Development and validation of the low-cost pregnant female physical phantom for fetal dosimetry in MV photon radiotherapy.

BACKGROUND: Monte Carlo (MC) simulations or measurements in anthropomorphic phantoms are recommended for estimating fetal dose in pregnant patients in radiotherapy. Among the many existing phantoms, there is no commercially available physical phantom representing the entire pregnant woman. PURPOSE: In this study, the development of a low-cost, physical pregnant female phantom was demonstrated using commercially available materials. This phantom is based on the previously published computational phantom. METHODS: Three tissue substitution materials (soft tissue, lung and bone tissue substitution) were developed. To verify Tena's substitution tissue materials, their radiation properties were assessed and compared to ICRP and ICRU materials using MC simulations in MV radiotherapy beams. Validation of the physical phantom was performed by comparing fetal doses obtained by measurements in the phantom with fetal doses obtained by MC simulations in computational phantom, during an MV photon breast radiotherapy treatment. RESULTS: Materials used for building Tena phantom are matched to ICRU materials using physical density, radiation absorption properties and effective atomic number. MC simulations showed that percentage depth doses of Tena and ICRU material comply within 5% for soft and lung tissue, up to 25 cm depth. In the bone tissue, the discrepancy is higher, but again within 5% up to the depth of 5 cm. When the phantom was used for fetal dose measurements in MV photon breast radiotherapy, measured fetal doses complied with fetal doses calculated using MC simulation within 15%. CONCLUSIONS: Physical anthropomorphic phantom of pregnant patient can be manufactured using commercial materials and with low expenses. The files needed for 3D printing are now freely available. This enables further studies and comparison of numerical and physical experiments in diagnostic radiology or radiotherapy.

Management of pregnant or potentially pregnant patients undergoing diagnostic and interventional radiology procedures: Investigation of clinical routine practice.

It is well known that foetuses are highly sensitive to ionising radiation and special attention to justification and optimisation of radiological procedures involving a pregnant patient is required. A task to review, validate and compare different approaches to managing the pregnant patient and to estimating the associated foetal doses arising from a diagnostic or interventional radiology (DIR) procedure was designed in the framework of EURADOS working group 12. As a first step, a survey of radiation protection practice including dosimetry considerations among EURADOS members was performed using online questionnaire. Then, to evaluate the possible differences in the estimated foetal doses, a comparison of assessed dose values was made for three cases of pregnant patients that underwent different CT procedures. More than 120 professionals from 108 institutions and 17 countries that are involved in managing pregnant patients undergoing DIR procedures answered the questionnaire. Most of the respondents use national or hospital guidelines on the management of pregnant patients undergoing DIR procedures. However, the guidelines differ considerably among respondents. Comparison of foetal dose assessments performed by dosimetry experts showed the variety of methods used as well as large variability of estimated foetal doses in all three cases. Although European and International commission on radiation protection guidelines already exist, they are more than 20 years old and, in some aspects, they are obsolete. This paper shows that there is a need to revise and update these guidelines.

Identification of SH2 Domain-Containing Protein 3C as a Novel, Putative Interactor of Dipeptidyl Peptidase 3.

Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent exopeptidase with broad specificity for four to eight amino acid residue substrates. It has a role in the regulation of oxidative stress response NRF2-KEAP1 pathway through the interaction with KEAP1. We have conducted stable isotope labeling by amino acids in a cell culture coupled to mass spectrometry (SILAC-MS) interactome analysis of TRex HEK293T cells using DPP3 as bait and identified SH2 Domain-Containing Protein 3C (SH2D3C) as prey. SH2D3C is one of three members of a family of proteins that contain both the SH2 domain and a domain similar to guanine nucleotide exchange factor domains of Ras family GTPases (Ras GEF-like domain), named novel SH2-containing proteins (NSP). NSPs, including SH2D3C (NSP3), are adaptor proteins involved in the regulation of adhesion, migration, tissue organization, and immune response. We have shown that SH2D3C binds to DPP3 through its C-terminal Ras GEF-like domain, detected the colocalization of the proteins in living cells, and confirmed direct interaction in the cytosol and membrane ruffles. Computational analysis also confirmed the binding of the C-terminal domain of SH2D3C to DPP3, but the exact model could not be discerned. This is the first indication that DPP3 and SH2D3C are interacting partners, and further studies to elucidate the physiological significance of this interaction are on the way.

Identification of an Additional Metal-Binding Site in Human Dipeptidyl Peptidase III.

Dipeptidyl peptidase III (DPP III, EC 3.4.14.4) is a monozinc metalloexopeptidase that hydrolyzes dipeptides from the N-terminus of peptides consisting of three or more amino acids. Recently, DPP III has attracted great interest from scientists, and numerous studies have been conducted showing that it is involved in the regulation of various physiological processes. Since it is the only metalloenzyme among the dipeptidyl peptidases, we considered it important to study the process of binding and exchange of physiologically relevant metal dications in DPP III. Using fluorimetry, we measured the Kd values for the binding of Zn2+, Cu2+, and Co2+ to the catalytic site, and using isothermal titration calorimetry (ITC), we measured the Kd values for the binding of these metals to an additional binding site. The structure of the catalytic metal's binding site is known from previous studies, and in this work, the affinities for this site were calculated for Zn2+, Cu2+, Co2+, and Mn2+ using the QM approach. The structures of the additional binding sites for the Zn2+ and Cu2+ were also identified, and MD simulations showed that two Cu2+ ions bound to the catalytic and inhibitory sites exchanged less frequently than the Zn2+ ions bound to these sites.

Canine Crown Sexual Dimorphism in a Sample of the Modern Croatian Population.

Sex assessment is a key part of forensic analysis to establish the identity of unknown deceased individuals. Previous studies have shown that canines are the most dimorphic teeth, but population-specific data are necessary for forensic methods. This study explores sex dimorphism in canine crown dimensions and morphology in a contemporary Croatian population. The material consisted of 302 dental casts (147 females, 155 males) of orthodontic patients and dental students (11-25 years). The distal accessory ridge (DAR) of the upper and lower canines was evaluated using the Arizona State University Dental Anthropology System. Mesiodistal (MD) and buccolingual (BL) crown dimensions were measured on 120 casts. Sex differences in MD and BL dimensions were significant (p < 0.05) for all the canines (upper and lower, left and right), while in DAR only for lower canines (p < 0.000001). When all variables were put into the model, backward stepwise discriminant function analysis isolated lower canine DAR and lower left canine MD as the two independent variables differentiating sex. Using these two variables, a discriminant function formula allowed for sex determination with an accuracy of 73.5%. This study shows that both canine crown morphology and dimensions are useful for sex determination, especially for lower canines. These methods can be applied to children, as lower canines erupt at about 9 years of age.

Artificial neural network model for predicting sex using dental and orthodontic measurements.

Objective: To investigate sex-specific correlations between the dimensions of permanent canines and the anterior Bolton ratio and to construct a statistical model capable of identifying the sex of an unknown subject. Methods: Odontometric data were collected from 121 plaster study models derived from Caucasian orthodontic patients aged 12-17 years at the pretreatment stage by measuring the dimensions of the permanent canines and Bolton's anterior ratio. Sixteen variables were collected for each subject: 12 dimensions of the permanent canines, sex, age, anterior Bolton ratio, and Angle's classification. Data were analyzed using inferential statistics, principal component analysis, and artificial neural network modeling. Results: Sex-specific differences were identified in all odontometric variables, and an artificial neural network model was prepared that used odontometric variables for predicting the sex of the participants with an accuracy of > 80%. This model can be applied for forensic purposes, and its accuracy can be further improved by adding data collected from new subjects or adding new variables for existing subjects. The improvement in the accuracy of the model was demonstrated by an increase in the percentage of accurate predictions from 72.0-78.1% to 77.8-85.7% after the anterior Bolton ratio and age were added. Conclusions: The described artificial neural network model combines forensic dentistry and orthodontics to improve subject recognition by expanding the initial space of odontometric variables and adding orthodontic parameters.

Teeth macroabrasion for determination of dental age and diet in the Illyrian population from the Kopila necropolis on the Island of Korcula, Croatia.

This paper presents the changes caused by macroabrasion of teeth on skeletal remains found in tomb No 4 in the west necropolis of the archeological site Kopila near Blato on the island of Korcula. The site archeologically dates back to the Late Iron Age, when the island was inhabited by the Illyrians. The aim of this study was to assess the dental age of the buried individuals at death and determine the type of their diet, which could give us a preliminary insight into the socio-economic standard of the inhabitants of the settlement. The analyzed sample is part of the collection of excavated skeletal remains kept in the Vela Luka Cultural Center on the island of Korcula. 284 permanent teeth, 19 fragments of the maxilla and 20 fragments of the mandible were found in the tomb, which were classified into 32 individuals and by sex. Teeth were analyzed by metric and non-metric methods of determining dental status in order to assess the dental age at the time of death and the diet of the inhabitants. The dental age of individuals was determined by the Lovejoy method and the degree of tooth wear by the Smith-Knight method. The analysis of the stable isotope 14C determined the exact time of death of the analyzed individuals. The tooth wear changes were very pronounced and present on 92.9% of teeth, equally on incisors and molars (p = 0.236). There is no significant gender difference (p > 0.05 for all teeth and jaw parts). There was no difference in the degree of tooth wear of the teeth of the mandible and maxilla (t = -0.266, p = 0.791), nor in the degree of tooth wear of the teeth of the maxilla right and left (t = -0.392, p = 0.702) or in the degree of tooth wear of the teeth of the mandible right and left (t = -0.889, p = 0.390). The average age of the analyzed population sample was 35.6 (±3.1) years. They were buried between 360-40 BC. Tooth wear changes observed on the analyzed teeth indicate a diet rich in hard, weakly cariogenic food with particles that were probably of inorganic origin, which caused an increased wear of tooth structures. The population was sedentary, agricultural type and the life expectancy was normal for the Late Iron Age. Besides, their socio-economic status was good. The age at the time of their death was between 30 and 40 years. Further studies should include more accurate and standardized methods for assessing the condition.

Development of a computational pregnant female phantom and calculation of fetal dose during a photon breast radiotherapy.

BACKGROUND: The incidence of carcinoma during pregnancy is reported to be 1:1000-1:1500 pregnancies with the breast carcinoma being the most commonly diagnosed. Since the fetus is most sensitive to ionizing radiation during the first two trimesters, there are mixed clinical opinions and no uniform guidelines on the use of radiotherapy during pregnancy. Within this study the pregnant female phantom in the second trimester, that can be used for radiotherapy treatment planning (as DICOM data), Monte Carlo simulations (as voxelized geometry) and experimental dosimetry utilizing 3D printing of the molds (as .STL files), was developed. MATERIALS AND METHODS: The developed phantom is based on MRI images of a female patient in her 18th week of pregnancy and CT images after childbirth. Phantom was developed in such a manner that a pregnant female was scanned "in vivo" using MRI during pregnancy and CT after childbirth. For the treatment of left breast carcinoma, 3D conformal radiotherapy was used. The voxelized geometry of the phantom was used for Monte Carlo (MC) simulations using Monte Carlo N-Particle transport codeTM 6.2 (MCNP). CONCLUSIONS: The modeled photon breast radiotherapy plan, applied to the phantom, indicated that the fetus dose is 59 mGy for 50 Gy prescribed to the breast. The results clearly indicate that only 9.5% of the fetal dose is caused by photons that are generated in the accelerator head through scattering and leakage, but the dominant component is scattered radiation from the patient's body.

The Cameriere, Haavikko, Demirjian, and Willems methods for the assessment of dental age in Croatian children.

AIM: This study aimed to evaluate the accuracy and precision of the Cameriere European formula, Demirjian, Haavikko, and Willems methods for estimating dental age in a sample of children with permanent dentition in Croatia. MATERIAL AND METHODS: The study consisted of a sample of 1576 panoramic radiographs; a sub-sample of 84 OPGs, in which all first seven mandibular teeth were maturated, was excluded from the study. A final sample of 1492 (704 males and 788 females) aged 6.0 to 13.9 years was evaluated. Seven mandibular teeth from the left side of the mandible were analyzed, and dental age (DA) was determined by the Cameriere European formula, Demirjian method from 1976, Haavikko, and Willems methods and compared to chronological age (CA). In addition, the mean age difference (DA-CA), the mean absolute error (MAE) between dental and chronological age, the percentage of the individuals of dental age within ± 0.25 to ± 2 years of chronological age, and intra-observer and inter-observer statistics were calculated. RESULTS: The Cameriere European formula estimated the best dental age compared to the chronological age; the mean underestimation was - 0.4 years for both sexes, Haavikko underestimated by - 0.17 years, while Demirjian and Willems overestimated by 1.02 years and 0.48 years, respectively. The most significant difference showed the Demirjian method in 11-year-old and 12-year-old females. The MAE were 0.50 years, 1.01 years, 0.61 years, and 0.78 years in males and 0.51 years, 1.18 years, 0.61 years, and 0.70 years in females for the Cameriere European formula, Haavikko, Willems, and Demirjian methods, respectively. Furthermore, the Cameriere European formula showed the highest proportions of individuals with DA within ± 0.5 year difference of the CA, 61.5% in males and 59.6% in females. In addition, the Cameriere method showed the best intra-observer and inter-observer agreements. CONCLUSIONS: Although the Demirjian method was used previously in Croatian children for legal, medical, and clinical purposes, the Cameriere European formula, Haavikko, and Willems were more accurate in the tested sample. According to our findings, the Cameriere European formula showed the best accuracy and precision in dental age assessment in Croatian children following Haavikko, and we recommend it as the method of the first choice in forensic and clinical analyses.

DETERMINATION OF THE NEUTRON CONTAMINATION DURING BRAIN RADIOTHERAPY USING A MODERATED-BORON TRIFLUORIDE DETECTOR AND THE MCNP MONTE CARLO CODE.

This study aimed to determine the neutron dose equivalent to the thyroid gland and eye lens in brain tumor radiation therapy with 15- and 18-MV three-dimensional conformal methods (3D-CRT). A Monte Carlo simulation was performed using the Monte Carlo N-particle transport code to calculate neutron fluence and ambient dose equivalent (H*(10)). Afterward, these parameters were measured using a model NRD roentgen equivalent in man (REM) neutron detector (Thermo Electron Corporation, USA) equipped with Eberline's ASP-2e rate meter. Finally, the organ neutron dose equivalent was obtained by applying depth corrections to the measured ambient dose equivalent at the distance of the organ center from the central beam axis. The ratio of the out-of-field photon dose equivalent, measured previously, to the neutron dose equivalent in the eye lens was high due to its proximity to the radiation field. In contrast, this ratio remained unexpectedly high in the thyroid gland that is far from the central beam axis (about 15 cm). The calculated neutron parameters agreed with the measurements. The present study findings indicate that external field photon dose is the main source of thyroid gland biological effects in radiotherapy of brain tumors. In addition, it is appropriate to apply the model NRD REM neutron detector for measuring neutron contamination from high-energy linear accelerators inside and outside the treatment field.

Unravelling the inhibitory zinc ion binding site and the metal exchange mechanism in human DPP III.

Dipeptidyl peptidase III (DPP III), a zinc-dependent exopeptidase, is widely distributed in organisms and present in almost all human tissues. In addition to its involvement in protein catabolism, it plays a role in oxidative stress and blood pressure regulation, and there is evidence of its involvement in pain modulation. Excess zinc ions have been found to inhibit its hydrolytic activity, but the binding affinity, binding site geometry, and mechanism of inhibitory activity have been unknown. Using several different computational approaches, we determined the inhibitory zinc ion binding site, its coordination and relative binding affinity. During some simulations the translocation of the zinc ion from the inhibitory to the catalytic binding site was observed, accompanied by movement of the catalytic zinc ion toward the exit of the substrate binding site. The traced behavior suggests an associative type of metal ion exchange, in which the formation of the ternary complex between enzyme and two metal ions precedes the exit of the catalytic metal ion. Differently from our previous findings that binding of a peptide induces partial opening of hDPP III, the globularity of the protein did not change in MD simulations of the hermorphin-like peptide bound to hDPP III with two zinc ions. However, the entrance to the interdomain cleft widens during Zn diffusion into the protein and was found to be the highest energy barrier in the process of metal translocation from the solvent to the active site. Finally, we discuss why excess zinc reduces enzyme activity.

Binding of dipeptidyl peptidase III to the oxidative stress cell sensor Kelch-like ECH-associated protein 1 is a two-step process.

This work is about synergy of theory and experiment in revealing mechanism of binding of dipeptidyl peptidase III (DPP III) and Kelch-like ECH-associated protein 1 (KEAP1), the main cellular sensor of oxidative stress. The NRF2 ̶ KEAP1 signaling pathway is important for cell protection, but it is also impaired in many cancer cells where NRF2 target gene expression leads to resistance to chemotherapeutic drugs. DPP III competitively binds to KEAP1 in the conditions of oxidative stress and induces release of NRF2 and its translocation into nucleus. The binding is established mainly through the ETGE motif of DPP III and the Kelch domain of KEAP1. However, although part of a flexible loop, ETGE itself is firmly attached to the DPP III surface by strong hydrogen bonds. Using combined computational and experimental study, we found that DPP III ̶ Kelch binding is a two-step process comprising the endergonic loop detachment and exergonic DPP III ̶ Kelch interaction. Substitution of arginines, which keep the ETGE motif attached, decreases the work needed for its release and increases DPP III ̶ Kelch binding affinity. Interestingly, mutations of one of these arginine residues have been reported in cBioPortal for cancer genomics, implicating its possible involvement in cancer development. Communicated by Ramaswamy H. Sarma.

Dental medicine and COVID-19 pandemic.

Specific airborne infection with characteristic symptoms - high fever, headache, persisting dry cough, loss of taste and smell and overall tiredness originates from Wuhan in China where it was discovered in December 2019. Due to rapid dissemination the epidemic has become a pandemic caused by coronavirus on March 11 2020. It changed the world over night and made human life different; for some it was the ultimate change. In these fluctuating times the dental medicine, especially in the developed and advancing areas, completely stopped. Responsible behaviour of dentists, aimed at stopping the spread of the virus from dental offices showed that only emergency procedures were to be performed, in cases of toothache, trauma and odontogenic infections that might put organs or systems at risk. At the same time, with the cessation of all types of treatments, there was an immediate cessation of teaching processes in all university settings for dental medicine, since the data from China strongly suggested death rates among doctors and students in close contact with infected persons. Stress and unease that have grown among people due to isolation and quarantine, the only ways of prevention of the spread of the invisible enemy will have long-lasting and visible effect on mental health of the people. Health issues in the oral cavity will most certainly occur due to the lack of regular check-ups and care. Caries and periodontal disease will appear more frequently. While we are expecting an efficient vaccine, the only way to counter the virus are epidemiological measures and responsible behaviour of every individual, in order to stop the spread of COVID-19 virus.

A Method of High-Resolution Radiotherapy Delivery Fluences with a Pair of Fields with Orthogonal Collimator Settings: A Study on Ten Head-and-Neck Cancer Patients.

CONTEXT: Introduction of dual-layer multileaf collimator (MLC) radiotherapy linear accelerators into clinical practice is an important development in advanced external beam radiotherapy. A method of delivering comparable high-resolution fluences with a single-layer MLC is presented. AIMS: The aims of this study are to present new algorithms and approaches to define high-resolution hypermodulated fluences, obtain orthogonal decomposition of fluences, and deliver them on a linear accelerator with single MLC from two perpendicular collimator settings. MATERIALS AND METHODS: High-resolution fluences were defined using Monte Carlo (MC) calculation. A novel use of a limited-memory, bounded, Broyden-Fletcher-Goldfarb-Shanno algorithm was used to decompose such fluences to ones deliverable with a pair of fields with mutually orthogonal collimator settings. Such a technique, here named cross motion leaf calculator (XMLC), is compared against single sliding window (SSW) technique typically used in intensity-modulated radiation therapy (IMRT). An electronic portal imaging device (EPID) is used, and the results were compared with gamma analysis. Furthermore, MC was used to determine dose distributions for computed tomography images of ten head-and-neck cancer patients. RESULTS: Gamma analysis (3%, 3 mm) against ideal fluence is considerably more favorable to XMLC (94% ± 4%) versus SSW (76% ± 5%). Furthermore, the dose-volume histogram (DVH) analysis showed that XMLC enables delivery of fluences superior to that of IMRT and these results in clinically relevant enhancements in DVH results. CONCLUSIONS: At the time of writing of this study, there were more than 12,000 medical linear accelerators in clinical use, and XMLC can prove itself useful wherever linac is equipped with MLC but cannot delivery latest techniques, such as volumetric modulated arc therapy.

The influence of shielding reinforcement in a vault with limited dimensions on the neutron dose equivalent in vicinity of medical electron linear accelerator.

Background High energy electron linear accelerators (LINACs) producing photon beams with energies higher than 10 MeV are widely used in radiation therapy. In these beams, fast neutrons are generated, which results in undesired contamination of the therapeutic beam. In this study, measurements and Monte Carlo (MC) simulations were used to obtain neutron spectra and dose equivalents in vicinity of linear accelerator. Materials and methods LINAC Siemens Oncor Expression in Osijek University Hospital is placed in vault that was previously used for 60Co machine. Then, the shielding of the vault was enhanced using lead and steel plates. Measurements of neutron dose equivalent around LINAC and the vault were done using CR-39 solid state nuclear track detectors. To compensate energy dependence of detectors, neutron energy spectra was calculated in measuring positions using MC simulations. Results The vault is a source of photoneutrons, but a vast majority of neutrons originates from accelerator head. Neutron spectra obtained from MC simulations show significant changes between the measuring positions. Annual neutron dose equivalent per year was estimated to be less than 324 µSv in the measuring points outside of the vault. Conclusions Since detectors used in this paper are very dependent on neutron energy, it is extremely important to know the neutron spectra in measuring points. Though, patient dosimetry should include neutrons, estimated annual neutron doses outside the vault were far below exposure limit of ionizing radiation for workers.

New Zinc Ion Parameters Suitable for Classical MD Simulations of Zinc Metallopeptidases.

The main aim of this work was to find parameters for the zinc ion in human dipeptidyl peptidase III (DPP III) active site that would enable its reliable modeling. Since the parameters publicly available failed to reproduce the zinc ion coordination in the enzyme, we developed a new set of the hybrid bonded/nonbonded parameters for the zinc ion suitable for molecular modeling of the human DPP III, dynamics, and ligand binding. The parameters allowed exchange of the water molecules coordinating the zinc ion and proved to be robust enough to enable reliable modeling not only of human DPP III and its orthologues but also of the other zinc-dependent peptidases with the zinc ion coordination similar to that in dipeptidyl peptidases III, i.e., peptidases with the zinc ion coordinated with two histidines and one glutamate. The new parameters were tested on a set of 21 different systems comprising 8 different peptidases, 5 DPP III orthologues, thermolysin, neprilysin, and aminopeptidase N, and the results are summarized in the second part of the article.

Accuracy of four dental age estimation methodologies in Brazilian and Croatian children.

OBJECTIVE: To compare and analyse the accuracy of four age estimation methods using the mineralisation stages of the permanent teeth (Cameriere et al. [16] [CAM], Liliequist and Lundberg [LLH] and Nolla without third molars [NOL7] or with them [NOL8]) in a mixed population of Brazilians and a homogeneous population of Croatians. METHODS: Orthopantomograms of 930 Brazilians (366 males and 564 females) and 924 Croatians (365 males and 556 females) aged between 8 and 14.99 years were analysed using the CAM, LLH, NOL7 and NOL8 age estimation methodologies. RESULTS: LLH presented the best absolute differences (ADs) among both populations without sex stratification, while CAM presented the worst results. In addition, the mean differences revealed underestimations, except when the LLH and NOL7 methods were used for the Brazilians. When the sample was stratified by sex, the best AD values were found with NOL7 (0.80) for the Brazilians and with LLH (0.98) for the Croatians. When the sample was stratified by sex and age, CAM presented high accuracy at the early ages, and LLH presented high accuracy at the older ages. The results obtained with the Nolla methods (NOL7 and NOL8) were mostly similar, but NOL7 yielded slightly better results. CONCLUSIONS: The values for the Brazilians and the Croatians were relatively similar, and the techniques were properly applied in both population samples. The best method for evaluating both countries was LLH, followed by NOL7, NOL8 and CAM.

Tooth Crown Morphology in Turner and Klinefelter Syndrome Individuals from a Croatian Sample.

OBJECTIVE: Turner syndrome (TS) and Klinefelter syndrome (KS) represent the two most common X chromosome aneuploidies, each associated with systemic disruptions to growth and development. Effects of these conditions on tooth crown morphology are explored in a sample of Croatian individuals. MATERIALS AND METHODS: The sample included 57 TS, 37 KS and 88 control individuals. Dental crown morphology was scored on dental casts according to the Turner-Scott Dental Anthropology System. RESULTS: Incisor shoveling and the hypocone were significantly different between TS individuals and both control and KS individuals. Individuals with TS exhibit lower grades of expression than either group. Furthermore, the number of lingual cusps on the mandibular premolars, the hypoconulid on the mandibular second molar, and cusp 7 on the mandibular first molar were significantly different, though pair-wise comparisons did not elucidate these differences. Tuberculum dentale, distal accessory ridge, and Carabelli's trait were expressed similarly to the control. KS individuals were not significantly different from control individuals for any trait, though this may be related to sample size. CONCLUSIONS: Previous studies suggest the loss of an X chromosome has a reducing effect on dental crown morphology, which is confirmed in this research. TS individuals exhibit generally simpler dental morphology compared to the control sample, though some traits are expressed comparably to the control sample. The effects of KS are less clear. Though previous studies suggest that the presence of an extra X chromosome increases dental crown dimensions, there was no notable effect on crown morphology in this study.

Aprotinin interacts with substrate-binding site of human dipeptidyl peptidase III.

Human dipeptidyl peptidase III (hDPP III) is a zinc-exopeptidase of the family M49 involved in final steps of intracellular protein degradation and in cytoprotective pathway Keap1-Nrf2. Biochemical and structural properties of this enzyme have been extensively investigated, but the knowledge on its contacts with other proteins is scarce. Previously, polypeptide aprotinin was shown to be a competitive inhibitor of hDPP III hydrolytic activity. In this study, aprotinin was first investigated as a potential substrate of hDPP III, but no degradation products were demonstrated by MALDI-TOF mass spectrometry. Subsequently, molecular details of the protein-protein interaction between aprotinin and hDPP III were studied by molecular modeling. Docking and long molecular dynamics (MD) simulations have shown that aprotinin interacts by its canonical binding epitope with the substrate binding cleft of hDPP III. Thereby, free N-terminus of aprotinin is distant from the active-site zinc. Enzyme-inhibitor complex is stabilized by intermolecular hydrogen bonding network, electrostatic and hydrophobic interactions which mostly involve constituent amino acid residues of the hDPP III substrate binding subsites S1, S1', S2, S2' and S3'. This is the first study that gives insight into aprotinin binding to a metallopeptidase. Communicated by Ramaswamy H. Sarma.

Essential considerations for accurate evaluation of photoneutron contamination in Radiotherapy.

Nowadays, high-energy X-rays produced by medical linear accelerators (LINACs) are widely used in many Radiation Therapy (RT) centers. High-energy photons (> 8 MeV) produce undesired neutrons in the LINAC head which raise concerns about unwanted neutron dose to the patients and RT personnel. Regarding the significance of radiation protection in RT, it is important to evaluate photoneutron contamination inside the RT room. Unfortunately, neutron dosimeters used for this purpose have limitations that can under the best conditions cause to > 10% uncertainty. In addition to this uncertainty, the present Monte Carlo (MC) study introduces another uncertainty in measurements (nearly up to 20%) when neutron ambient dose equivalent (Hn*(10)) is measured at the patient table or inside the maze and the change in neutron energy is ignored. This type of uncertainty can even reach 35% if Hn*(10) is measured by dosimeters covered by a layer of 10B as converter. So, in these cases, neglecting the change in neutron energy can threaten the credibility of measured data and one should attend to this energy change in order to reduce measurement uncertainty to the possible minimum. This study also discusses the change in neutron spectra and Hn*(10) at the patient table caused by removing a typical RT room from MC simulations. Under such conditions, neutron mean energy (En) overestimated by 0.2-0.4 MeV at the patient table. Neutron fluence (φn) at the isocenter (IC) was underestimated by 23-54% for different field sizes that caused Hn*(10) to be miscalculated up to 24%. This finding informs researchers that for accurate evaluation of Hn*(10) at the patient table, simulating the RT room is an effective parameter in MC studies.