Preliminary analysis testing the accuracy of radiographic visibility of root pulp in the mandibular first molars as a maturity marker at age threshold of 18 years

International Journal of Legal Medicine - Forensic age estimation, after completion of third molar mineralization, regressive features such as apposition of secondary dentin, which is seen as...     

Two step,one-pot sequential synthesis of functionalized hybrid polyheterocyclic scaffolds via a solid state melt reaction (SSMR)

A new one pot assembly of highly functionalized benzo[a]phenazinone fused chromene/bicyclic scaffolds via a domino Knoevenagel intramolecular hetero-Diels–Alder (IMHDA) strategy using a solid state melt reaction (SSMR) of 2-hydroxynaphthalene 1,4-dione, o-phenylenediamine, O-allyl salicylaldehyde/O-vinyl salicylaldehyde derivatives is reported. The formation of five new bonds (two C–C bonds and three C–O bonds), three six-membered rings, and three stereogenic centers in a one-pot manner is very attractive. Ease of reaction with short time, good yields with water as the only byproduct and work up free procedure are some of the excellent features of the present protocol.

A new one pot assembly of highly functionalized benzo[a]phenazinone fused chromene/bicyclic scaffolds via a domino Knoevenagel intramolecular hetero-Diels–Alder (IMHDA) strategy using a solid state melt reaction (SSMR) is reported.

Multicomponent reactions (MCRs)¹ are known to construct complex structures from simple starting materials in a rapid and highly efficient manner where the production of wastes is minimized. Those multicomponent reactions which are carried out in a ‘one-pot’ MC sequential manner provide a high degree of reaction mass efficiency, which is crucial in the development of modern synthetic methodology for drug discovery and pharmaceutical programs.² Enormous work has been carried out in the field of multicomponent reactions in the past decade where several MCRs have been developed and extensively used in natural product synthesis and drug discovery. The Ugi reaction is a prime example of a four-component reaction that has been found to be a powerful and efficient method for the preparation of α-amino amides both in academia and industry.³ Therefore, the development of new MCRs for the synthesis of biologically active molecules continues to attract considerable attention for their atom- and step economy features.Heterocycles having nitrogen atom are widely available in nature and possess diverse and important biological activities.⁴ Phenazines are a group of organic compounds known to the mankind since past 150 years and are known to exhibit significant biological activities such as antimalarial, fungicidal, trypanocidal, antiplatelet, etc.⁵ A large number of drug molecules bearing the phenazine scaffold have been designed and evaluated in the recent years. The phenazines motif possess two dentate N atoms with three fused aromatic rings and an electron deficient conjugated system. The presence of the above features in phenazines give them an ability to form hydrogen bonds, ionic bonds, and π–π interactions with relative ease, and their use has also been demonstrated in supramolecular chemistry for molecular recognition (MR), supramolecular self-assembly (MS-A), and organic optic electronics materials.⁶ Few representative examples of phenazine and its derivatives are shown in the Fig. 1.Open in a separate windowFig. 1Some of naturally occurring phenazine derivatives.Chromenes and their derivatives are privileged scaffolds due to their ubiquitous presence in many natural products and synthetic molecules.⁷ Chromenes are also an important class of compounds displaying interesting biological activities against prostate cancer (DU-145) and breast cancer (MCF-7).⁸ Additionally, they have medicinal qualities such as antiviral and antimicrobial activity.⁹ Chromenes have also found their use in medicine, health-promoting agents, and photochromic materials.¹⁰In recent years, the domino-Knoevenagel-hetero-Diels–Alder reaction (DKHDA) which was extensively studied by Tietze''s group constitutes an important process for the preparation of complex compounds having interesting biological properties.¹¹ The Diels–Alder reaction is important since it allows the formation of functionalized rings where there is complete control on regio-, diastereo-, and enantioselectivity. Moreover, the concerted nature of the Diels–Alder reactions allow the selective formation of up to three stereogenic centers in a single reaction step. Majority of the reactions reported on DKHDA have utilized 1,3-dicarbonyl compounds such as dimethyl barbituric acid, Meldrum''s acid and 1,3-indanedione.¹² Additionally, other active methylene compounds like 1-phenyl-3-methyl pyrazolone, 4-hydroxy-coumarin, dihydroindole-2-thione, benzoylacetonitrile, 4-hydroxydithiocoumarin have been also used;¹³ but phenazinones have never been employed in DKHDA reactions. To the best of our knowledge, there are no reports on intramolecular DKHDA reactions using phenazinone as the coupling partner. Due to our interest in the construction of bioactive fused chromenophenazinone derivatives and since this molecule contains a 1,3-dicarbonyl as well as a 1,3-imine moiety, it would be very challenging to control the regioselectivity of the molecule; therefore phenazinone scaffold can act as a model substrate for an intramolecular DKHDA. We envisaged that a series of angular polycyclic chromeno fused phenazinone derivatives could be obtained and it is possible that the final hybrid compounds will result in being more selective and efficient than chromene and phenazinone compounds in biological assays.In this direction, we have decided to develop a new method for the preparation of novel benzo[a]phenazinone fused chromene/bicyclic scaffolds via a domino Knoevenagel intramolecular hetero-Diels–Alder (IMHDA) strategy using a solid state melt reaction (SSMR). As part of our research program for the development of new synthetic methods in heterocyclic chemistry¹⁴ and solid state melt reactions,^15,16 we would like to report a simple and a general domino three-component reaction of 2-hydroxynaphthalene-1,4-dione, o-phenylenediamine and O-allylated/vinylated salicylaldehyde for the synthesis of pentacyclic benzo[a]phenazinone fused chromene/bicyclic scaffolds under environmentally benign reaction conditions (Scheme 1).Open in a separate windowScheme 1Synthetic approach to benzo[a]phenazinone fused chromenes.We have started this study by melting 2-hydroxynaphthalene-1,4-dione (2), o-phenylenediamine (1), and (E)-methyl 2-((2-formylphenoxy)methyl)-3-phenylacrylate (3) at 180 °C for 1 h in solvent free condition. Unfortunately, we could not obtain any desired product and the formation of a complex mixture was observed. To minimize the formation of the side products, the 2-hydroxynaphthalene-1,4-dione (2) and o-phenylenediamine (1) were first melted at 180 °C for 10 minutes to form the intermediate benzo[a]phenazin-5-ol. Subsequently, (E)-methyl 2-((2-formylphenoxy)methyl)-3-phenylacrylate 3a was added and the mixture was melted under the same temperature for 1 h which afforded the desired hybrid product chromene fused benzo[a]phenazinone 4a (ester moiety in ring junction) in 78% yield as shown in

The rs594445 in MOCOS gene is associated with risk of autism spectrum disorder

Metabolic Brain Disease - Molybdenum cofactor sulfurase (MOCOS) gene encodes an enzyme which is involved in purine metabolism. Recent experiments have shown down-regulation of MOCOS in adult nasal...     

Determination of Heavy Metal (Zn, Pb, Cd and Cr) Concentration in Benthic Fauna Tissues Collected from the Southeast Caspian Sea, Iran

The aim of the present study was to determine zinc (Zn), chromium (Cr), cadmium (Cd) and lead (Pb) content of benthic fauna in the southeast coast of the Caspian Sea, where the major fish restocking programs are conducted. Seasonal sampling was performed in three sampling sites: north Miankaleh (NM), south Miankaleh (SM) and Gharesoo coast (GC). Results showed that sampling sites, sampling seasons and sampling sites × sampling seasons interaction had a significant effect on the heavy metal levels (p < 0.05). The yearly heavy metal concentration order was as follows: Zn > Pb > Cd > Cr. Yearly Pb levels of the NM site were significantly higher than the other sites. Also, yearly Cr levels of the SM site were significantly higher than site GC. Comparison of the benthos heavy metal levels with the available reference values suggests that the benthos tissues might be highly polluted which can intoxicate the fish feeding on them.     

Increasing circulating levels of Tenascin C in response to the Wingate anaerobic test

Aim

Tenascin C (TNC) is a large extracellular matrix glycoprotein. It is involved in development and upregulated both during tissue repair and in several pathological conditions, including cardiovascular disease. Extracellular matrix proteins play a role in promoting exercise responses, leading to adaptation, regeneration, and repair. The main goal of this study was to investigate whether a short anaerobic effort leads to increased levels of TNC in serum.

Methods

Thirty-nine healthy men performed a Wingate test followed by a muscle biopsy. Myoblasts were isolated from the muscle biopsies and differentiated to myotubes ex vivo. TNC RNA was quantified in the biopsies, myotubes and myoblasts using RNA sequencing. Blood samples were drawn before and 5 min after the Wingate test. Serum TNC levels were measured using enzyme-linked immunosorbent assay.

Results

After the Wingate test, serum TNC increased on average by 23% [15–33], median [interquartile range]; P_Wilcoxon < 0.0001. This increase is correlated with peak power output and power drop, but not with VO_2max. TNC RNA expression is higher in myoblasts and myotubes compared to skeletal muscle tissue.

Conclusion

TNC is secreted systemically as a response to the Wingate anaerobic test in healthy males. The response was positively correlated with peak power and power drop, but not with VO_2max which implicates a relation to mechanical strain and/or blood flow. With higher expression in undifferentiated myoblast cells than muscle tissue, it is likely that TNC plays a role in muscle tissue remodelling in humans. Our findings open for research on how TNC contributes to exercise adaptation.     

Contribution of depression and anxiety to impaired quality of life in survivors of myocardial infarction

Objective. To quantify the adverse influence of depression and anxiety assessed at the time of myocardial infarction, on the quality of life 5 years after the infarction. Methods. The Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) were completed in a group of 196 patients admitted in the hospital following non-fatal myocardial infarction, and the SF-12 quality of life questionnaire was administered during the 5- year follow-up. Results. Regression analysis showed a strong association between baseline depression and QoL in both the physical and mental domains; the higher the depression scores, the poorer the QoL. However, anxiety present at the time of myocardial infarction did not predict later QoL. Conclusions. Depression but not anxiety following MI predicts longer-term quality of life in myocardial infarction survivors.     

Cortical Porosity Identifies Women With Osteopenia at Increased Risk for Forearm Fractures

Most fragility fractures arise among the many women with osteopenia, not the smaller number with osteoporosis at high risk for fracture. Thus, most women at risk for fracture assessed only by measuring areal bone mineral density (aBMD) will remain untreated. We measured cortical porosity and trabecular bone volume/total volume (BV/TV) of the ultradistal radius (UDR) using high‐resolution peripheral quantitative computed tomography, aBMD using densitometry, and 10‐year fracture probability using the country‐specific fracture risk assessment tool (FRAX) in 68 postmenopausal women with forearm fractures and 70 age‐matched community controls in Olmsted County, MN, USA. Women with forearm fractures had 0.4 standard deviations (SD) higher cortical porosity and 0.6 SD lower trabecular BV/TV. Compact‐appearing cortical porosity predicted fracture independent of aBMD; odds ratio (OR) = 1.92 (95% confidence interval [CI] 1.10–3.33). In women with osteoporosis at the UDR, cortical porosity did not distinguish those with fractures from those without because high porosity was present in 92% and 86% of each group, respectively. By contrast, in women with osteopenia at the UDR, high porosity of the compact‐appearing cortex conferred an OR for fracture of 4.00 (95% CI 1.15–13.90). In women with osteoporosis, porosity is captured by aBMD, so measuring UDR cortical porosity does not improve diagnostic sensitivity. However, in women with osteopenia, cortical porosity was associated with forearm fractures. © 2014 American Society for Bone and Mineral Research.     

Robot‐assisted laparoscopic retroperitoneal lymph node dissection for left clinical stage I non‐seminomatous germ cell testicular cancer: Focus on port placement and surgical technique

The aim of our report was to describe the feasibility of robotic retroperitoneal lymph node dissection in the contemporary era. We suggest the linear port location and 90° robotic docking as the main key to minimizing instrument clashing and improving the range of surgical accessibility.     

A multimodal MR-compatible olfactometer with real-time controlling capability

Abstract

Design of an MR-compatible and computer-controlled odour stimuli system is essential in the studies of human olfactory function. Olfactometers are used to deliver odours to the subjects in an objective manner. We present a portable, computer-controlled eight channels olfactometer able to stimulate olfaction by employing liquid odorant stimuli. We used a high-pressure pump to generate medical grade airflow. After passing through solenoid valve-controlled odour reservoirs, odorant stimulus is conveyed to the nasal mask. The odour delivery delay of the device was measured using photo-ionisation detectors. To assess the application of the designed olfactometer, an fMRI experiment was done with 9 healthy subjects. Two odour stimuli (Vanillin and Rose) were presented to each subject in an alternating block design task of odour and non-odour conditions. The response time of each subject was gathered using the response box. Group analysis revealed a significant BOLD signal change in some regions of olfactory and trigeminal networks including the orbitofrontal cortex, insula, inferior frontal gyrus, hippocampus, cingulate gyrus and piriform cortex. The odour delivery delay measured by photo-ionisation detector was 190?ms, and the subjects’ response showed 205?ms for the Vanillin and 243?ms for the Rose odour stimuli. Our portable MR-compatible olfactometer as a stimulation device is capable of creating adequate stimulation suitable for olfactory fMRI experiments.     

From genes polymorphisms to mucosal expression of cytokines: evaluating IL-23/IL-17 axis in adult patients with gastritis

Background and ObjectiveChronic inflammation is the typical sign of gastritis that may shift into gastric cancer. IL-17A and IL-17F as a novel inflammatory cytokines subset of CD4+Th play the main role in inflammation. A key cytokine receptor in the inflammatory IL-17/IL-23 axis, the interleukin 23 receptor (IL23R), may be related to gastritis. We evaluated the correspondence between IL-17A G197A, IL-17F A7488G and IL23R+2199 A/C polymorphisms with TGF-β1, IL-6, IL-17, IL-21 and IL-23 mucosal mRNAs expression in uninfected H. Pylori (HP) chronic gastritis patients.Materials and MethodsTotal RNA and genomic DNA were separated from gastric biopsies of 44 patients with gastritis. Subsequently, mucosal mRNAs expression of TGF-β1, IL-6, IL-17, IL-21 and IL-23 were assessed by real-time PCR. To polymorphisms determination of IL-17A G197A, IL-17F A7488G and IL-23R +2199A/C the PCR-RFLP was used in gastric biopsies.ResultsResults point that IL-17A G197A, IL-17F A7488G and IL23R +2199A/C polymorphisms did not influence the mucosal expression of TGF-β1, IL-6, IL-17 and IL-21 (p> 0.05). In an opposite result, we don''t find a correspondence between IL-17A G197A, IL-17F A7488G polymorphisms and mucosal expression of IL-23 (p> 0.05). In a contrary, we found a correlation between IL23R +2199A/C polymorphism and mucosal expression of IL-23 in patients with chronic gastritis (p< 0.05).ConclusionThese findings propose that IL23R +2199A/C polymorphism may change the mucosal expression of IL-23 pattern in patients with gastritis disease in the absence of HP, but to support the conclusion, more research may be required.