Comparative Mechanical Testing for Digitally Produced Provisional Fixed Partial Dentures vs the Conventional Method: An In Vitro Study

PURPOSE: To examine and compare the fracture strength of implant-cemented fixed partial denture (FPD) prostheses fabricated with digital vs conventional chairside methods. MATERIALS AND METHODS: Three groups of seven specimens each were produced: group A (3D printing); group B (milling); and group C (conventional chairside manufacturing), which served as a control. All groups were cemented to standard implant abutments placed in artificial bone blocks. Fracture strength testing was performed using a universal testing machine. Statistical analysis of the resultant maximum forces was performed using SPSS version 25 software (Mann- Whitney U test, P < .05). RESULTS: The mean fracture load value of the group A FPDs was 260.14 N ± 28.88, for group B was 663.57 N ± 140.55, and for group C was 266.65 N ± 63.66. CONCLUSIONS: Milled provisional FPDs showed a higher fracture resistance compared to 3D-printed and control groups. However, no such difference could be detected between the 3D-printed and control groups.

AFM Analysis of a Three-Point Flexure Tested, 3D Printing Definitive Restoration Material for Dentistry.

BACKGROUND: Three-dimensional printing is a rapidly developing technology across all industries. In medicine recent developments include 3D bioprinting, personalized medication and custom prosthetics and implants. To ensure safety and long-term usability in a clinical setting, it is essential to understand material specific properties. This study aims to analyze possible surface changes of a commercially available and approved DLP 3D printed definitive restoration material for dentistry after three-point flexure testing. Furthermore, this study explores whether Atomic Force Microscopy (AFM) is a feasible method for examination of 3D printed dental materials in general. This is a pilot study, as there are currently no studies that analyze 3D printed dental materials using an AFM. METHODS: The present study consisted of a pretest followed by the main test. The resulting break force of the preliminary test was used to determine the force used in the main test. The main test consisted of atomic force microscopy (AFM) surface analysis of the test specimen followed by a three-point flexure procedure. After bending, the same specimen was analyzed with the AFM again, to observe possible surface changes. RESULTS: The mean root mean square (RMS) roughness of the segments with the most stress was 20.27 nm (±5.16) before bending, while it was 26.48 nm (±6.67) afterward. The corresponding mean roughness (Ra) values were 16.05 nm (±4.25) and 21.19 nm (±5.71) Conclusions: Under three-point flexure testing, the surface roughness increased significantly. The p-value for RMS roughness was p = 0.003, while it was p = 0.006 for Ra. Furthermore, this study showed that AFM surface analysis is a suitable procedure to investigate surface changes in 3D printed dental materials.

Thermodynamic basis of the α-helix and DNA duplex.

Analysis of calorimetric and crystallographic information shows that the α-helix is maintained not only by the hydrogen bonds between its polar peptide groups, as originally supposed, but also by van der Waals interactions between tightly packed apolar groups in the interior of the helix. These apolar contacts are responsible for about 60% of the forces stabilizing the folded conformation of the α-helix and their exposure to water on unfolding results in the observed heat capacity increment, i.e. the temperature dependence of the melting enthalpy. The folding process is also favoured by an entropy increase resulting from the release of water from the peptide groups. A similar situation holds for the DNA double helix: calorimetry shows that the hydrogen bonding between conjugate base pairs provides a purely entropic contribution of about 40% to the Gibbs energy while the enthalpic van der Waals interactions between the tightly packed apolar parts of the base pairs provide the remaining 60%. Despite very different structures, the thermodynamic basis of α-helix and B-form duplex stability are strikingly similar. The general conclusion follows that the stability of protein folds is primarily dependent on internal atomic close contacts rather than the hydrogen bonds they contain.

Sacral Insufficiency Fracture Following Pelvic Radiotherapy in Gynaecological Malignancies: Development of a Predictive Model.

AIMS: To investigate the time-to-event and the evolution of sacral insufficiency fractures in gynaecological patients receiving pelvic external beam radiotherapy (EBRT) in relation to dosimetric and imaging parameters across a spectrum of radiotherapy delivery techniques, and to develop a predictive model with a clinical nomogram to identify those at risk of sacral insufficiency fracture. MATERIALS AND METHODS: Patients who received radical or adjuvant pelvic EBRT for gynaecological malignancy between 2014 and 2019 were identified. The data collected were: demographics and clinical details; radiotherapy planning data: dose, fractionation, technique (fixed-field intensity-modulated radiotherapy, adaptive arc, and non-adaptive arc), 60 Gy simultaneous integrated boost. Each plan was examined to determine the sacral dose in 5%/Gy3 increments. Follow-up magnetic resonance scans were reviewed for insufficiency fractures, defined as linear low T1-weighted signal intensity with a high short-T1 inversion recovery (STIR) signal. The site of insufficiency fracture was recreated on the planning computed tomography, the dose to insufficiency fracture contours was recorded and insufficiency fractures were determined as healed with resolution of high STIR signal. Univariable analysis was conducted of the clinical variables. The area under the receiver operator characteristic curve and odds ratio of the risk prediction model with 95% confidence interval are reported with a nomogram for use in clinical practice. RESULTS: 115 patients were identified; the median imaging follow-up was 12 months (2-47). 37.4% developed sacral insufficiency fractures; 93.0% were detected within 12 months of EBRT. At the final radiological follow-up, 83.7% of insufficiency fractures remained active. The radiotherapy delivery technique was not associated with insufficiency fracture after adjusting for patient age (P = 0.115). The location of the 60 Gy simultaneous integrated boost planning target volume did not impact upon the site of insufficiency fracture or the dose received by the insufficiency fracture sites. Age and V40Gy3 are predictors for insufficiency fracture and form the clinical risk model (receiver operator characteristic 0.72). CONCLUSIONS: Age and V40Gy3 predict sacral insufficiency fractures; future work should focus on optimising radiotherapy planning with adoption of a bone-sparing planning approach for those patients at high risk of insufficiency fracture.

Rare case of venous tumour thrombus from acinic cell carcinoma of the parotid gland.

Head and neck tumour thrombus is a rare pathology and at present there are no reported cases of tumour thrombus secondary to acinic cell carcinoma of the parotid gland. We report a case of an 81-year-old man with an acinic cell carcinoma of the left parotid and an intravenous tumour thrombus extending from the retromandibular vein into the internal jugular vein. This case also highlights the importance of radiological imaging in the management of tumour thrombus.

Predicting culturable enterococci exceedances at Escambron Beach, San Juan, Puerto Rico using satellite remote sensing and artificial neural networks.

Predicting recreational water quality is key to protecting public health from exposure to wastewater-associated pathogens. It is not feasible to monitor recreational waters for all pathogens; therefore, monitoring programs use fecal indicator bacteria (FIB), such as enterococci, to identify wastewater pollution. Artificial neural networks (ANNs) were used to predict when culturable enterococci concentrations exceeded the U.S. Environmental Protection Agency (U.S. EPA) Recreational Water Quality Criteria (RWQC) at Escambron Beach, San Juan, Puerto Rico. Ten years of culturable enterococci data were analyzed together with satellite-derived sea surface temperature (SST), direct normal irradiance (DNI), turbidity, and dew point, along with local observations of precipitation and mean sea level (MSL). The factors identified as the most relevant for enterococci exceedance predictions based on the U.S. EPA RWQC were DNI, turbidity, cumulative 48 h precipitation, MSL, and SST; they predicted culturable enterococci exceedances with an accuracy of 75% and power greater than 60% based on the Receiving Operating Characteristic curve and F-Measure metrics. Results show the applicability of satellite-derived data and ANNs to predict recreational water quality at Escambron Beach. Future work should incorporate local sanitary survey data to predict risky recreational water conditions and protect human health.

Application of Artificial Neural Networks for Dengue Fever Outbreak Predictions in the Northwest Coast of Yucatan, Mexico and San Juan, Puerto Rico.

Modelling dengue fever in endemic areas is important to mitigate and improve vector-borne disease control to reduce outbreaks. This study applied artificial neural networks (ANNs) to predict dengue fever outbreak occurrences in San Juan, Puerto Rico (USA), and in several coastal municipalities of the state of Yucatan, Mexico, based on specific thresholds. The models were trained with 19 years of dengue fever data for Puerto Rico and six years for Mexico. Environmental and demographic data included in the predictive models were sea surface temperature (SST), precipitation, air temperature (i.e., minimum, maximum, and average), humidity, previous dengue cases, and population size. Two models were applied for each study area. One predicted dengue incidence rates based on population at risk (i.e., numbers of people younger than 24 years), and the other on the size of the vulnerable population (i.e., number of people younger than five years and older than 65 years). The predictive power was above 70% for all four model runs. The ANNs were able to successfully model dengue fever outbreak occurrences in both study areas. The variables with the most influence on predicting dengue fever outbreak occurrences for San Juan, Puerto Rico, included population size, previous dengue cases, maximum air temperature, and date. In Yucatan, Mexico, the most important variables were population size, previous dengue cases, minimum air temperature, and date. These models have predictive skills and should help dengue fever mitigation and management to aid specific population segments in the Caribbean region and around the Gulf of Mexico.

Diffusion tensor imaging findings in the multiple sclerosis patients and their relationships to various aspects of disability.

BACKGROUND: The aim of the study was to assess microstructural changes within strategic brain regions in multiple sclerosis (MS) patients, using diffusion tensor imaging (DTI), with regard to various aspects of disability. MATERIAL AND METHODS: The study comprised 50 patients with relapsing-remitting MS (37 women, 13 men, mean age 36.4 yrs) and 27 age- and sex-matched controls. Using DTI, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained within corpus callosum (CC), both thalami (TH) and middle cerebellar peduncles (MCP). Disability was assessed using Expanded Disability Status Scale (EDSS), MS Functional Composite (MSFC), Symbol Digit Modalities Test (SDMT) and Fatigue Severity Scale (FSS). DTI indices were compared between the patients and controls and in the MS group - referred to disability measures. RESULTS: Significant decrease in FA and increase in ADC within CC and both TH were found in MS patients compared to the controls. DTI indices within CC and TH correlated significantly with SDMT score, and within TH and MCP - with MSFC manual dexterity measure. CONCLUSIONS: Changes in DTI measures in normal appearing white and grey matter in the MS patients indicate subtle alterations of the tissue integrity. An occult damage to the strategic brain regions may contribute to various aspects of disability due to MS.

Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol.

OBJECTIVE: To evaluate correlation between cumulative dose of gadobutrol and signal intensity (SI) within dentate nucleus and globus pallidus on unenhanced T1-weighted images in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios, and renal and liver functions, were evaluated after multiple intravenous administrations of 0.1 mmol/kg gadobutrol at 27, 96-98, and 168 weeks. We compared SI ratios based on the number of administrations, total amount of gadobutrol administered, and time between injections. RESULTS: Globus pallidus-to-thalamus (p = 0.025) and dentate nucleus-to-pons (p < 0.001) SI ratios increased after multiple gadobutrol administrations, correlated with the number of administrations (ρ = 0.263, p = 0.046, respectively) and depended on the length of administration (p = 0.017, p = 0.037, respectively). Patients receiving gadobutrol at 27 weeks showed the greatest increase in both SI ratios (p = 0.006; p = 0.014, respectively, versus 96-98 weeks). GGT increased at the end of the study (p = 0.004). CONCLUSION: In patients with RRMS, SI within the dentate nucleus and globus pallidus increased on unenhanced T1-weighted images after multiple gadobutrol injections. Administration of the same total amount of gadobutrol over a shorter period caused greater SI increase. KEY POINTS: Gadolinium deposition may occur within the human brain after multiple gadolinium contrast administrations. Increasing T1W signal intensity occurs within the dentate nucleus and globus pallidus. Increasing signal intensity may be a consequence of multiple administrations of gadobutrol. Administration of gadobutrol over a shorter period causes greater signal intensity increase.

EFFECT OF TRPA1 RECEPTOR ACTIVATION ON TRPV1 CHANNEL DESENSITIZATION IN RAT DORSAL GANGLION NEURONS.

The activity of TRPA1 and TRPV1 channels, their sensitivity to selective activators - allyl isothiocyanate (AITC) and capsaicin (Caps), especially their interaction were studied. The method of microfluorescent microscopy and Ca2+ sensitive dye fura- 2AM. Registration of changes in the concentration of intracellular Ca2+ was performed by using the ratio of fluorescence signals measured at two wavelengths (R = F1/ F2). Researches were conducted on cultured neurons of rat dorsal ganglia (DRG neurons). Application of AITC and Caps on soma of DRG neurons resulted in an increase in intracellular Ca2+. Consistent repeated Caps applications resulted in a significant reduction in the amplitude of Ca2+ transients ( desensitization of TRPV1 channels), which accounted 20,7% of initial value. Further application of selective TRPA1 channel agonist (AITC) resulted in restoration of sensitivity to capsaicin TRPV1 channels ( resensitization TRPV1 channels). Thus, we have established the presence of regulation of TRPV1 channel activity by TRPA1 channels.

Interdisciplinary assessment of sea-level rise and climate change impacts on the lower Nile delta, Egypt.

CLImate-induced changes on WAter and SECurity (CLIWASEC) was a cluster of three complementary EC-FP7 projects assessing climate-change impacts throughout the Mediterranean on: hydrological cycles (CLIMB - CLimate-Induced changes on the hydrology of Mediterranean Basins); water security (WASSERMed - Water Availability and Security in Southern EuRope and the Mediterranean) and human security connected with possible hydro-climatic conflicts (CLICO - CLImate change hydro-COnflicts and human security). The Nile delta case study was common between the projects. CLIWASEC created an integrated forum for modelling and monitoring to understand potential impacts across sectors. This paper summarises key results from an integrated assessment of potential challenges to water-related security issues, focusing on expected sea-level rise impacts by the middle of the century. We use this common focus to illustrate the added value of project clustering. CLIWASEC pursued multidisciplinary research by adopting a single research objective: sea-level rise related water security threats, resulting in a more holistic view of problems and potential solutions. In fragmenting research, policy-makers can fail to understand how multiple issues can materialize from one driver. By combining efforts, an integrated assessment of water security threats in the lower Nile is formulated, offering policy-makers a clearer picture of inter-related issues to society and environment. The main issues identified by each project (land subsidence, saline intrusion - CLIMB; water supply overexploitation, land loss - WASSERMed; employment and housing security - CLICO), are in fact related. Water overexploitation is exacerbating land subsidence and saline intrusion, impacting on employment and placing additional pressure on remaining agricultural land and the underdeveloped housing market. All these have wider implications for regional development. This richer understanding could be critical in making better policy decisions when attempting to mitigate climate and social change impacts. The CLIWASEC clustering offers an encouraging path for the new European Commission Horizon 2020 programme to follow.

ALCAM and CD6--multiple sclerosis risk factors.

ALCAM and CD6 may play an important role in the pathogenesis of multiple sclerosis (MS), since they are involved in the transmigration of leukocytes across the blood-brain barrier. In this study, we confirmed our previous findings about the association of the ALCAM gene with risk, development and progression of MS. Additionally, we showed that in the case of the CD6 gene (encoding receptor of ALCAM) not only polymorphisms but also mRNA expression level are associated with MS. Our analysis revealed that the risk of the disease for AA individuals in rs12360861 was almost 3.0-fold lower in comparison to GG individuals (OR=0.34; CI95%=0.12; 0.81). Moreover, we observed lower expression of CD6 mRNA in patients than in healthy individuals (T(2)2,74=6.678; p=0.002).

Investigation of gene-gene interactions between CD40 and CD40L in Polish multiple sclerosis patients.

CD40-CD40L interaction is necessary for the activation of both humoral and cellular immune response and has been suggested to play a role in the pathogenesis of multiple sclerosis (MS). Therefore, we analyzed the combined influence of the CD40 and CD40L variants on MS susceptibility and progression on well-defined Polish population. Our investigation revealed that CT individuals in rs1883832 locus of CD40 possessed almost 1.5-fold higher risk for MS than CC individuals (OR = 1.44; 95%CI = 1.03-2.1; p = 0.032), while this risk for TT individuals was almost 2.5-fold higher (OR = 2.36; 95%CI = 1.19-4.78; p = 0.014). Moreover, for the first time, we observed the association of CD40 gene with MS development and progression. We observed that for the rs1883832CC individuals the age at diagnosis was on average 2 years lower than for the rs1883832CT and rs1883832TT individuals (CI95% = -3.69-(-0.29); p = 0.023). Additionally, we detected that individuals with TT and CT genotypes showed lower risk of developing secondary progressive course in comparison to those with CC genotype. For rs1883832TT individuals this risk was 4-fold lower (HR = 0.24; CI95% = 0.10-0.53; p = 0.00062). Despite the fact that CD40-CD40L pathway plays a key role in development of autoimmune diseases, we were not able to detect gene-gene interactions between CD40 and CD40L polymorphisms associated with multiple sclerosis.

In vivo evaluation of brain damage in the course of systemic lupus erythematosus using magnetic resonance spectroscopy, perfusion-weighted and diffusion-tensor imaging.

Twenty-two neuropsychiatric (NPSLE) and 13 systemic lupus erythematosus (SLE) patients with a normal appearing brain on plain magnetic resonance (MR) as well as 20 age-matched healthy controls underwent MR spectroscopy (MRS), perfusion-weighted (PWI) and diffusion-tensor imaging (DTI). In MRS NAA/Cr, Cho/Cr and mI/Cr ratios were calculated from the posterior cingulate cortex and left parietal white matter. In PWI, values of cerebral blood volume (CBV) were assessed from 14 regions, including gray and white matter. In DTI fractional anisotropy (FA) values were obtained from 14 white matter tracts including projection, commissural and association fibers. All MR measurements were correlated with clinical data. SLE and NPSLE patients showed significantly (p < 0.05) lower NAA/Cr ratios within both evaluated regions and FA values within the cingulum, as well as a tendency to cortical hypoperfusion. Compared to SLE, NPSLE subjects revealed lower FA values within a wide range of association fibers and corpus callosum. Advanced MR techniques are capable of in vivo detection of complex microstructural brain damage in SLE and NPSLE subjects regarding neuronal loss, mild hypoperfusion and white matter disintegrity. MRS and DTI seem to show the highest usefulness in depicting early changes in normal appearing gray and white matter in SLE patients.

Direct skin involvement of cervical lymph node metastasis from mucosal squamous cell carcinoma of the head and neck.

INTRODUCTION: Direct skin involvement of nodal metastasis from mucosal head and neck squamous cell carcinoma has traditionally been considered a poor prognostic indicator. METHODS: This retrospective review identified eight patients (five with mucosal upper aerodigestive and three with occult primary squamous cell carcinoma) who presented between 2000 and 2007 with direct skin involvement of nodal metastasis. RESULTS: Five patients were treated with extended radical and three with extended modified radical neck dissection. Closure was achieved directly (four cases), with local (two) or pedicled (two) flaps. Surgery was always followed by radiotherapy (pan-mucosal or to the primary site). The five-year recurrence-free and disease-specific survival rates were 100 per cent. CONCLUSION: It is exceptionally rare to encounter direct skin involvement of metastatic lymph nodes from mucosal head and neck squamous cell carcinoma without evidence of involvement of other anatomical structures. Surgical intervention is possible and combined modality treatment with curative intent is essential, as most patients can have a favourable outcome.

A multi-objective optimisation model for sewer rehabilitation considering critical risk of failure.

A unique methodology for the optimal specification of sewer rehabilitation investment is presented in this paper. By accounting for the critical risk of asset failure, this methodology builds on previously successful work which explored the application of multi-objective optimisation tools to assist engineers with the specification of optimal rehabilitation strategies. The conventional sewerage rehabilitation specification process relies on the expertise of professional engineers to manually evaluate CCTV inspection information when determining the nature and extent of the rehabilitation solution. This process is not only tedious and subjective but it has no quantifiable means of identifying optimal solutions or possible combinations of optimal solutions in the delivery of catchment wide rehabilitation programmes. Therefore, the purely manual process of sewer rehabilitation design leaves a number of unanswered questions, such as: (1) Does the solution offer the greatest structural benefit to the network? (2) Is the solution the most cost-effective solution available? (3) Does the solution most greatly reduce the risk of critical asset failure? The application of a multi-objective genetic algorithm optimisation model, coupled with an enhanced critical risk methodology, has successfully answered these questions when applied to a case study data set provided by South West Water (UK).

Integrated System Dynamics Modelling for water scarcity assessment: case study of the Kairouan region.

A System Dynamics Model (SDM) assessing water scarcity and potential impacts of socio-economic policies in a complex hydrological system is developed. The model, simulating water resources deriving from numerous catchment sources and demand from four sectors (domestic, industrial, agricultural, external pumping), contains multiple feedback loops and sub-models. The SDM is applied to the Merguellil catchment, Tunisia; the first time such an integrated model has been developed for the water scarce Kairouan region. The application represents an early step in filling a critical research gap. The focus of this paper is to a) assess the applicability of SDM for assessment of the evolution of a water-scarce catchment and b) to analyse the current and future behaviour of the catchment to evaluate water scarcity, focusing on understanding trends to inform policy. Baseline results indicate aquifer over-exploitation, agreeing with observed trends. If current policy and social behaviour continue, serious aquifer depletion is possible in the not too distant future, with implications for the economy and environment. This is unlikely to occur because policies preventing depletion will be implemented. Sensitivity tests were carried out to show which parameters most impacted aquifer behaviour. Results show non-linear model behaviour. Some tests showed negligible change in behaviour. Others showed unrealistic exponential changes in demand, revenue and aquifer water volume. Policy-realistic parameters giving the greatest positive impact on model behaviour were those controlling per-capita domestic water demand and the pumped volume to coastal cities. All potentially beneficial policy options should be considered, giving the best opportunity for preservation of Kairouan aquifer water quantity/quality, ecologically important habitats and the agricultural socio-economic driver of regional development. SDM is a useful tool for assessing the potential impacts of possible policy measures with respect to the evolution of water scarcity in critical regions. This work was undertaken for the EC FP7 project 'WASSERMed'.

SYBR Green I: fluorescence properties and interaction with DNA.

In this study, we have investigated the fluorescence properties of SYBR Green I (SG) dye and its interaction with double-stranded DNA (dsDNA). SG/dsDNA complexes were studied using various spectroscopic techniques, including fluorescence resonance energy transfer and time-resolved fluorescence techniques. It is shown that SG quenching in the free state has an intrinsic intramolecular origin; thus, the observed >1,000-fold SG fluorescence enhancement in complex with DNA can be explained by a dampening of its intra-molecular motions. Analysis of the obtained SG/DNA binding isotherms in solutions of different ionic strength and of SG/DNA association in the presence of a DNA minor groove binder, Hoechst 33258, revealed multiple modes of interaction of SG inner groups with DNA. In addition to interaction within the DNA minor groove, both intercalation between base pairs and stabilization of the electrostatic SG/DNA complex contributed to increased SG affinity to double-stranded DNA. We show that both fluorescence and the excited state lifetime of SG dramatically increase in viscous solvents, demonstrating an approximate 200-fold enhancement in 100 % glycerol, compared to water, which also makes SG a prospective fluorescent viscosity probe. A proposed structural model of the SG/DNA complex is compared and discussed with results recently reported for the closely related PicoGreen chromophore.