histological and ultrastructural changes were observed in testicular tissues of TXL-intoxicated rats including thickening of tunica albuginea and degenerative alterations in spermatogenic, Sertoli, and Leydig cells. A significant increase (P≤0.05) was found in the thickness of tunica albuginea and numbers of tubules without sperm, apoptotic germinal epithelia, and apoptotic Leydig cells, whereas the diameter of tubules and height of germinal epithelia displayed a significant decrease (P≤0.05) compared with the control, sham, and MLT-treated groups. Immunohistochemically, a marked decrease (P≤0.05) in Bcl-2 immunoreactivity and significant elevation (P≤0.05) in P53 and caspase-3 immunoreactivities were recorded. Co-treatment of MLT and TXL modulated such histological, histomorphometrical, and ultrastructural changes induced by TXL. Also, MLT had a protective effect against testicular apoptosis induced by TXL, as shown by the elevated expression of Bcl-2 and decreased expression of P53 and caspase-3. In conclusion, the current investigation proved that MLT had a protective role against TXL-induced testicular cytotoxicity, which may be a result of inhibition of testicular apoptosis.

Spectroscopic and electrochemical studies of ruthenium and osmium complexes of salicylideneimine-2-thiophenol Schiff base.

The reactions between [M(3)(CO)(12)], M = Ru and Os, and salicylideneimine-2-thiophenol Schiff base in THF under reflux gave [Ru(CO)(4)(satpH)] and [Os(CO)(3)(satpH(2))] complexes. Structures of the two complexes were proposed on the basis of spectroscopic studies. Magnetic study of [Ru(CO)(4)(satpH)] suggested that a change in oxidation state of the ruthenium atom from zero to +1 was achieved via oxidative addition of the SH group with a proton displacement to give a low-spin d(7) electronic configuration. UV-Vis spectra of the two complexes in different solvents exhibited visible bands due to metal-to-ligand charge transfer. Electrochemical investigation of the free ligand and complexes showed some cathodic and anodic irreversible peaks due to interconversions through electron transfer.

Thoracoscopic internal mammary artery harvesting: technical considerations.

BACKGROUND: Technical details of thoracoscopic harvesting of the internal mammary artery (IMA) are reported. This procedure allows a complete dissection of the left IMA from its origin at the subclavian artery to the sixth intercostal branches with transection of all collateral branches. METHODS: Between September 1995 and September 1996, thoracoscopic harvesting of the left IMA was performed on 32 patients who had undergone a minimally invasive coronary artery bypass grafting procedure. RESULTS: There were no conversions to a standard approach because of an injury to the graft and no reoperations for bleeding. The mean duration of the IMA harvesting procedure was 58.7 minutes (range, 20 to 130 minutes). CONCLUSIONS: This procedure enlarges the field of minimally invasive coronary artery bypass grafting techniques. The thoracoscopic harvest of the full length of the IMA allows the procedure to more closely replicate the open approach.

Nonpenetrating clips for coronary anastomosis.

BACKGROUND: A nonsuture clip technique (nonpenetrating titanium clips applied to everted tissue edges at high compressive forces) was used to perform coronary anastomoses in a clinical setting. METHODS: Clipped coronary anastomoses were performed in 10 patients. The anastomoses incorporated the left internal mammary artery to the left anterior descending artery (n = 1) and the saphenous vein to the right coronary artery (n = 5), the posterior descending artery (n = 2), the diagonal artery (n = 2), and one vein-to-vein proximal anastomosis (n = 1). RESULTS: The mean duration for completion of the anastomoses was 15 minutes (range, 7 to 20 minutes). This time was reduced from 20 minutes at the beginning of the clinical experience to 7 minutes for the last 3 patients. No technical complication was related to clip application and all patients had uneventful outcomes. Three anastomoses studied by coronary angiography were patent without stenosis. CONCLUSION: The clipped anastomotic technique has a rapid learning curve, the same safety as suture methods, and the potential for facilitating endoscopic vascular reconstructions.

Beneficial effect of HEPES buffer in repeated coronary reperfusion.

BACKGROUND: We have demonstrated previously that, when repeated reperfusion is performed after reocclusion, there is a decrease in the amount of myocardial salvage, despite early reperfusion. Treatment with nisoldipine induced a beneficial effect by reduction of infarct size in this experimental model. OBJECTIVE: To study the effect of HEPES buffer on infarct size, using a repeated-reperfusion model. METHODS: The left anterior descending coronary artery was occluded in anesthetized dogs. Thirty minutes after the occlusion, dogs were allocated randomly to either the treatment group (n = 7; HEPES 0.64 mmol/l infused intravenously throughout the experiment) or the control group (n = 8; saline). Occlusion was maintained for 2 h, followed by 1 h of reperfusion, then 1 h of reocclusion and 2 h of second reperfusion. An in-vivo area at risk was determined by gentian violet staining, and infarct size was defined and quantitated by triphenyl-tetrazolium chloride staining. RESULTS: Hemodynamic measurements were similar in both groups. Mass of necrosis/mass at risk was significantly smaller in the HEPES group (30.7 +/- 1.6%, mean +/- SEM) compared with controls (50.6 +/- 3.8%, P < 0.001). CONCLUSION: Treatment with HEPES induces a beneficial effect by reduction of infarct size in repeated coronary reperfusion.

Retrocaval in situ RIMA for distal marginal arteries grafting.

The length of the in situ right internal mammary artery (RIMA) often restricts its use as a graft to distal marginal arteries. We describe herein a retrocaval supra-azygous extra-pleural passage of the RIMA that allows a significant gain in length. We report our experience in 30 patients with distal marginal lesions or with large hearts.

Video-assisted coronary bypass surgery: clinical results.

OBJECTIVE: Clinical experience with a video-assisted coronary artery bypass grafting procedure using the internal mammary artery is reported. The technique consists of a videoscopic harvesting of the left internal mammary artery (LIMA) to revascularise the left anterior descending artery (LAD) through a 4-cm left thoracotomy. METHODS: Between September 1995 and July 1996, we performed this procedure on 30 patients (29 males, 1 female; aged 38-71) with an isolated proximal LAD stenosis (n = 21) or occlusion (n = 9). All patients were symptomatic despite appropriate medication. A history of non-transmural myocardial infarction with myocardial viability was found in nine patients. Fourteen patients had a restenosis after previous percutaneous transluminal coronary angioplasty (PTCA). Mean left ventricular ejection fraction was 0.61 (< 0.3 in two patients). The LAD LIMA anastomosis was performed on the beating heart without cardiopulmonary bypass (CPB) in 26 patients. Femoral-femoral CPB was used in three patients because of unstable angina (n = 1) and intramyocardial LAD (n = 2). Conversion to sternotomy and standard CPB was necessary in one patient for extensive endarterectomy of the LAD. RESULTS: There were no operative complications and no reoperations for haemorrhage. Pulmonary infection was observed in one patient and wound infection in one patient. Patients who underwent the complete procedure on the beating heart without conversion or CPB were ready for discharge on the 5th postoperative day (36 h-13 days). Control coronary angiography was performed in 20 patients. In all cases, the graft was patent. In 17 cases, there was a patent graft with no evidence of anastomotic stenosis. An occlusion of the distal segment of the LAD with a retrograde perfusion of the proximal segment and septal branches by the LIMA was found in one case. This patient was symptom-free and the stress test was negative. An anastomotic stenosis was noted in two patients and was treated by angioplasty (n = 1) or conventional surgery (n = 1). CONCLUSION: In conclusion, the efficiency of this minimally invasive approach should be prospectively compared with similar revascularisation with PTCA or surgical approaches using sternotomy with or without CPB.

Genital bovine papillomavirus infection in Saudi Arabia.

Genital bovine papillomavirus infection was observed for the first time in the Al-Ahsa region of Saudi Arabia. The disease involved 1 female and 2 male 2-4-year-old crossbred cattle. Fibropapillomas (warts) were limited to the prepuce and vulva. Electron micrographs of thin sections of the lesions revealed the presence of intranuclear viruslike particles. Using a broadly cross-reactive rabbit polyclonal antiserum directed against papillomavirus group-specific antigens, the infection was confirmed by immunohistochemical staining of paraffin-embedded tissues to be due to a papillomavirus. Staining with a series of monoclonal antibodies of various specificities indicated that the virus was bovine papillomavirus type 1. Attempts to propagate the virus by inoculation of tumor homogenates onto chorioallantoic membranes of chicken embryos were unsuccessful.

West Nile meningo-encephalitis infection in a kidney transplant recipient.

West Nile virus is an arbovirus known to cause meningo-encephalitis in immuno-competent as well as in immunocompromised patients. Herein, we describe a kidney transplant recipient in whom meningo-encephalitis infection was caused by the West Nile virus. The clinical presentation was fever, headache, photophobia, confusion, neck stiffness, and positive Kerning test. The patient was treated with IV acyclovir, cefuroxime, ampicillin, and fluids. During hospital stay, the patient did not experience any episode of allograft rejection. Fever resolved and at follow up he was doing well. West Nile virus infection should be considered in immunocompromised patients including transplant recipients with meningo-encephalitis, especially during epidemic outbreaks.

Position-related factors in mitral and tricuspid bioprostheses degenerative changes.

We report clinicopathological findings in 15 patients in whom the same bioprosthesis (BP) had been implanted simultaneously in both mitral and tricuspid positions. The aim of the study was to investigate whether position-related factors played an important role in BP degeneration. There were 14 women and 1 man with a mean age of 34 +/- 11 years. The indications for the initial operation were rheumatic in 14 cases and endocarditis in one patient. The mean interval before reoperation was 7.5 +/- 3.3 years. Predominant cause of reoperation was: structural deterioration of both mitral and tricuspid BPs (6), mitral regurgitation (5), tricuspid BP dysfunction (1), para-aortic leak (1), mitro-aortic thrombi (1). Calcific deposits were the principal cause of early deterioration of mitral BPs and the major cause of late tricuspid BPs dysfunction. This lesion was predominantly related to local factors. Cuspal tears were the principal cause of late (> 9 yrs) mitral BP failure and most probably related to mechanical stress. Extensive fibrosis affected only tricuspid bioprostheses. In 7 patients more extensive degenerative changes occurred in bioprostheses in the mitral rather than the tricuspid position (Group I). However, in the remaining eight the magnitude of the changes was very similar in the two positions (Group II). The interval before reoperation was significantly longer in patients of Group II (9.8 yrs, range 5-13) than patients in Group I (4.9 yrs, range 3-6), (p < 0.01). We concluded that position-related factors exert a major role in bioprosthetic failure. These factors are more deleterious in the mitral position than in the tricuspid position.