Brain stem death induces pro-inflammatory cytokine production and cardiac dysfunction in sheep model.

INTRODUCTION: Organs procured following brain stem death (BSD) are the main source of organ grafts for transplantation. However, BSD is associated with inflammatory responses that may damage the organ and affect both the quantity and quality of organs available for transplant. Therefore, we aimed to investigate plasma and bronchoalveolar lavage (BAL) pro-inflammatory cytokine profiles and cardiovascular physiology in a clinically relevant 6-h ovine model of BSD. METHODS: Twelve healthy female sheep (37-42 Kg) were anaesthetized and mechanically ventilated prior to undergoing BSD induction and then monitored for 6 h. Plasma and BAL endothelin-1 and cytokines (IL-1ß, 6, 8 and tumour necrosis factor alpha (TNF-α)) were assessed by ELISA. Differential white blood cell counts were performed. Cardiac function during BSD was also examined using echocardiography, and cardiac biomarkers (A-type natriuretic peptide and troponin I were measured in plasma. RESULTS: Plasma concentrations big ET-1, IL-6, IL-8, TNF-α and BAL IL-8 were significantly (p < 0.01) increased over baseline at 6 h post-BSD. Increased numbers of neutrophils were observed in the whole blood (3.1 × 109 cells/L [95% confidence interval (CI) 2.06-4.14] vs. 6 × 109 cells/L [95%CI 3.92-7.97]; p < 0.01) and BAL (4.5 × 109 cells/L [95%CI 0.41-9.41] vs. 26 [95%CI 12.29-39.80]; p = 0.03) after 6 h of BSD induction vs baseline. A significant increase in ANP production (20.28 pM [95%CI 16.18-24.37] vs. 78.68 pM [95%CI 53.16-104.21]; p < 0.0001) and cTnI release (0.039 ng/mL vs. 4.26 [95%CI 2.69-5.83] ng/mL; p < 0.0001), associated with a significant reduction in heart contractile function, were observed between baseline and 6 h. CONCLUSIONS: BSD induced systemic pro-inflammatory responses, characterized by increased neutrophil infiltration and cytokine production in the circulation and BAL fluid, and associated with reduced heart contractile function in ovine model of BSD.

Endothelin receptor antagonist improves donor lung function in an ex vivo perfusion system.

BACKGROUND: A lung transplant is the last resort treatment for many patients with advanced lung disease. The majority of donated lungs come from donors following brain death (BD). The endothelin axis is upregulated in the blood and lung of the donor after BD resulting in systemic inflammation, lung damage and poor lung graft outcomes in the recipient. Tezosentan (endothelin receptor blocker) improves the pulmonary haemodynamic profile; however, it induces adverse effects on other organs at high doses. Application of ex vivo lung perfusion (EVLP) allows the development of organ-specific hormone resuscitation, to maximise and optimise the donor pool. Therefore, we investigate whether the combination of EVLP and tezosentan administration could improve the quality of donor lungs in a clinically relevant 6-h ovine model of brain stem death (BSD). METHODS: After 6 h of BSD, lungs obtained from 12 sheep were divided into two groups, control and tezosentan-treated group, and cannulated for EVLP. The lungs were monitored for 6 h and lung perfusate and tissue samples were processed and analysed. Blood gas variables were measured in perfusate samples as well as total proteins and pro-inflammatory biomarkers, IL-6 and IL-8. Lung tissues were collected at the end of EVLP experiments for histology analysis and wet-dry weight ratio (a measure of oedema). RESULTS: Our results showed a significant improvement in gas exchange [elevated partial pressure of oxygen (P = 0.02) and reduced partial pressure of carbon dioxide (P = 0.03)] in tezosentan-treated lungs compared to controls. However, the lungs hematoxylin-eosin staining histology results showed minimum lung injuries and there was no difference between both control and tezosentan-treated lungs. Similarly, IL-6 and IL-8 levels in lung perfusate showed no difference between control and tezosentan-treated lungs throughout the EVLP. Histological and tissue analysis showed a non-significant reduction in wet/dry weight ratio in tezosentan-treated lung tissues (P = 0.09) when compared to control. CONCLUSIONS: These data indicate that administration of tezosentan could improve pulmonary gas exchange during EVLP.

Anti-inflammatory and immune properties of the peltatoside, isolated from the leaves of Annona crassiflora Mart., in a new experimental model zebrafish.

Establishing new animal models for the study of inflammation is very important in the process of discovering new drugs, since the inflammatory event is the basis of many pathological processes. Whereas rodent models have been the primary focus of inflammation research, we defend the zebrafish (Danio rerio) test as a feasible alternative for preclinical studies. Moreover, despite all the technological development already achieved by humanity, nature can still be considered a relevant source of new medicines. In this context, the aim of this work was to evaluate the anti-inflammatory effect of a substance isolated from the medicinal plant Annona crassilfora Mart, the peltatoside, in an inflammatory model of zebrafish. It was determined: (i) total leukocyte count in the coelomate exudate; (ii) N-acetyl-ß-d-glucuronidase (NAG); (iii) myeloperoxidase (MPO); (iv) and the histology of liver, intestine and mesentery. Peltotoside (25, 50 and 100 µg) and dexamethasone (25 µg) were administered intracelomatically (i.c.) 30 min before carrageenan (i.c.). Pretreatment with peltatoside at three doses significantly inhibited leukocyte recruitment in the coelomic cavity, and inhibited NAG and MPO activity against the action of Cg, in a similar manner as dexamethasone. However, some microlesions in the evaluated organs were detected. The dose of 25 µg showed an anti-inflammatory effect with lower undesirable effects in the tissues. Our results suggest that the zebrafish test was satisfactory in performing our analyzes and that the peltotoside has a modulatory action in reducing leukocyte migration.

Intellectual, adaptive and behavioural characteristics in four patients with 18p deletion syndrome.

BACKGROUND: The association of behavioural phenotype assessment with cytogenomic characterisation may provide a better comprehension of genotype-phenotype correlations in syndromes caused by chromosomal abnormalities, such as 18p deletion syndrome. METHOD: We report on four Brazilian patients with 18p deletion syndrome characterised by cytogenomic techniques and detailed neuropsychological evaluation. Intellectual, adaptive and behavioural characteristics were assessed through the Wechsler's Scales, the Vineland-II Scale and the Child Behaviour Checklist, respectively. Socio-economic measures including main caretaker educational level and family income as defined by Brazilian criteria for social class classification were also collected to evaluate a possible contribution of environmental factors in neurocognitive variability. RESULTS: Two out of four patients showed intellectual disability (IQ < 70). Wechsler's scale results suggest that in our sample, interpretation of social situations based on observation of non-verbal behaviour constitute a cognitive strength while judgement of social rules and language skills associated with word knowledge and verbal fluency may be a cognitive weakness. Concerning adaptive behaviour, motor and socialisation domains showed to better develop than communication and daily living skills on the Vineland-II Scale. Only one patient presented internalising behavioural problems based on the Child Behaviour Checklist. Our results also suggested that socio-economic status may contribute to overall patient development. CONCLUSION: Our results suggest that some 18p deletion syndrome patients may present average intellectual performance and that the segment deletion size and some families' socio-economic conditions may influence cognitive development.

Analysis of conditions sensitive to primary care in a successful experience of primary healthcare expansion in Brazil, 1998-2015.

OBJECTIVE: To analyze trends in expansion of coverage of the family health strategy and hospitalization for conditions sensitive to primary care (CSPC) in a successful experience of primary healthcare expansion in Brazil. STUDY DESIGN: Ecological study with data from the Brazilian National Health Information System. METHODS: CSPC were analyzed between 1998 and 2015 in Rio de Janeiro, Brazil, by cause groups. Trends, variation, and correlation between indicators in the period were evaluated. RESULTS: Most of the cause groups showed a reduction in hospitalization rate, particularly cardiovascular diseases and asthma, but an increase was seen for obstetric causes. The main causes of hospitalization were heart failure, cerebrovascular diseases, and bacterial pneumonia. The contribution of vaccine-preventable diseases, cardiovascular diseases, diabetes, nutritional deficiencies, and chronic lung diseases to the total number of hospitalizations was seen to decrease. CONCLUSIONS: Analysis demonstrates that the family health strategy, as access to the healthcare system, decreases the majority of CSPC hospitalization rates.

Lower airway flow influences peak nasal inspiratory flow in school-aged children.

BACKGROUND: Rhinitis and asthma frequently coexist. Peak nasal inspiratory flow (PNIF) objectively evaluates nasal obstruction. Lower airway flow's impact on PNIF has seldom been analysed in children. We aimed to study the associations between PNIF and: 1)forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) in children with allergic rhinitis and asthma and healthy controls; 2)allergic rhinitis and asthma control subjective evaluation. METHODS: Sequential assessments of PNIF before and after nasal decongestion and spirometry with bronchodilation test were performed in 65 children (6-12 years) with allergic rhinitis and asthma, and 24 gender, age-matched healthy controls. The Control of Allergic Rhinitis and Asthma Test in children (CARATkids) was used for control assessment. Associations were investigated by multiple linear regression models. RESULTS: Baseline and decongested PNIF correlated with baseline and post-bronchodilation FEV1 and PEF, observed independently of rhinitis and asthma diagnosis. The best model for PNIF included PEF, age and gender. No association was found between PNIF and CARATkids scores, except for nasal obstruction self-report. CONCLUSION: In school-aged children, besides age and gender, PEF values should ideally be known to interpret PNIF values. PNIF can be complementary to subjective control assessment in children with allergic rhinitis and asthma.

Cri du Chat syndrome: Characteristics of 73 Brazilian patients.

BACKGROUND: Cri du Chat syndrome (CdCS) is a genetic syndrome caused by deletions in the short arm of chromosome 5. Although the main clinical features of CdCS are well known, the neurocognitive and behavioural characteristics of the phenotype are rarely described in detail in the literature. In this study, we analysed the main phenotypic features of CdCS from a parental perspective. METHOD: A questionnaire was sent to 700 Brazilian families that were registered in the Brazilian Association of CdCS. The questions involved specific domains of CdCS, such as pregnancy and birth conditions, recurrence of the disease in the family, current major health problems, and aspects of cognitive development. RESULTS: In total, 73 questionnaires were completed: 44 females and 29 males, ranging from 9.5 months old to 40 years old (mean = 13.8 years; median = 12 years). Most of the parents noticed the typical cat-like cry at birth (94.4%). The age at diagnosis of CdCS ranged from the time of birth to 180 months (mean = 14 months; median = 6 months), while one case was diagnosed during pregnancy. In all of the cases, the diagnosis of CdCS was made by G-banding karyotype analysis. In 66.2% of the cases, the parents underwent cytogenetic investigation. A total of 52.1% of the parents answered that they did not remember what the recurrence risk of CdCS was in their family. The main health problems that were reported were as follows: swallowing problems (80.3%), feeding problems (80.3%), congenital heart disease (31.5%), spine abnormalities (28.8%), and neurological symptoms (20.5%), including seizures (11%). The behavioural problems that were reported were as follows: aggressive behaviour, stereotypies, anxiety, phobias, and genital manipulation/masturbation. Neurodevelopmental delay was reported in all of the cases. Independent walking was achieved in 72.2% of the patients. Approximately 50% of the patients never presented expressive language, and most of the patients are dependent on others for their daily activities. CONCLUSIONS: The questionnaire was a pioneer initiative in the CdCS support group, and the answers used in this study can improve the health care assistance to these patients because they focus attention on the demands from a parental perspective. In addition, nearly half of the families stated that they did not remember information regarding recurrence risk, which reinforces the importance of genetic counselling follow-up and the need for the expansion of genetic services in Brazil.

Acquired von Willebrand syndrome in respiratory extracorporeal life support: a systematic review of the literature.

BACKGROUND AND OBJECTIVE: Venovenous extracorporeal membrane oxygenation (VV ECMO) and extracorporeal CO2 removal (ECCO2R) are increasingly used in the management of severe respiratory failure. With bleeding complications being one of the major risks of these techniques, our aim in this systematic review was to assess the available literature on acquired von Willebrand syndrome (AvWS) and extracorporeal support. AvWS has previously been associated with bleeding and shear stress. DESIGN AND DATA SOURCES: A systematic review, using Medline via PubMed, was performed to identify eligible studies up to January 2017. RESULTS AND CONCLUSION: The prevalence of AvWF among patients on VV ECMO or ECCO2R is high, but only a limited number of studies are reported in the literature. AvWS testing should be performed, including vWF multimer analysis, vWF activity and vWF antigen concentration. The extent to which vWF contributes to bleeding during ECMO, or how much changes in ECMO management can influence high molecular weight vWF multimer levels, cannot be answered from the currently available evidence and there remains a need for future studies.

GAND classification and volumetric assessment of unilateral cleft lip and palate malformations using cone beam computed tomography.

The aim of this study was to propose a classification for unilateral cleft lip and palate (UCLP) malformations based on cone beam computed tomography (CBCT) images, as well as to estimate the amount of bone necessary for grafting, and to evaluate the relationship of this volume with scores obtained using the classification. CBCT images of 33 subjects with UCLP were evaluated according to gap, arch, nasal, and dental parameters (GAND classification). Additionally, these defects were segmented and the amount of graft needed for alveolar bone grafting was estimated. The reproducibility of GAND classification was analyzed by weighted kappa test. The association of volume assessment with the classification (gap and nasal parameters) was verified using analysis of variance, while the intra-observer agreement was analyzed using the intra-class correlation coefficient. The intra-observer reproducibility of the classification ranged from 0.29 to 0.92 and the inter-observer agreement ranged from 0.29 to 0.91. There were no statistically significant values when evaluating the association of the volume with the classification (P>0.05). The GAND classification is a novel system that allows the quick estimation of the extent and complexity of the cleft. It is not possible to estimate the amount of bone needed for alveolar bone grafting based on the classification; individualized surgical planning should be done for each patient specifically.

Rating of perceived exertion as a tool for prescribing and self regulating interval training: a pilot study.

The aim of the present study was to analyse the usefulness of the 6-20 rating of perceived exertion (RPE) scale for prescribing and self-regulating high-intensity interval training (HIT) in young individuals. Eight healthy young subjects (age = 27.5±6.7 years) performed maximal graded exercise testing to determine their maximal and reserve heart rate (HR). Subjects then performed two HIT sessions (20 min on a treadmill) prescribed and regulated by their HR (HR: 1 min at 50% alternated with 1 min at 85% of reserve HR) or RPE (RPE: 1 minute at the 9-11 level [very light-fairly light] alternated with 1 minute at the 15-17 level [hard-very hard]) in random order. HR response and walking/running speed during the 20 min of exercise were compared between sessions. No significant difference between sessions was observed in HR during low- (HR: 135±15 bpm; RPE: 138±20 bpm) and high-intensity intervals (HR: 168±15 bpm; RPE: 170±18 bpm). Walking/running speed during low- (HR: 5.7±1.2 km · h(-1); RPE: 5.7±1.3 km · h(-1)) and high-intensity intervals (HR: 7.8±1.9 km · h(-1); RPE: 8.2±1.7 km · h(-1)) was also not different between sessions. No significant differences were observed in HR response and walking/running speed between HIT sessions prescribed and regulated by HR or RPE. This finding suggests that the 6-20 RPE scale may be a useful tool for prescribing and self-regulating HIT in young subjects.

Clinical care in craniofacial microsomia: a review of current management recommendations and opportunities to advance research.

Craniofacial microsomia (CFM) is a complex condition associated with microtia, mandibular hypoplasia, and preauricular tags. It is the second most common congenital facial condition treated in many craniofacial centers and requires longitudinal multidisciplinary patient care. The purpose of this article is to summarize current recommendations for clinical management and discuss opportunities to advance clinical research in CFM.

Aporphine alkaloids and feruloylamides from the bark of Xylopia benthamii R.E. Fries (Annonaceae).

The bark of Xylopia benthamii R.E. Fries was investigated in a search for new bioactive compounds. The ethanolic extract of the air-dried bark of X. benthamii was obtained and submitted to an acidic extraction procedure to obtain an alkaloid mixture. Chromatographic fractionation led to the isolation of two aporphine alkaloids, nornantenine and laurotetanine, and a mixture of trans- and cis-feruloyltyramine, isolated for the first time in this genus. Structures were established by spectroscopic methods as NMR (1D and 2D) and mass spectrometry (ESI-MS).

Avaliação da atividade citotóxica das sementes de Annona cornifolia A. St.-Hil. (Annonaceae) / Evaluation of the cytotoxic activity of seeds of Annona cornifolia A. St.-Hil. (Annonaceae)

Na família Annonaceae, especialmente o gênero Annona é muito apreciado por fornecer frutos comestíveis. Espécies desse gênero são utilizadas na medicina popular contra diabetes, malária e infecções. Muitas dessas atividades biológicas têm sido relacionadas às acetogeninas de anonáceas. O objetivo deste estudo foi avaliar a atividade citotóxica dos grupos e de uma acetogenina pura (cornifolina) obtidos a partir do extrato etanólico das sementes de Annona cornifolia A. St.-Hil. (Annonaceae). Esta atividade foi avaliada pelo ensaio colorimétrico MTT. Cornifolina (1), a única substância pura testada, apresentou citotoxicidade positiva sobre todas as linhagens tumorais avaliadas. Os grupos testados, todos caracterizados por espectroscopia no infravermelho (IV), apresentaram 68,7% dos valores de CI50 menores que 20,0 µg mL-1, sendo também considerados citotóxicos. As amostras testadas foram mais ativas que o taxol sobre melanoma humano (MeWo) e, ainda, o grupo G10-5 apresentou melhor atividade sobre fibroblasto tumorigênico de camundongo (L929). Além disso, os grupos mostraram menor citotoxidade do que o taxol sobre a linhagem normal (CHO).

The family Annonaceae, especially the genus Annona, is greatly appreciated for providing edible fruits. Species of this genus are used in folk medicine against diabetes, malaria and infections. Many of these biological activities have been related to annonaceous acetogenins. The aim of this study was to evaluate the cytotoxic activity of groups and a pure acetogenin (cornifolin) obtained from the ethanol extract of the seeds of Annona cornifolia A. St.-Hil. (Annonaceae). This activity was evaluated by using MTT colorimetric assay. Cornifolin (1), the only tested substance that was pure, showed positive cytotoxicity on all evaluated tumor cell lines. The tested groups, all characterized by infrared spectroscopy (IR), showed 68.7% of the IC50 values lower than 20.0 µg mL-1, also considered cytotoxic. The tested samples were more active than taxol on human melanoma (MeWo) and the group G10-5 showed better activity on mouse tumorigenic fibroblast (L929). In addition, the tested groups showed less cytotoxicity than taxol on the normal line (CHO).

Effects of physical exercises on the ventricular myocardium

It is known that people who exercise regularly are less likely to develop heart diseases such as hypertension, obesity, diabetes mellitus, and dyslipidemia decreasing the occurrence of atherosclerosis and its complications: heart failure, stroke, and peripheral vascular disease. In the presence of physical exercises, the myocardium adjusts to the work loads metabolically and mechanically. There are two kinds of physical exercises: aerobic exercise and strength exercise or resistance training. Nowadays, strength exercises have become very popular due to several different reasons. Strength exercises are those performed against a specific opposing gradual resistance to muscular contraction such as weights. According to the literature, both types of exercises have effects on different body tissues. In the present work, a literature review, including scientific articles since 1980, on the effects of aerobic and strength exercises on the ventricular myocardium was conducted. The low and high-intensity strength exercises have different effects, but none of them causes major effects on the cardiovascular function chronically. The most evident alteration of the myocardium subjected to strength exercises is the increase in the cross-sectional area of the cardiac myocytes leading to myocardial hypertrophy.

Decarboxylation of oxidized single-wall carbon nanotubes.

A classical protocol widely used in organic chemistry of aromatic and polyaromatic molecules has been successfully applied in this work for the decarboxylation of oxidized single-wall carbon nanotube (SWNT) to rend C-H SWNT derivatives. SWNT produced by arc discharge method have been oxidized during a purification process using strongly oxidant agents, such as hydrogen peroxide and nitric acid. The decarboxylation of oxidized SWNT has been conduced with copper(I) oxide in a 50:50 solution of N-methylpyrrolidone and quinoline. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and acid-base potentiometric titration analyses were carried out to characterize quali and quantitatively the changes in the chemical environment on the SWNT surface in each step of the purification and the decarboxylation process. Those techniques showed the appearance of mainly carboxylic and phenolic groups after the purification process and the disappearance of the carboxylic groups after the decarboxylation reaction. Fourier transform infrared spectroscopy analysis indicated also the formation of aliphatic and aromatic C-H groups. X-ray photoelectron spectroscopy and potentiometric titration results determined an efficiency higher than 90% for our decarboxylation procedure. The purity and structural quality of the SWNT sample used in the decarboxylation process were evaluated by thermogravimetry and Raman spectroscopy. Thermogravimetric analysis identified a purified sample with approximately 80 wt% of SWNT, in fractions distributed in highly structured SWNTs (25 wt%), with distribution in composition, length and structural quality (35 wt%) and with very defective and short tubes (25 wt%). The damages on the purified SWNT walls were characterized by the Raman scattering analysis.

EDTA treatment improves resin-dentin bonds' resistance to degradation.

The existence of unprotected collagen fibrils within the hybrid layer compromises the longevity of restorations. This phenomenon may be avoided if solutions other than strong acids are used for dentin demineralization. The hypothesis to be tested is that bond durability may be improved by EDTA demineralization. Dentin surfaces (human and bovine) were bonded: (1) after phosphoric-acid-etching, and after EDTA demineralization with (2) a total-etch adhesive and (3) a self-etching adhesive. After the teeth were sectioned into beams, half of the specimens were immersed in NaOCl, while the other half was immersed in water. Beams were tested to failure in tension. ANOVA and multiple-comparisons tests were used (P < 0.05). No differences in bond strength were found among the 3 bonding procedures, although bonds made to human molars were 43-61% higher than those to bovine incisors. After NaOCl immersion, only specimens subjected to EDTA demineralization maintained the initial bond strength. We conclude that the collagen network is better-preserved after EDTA demineralization.

Effect of thermal and mechanical load cycling on microtensile bond strength of a total-etch adhesive system.

To evaluate the effect of thermal and mechanical cycles on dentin bond strength to cervical margins of Class II restorations, 80 box-type Class II cavities were prepared on the surfaces of bovine incisors. The cavities were restored with Single Bond (3M-ESPE) and Z-250 composite (3M-ESPE) according to manufacturer's instructions. The incisors were divided into four groups: G1-Control, G2- Thermal cycling (2,000 cycles, 5 degrees C-55 degrees C), G3- Mechanical cycling (100,000 cycles; 50N) and G4- Thermal and mechanical cycling (2,000 cycles 5 degrees C-55 degrees C/100,000 cycles; 50N). The restorations were sectioned perpendicular to the cervical bonded interface into 0.7 +/- 0.2 mm-thick slabs. The slabs were further trimmed at the interface to 1.4 +/- 0.2 mm with a fine diamond bur to produce a cross-sectional surface area of 1 mm2. All specimens were then subjected to microtensile bond testing. Means and standard deviations were expressed in MPa. The bond strength data were analyzed by one-way ANOVA and Fisher's PLSD test (p<0.05). Fracture mode analysis was performed using SEM. Bond strengths were significantly lower when thermal and mechanical cycling were performed [G4-2.41 (8.57)] when compared to the other groups [G1-28.15 (14.03); G2-27.60 (10.14); G3-27.59 (8.67)]. No differences were observed among Groups 1, 2 and 3. Interfacial fracture of the control (G1) and thermocycling (G2) groups mainly occurred between the deepest portion of the adhesive resin and the top layer of the demineralized dentin (Interphase). Mixed failure was predominant and increased when mechanical cycling was applied (G3 and G4).

Effect of different filling materials in combination with intraradicular posts on the resistance to fracture of weakened roots.

The preservation and restoration of severely weakened pulpless teeth is a difficult and relatively unpredictable procedure. This study evaluated the resistance to fracture of experimentally weakened bovine roots internally reconstructed with different filling materials in combination with prefabricated post compared with restored roots that were relatively intact. The roots of 75 mandibular bovine incisors with similar bulks were selected. Of these, 60 were internally prepared to standardized dimensions, thereby simulating weakness. All roots were filled with different restorative materials. The specimens were submitted to the fracture resistance testing with the application of a tangential compressive loading at an angle of 135 degrees in relation to the long axes of the roots. Results indicated statistically significant differences in relation to the root conditions. Weakened roots were less resistant to fracture than were controls. The roots restored with the resin cement demonstrated the lowest fracture resistance values, but statistically significant differences were observed only when compared with those restored by the resin-modified glass-ionomer cement. Resin-modified glass-ionomer cement, polyacid-modified resin composite and resin composite behaved similarly without statistically significant differences among them. None of the materials evaluated were capable of achieving the fracture resistance recorded for unweakened controls.