Expanding horizons of reconstructive microsurgery in Lebanon: Reconstruction of complex traumatic wounds with anterolateral thigh perforator flaps in paediatrics patients less than 10 years of age.

Paediatric complex wounds pose a challenge to the reconstructive surgeon due to the intricacy of reconstructive options required. Developments in microsurgery and microsurgical technique have brought free tissue transfer ever closer to the comfort zone of the reconstructive surgeon for reconstruction of paediatric traumatic complex wounds. We present our experience of microsurgical reconstruction in Lebanon for complex traumatic wounds in paediatric patients under the age of 10 years using the free anterolateral thigh (ALT) flap. The ALT flap has proven its value as a safe, adaptable, and aesthetically acceptable reconstructive option in paediatric complex trauma.

The Pericranial Flap as a Salvage Procedure in Pediatric Neurosurgical Complications.

ABSTRACT: The pericranium is a vascularized structure that can be used for the treatment of complex scalp and skull defects. It is also utilized as a prophylactic measure to prevent wound complications in high-risk patients. In this study, we looked at the use of the pericranial flap in pediatric patients. A retrospective chart review was done in the American University of Beirut Medical Center from February 2010 to 2020. Ten pediatric patients were identified who required either prophylactic pericranial flap (n  =  3) or for treatment of a chronic draining sinus (n =  7). Patients were followed up for an average of 23 days. There were no cases of infection, hematoma, seroma, or meningitis. Only 1 case developed dehiscence of the skin. It was managed conservatively and healed within 2 weeks. The pericranial flap is a workhorse flap for scalp and skull reconstruction, with no donor site morbidity and thus should always be considered.

NUPR1 preserves insulin secretion of pancreatic ß-cells during inflammatory stress by multiple low-dose streptozotocin and high-fat diet.

Obesity is associated with dyslipidemia and subclinical inflammation that promotes metabolic disturbances including insulin resistance and pancreatic ß-cell dysfunction. The nuclear protein, transcriptional regulator 1 (NUPR1) responds to cellular stresses and features tissue protective properties. To characterize the role of NUPR1 in endocrine pancreatic islets during inflammatory stress, we generated transgenic mice with ß-cell-specific Nupr1 overexpression (ßNUPR1). Under normal conditions, ßNUPR1 mice did not differ from wild type (WT) littermates and display normal glucose homeostasis and ß-cell mass. For induction of inflammatory conditions, mice were treated with multiple low-dose streptozotocin (mld-STZ) and/or fed a high-fat diet (HFD). All treatments significantly worsened glycaemia in WT mice, while ßNUPR1 mice substantially preserved insulin secretion and glucose tolerance. HFD increased ß-cell mass in all animals, with ßNUPR1 mice tending to show higher values. The improved outcome of ßNUPR1 mice was accompanied by decreased NF-κB activation and lymphocyte infiltration in response to mld-STZ. In vitro, isolated ßNUPR1 islets preserved insulin secretion and content with insignificantly low apoptosis during culture stress and IL-1ß exposure. These findings suggest that NUPR1 plays a vital role in the protection of ß-cells from apoptosis, related degradation of insulin storages and subsequent secretion during inflammatory and obesity-related tissue stress.

Separation and detection of cyproconazole enantiomers and its stereospecific recognition with chiral stationary phase by high-performance liquid chromatography.

Cyproconazole, a chiral triazole fungicide, has been diffusely used and analyzed. The development of an effective analytical method for cyproconazole enantiomers can support their residual monitoring and risk assessment. In the present study, the absolute configuration of the cyproconazole enantiomers was confirmed by electronic circular dichroism and time-dependent density functional theory. The enantioseparation parameters were optimized by the response surface methodology using the Box-Behnken design on Lux Cellulose-2. The elution order of (2S,3R)-(+)-, (2S,3S)-(+)-, (2R,3S)-(-)-, and (2R,3R)-(-)-cyproconazole was simulated with molecular docking. The enantiomers were completely separated primarily via halogen bond and hydrogen bond interactions with the chiral stationary phases. The mean recoveries of the cyproconazole enantiomers in the four matrices were 71.8-102.0% with intraday relative standard deviations (RSDs) of 0.3-11.9% and interday RSDs of 0.9-10.6%. The results showed the chiral recognition mechanism clearly and confirmed that the method was accurate and convenient for the simultaneous detection of cyproconazole enantiomers in environmental and food matrices.

Sitagliptin protects diabetic rats with acute myocardial infarction through induction of angiogenesis: role of IGF-1 and VEGF.

Angiogenesis is regulated in a tissue-specific manner in all patients, especially those with diabetes. In this study, we describe a novel molecular pathway of angiogenesis regulation in diabetic rats with myocardial infarction (MI) and examine the cardioprotective effects of different doses of sitagliptin. Male rats were divided into 5 groups: normal vehicle group, diabetic group, diabetic + MI, diabetic + MI + 5 mg/kg sitagliptin, and diabetic + MI + 10 mg/kg sitagliptin. Isoproterenol in diabetic rats resulted in significant (p < 0.05) disturbance to the electrocardiogram, cardiac histopathological manifestations, and an increase in inflammatory markers compared with the vehicle and diabetic groups. Treatment with sitagliptin improved the electrocardiogram and histopathological sections, upregulated vascular endothelial growth factor (VEGF) and transmembrane phosphoglycoprotein protein (CD34) in cardiac tissues, and increased serum insulin-like growth factor 1 (IGF-1) and decreased cardiac tissue homogenate for interleukin 6 (IL-6) and cyclooxygenase 2 (COX-2). A relationship was found between serum IGF-1 and cardiac VEGF and CD34 accompanied by an improvement in cardiac function of diabetic rats with MI. Therefore, the observed effects of sitagliptin occurred at least partly through an improvement in angiogenesis and the mitigation of inflammation. Consequently, these data suggest that sitagliptin may contribute, in a dose-dependent manner, to protection against acute MI in diabetic individuals.

Stereoselective bioactivity of the chiral triazole fungicide prothioconazole and its metabolite.

Chiral triazole fungicides have played a significant role in plant pathogen control. Although their enantiomers often exhibit different bioactivity, the mechanism of the stereoselectivity has not been well studied. The stereoselective bioactivity and mechanisms of prothioconazole and its chiral metabolite against plant pathogenic fungi were investigated. The results indicated that the metabolite exerted more fungicidal activities than the activities of the parent compound. R-Prothioconazole and R-prothioconazole-desthio were 6-262 and 19-954 times more potent against pathogenic fungi than the S-enantiomers, respectively. The R-enantiomers were more effective than in inhibiting the biosynthesis of ergosterol and deoxynivalenol the S-enantiomer. Homology modeling and molecular docking suggested that the R-enantiomers of prothioconazole and prothioconazole-desthio possessed better binding modes than S-enantiomers to CYP51B. Moreover, exposure to prothioconazole and its metabolite enantiomers significantly changed the transcription levels of the CYP51 (CYP 51A, CYP51B, CYP 51C) and Tri (Tri5, Tri6, Tri12) genes. The results showed that application of the R-prothioconazole could require a smaller application amount to eliminate the carcinogenic mycotoxins and any environmental risks.

The External Jugular Vein Used as Recipient Vessel in Head and Neck Free Flap Reconstruction: Outcomes Compared to the Internal Jugular Vein.

BACKGROUND: Contradictory data exists on the success rates of employing the external jugular (EJ) vein as a recipient vessel for venous outflow in free flap head and neck reconstruction compared with the internal jugular (IJ) vein. The authors hereby present a retrospective study of prospectively collected data over a 14-year period. METHODS: Five hundred seventy-eight patients underwent 639 free flap head and neck over 14 years. Two hundred seventy-eight free flaps employed the EJ vein as the recipient vessel while 326 free flaps employed the IJ vein. Rates of acute and late complications were compared. RESULTS: There were no differences in rates of complications: flap loss, venous thrombosis, arterial thrombosis, bleeding, hematoma, or infection between the EJ and IJ vein groups. CONCLUSION: The external jugular vein as a recipient vessel for venous outflow in head and neck free flap reconstruction of postoncologic resection defects is a valid option for both primary reconstructions and secondary surgeries.

Reconstruction of composite leg defects post-war injury.

BACKGROUND: In a high conflict region, war injuries to the distal lower extremity are a major source of large composite defects involving bone and soft tissues. These defects are at the edge between using a single free flap [osteo-(+/-myo) cutaneous] vs double free flap reconstruction (bone and soft tissue). In this paper, we present our experience and outcomes in treating patients with leg war injury reconstructed using a single free fibula flap. METHODS: Fifteen patients with distal leg composite defects secondary to war injuries were treated between January 2015 and March 2016. All patients were reconstructed using single barrel free fibula osteo-(+/-myo)cutaneous flap where single or double skin paddles were used according to the soft tissue defect requiring coverage. RESULTS: There were no cases of total or partial flap loss. Complications were limited to three cases including traumatic fibula fracture, venous congestion with negative findings, and residual soft tissue defect requiring coverage. There were no cases of wound dehiscence or infection. Mean follow-up time was 418.8 days. Mean bone healing time was nine months after which patients were allowed full weight bearing. CONCLUSION: A single barrel free fibula osteo-(+/-myo)cutaneous flap is a valid and reliable tool for reconstruction composite lower extremity defects post-war injury. Adequate planning of fibula flap soft tissue components (skin, muscle) rearrangement is essential for success in such challenging reconstructions.

New Perspective Enteric-Coated Tablet Dosage Form for Oral Administration of Ceftriaxone: In Vitro and In Vivo Assessments.

Ceftriaxone (CTX) is a widely used injectable third-generation cephalosporin that exhibits broad-spectrum antibacterial activity. Unfortunately, the oral route of this drug suffers different encumbrances, such as instability in the upper part of the GIT and enzymatic degradation, as well as poor permeability. There is no reported tablet dosage form for this drug. In this respect, the authors investigated the possibility of developing an enteric-coated oral tablet of CTX that would be helpful for better patient compliance. The tablet consists of directly compressed core of CTX, citric acid (CA), sodium chloride (NaCl), and two biopolymers-chitosan (CH), a permeation enhancer, and silicified microcrystalline cellulose (SMCC), a wicking agent. Both biopolymers are naturally occurring polysaccharides that are biodegradable in the colon and able to incorporate acid labile drugs. CA is a pH modulator to protect CTX from protease enzymes, while NaCl is a translocation enhancer that helps drug penetration. The enteric coat of the core was shellac (SH) with plasticizer glycerol tristearate (GTS) and CA that was applied by direct compression (dry coating). The solventless heat curable coat resulted in an enteric-coated tablet that complies with the USP pharmacopeia. The optimized formula was further subjected to in vitro release and stability studies, as well as ingredient compatibility. In vivo oral bioavailability of the enteric-coated tablets in rabbits gave promising results (absolute bioavailability of about 80%). Synergistically, all ingredients together augmented oral bioavailability of CTX. This developed formula could be a perspective delivery system for those drugs intended to be absorbed from the colon such as peptides and peptide-like drugs.

Slow-Binding Inhibition of Mycobacterium tuberculosis Shikimate Kinase by Manzamine Alkaloids.

Tuberculosis represents a significant public health crisis. There is an urgent need for novel molecular scaffolds against this pathogen. We screened a small library of marine-derived compounds against shikimate kinase from Mycobacterium tuberculosis ( MtSK), a promising target for antitubercular drug development. Six manzamines previously shown to be active against M. tuberculosis were characterized as MtSK inhibitors: manzamine A (1), 8-hydroxymanzamine A (2), manzamine E (3), manzamine F (4), 6-deoxymanzamine X (5), and 6-cyclohexamidomanzamine A (6). All six showed mixed noncompetitive inhibition of MtSK. The lowest KI values were obtained for 6 across all MtSK-substrate complexes. Time-dependent analyses revealed two-step, slow-binding inhibition. The behavior of 1 was typical; initial formation of an enzyme-inhibitor complex (EI) obeyed an apparent KI of ∼30 µM with forward ( k5) and reverse ( k6) rate constants for isomerization to an EI* complex of 0.18 and 0.08 min-1, respectively. In contrast, 6 showed a lower KI for the initial encounter complex (∼1.5 µM), substantially faster isomerization to EI* ( k5 = 0.91 min-1), and slower back conversion of EI* to EI ( k6 = 0.04 min-1). Thus, the overall inhibition constants, KI*, for 1 and 6 were 10 and 0.06 µM, respectively. These findings were consistent with docking predictions of a favorable binding mode and a second, less tightly bound pose for 6 at MtSK. Our results suggest that manzamines, in particular 6, constitute a new scaffold from which drug candidates with novel mechanisms of action could be designed for the treatment of tuberculosis by targeting MtSK.

The molecular basis of cytotoxicity of α-spinasterol from Ganoderma resinaceum: Induction of apoptosis and overexpression of p53 in breast and ovarian cancer cell lines.

Despite advances in therapy of breast and ovarian cancers, they still remain among the most imperative causes of cancer death in women. The first can be considered one of the most widespread diseases among females, while the latter is more lethal and needs prompt treatment. Thus, the research field can still benefit from discovery of new compounds that can be of potential use in management of these grave illnesses. We hereby aimed to assess the antitumor activity of the phytosterol α-spinasterol isolated from Ganoderma resinaceum mushroom on human breast cancer cell lines (MCF-7, MDA-MB-231), as well as, on human ovarian cancer cell line (SKOV-3). The anti-tumor activity of α-spinasterol, isolated from the mycelial extract of the Egyptian G. resinaceum, on human breast and ovarian cancer cell lines was evaluated by MTT cell viability assay and AnnexinV/propidium iodide apoptosis assay. The molecular mechanism underlying this effect was assessed by the relative expression of the following markers; tumor suppressor (p53, BRCA1, BRCA2), apoptotic marker (Bax) and cell cycle progression markers (cyclin dependent kinases cdk4/6) using real-time PCR. Cell cycle analysis was performed for the three investigated cancer cell lines to explore the effect on cell cycle progression. Our findings showed that α-spinasterol exhibited a higher antitumor activity on MCF-7 cells relative to SKOV-3 cells, while its lowest antitumor activity was against MDA-MB-231 cells. A significant increase in the expression of p53 and Bax was observed in cells treated with α-spinasterol, while cdk4/6 were significantly down-regulated upon exposure to α-spinasterol. Cell cycle analysis of α-spinasterol treated cells showed a G0 -G1 arrest. In conclusion, α-spinasterol isolated from G. resinaceum mushroom exerts a potent inhibitory activity on breast and ovarian cancer cell lines in a time- and dose-dependent manner. This can be reasonified in lights of the compound's ability to increase p53 and Bax expressions, and to lower the expression of cdk4/6.

Interventions for preventing cardiomyopathy due to anthracyclines: a Bayesian network meta-analysis.

Background: The relative efficacy of interventions for primary prevention of anthracycline-associated cardiotoxicity is unknown. Methods: We conducted a systematic review of randomized controlled trials for primary prevention of anthracycline-associated cardiotoxicity in adult cancer patients. We used hierarchal outcome definitions in the following order of priority: (1) composite of heart failure or decline in left ventricular ejection fraction, (2) decline in ejection fraction, or (3) heart failure. Data were analyzed using a Bayesian network meta-analysis with random effects. Results: A total of 16 trials reported cardiotoxicity as a dichotomous outcome among 1918 patients, evaluating dexrazoxane, angiotensin antagonists, beta-blockers, combination angiotensin antagonists and beta-blockers, statins, Co-enzyme Q-10, prenylamine, and N-acetylcysteine. Compared with control, dexrazoxane reduced cardiotoxicity with a pooled odds ratio (OR) of 0.26 (95% credible interval [CrI] 0.11-0.74) and had the highest probability (33%) of being most effective. No other agent was demonstrably better than placebo. Angiotensin antagonists had an 84% probability of being most effective in a sensitivity analysis excluding one outlying study (OR 0.06 [95% CrI 0.01- 0.24]). When the outcome was restricted to heart failure, dexrazoxane was associated with an OR of 0.12 (95% CrI 0.06-0.23) relative to control and had 58% probability of being most effective, while angiotensin antagonists had an OR of 0.18 (95% CrI 0.05-0.55). Available data suggested that dexrazoxane and angiotensin antagonists did not affect malignancy response rate or risk of death. Conclusion: Moderate quality data suggest that dexrazoxane, and low quality data suggest angiotensin antagonists, are likely to be effective for cardiotoxicity prevention.

Strain-specific innate immune signaling pathways determine malaria parasitemia dynamics and host mortality.

Malaria infection triggers vigorous host immune responses; however, the parasite ligands, host receptors, and the signaling pathways responsible for these reactions remain unknown or controversial. Malaria parasites primarily reside within RBCs, thereby hiding themselves from direct contact and recognition by host immune cells. Host responses to malaria infection are very different from those elicited by bacterial and viral infections and the host receptors recognizing parasite ligands have been elusive. Here we investigated mouse genome-wide transcriptional responses to infections with two strains of Plasmodium yoelii (N67 and N67C) and discovered differences in innate response pathways corresponding to strain-specific disease phenotypes. Using in vitro RNAi-based gene knockdown and KO mice, we demonstrated that a strong type I IFN (IFN-I) response triggered by RNA polymerase III and melanoma differentiation-associated protein 5, not Toll-like receptors (TLRs), binding of parasite DNA/RNA contributed to a decline of parasitemia in N67-infected mice. We showed that conventional dendritic cells were the major sources of early IFN-I, and that surface expression of phosphatidylserine on infected RBCs might promote their phagocytic uptake, leading to the release of parasite ligands and the IFN-I response in N67 infection. In contrast, an elevated inflammatory response mediated by CD14/TLR and p38 signaling played a role in disease severity and early host death in N67C-infected mice. In addition to identifying cytosolic DNA/RNA sensors and signaling pathways previously unrecognized in malaria infection, our study demonstrates the importance of parasite genetic backgrounds in malaria pathology and provides important information for studying human malaria pathogenesis.

Characterisation of electrospun gelatine nanofibres encapsulated with Moringa oleifera bioactive extract.

BACKGROUND: Drumstick (Moringa oleifera) leaves have been used as a folk herbal medicine across many cultures since ancient times. This is most probably due to presence of phytochemicals possessing antioxidant properties, which could retard oxidative stress, and their degenerative effect. The current study deals with nanoencapsulation of Moringa oleifera (MO) leaf ethanolic extract within fish sourced gelatine matrix using electrospinning technique. RESULTS: The total phenolic and flavonoid content, radical scavenging (IC50 ) and metal reducing properties were 67.0 ± 2.5 mg GAE g-1 sample 32.0 ± 0.5 mg QE g-1 extract, 0.08 ± 0.01 mg mL-1 and 510 ± 10 µmol eq Fe(II) g-1 extract, respectively. Morphological and spectroscopic analysis of the fibre mats confirmed successful nanoencapsulation of MO extract within defect free nanofibres via electrospinning process. The percentage encapsulation efficiency (EE) was between 80% and 85%. Furthermore, thermal stability of encapsulated fibres, especially at 3% and 5% of core loading content, was significantly improved. Toxicological analysis revealed that the extract in its original and encapsulated form was safe for oral consumption. CONCLUSION: Overall, the present study showed the potential of ambient temperature electrospinning process as a safe nanoencapsulation method, where MO extract retained its antioxidative capacities. © 2016 Society of Chemical Industry.

Impact of the pan-Canadian Oncology Drug Review on provincial concordance with respect to cancer drug funding decisions and time to funding.

BACKGROUND: The pan-Canadian Oncology Drug Review (pcodr) was implemented in 2011 to address uneven drug coverage and lack of transparency with respect to the various provincial cancer drug review processes in Canada. We evaluated the impact of the pcodr on provincial decision concordance and time from Notice of Compliance (noc) to drug funding. METHODS: In a retrospective review, Health Canada's Drug Product Database was used to identify new indications for cancer drugs between January 2003 and May 2014, and provincial formulary listings for drug-funding dates and decisions between 1 January 2003 and 31 December 2014 were retrieved. Multiple linear models and quantile regressions were used to evaluate changes in time to decision-making before and after the implementation of the pcodr. Agreement of decisions between provinces was evaluated using kappa statistics. RESULTS: Data were available from 9 provinces (all Canadian provinces except Quebec), identifying 88 indications that represented 51 unique cancer drugs. Two provinces lacked available data for all 88 indications at the time of data collection. Interprovincial concordance in drug funding decisions significantly increased after the pcodr's implementation (Brennan-Prediger coefficient: 0.54 pre-pcodr vs. 0.78 post-pcodr; p = 0.002). Nationwide, the median number of days from Health Canada's noc date to the date of funding significantly declined (to 393 days from 522 days, p < 0.001). Exploratory analyses excluding provinces with incomplete data did not change the results. CONCLUSIONS: After the implementation of the pcodr, greater concordance in cancer drug funding decisions between provinces and decreased time to funding decisions were observed.

Effect of ultrasound-enhanced fat separation on whey powder phospholipid composition and stability.

Fat from freshly pasteurized liquid whey was partially separated by gravity for 5, 10, and 30min, with and without simultaneous application of ultrasound. Ultrasound treatments were carried out at 400 and 1,000 kHz at different specific energy inputs (23-390 kJ/kg). The fat-enriched top layers (L1) and the fat-depleted bottom layers (L2) were separately removed and freeze-dried. Nonsonicated and sonicated L2 powders were stored for 14d at ambient temperature to assess their oxidative stability. Creaming was enhanced at both frequencies and fat separation increased with higher ultrasonic energy, extended sonication, or both. The oxidative volatile compound content decreased in defatted whey powders below published odor detection threshold values for all cases. Sonication had a minor influence on the partitioning of phospholipids with fat separation. The current study suggested that ultrasonication at high frequency enhanced fat separation from freshly pasteurized whey while improving whey powder oxidative stability.

Immune characterization of Plasmodium falciparum parasites with a shared genetic signature in a region of decreasing transmission.

As the intensity of malaria transmission has declined, Plasmodium falciparum parasite populations have displayed decreased clonal diversity resulting from the emergence of many parasites with common genetic signatures (CGS). We have monitored such CGS parasite clusters from 2006 to 2013 in Thiès, Senegal, using the molecular barcode. The first, and one of the largest observed clusters of CGS parasites, was present in 24% of clinical isolates in 2008, declined to 3.4% of clinical isolates in 2009, and then disappeared. To begin to explore the relationship between the immune responses of the population and the emergence and decline of specific parasite genotypes, we have determined whether antibodies to CGS parasites correlate with their prevalence. We measured (i) antibodies capable of inhibiting parasite growth in culture and (ii) antibodies recognizing the surfaces of infected erythrocytes (RBCs). IgG obtained from volunteers in 2009 showed increased reactivity to the surfaces of CGS-parasitized erythrocytes over IgG from 2008. Since P. falciparum EMP-1 (PfEMP-1) is a major variant surface antigen, we used var Ups quantitative reverse transcription-PCR (qRT-PCR) and sequencing with degenerate DBL1α domain primers to characterize the var genes expressed by CGS parasites after short-term in vitro culture. CGS parasites show upregulation of UpsA var genes and 2-cysteine-containing PfEMP-1 molecules and express the same dominant var transcript. Our work indicates that the CGS parasites in this cluster express similar var genes, more than would be expected by chance in the population, and that there is year-to-year variation in immune recognition of surface antigens on CGS parasite-infected erythrocytes. This study lays the groundwork for detailed investigations of the mechanisms driving the expansion or contraction of specific parasite clones in the population.

Neutrophil-to-lymphocyte ratio as a prognostic biomarker for men with metastatic castration-resistant prostate cancer receiving first-line chemotherapy: data from two randomized phase III trials.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a marker of host inflammation, has been associated with poor outcome in several solid tumors. Here, we investigated associations of the derived NLR (dNLR) and duration of initial androgen deprivation therapy (ADT) with survival of men with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line chemotherapy. PATIENTS AND METHODS: Data from the multinational randomized phase III studies VENICE and TAX327 included a total of 2230 men with mCRPC randomized to receive first-line chemotherapy, and were used as training and validation sets, respectively. Associations of dNLR and duration of initial ADT with overall survival (OS) were evaluated by multivariable Cox regression analysis in the training set stratified for performance status and treatment arm. The model was then tested in the validation set. Subsequently, we investigated the treatment effect of docetaxel on OS in subgroups according to dNLR and duration of initial ADT. RESULTS: In the training set, both dNLR ≥median (2) and duration of initial ADT

Birth-Weight, Pregnancy Term, Pre-Natal and Natal Complications Related to Child's Dental Anomalies.

OBJECTIVES: This cross-sectional study was aimed at determining whether certain pre-natal and natal conditions can predict specific dental anomalies. The conditions observed were: low birth-weight, preterm birth, pre-natal & natal complications. The dental anomalies observed were: enamel defects, total number of decayed, missing and filled teeth (total DMFT), disturbances in the tooth shape and disturbances in the number of teeth. STUDY DESIGN: Out of more than 2000 medical files of children aged 2-17 years old which were reviewed, 300 files met the selection criteria. Information recorded from the files included: age, gender, health status (the ASA physical status classification system by the American Society of Anesthesiologists), birth week, birth weight, total DMFT, hypomineralization, abnormal tooth shape, abnormal number of teeth and hypoplasia. RESULTS: Twenty one children out of 300 (7%) were born after a high-risk pregnancy, 25 children (8.3%) were born after high-risk birth, 20 children (6.7%) were born preterm - before week 37, and 29 children (9.7%) were born with a low birth weight (LBW) - 2500 grams or less. A relationship between a preterm birth and LBW to hypomineralization was found. And a relationship between a preterm birth and high-risk pregnancy to abnormal number of teeth was found. No relationship was found between birth (normal/high-risk) and the other parameters inspected. CONCLUSION: Preterm birth and LBW may predict hypomineralization in both primary and permanent dentitions. Furthermore, the study demonstrated that preterm birth and high-risk pregnancy may predict abnormal number of teeth in both dentitions.

Economic evaluation of hormonal therapies for postmenopausal women with estrogen receptor-positive early breast cancer in Canada.

BACKGROUND: Aromatase inhibitor (ai) therapy has been subjected to numerous cost-effectiveness analyses. However, with most ais having reached the end of patent protection and with maturation of the clinical trials data, a re-analysis of ai cost-effectiveness and a consideration of ai use as part of sequential therapy is desirable. Our objective was to assess the cost-effectiveness of the 5-year upfront and sequential tamoxifen (tam) and ai hormonal strategies currently used for treating patients with estrogen receptor (er)-positive early breast cancer. METHODS: The cost-effectiveness analysis used a Markov model that took a Canadian health system perspective with a lifetime time horizon. The base case involved 65-year-old women with er-positive early breast cancer. Probabilistic sensitivity analyses were used to incorporate parameter uncertainties. An expected-value-of-perfect-information test was performed to identify future research directions. Outcomes were quality-adjusted life-years (qalys) and costs. RESULTS: The sequential tam-ai strategy was less costly than the other strategies, but less effective than upfront ai and more effective than upfront tam. Upfront ai was more effective and less costly than upfront tam because of less breast cancer recurrence and differences in adverse events. In an exploratory analysis that included a sequential ai-tam strategy, ai-tam dominated based on small numerical differences unlikely to be clinically significant; that strategy was thus not used in the base-case analysis. CONCLUSIONS: In postmenopausal women with er-positive early breast cancer, strategies using ais appear to provide more benefit than strategies using tam alone. Among the ai-containing strategies, sequential strategies using tam and an ai appear to provide benefits similar to those provided by upfront ai, but at a lower cost.