Machine Learning Support for Decision-Making in Kidney Transplantation: Step-by-step Development of a Technological Solution.

BACKGROUND: Kidney transplantation is the preferred treatment option for patients with end-stage renal disease. To maximize patient and graft survival, the allocation of donor organs to potential recipients requires careful consideration. OBJECTIVE: This study aimed to develop an innovative technological solution to enable better prediction of kidney transplant survival for each potential donor-recipient pair. METHODS: We used deidentified data on past organ donors, recipients, and transplant outcomes in the United States from the Scientific Registry of Transplant Recipients. To predict transplant outcomes for potential donor-recipient pairs, we used several survival analysis models, including regression analysis (Cox proportional hazards), random survival forests, and several artificial neural networks (DeepSurv, DeepHit, and recurrent neural network [RNN]). We evaluated the performance of each model in terms of its ability to predict the probability of graft survival after kidney transplantation from deceased donors. Three metrics were used: the C-index, integrated Brier score, and integrated calibration index, along with calibration plots. RESULTS: On the basis of the C-index metrics, the neural network-based models (DeepSurv, DeepHit, and RNN) had better discriminative ability than the Cox model and random survival forest model (0.650, 0.661, and 0.659 vs 0.646 and 0.644, respectively). The proposed RNN model offered a compromise between the good discriminative ability and calibration and was implemented in a technological solution of technology readiness level 4. CONCLUSIONS: Our technological solution based on the RNN model can effectively predict kidney transplant survival and provide support for medical professionals and candidate recipients in determining the most optimal donor-recipient pair.

Effect of decontamination on micro-shear bond strength of silorane-based composite increments.

AIM: The aim of the present study was to evaluate the micro-shear bond strength of silorane-based composites after saliva/blood decontamination. METHODS: A transparent mold (1 × 2 × 1 cm) was used to make 11 flat, silorane-based composite blocks. One block served as the control. After contamination, the blocks were treated as follows: group 1: 10-s air spray; group 2: 10-s water spray + 10-s air spray; group 3: 10-s water spray + 10-s air spray + 10-s etching with phosphoric acid; group 4: 10-s air spray + 10-s etching + bonding; group 5: 10-s water spray + 10-s air spray + 10-s etching + bonding; and groups 6-10: treated the same as groups 1-5, the only difference being that blood was used instead of saliva. Ten tubes (0.7 mm × 1 mm) containing silorane-based composites were attached to each decontaminated block and light cured for 40 s. After 24-h storage in distilled water, specimens were tested under micro-shear loading at a cross-head speed of 0.5 mm/min. Data were analyzed using one-way anova and Tukey's honest significant difference (HSD) test (P < 0.05). RESULTS: One-way anova showed significant differences in the micro-shear bond strength among the experimental groups (P < 0.001). Tukey's HSD test revealed that the bond strengths in groups 5, 9, and 10 were similar to the control group (P > 0.05). CONCLUSION: Decontamination by water and air spray, etching, and bonding was effective in restoring the bond strength of silorane-based composite increments.

Effect of Bonding Application Time on Bond Strength of Composite Resin to Glass Ionomer Cement.

OBJECTIVES: This experimental study evaluated the effect of bonding application time on the microshear bond strength of composite resin to different types of glass ionomer cements (GICs). MATERIALS AND METHODS: One-hundred and sixty specimens (two conventional and two resin-modified GICs) were prepared and divided into 16 groups. The surface of all specimens was prepared using two different bonding systems (Frog and Stea) at three different times. After setting, the composite resin (Z100) was placed over the GICs. The specimens were then stored in distilled water for 24 hours (37°C) and exposed to microshear stresses at a crosshead speed of 1 mm/min. The results were analyzed using three-way ANOVA and Tukey's test (P<0.05). RESULTS: In conventional GICs, bond strength was affected by the type of bonding system at different times, and bond strength was significantly higher in the Fuji II group compared to Riva Self Cure group. In the Riva Self Cure group, bond strength was significantly affected by time; whereas, the type of bonding system failed to exert a significant effect on bond strength. There was no significant correlation between the type of bonding system and the two brands of resin-modified GICs. Bond strength was not affected by the type of bonding agent; however, among the two brands of resin-modified GICs, Fuji II LC yielded a significantly stronger bond. CONCLUSION: It appears that the type of bonding agent does not affect the microshear bond strength, and the bonding application time affects the microshear bond strength in Riva Self Cure GICs.

The Influence of Composite Thickness with or without Fibers on Fracture Resistance of Direct Restorations in Endodontically Treated Teeth.

INTRODUCTION: This in vitro study evaluated the influence of composite thickness (with or without fiber reinforcement) on fracture resistance of direct restorations in endodontically treated teeth. METHODS AND MATERIALS: Fifty-six intact human premolars were chosen and randomly divided into four groups (n=14). After preparation of a mesio-occluso-distal (MOD) cavities and cusp reduction, the teeth were endodontically treated. Subsequently, the samples were restored with composite resin using the following protocols: group 1; composite onlay with cusp coverage of 1.5 mm, group 2; composite onlay with cusp coverage of 2.5 mm, group 3; composite onlay (including resin-impregnated fiber) with cusp coverage of 1.5 mm and group 4; composite onlay (including resin-impregnated fiber) with cusp coverage of 2.5 mm. The fracture resistance of teeth in all test groups was calculated by subjecting them to a progressively increasing compressive axial force in the universal testing machine with the cross-head speed of 1 mm/min to the point of fracture. The data were analyzed using the Kruskal-Wallis test. RESULTS: The mean fracture strengths and obtained standard error were 1263.85±74.03 N, 1330.26±128.01 N, 1344.92±64.40 N and 1312.54±75.63 N for groups 1 to 4, respectively. Statistical analysis revealed no significant difference between groups. CONCLUSION: Cusp coverage of 1.5 and 2.5 mm in MOD access cavities with or without insertion of resin impregnated fiber had similar fracture rates in the endodontically treated teeth.

Continuous intraperitoneal carboplatin delivery for the treatment of late-stage ovarian cancer.

The rate of failure of chemotherapy treatment in ovarian cancer remains high, resulting in a low 5-year survival rate of 20-40% in patients that present with advanced-stage disease. Treatment-free periods between cycles of chemotherapy may contribute to accelerated tumor cell proliferation and decreased treatment response. The elimination of treatment-free breaks has been deemed beneficial in the context of cell-cycle-specific agents. The potential benefit of this approach for non-cell-cycle-specific agents has not yet been elucidated. The present study is the first to address this issue by investigating the impact of continuous versus intermittent intraperitoneal administration of carboplatin over a 14 day period to SCID mice bearing SKOV-3 ovarian cancer xenografts. Immunostaining of tumor sections was employed to quantify tumor proliferation, angiogenesis, and apoptosis using Ki-67, CD-31, caspase-3 (CASP3), and terminal deoxytransferase-mediated dUTP nick-end labeling (TUNEL). Continuous ip administration of carboplatin resulted in greater tumor growth inhibition than intermittent therapy (p < 0.05). Significantly greater tumor cell apoptosis and less cell proliferation and angiogenesis were measured in tumors of mice treated with continuous carboplatin as compared to both intermittent and control groups. These results indicate that continuous local administration may be a promising approach to improve the effectiveness of platinum-based chemotherapy regimens.

Apical Sealing Ability of MTA in Different Liquid to Powder Ratios and Packing Methods.

INTRODUCTION: In apical surgery, after apicoectomy and retro-preparation of canal, a retrofil material is applied to seal the apical region of the root canal. Mineral trioxide aggregate (MTA) is the gold standard material for this purpose. Changing water/powder ratios of MTA affects its properties. The purpose of this in vitro study was to determine the effect of liquid/powder ratio of retrofil MTA on apical dye leakage, and also compare two packing techniques for MTA. MATERIALS AND METHODS: In this in vitro study, 126 intact single-root extracted teeth were instrumented using step-back technique, and obturated with lateral condensation method. The apical 3 mm of roots was resected, and retrograde preparation was performed by an ultrasonic device. Specimens were randomly assigned to 6 groups of 20 each and 6 teeth served as positive and negative controls. All teeth were retrofilled with White ProRoot MTA. Three groups were retrofilled with 0.28, 0.33, and 0.40 water/powder ratios of MTA and packed with plugger; the other three groups were retrofilled with 0.28, 0.33, and 0.40 water/powder ratios and packed with wet-cotton. Linear dye leakage was used to check apical sealing ability, and data were statistically analyzed using Kruskal-Wallis test. RESULTS: In 0.40 liquid/powder ratio the best applicator for packing MTA was plugger. In 0.28 liquid/powder ratio, moist cotton pellet was the best applicator; in 0.33 liquid/powder ratio, there was no significant difference between the two techniques. CONCLUSION: Under the condition of this in vitro study, packing with moist cotton pellet in lower liquid/powder ratios of MTA, as well as packing with a plugger in higher liquid/powder ration decreased apical dye leakage.

The microclimate pH in poly(D,L-lactide-co-hydroxymethyl glycolide) microspheres during biodegradation.

The microclimate pH (µpH) in biodegradable polymers, such as poly(D,L-lactic-co-glycolic acid) (PLGA) 50/50, commonly falls to deleterious acidic levels during biodegradation, resulting in instability of encapsulated acid-labile molecules. The µpH distribution in microspheres of a more hydrophilic polyester, poly(D,L-lactide-co-hydroxymethyl glycolide) (PLHMGA), was measured and compared to that in PLGA 50/50 of similar molecular weight and degradation time scales. pH mapping in the polymers was performed after incubation under physiological conditions by using a previously validated ratiometric method employing confocal laser scanning microscopy (CLSM). Confocal µpH maps revealed that PLHMGA microspheres, regardless of copolymer composition, developed a far less acidic µpH during 4 weeks of incubation compared with microspheres from PLGA. A pH-independent fluorescent probe marker of polymer matrix diffusion of µpH-controlling water-soluble acid degradation products, bodipy, was observed by CLSM to diffuse ~3-7 fold more rapidly in PLHMGA compared to PLGA microspheres, consistent with much more rapid release of acids observed from the hydrophilic polymer during bioerosion. Hence, PLHMGA microspheres are less susceptible to acidification during degradation as compared to similar PLGA formulations, and therefore, PLHMGA may be more suitable to deliver acid labile molecules such as proteins.

Controlled release of octreotide and assessment of peptide acylation from poly(D,L-lactide-co-hydroxymethyl glycolide) compared to PLGA microspheres.

PURPOSE: To investigate the in vitro release of octreotide acetate, a somatostatin agonist, from microspheres based on a hydrophilic polyester, poly(D,L-lactide-co-hydroxymethyl glycolide) (PLHMGA). METHODS: Spherical and non-porous octreotide-loaded PLHMGA microspheres (12 to 16 µm) and loading efficiency of 60-70% were prepared by a solvent evaporation. Octreotide release profiles were compared with commercial PLGA formulation (Sandostatin LAR(®)); possible peptide modification with lactic, glycolic and hydroxymethyl glycolic acid units was monitored. RESULTS: PLHMGA microspheres showed burst release (~20%) followed by sustained release for 20-60 days, depending on the hydrophilicity of the polymer. Percentage of released loaded peptide was high (70-90%); > 60% of released peptide was native octreotide. PLGA microspheres did not show peptide release for the first 10 days, after which it was released in a sustained manner over the next 90 days; > 75% of released peptides were acylated adducts. CONCLUSIONS: PLHMGA microspheres are promising controlled systems for peptides with excellent control over release kinetics. Moreover, substantially less peptide modification occurred in PLHMGA than in PLGA microspheres.

Enhanced gentamicin loading and release of PLGA and PLHMGA microspheres by varying the formulation parameters.

The purpose of this study was to develop a suitable formulation for gentamicin sulfate (GS) that gives a sustained release of the drug. Therefore this drug was loaded into poly(D,L-lactide-co-glycolide) (PLGA) and poly(lactic-co-hydroxymethyl glycolic acid) (PLHMGA) microspheres. The effects of various formulation parameters (ethanol, surfactant, osmotic value of the external phase, polymer type and concentration) on particle characteristics (size, loading and release) were investigated. The GS loaded microspheres were prepared using a double emulsion evaporation technique. The results demonstrate that neither ethanol nor surfactants had beneficial effects on the drug loading efficiency (around 4-10%). However, an increase in buffer concentration (and thus osmotic pressure) of the external phase resulted in a substantial increase of GS-loading (from 10 to 28%). Further, an increase of concentration of PLGA in DCM from 10% to 15/20% caused a 4-time increase of the drug loading. The best formulation identified in this study had a loading efficiency of around 70% resulting in PLGA microspheres with a 6% (w/w) loading. The particles showed a burst release of the drug depending on their porosity, followed by a phase of 35 days where hardly any release occurred. The drug was then slowly released for around 25 days likely due to degradation of the microspheres. The drug loading efficiency of GS in PLHMGA was not significantly different from PLGA microspheres (64%). The release of GS from PLHMGA microspheres was faster than that of PLGA because the degradation rate of PLHMGA is more rapid than PLGA. This study shows that prolonged release of gentamicin can be obtained by loading this drug into microspheres made of biodegradable aliphatic polyesters.

Functional aliphatic polyesters for biomedical and pharmaceutical applications.

Functional aliphatic polyesters are biodegradable polymers with many possibilities to tune physico-chemical characteristics such as hydrophilicity and degradation rate as compared to traditional polyesters (e.g. PLLA, PLGA and PCL), making the materials suitable for drug delivery or as scaffolds for tissue engineering. Lately, a large number of polyesters have been synthesized by homopolymerization of functionalized monomers or co-polymerization with other monomers mainly via ring-opening polymerization (ROP) of cyclic esters. This review presents the recent trends in the synthesis of these materials and their application for protein delivery and tissue engineering.

Hydrophilic polyester microspheres: effect of molecular weight and copolymer composition on release of BSA.

PURPOSE: To study the release of a model protein, bovine serum albumin (BSA), from microspheres of an hydroxylated aliphatic polyester, poly(lactic-co-hydroxymethyl glycolic acid) (PLHMGA). METHODS: BSA-loaded microspheres were prepared by a double emulsion solvent evaporation method. The effect of copolymer composition and the molecular weight of the copolymer on in vitro release and degradation were studied. The integrity of the released BSA was studied by fluorescence spectroscopy and size exclusion chromatography (SEC). RESULTS: Microspheres prepared from PLHMGA with 50% hydroxymethyl glycolic acid (HMG) showed a burst release followed by a sustained release in 5-10 days. PLHMGA microspheres prepared from a copolymer with 35% and 25% HMG showed a sustained release of BSA up to 80% for 30 and 60 days, respectively. The release of BSA was hardly affected by the molecular weight of the polymer. Fluorescence spectroscopy and SEC showed that the released BSA preserved its structural integrity. Microspheres were fully degradable, and the degradation time increased from approximately 20 days to 60 days when the HMG content decreased from 50% to 25%. CONCLUSIONS: Taking the degradation and release data together, it can be concluded that the release of BSA from PLHMGA microspheres is governed by degradation of the microspheres.

Should silane coupling agents be used when bonding brackets to composite restorations? An in vitro study.

The purpose of this in vitro study was to determine a safe and efficient method for bonding brackets to resin composite (RC), permitting the brackets to tolerate shear forces and allowing removal without causing surface damage to the aesthetic restoration. The shear bond strength (SBS) of 60 brackets bonded to silanated and non-silanated RC surfaces were compared. A Bis-GMA containing orthodontic adhesive system was used to bond stainless steel upper lateral incisor brackets to 60 composite discs, half of which had surface treatment with a silane coupling agent. SBS testing was performed with an Instron universal testing machine. After debond, the bracket base and corresponding RC discs were examined under a stereomicroscope and analyzed using the Adhesive Remnant Index (ARI). Non-parametric tests (Mann-Whitney U) indicated significant differences between the two groups (P < 0.009). Lower bond strengths were found for the silanated group implying that silane agents may be an unnecessary step. However, both groups had a clinically acceptable mean SBS [silanated group = 13.1 megapascals (Mpa), non-silanated group = 19.4 MPa]. Bond failure occurred at the bracket-adhesive interface in both groups. There would appear to be no advantage in using a silane agent when bonding metal orthodontic brackets to filled RCs.

Knowledge of Dentistry, Medicine, and Pharmacy Students about Psychedelic Drugs in Kerman University of Medical Sciences.

BACKGROUND: Psychedelic drugs can cause one to get out of normal status and permanent cerebral defects, via affecting central nervous system. Consumption of theses drugs seems to be increasing nowadays especially among the youth and university educated population. We conducted a study to evaluate the awareness of medical science students of Kerman University of medical science who are going to be the future medical population. METHODS: This cross-sectional study was carried out on 471 of students of medicine, dentistry and pharmacy which were in the first to forth year of their education about psychedelic drugs (Ecstasy, LSD, Ice, crack and Yaba). To evaluate the students' awareness of drugs we used questionnaire with reliability and validity proven via pilot study. Statistics analysis was performed using SPSS13 software. FINDINGS: Average of their age was 3.2 ± 20.4. Overall among the students, 56.7% were in the low level of insight, 34.3% in medium and 6.9% in good level and 2.2% had best insight of the drugs. Also only 32.2% of students had the full information about the name of drug, 25.7 % had information about the form of them, 24% about the addiction with them, 7% about their complication and only 5% about the origin of drugs. The information about all psychedelic drugs was higher among pharmacy students, students of the third year and males. CONCLUSION: Our study showed a low insight about psychedelic drugs like Ecstasy, LSD, Ice, Crack, and Yaba among the students. According to this lack of information of these groups, it is suggested that educational courses about the complication, signs and symptoms of these drugs be held.