Monte Carlo investigation of electron specific energy distribution in a single cell model.

Knowledge of microdosimetric quantities of certain radionuclides is important in radio immune cancer therapies. Specific energy distribution of radionuclides, which are bound to the cell, is the microdosimetric quantity essential in the process of radionuclide selection for patient tumour treatment. The aim of this paper is to establish an applicable method to determine microdosimetric quantities for various radionuclides. The established method is based on knowledge of microdosimetric quantities of monoenergetic electrons. In this paper these quantities are determined for the single-cell model for a range of electron energies up to [Formula: see text], using the Monte Carlo transport code PENELOPE. The results show that using monoenergetic specific energies, reconstruction of the specific energy of beta-emitting radionuclides can be successfully done with very high accuracy. Microdosimetric quantities share information about the physical processes involved and give insight about energy depositions, which is of use in the procedure of radionuclide selection for a given type of therapy.

Brain structural and functional signatures of impulsive-compulsive behaviours in Parkinson's disease.

This study assessed brain structural and functional alterations in patients with Parkinson's disease and impulsive-compulsive behaviours (PD-ICB) compared with controls and PD no-ICB cases. Eighty-five PD patients (35 PD-ICB) and 50 controls were recruited. All subjects underwent three-dimensional T1-weighted, diffusion tensor (DT), and resting state functional magnetic resonance imaging (RS fMRI). We assessed cortical thickness with surface-based morphometry, subcortical volumes using FIRST, DT MRI metrics using region of interest and tractography approaches, and RS fMRI using a model free approach. Compared with controls, both PD groups showed a pattern of brain structural alterations in the basal ganglia (more evident in PD no-ICB patients), sensorimotor and associative systems. Compared with PD no-ICB, PD-ICB cases showed left precentral and superior frontal cortical thinning, and motor and extramotor white matter tract damage. Compared with controls, all patients had an increased functional connectivity within the visual network. Additionally, PD no-ICB showed increased functional connectivity of bilateral precentral and postcentral gyri within the sensorimotor network compared with controls and PD-ICB. Severity and duration of PD-ICB modulated the functional connectivity between sensorimotor, visual and cognitive networks. Relative to PD no-ICB, PD-ICB patients were characterised by a more severe involvement of frontal, meso-limbic and motor circuits. These data suggest ICB in PD as the result of a disconnection between sensorimotor, associative and cognitive networks with increasing motor impairment, psychiatric symptoms, and ICB duration. These findings may have important implications in understanding the neural substrates underlying ICB in PD.

10 GHz pulse repetition rate Er:Yb:glass laser modelocked with quantum dot semiconductor saturable absorber mirror.

Semiconductor saturable absorber mirror (SESAM) modelocked high pulse repetition rate (≥10 GHz) diode-pumped solid-state lasers are proven as an enabling technology for high data rate coherent communication systems owing to their low noise and high pulse-to-pulse optical phase-coherence. Compared to quantum well, quantum dot (QD)-based SESAMs offer potential advantages to such laser systems in terms of reduced saturation fluence, broader bandwidth, and wavelength flexibility. Here, we describe the first 10 GHz pulse repetition rate QD-SESAM modelocked laser at 1.55 µm, exhibiting 2 ps pulse width from an Er-doped glass oscillator (ERGO). The 10 GHz ERGO laser is modelocked with InAs/GaAs QD-SESAM with saturation fluence as low as 9 µJ/cm2.

Possible implications of TGF-alpha in oesophageal dysmotility in systemic sclerosis.

OBJECTIVES: Hypoxia is a characteristic feature of systemic sclerosis (SSc).Transforming growth factor alpha (TGF-α) has an important role in excessive inflammation under hypoxic conditions. Since oesophageal dysmotility is one of the most common signs of SSc, the aim of this study was to explore the relation between TGF-α and oesophageal dysmotility in SSc. METHODS: The study included 35 patients with SSc and 32 healthy controls matched for sex and age. Serum concentrations of TGF-α were measured using ELISA. Oesophageal motility was assessed by oesophageal scintigraphy. A multiple-swallow test was performed in the study population with 99mTc-DTPA. A region of interest over the entire oesophagus was defined and the retention index (RI) was calculated. RESULTS: Statistically significant differences in serum concentration of TGF-α as well as of RI of 99mTc-DTPA were found between patients with SSc and healthy controls. A statistically significant correlation was found between serum concentrations of TGF-α and RIs of 99mTc-DTPA. This correlation was inverse, i.e. when serum concentrations of TGF-α increased, the RI of 99mTc-DTPA decreased (Spearman rho =-0361, p=0.033). CONCLUSIONS: These results point to a possible relation between TGF-α and oesophageal dysmotility in SSc. Although the results do not explain the exact role of this cytokine in the pathogenesis of esophageal changes, the finding of inverse correlation between TGF-α and oesophageal dysmotility is intriguing and requires further investigation.

Doppler parameters of maternal renal blood flow in normal pregnancy.

UNLABELLED: The purpose of this investigation was to evaluate changes in maternal renal arterial blood flow during pregnancy. MATERIALS AND METHODS: The study included 40 non-pregnant, 200 pregnant, and 30 women after delivery. The authors measured pulsatility index (Pi) and resistance index (Ri) in the right and left renal arteries in the hilus. The authors compared the values between non-pregnant and women during first, second, and third trimester and post-partum period and tested correlation with gestational age. RESULTS: The authors did not find a statistical difference in Pi and Ri between the right and left kidneys. There was no difference in Pi and Ri in pregnancy trimester compared to the non-pregnant state. There was no correlation between the values of Pi and Ri and gestational weeks. CONCLUSION: During pregnancy there are no changes in the values of maternal renal Pi and renal Ri. Unchanged total vascular resistance may result from physiological changes of the glomerular filtration rate.

Doses from radon progeny as a source of external beta and gamma radiation.

Great deal of work has been devoted to determine doses from alpha particles emitted by (222)Rn and its progeny. In contrast, contribution of beta particles and following gamma radiation to total dose has mostly been neglected so far. The present work describes a study of the detriment of (222)Rn progeny for humans due to external exposure. Doses and dose conversion factors (DCFs) were determined for beta and gamma radiation in main organs and remainder tissue of the Oak Ridge National Laboratory phantom, taking into account (222)Rn progeny (214)Pb and (214)Bi distributed in the middle of a standard or typical room with dimensions 4 m × 5 m × 2.8 m. The DCF was found to be 7.37 µSv/WLM. Skin and muscle tissue from remainder tissue receives largest dose. Beta and gamma radiation doses from external exposure were compared with alpha, beta, and gamma doses from internal exposure where the source of radioactivity was the lungs. Total doses received in all main organs and remainder tissues were obtained by summing up the doses from external and internal exposure and the corresponding DCF was found to be 20.67 µSv/WLM.

Structures of chaos in open reaction systems.

By numerically simulating the Bray-Liebhafsky (BL) reaction (the hydrogen peroxide decomposition in the presence of hydrogen and iodate ions) in a continuously fed well stirred tank reactor (CSTR), we find "structured" types of chaos emerging in regular order with respect to flow rate as the control parameter. These chaotic "structures" appear between each two successive periodic states, and have forms and evolution resembling to the neighboring periodic dynamics. More precisely, in the transition from period-doubling route to chaos to the arising periodic mixture of different mixed-mode oscillations, we are able to recognize and qualitatively and quantitatively distinguish the sequence of "period-doubling" chaos and chaos consisted of mixed-mode oscillations (the "mixed-mode structured" chaos), both appearing in regular order between succeeding periodic states. Additionally, between these types of chaos, the chaos without such recognizable "structures" ("unstructured" chaos) is also distinguished. Furthermore, all transitions between two successive periodic states are realized through bifurcation of chaotic states. This scenario is a universal feature throughout the whole mixed-mode region, as well as throughout other mixed-mode regions obtained under different initial conditions.

Function after intersphincteric resection for low rectal cancer and its influence on quality of life.

AIM: The aim of the study was to investigate function and quality of life after different types of intersphincteric resection (ISR). METHOD: Between January 2006 and February 2008, 45 patients (34 men and 11 women) with distal third rectal cancer underwent curative ISR. Function was evaluated using the Memorial Sloan Kettering Cancer Center bowel function questionnaire and Wexner score, anal manometry and measurements of rectal capacity were also performed. Quality of life was assessed using the Serbian version of the European Organisation for Research and Treatment of Cancer, quality of life questionnaire (EORTC QLQ-C30) and the translated version of the fecal incontinence quality of life scale (FIQL). RESULTS: There were no postoperative deaths. Partial ISR was performed in 22 (48.9%) patients, subtotal ISR was performed in 19 (42.2%) patients and total ISR was performed in four (8.9%) patients. Anastomotic leakage occurred in nine (20%) patients. Five (11.1%) of 45 patients had major (complete) incontinence and a further six (13.3%) patients had continuing frequent faecal leakage 12 months after ileostomy reversal. There was no significant difference in quality of life between the groups in the EORTC QLQ-C30 scale, but this was significantly altered by internal anal sphincter resection in two of the FIQL scales (coping/behaviour and depression/self-perception). CONCLUSION: Although ISR does not affect quality of life in general, the extent of internal anal sphincter resection has a negative impact on symptom-specific quality of life owing to faecal incontinence.

Doses from beta radiation in sensitive layers of human lung and dose conversion factors due to 222Rn/220Rn progeny.

Great deal of work has been devoted to determine doses from alpha particles emitted by (222)Rn and (220)Rn progeny. In contrast, contribution of beta particles to total dose has been neglected by most of the authors. The present work describes a study of the detriment of (222)Rn and (220)Rn progeny to the human lung due to beta particles. The dose conversion factor (DCF) was introduced to relate effective dose and exposure to radon progeny; it is defined as effective dose per unit exposure to inhaled radon or thoron progeny. Doses and DCFs were determined for beta radiation in sensitive layers of bronchi (BB) and bronchioles (bb), taking into account inhaled (222)Rn and (220)Rn progeny deposited in mucus and cilia layer. The nuclei columnar secretory and short basal cells were considered to be sensitive target layers. For dose calculation, electron-absorbed fractions (AFs) in the sensitive layers of the BB and bb regions were used. Activities in the fast and slow mucus of the BB and bb regions were obtained using the LUNGDOSE software developed earlier. Calculated DCFs due to beta radiation were 0.21 mSv/WLM for (222)Rn and 0.06 mSv/WLM for (220)Rn progeny. In addition, the influence of Jacobi room parameters on DCFs was investigated, and it was shown that DCFs vary with these parameters by up to 50%.

Systolic right ventricular adaptive changes in athletes as predictors of the maximal functional capacity: a pulsed tissue Doppler study.

AIM: The aim of this study was to extend the analysis of the systolic right ventricular (RV) adaptation to combined endurance and strength training, to assess the utility of tissue Doppler imaging in detecting the degree of these changes and to find independent RV predictors of the maximal functional capacity. METHODS: Standard Doppler and TDI were used to assess cardiac parameters at rest in 37 elite male athletes (16 wrestlers, 21 water polo players) and 20 sedentary subjects of similar age. Progressive maximal test on treadmill was used to assess VO2max. The obtained parameters were adjusted for HR, FFM, and BSA. RESULTS: Wrestlers showed higher VO2max than controls, but lesser than water polo players. RV diameter was larger in athletes. Right atrial pressure (RVE/e) was higher in water polo players than in other groups. Systolic function assessed by tricuspid annular plane systolic excursion (TAPSE) and RVs' was the highest in wrestlers. Global RV systolic parameters myocardial performance index (MPI) and preejection time/ejection time index (PET/ET) were similar. On multivariate analysis systolic parameters were independent predictors of VO2max only in wrestlers: RVs' (beta=3.18, P=0.001) and RV ET (beta=2.32, P=0.001). RVE/e` correlated with RVs' (r=-0.57, P=0.000). TAPSE correlated with RV ET (r=0.32, P=0.015) and RVs` (beta=0.28, P=0.033). CONCLUSION: Systolic function assessed by TAPSE and RVs` has more improved in less endurance athletes. RVs`and TDI ejection time predict VO2max in wrestlers, and possibly in other athletes with lesser right atrial pressure. TDI enables quantifying RV adaptation degree in athletes, but complementary to M-mode technique.

Lipid profile and lipid oxidative modification parameters in the first trimester of high- risk pregnancies - possibilities for preeclampsia prediction.

OBJECTIVES: The goal of this study was to investigate metabolic changes in lipids and oxidative stress parameters in the first trimester of pregnancy with the more specific aim of estimating the significance and strength of researched parameters in the prediction of preeclampsia. DESIGN AND METHODS: The study included 87 high-risk pregnant (HRG) female subjects, 14 with developed preeclampsia (PEC) and 43 healthy pregnant female subjects matched for gestational age (CG). Thiobarbituric acid-reactive substances (TBARS) concentration, lipid hydroperoxides (LOOH), pro-oxidant antioxidant balance (PAB) and total oxidative status (TOS) were measured as oxidative stress markers, while total antioxidant capacity (TAC) was measured as an antioxidative defense parameter. The Atherogenic Index of Plasma (AIP) was calculated as the base 10 logarithm of the ratio of the plasma concentration of triglycerides (TG) to the plasma concentration of high-density lipoprotein cholesterol (HDL-C), with each concentration expressed in mmol/L. RESULTS: The results have shown that lipid indices, especially AIP, were significantly higher in the first trimester of HRG (p < 0.001) and PEC (p < 0.001). Oxidative stress parameters were significantlly higher, while TAC was significantly lower in HRG vs. CG [0.7 ± 0.15 vs 1.1 ± 0.16; (p < 0.001)] and in PEC [0.6 ± 0.12 vs 1.1 ± 0.16; (p < 0.001)] vs. CG. Also, in the HRG, results have shown an independent association of AIP with the preeclampsia development (p < 0.05), while placental growth factor did not show the expected level of significance (p = 0.648). Analysis of the Receiver Operating Characteristics (ROC) curves indicated that certain parameters included in the research model have very good diagnostic accuracy for preeclampsia (AUC = 0.856). CONCLUSIONS: AIP is associated with high-risk pregnancies. Furthermore, our results firmly underscored AIP as a potential marker for preeclampsia prediction.

Identification of mutations in the PARK2 gene in Serbian patients with Parkinson's disease.

Mutations in the PARK2 (PRKN) gene are the most common cause of autosomal-recessive (AR) juvenile parkinsonism and young-onset Parkinson's disease (YOPD). >100 different variants have been reported, including point mutations, small indels and single or multiple exon copy number variations. Mutation screening of PARK2 was performed in 225 Serbian PD patients (143 males and 82 females) with disease onset before 50 years and/or positive family history with apparent AR inheritance. All coding regions and their flanking intronic sequences were amplified and directly sequenced. Whole exon multiplications or deletions were detected using Multiple Ligation Probe Amplification (MLPA) method. We identified 12 PD patients with PARK2 mutations (5.3%). Five patients (2.2%) had biallelic mutations and seven (3.1%) were single mutation carriers. Patients with compound heterozygous mutations had earlier onset of the disease compared to non-carriers (p = 0.005) or heterozygotes (p = 0.001). Other clinical features in mutation carriers were not different compared to non-carriers. In our cohort, sequence and dosage variants were equally represented in patients, inducing their first symptoms mainly before the age of 30. For efficient genetic testing strategy, patients with early, especially juvenile onset of PD were strong candidates for both dosage and sequence variants screening of PARK2 gene.

Is it possible to determine the origin of cyst in empty thyroid bed in patient with lingual thyroid?

Some patients with ectopic thyroid gland or athyreotic patients have one or more cysts in empty thyroid bed. The origin of these cysts is uncertain. We present the patient with lingual thyroid gland and small cyst in empty thyroid bed featuring the diagnostic algorithm used and discussing the possible etiologic scenarios.

Ecto-5'-nucleotidase. I. Expression in human normal and neoplastic lymphoid cell lines representing sequential stages of B-cell differentiation.

The possible association of ecto-5'-nucleotidase (5'-NT) with differentiation of B-cells was explored with the use of normal and neoplastic lymphoblastoid cell lines representing sequential stages of B-cell maturation. There was no relationship between patterns of enzyme expression in the cell lines and immunoglobulin (Ig) secretion, chromosome constitution, proliferative rate, cell volume, or the presence of B1 and B2 antigens. Pre-B-cell lines, which were negative for surface Ig or Ig secretion but positive for cytoplasmic mu-chains, showed the presence of 5'-NT, whereas 9 of 11 lymphoma cell lines, Burkitt's or non-Burkitt's type, both secreting and nonsecreting, did not exhibit enzyme activity. Four myeloma cell lines and 13 of 15 normal B-cell lines were positive for 5'-NT. These results suggested that 5'-NT was present in pre-B-cells and in some very early B-cells. 5'-NT usually disappeared from early and some intermediate B-cells and reappeared in mature B-cells and plasmacytoid cells.

X;14 translocation:an exception to the critical region hypothesis on the human X-chromosome.

We report on a family in which an X;14 translocation has been identified. A phenotypically normal female, carrier of an apparently balanced X-autosome translocation t(X;14)(q22;q24.3) in all her cells and a small interstitial deletion of band 15q112 in some of her cells had 2 offspring. She represents a fifth case of balanced X-autosome translocation with the break point inside the postulated critical region of Xq(q13 q26) associated with fertility. The break point in this case is located in Xq22, the same band as in four previously published exceptional cases. In most of her cells, the normal X was inactivated. Her daughter, the proposita, has an unbalanced karyotype 46,X,der(X), t(X;14)(q22;q24.3)mat, del(15)(q11.1q11.3)mat. She is mildly retarded and has some Prader-Willi syndrome manifestations. She has two normal 14 chromosomes, der(X), and deletion 15q11.2. Her clinical abnormalities probably could be attributed to the deletions 15q and Xq rather than 14q duplication. In most of cells, der(X) was inactivated. We assume that spreading of inactivation was extended to the 14q segment on the derivative X. Late replication and gene dose studies support this view. Another daughter, who inherited the balanced X;14 translocation and not deletion 15 chromosome, is phenotypically normal.

Moving satellites and unstable chromosome translocations: clinical and cytogenetic implications.

We describe 2 families in which acrocentric short arm material moved from one chromosome to another. In case 1, a meiotic event resulted in movement of an unusually large paternal 21p to chromosome 13 in the fetus. In case 2, a mitotic event resulted in fetal mosaicism. The short arm material from a paternal chromosome 15 moved to chromosome 14 in some of the fetal cells. Movement of acrocentric short arm material resulted from breakage and exchange in centromeric areas of repetitive DNA. We suggest the mechanism may be similar to that of previously reported "jumping" translocations. Failure to recognize movement of the short arms of acrocentric chromosomes can result in erroneous interpretation of prenatal cytogenetic results and of other cytogenetic assays dependent on acrocentric short arm polymorphisms.

Trisomy 15 mosaic derived from trisomic conceptus: report of a case and a review.

We report on a fetus with 47,XX,+15 chromosome abnormality detected on chorionic villus sampling (CVS). The pregnancy was terminated at 15.5 weeks of gestation and chromosome analysis done on amniocytes and fetal tissues showed a karyotype 46,XX/47,XX,+15. Autopsy showed multiple abnormalities. Short-arm polymorphisms of the three number 15 chromosomes were highly informative in the delineation of parental origin and the stage of meiotic error. Using fluorescent in situ hybridization (FISH) with D15Z1 and a chromosome 15 painting probe, in addition to DA/DAPI and G-banding, we were able to show that the trisomic conceptus was derived through maternal meiosis I error. The trisomic state was then partially corrected by the loss of one of the two maternal 15s resulting in mosaicism without uniparental disomy (UPD). Striking differences in the proportion of trisomic cells in kidneys, blood, intestine, and skin, and lower proportions of trisomic cells in transformed and frozen than in fresh tissues, illustrate the continuing cell selection in this fetus in favour of the normal cell line. Trisomy 15 conceptions are usually aborted spontaneously in the first trimester of pregnancy. The longer survival of this fetus is most probably the result of a chromosome 15 loss from the trisomic zygote. To the best of our knowledge, the presence of this lethal trisomy has been reported in only five live-born infants, and in five fetuses including the present case, it was detected prenatally and the pregnancies were terminated.

Family with 22-derived marker chromosome and late-onset dementia of the Alzheimer type: I. Application of a new model for estimation of the risk of disease associated with the marker.

We have identified 2 sisters with probable dementia of the Alzheimer type who have an unusual 22-derived marker chromosome with a greatly elongated short arm containing 2 well-separated nucleolus organizer regions. A marker chromosome similar in appearance is uncommon in the general population. Eleven of 24 of their biological relatives were also found to have the marker. The known pedigree of this family encompasses 6 generations in 2 of which there is evidence of 10 cases of dementia of the Alzheimer type. The average age-at-onset of dementia is 65.8 +/- 5.5 years; the average age-at-death among those apparently affected is 74.9 +/- 8.3 years. A new model for the estimation of risk was applied to the family data. Persons in this family with the marker were found to be 4 times more likely to develop dementia than those without the marker, the 95% confidence interval for this risk being 1-50. The probability that the association of dementia and the marker is due to chance alone is .05 (1 in 20).

Red cell superoxide dismutase, glutathione peroxidase and catalase in Down syndrome patients with and without manifestations of Alzheimer disease.

The activities of red blood cell enzymes that scavenge the superoxide radical and hydrogen peroxide were measured in severely to profoundly retarded adult Down syndrome (DS) patients with and without manifestations of Alzheimer disease (AD), and control individuals matched for sex, age, and time of blood sampling. Cu,Zn superoxide dismutase (SOD-1) and glutathione peroxidase (GSHPx) activities were significantly elevated (1.39-fold and 1.24-fold, respectively) in DS individuals without AD. When an adjustment was made for the SOD gene dosage effect, DS patients with AD manifestations had significantly lower SOD levels than the matched control individuals. In contrast, DS patients with and without AD had a similar elevation in GSHPx (an adaptive phenomenon). The mean catalase (CAT) activity was no different in DS and control individuals; however, in a paired regression analysis, DS patients without AD had marginally lower CAT activity than control individuals, whereas DS patients with AD had slightly but not significantly higher CAT activity. Thus, AD manifestations in this DS population are associated with changes in the red cell oxygen scavenging processes.

Age-associated chromosome 21 loss in Down syndrome: possible relevance to mosaicism and Alzheimer disease.

We previously observed low level mosaicism (2-4% normal cells) in phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL) in 29% of a small group of elderly persons with Down syndrome (DS). An analysis of cytogenetic data on 154 trisomy 21 cases (age 1 day to 68 years) showed that the proportion of diploid cells in such cultures significantly increased (P < 0.005) with advancing age. Thus, the "occult" mosaicism in PBL of the elderly persons with DS is likely due to the accumulation of cells that have lost a chromosome 21. A consequence of chromosome 21 loss could be uniparental disomy of the 2n cells, a factor that might have significant biological consequences if some chromosome 21 genes are imprinted. Loss of a chromosome 21 from trisomic cells might result in tissue-specific mosaicism and "classical" mosaicism in different age groups. Chromosome 21 loss might also be relevant to the development of Alzheimer-type dementia in DS and in the general population.