Regioselective [2 + 2 + 2] Alkyne Cyclotrimerizations to Hexasubstituted Benzenes: Syntheses of Fomajorin D and Fomajorin S.

Hexasubstituted benzenoids are prepared by regioselective bimolecular [2 + 2 + 2] alkyne cyclotrimerizations of diynes with alkynes. These convergent and efficient benzannulations are directed toward and lead to the first total syntheses of the illudalane sequiterpenes fomajorin D and S, in 10 and 7 steps, respectively, from commercially available dimedone. Control experiments suggest that hydrogen bonding may play a role in preorganizing the diyne and alkyne coupling partners for establishing the desired regioselectivity, but other factors are likely involved in the selective formation of other regioisomers.

The effect of humeral head positioning and incomplete backside contact on bone stresses following total shoulder arthroplasty with a short humeral stem.

BACKGROUND: The use of uncemented humeral stems in total shoulder arthroplasty (TSA) is known to be associated with stress shielding. This may be decreased with smaller stems that are well-aligned and do not fill the intramedullary canal; however, the effect of humeral head positioning and incomplete head backside contact has not yet been investigated. The purpose of this study was to quantify the effect of changes in humeral head position and incomplete head backside contact on bone stresses and expected bone response following reconstruction. METHODS: Three-dimensional finite element models of 8 cadaveric humeri were generated, which were then virtually reconstructed with a short-stem implant. An optimally sized humeral head was then positioned in both a superolateral and inferomedial position for each specimen that was in full contact with the humeral resection plane. Additionally, for the inferomedial position, 2 incomplete humeral head backside contact conditions were simulated whereby contact was defined between only the superior or inferior half of the backside of the humeral head and the resection plane. Trabecular properties were assigned based on computed tomography attenuation and cortical bone was applied uniform properties. Loads representing 45° and 75° of abduction were then applied, and the resulting differentials in bone stress versus the corresponding intact state and the expected time-zero bone response were determined and compared. RESULTS: The superolateral position reduced resorbing potential in the lateral cortex and increased resorbing potential in the lateral trabecular bone, while the inferomedial position produced the same effects but in the medial quadrant. For the inferomedial position, full backside contact with the resection plane was best in terms of changes in bone stress and expected bone response, although a small region of the medial cortex did experience no load transfer. The implant-bone load transfer of the inferior contact condition was concentrated at the midline of the backside of the humeral head, leaving the medial aspect largely unloaded as a result of the lack of lateral backside support. DISCUSSION: This study shows that inferomedial humeral head positioning loads the medial cortex at the cost of unloading the medial trabecular bone, with the same occurring for the superolateral position except that the lateral cortex is loaded at the cost of unloading the lateral trabecular bone. Inferomedial positioned heads also were predisposed to humeral head lift-off from the medial cortex, which may increase the risk of calcar stress shielding. For the inferomedial head position, full contact between the implant and resection plane was preferable.

Synthesis of 4,4-Dimethyl-1,6-heptadiyne and Other Neopentylene-Tethered (NPT) 1,6-Diynes.

Two divergent and complementary methodologies for preparing neopentylene-tethered (NPT) 1,6-diynes are described. These NPT 1,6-diynes are valuable π-systems for reaction discovery and building blocks for target-oriented synthesis. Ring-opening fragmentation of dimedone (and alkylation) produces alkyne-tethered ß-keto esters 6. One-pot dehydration with optional saponification produces diyne monoester 15 or monoacid 3, which can be further functionalized using traditional alkyne substitution chemistry and/or carboxylate manipulations. For example, copper-catalyzed decarboxylation of acid 3 provides 4,4-dimethyl-1,6-heptadiyne (1), now in ca. 76% yield over four steps from dimedone. A complementary approach using Zard fragmentation chemistry converts alkylated ß-keto esters into the corresponding monoalkylated NPT 1,6-diynes. The utility of substituted NPT 1,6-diynes in target-oriented synthesis is noted herein.

Synthesis of Coprinol and Several Alcyopterosin Sesquiterpenes by Regioselective [2 + 2 + 2] Alkyne Cyclotrimerization.

Alkyne [2 + 2 + 2] cyclotrimerization is a strategically attractive but tactically challenging approach to the synthesis of highly substituted benzene rings. Here, a bimolecular regioselective cyclotrimerization is applied to the total synthesis of the natural product coprinol and several related alcyopterosins from the illudalane family of sesquiterpenes. The synthesis of coprinol from dimedone was completed in six steps and a 57% overall yield. Alternative functional group manipulations lead to alcyopterosins A, B, and O and two additional congeners, all within six steps.

Accelerated thermal reaction kinetics by indirect microwave heating of a microwave-transparent substrate.

Macroscopically homogeneous mixtures of p-nitroanisole (pNA) and mesitylene (MES) can be selectively heated using microwave (MW) energy. The pNA solutes agglomerate into distinct phase domains on the attoliter-scale (1 aL = 10-18 L), and these agglomerates can be MW-heated selectively to temperatures that far exceed the boiling point of the surrounding MES solvent. Here, a 1 : 20 mixture of pNA : MES is used as a mixed solvent for aryl Claisen rearrangement of allyl naphthyl ether (ANE). ANE itself does not heat effectively in the MW, but selective MW heating of pNA allows for transfer of thermal energy to ANE to accelerate rearrangement kinetics above what would be expected based on Arrhenius kinetics and the measured bulk solution temperature. This focused study builds on prior work and highlights 1 : 20 pNA : MES as a mixed solvent system to consider for strategically exploiting MW-specific thermal effects.

Carbon substitution for oxygen in silicates in planetary interiors.

Amorphous silicon oxycarbide polymer-derived ceramics (PDCs), synthesized from organometallic precursors, contain carbon- and silica-rich nanodomains, the latter with extensive substitution of carbon for oxygen, linking Si-centered SiO(x)C(4-x) tetrahedra. Calorimetric studies demonstrated these PDCs to be thermodynamically more stable than a mixture of SiO2, C, and silicon carbide. Here, we show by multinuclear NMR spectroscopy that substitution of C for O is also attained in PDCs with depolymerized silica-rich domains containing lithium, associated with SiO(x)C(4-x) tetrahedra with nonbridging oxygen. We suggest that significant (several percent) substitution of C for O could occur in more complex geological silicate melts/glasses in contact with graphite at moderate pressure and high temperature and may be thermodynamically far more accessible than C for Si substitution. Carbon incorporation will change the local structure and may affect physical properties, such as viscosity. Analogous carbon substitution at grain boundaries, at defect sites, or as equilibrium states in nominally acarbonaceous crystalline silicates, even if present at levels at 10-100 ppm, might form an extensive and hitherto hidden reservoir of carbon in the lower crust and mantle.

Structural analysis of hollow versus solid-stemmed shoulder implants of proximal humeri with different bone qualities.

Stress shielding of the proximal humerus following total shoulder arthroplasty (TSA) can promote unfavorable bone remodeling, especially for osteoporotic patients. The objective of this finite element (FE) study was to determine if a hollow, rather than solid, titanium stem can mitigate this effect for healthy, osteopenic, and osteoporotic bone. Using a population-based model of the humerus, representative average healthy, osteopenic, and osteoporotic humerus FE models were created. For each model, changes in bone and implant stresses following TSA were evaluated for different loading scenarios and compared between solid versus hollow-stemmed implants. For cortical bone, using an implant decreased von Mises stress with respect to intact values up to 34.4%, with a more pronounced effect at more proximal slices. In the most proximal slice, based on changes in strain energy density, hollow-stemmed implants outperformed solid-stemmed ones through reducing cortical bone volume with resorption potential by 11.7% ± 2.1% (p = .01). For cortical bone in this slice, the percentage of bone with resorption potential for the osteoporotic bone was greater than the healthy bone by 8.0% ± 1.4% using the hollow-stemmed implant (p = .04). These results suggest a small improvement in bone-implant mechanics using hollow-stemmed humeral implants and indicate osteoporosis could exacerbate stress shielding to some extent. The hollow stems maintained adequate strength and using even thinner walls may further reduce stress shielding. After further developing these models, future studies could yield optimized implant designs tuned for varying bone qualities.

Humeral short stem varus-valgus alignment affects bone stress.

The use of uncemented humeral stems in total shoulder arthroplasty (TSA) is associated with stress shielding. Shorter length stems have shown to decrease stress shielding; however, the effect of stem varus-valgus alignment is currently not known. The purpose of this study was to quantify the effect of short stem distal humeral endosteal contact due to varus-valgus angulation on bone stresses after TSA. Three-dimensional models of eight male cadaveric humeri were constructed from computed tomography data. Bone models were reconstructed with a short stem humeral component implant in three positions (standard, varus, and valgus). Modeling was performed at 45° and 75° of abduction and the resulting differentials in bone stress compared to the intact state and the expected time-zero bone response were determined. In cortical and trabecular bone, the standard position (STD) altered bone stress less than the valgus (VAL) and varus (VAR) positions relative to the intact state. For both cortical (p = 0.033) and trabecular (p = 0.012) bone, the VAL position produced a larger volume of bone with resorbing potential compared to the STD position.

Modulation of attention and stress with arousal: The mental and physical effects of riding a motorcycle.

Existing theories suggest that moderate arousal improves selective attention, as would be expected in the context of competitive sports or sensation-seeking activities. Here we investigated how riding a motorcycle, an attention-demanding physical activity, affects sensory processing. To do so, we implemented the passive auditory oddball paradigm and measured the EEG response of participants as they rode a motorcycle, drove a car, and sat at rest. Specifically, we measured the N1 and mismatch negativity to auditory tones, as well as alpha power during periods of no tones. We investigated whether riding and driving modulated non-CNS metrics including heart rate and concentrations of the hormones epinephrine, cortisol, DHEA-S, and testosterone. While participants were riding, we found a decrease in N1 amplitude, increase in mismatch negativity, and decrease in relative alpha power, together suggesting enhancement of sensory processing and visual attention. Riding increased epinephrine levels, increased heart rate, and decreased the ratio of cortisol to DHEA-S. Together, these results suggest that riding increases focus, heightens the brain's passive monitoring of changes in the sensory environment, and alters HPA axis response. More generally, our findings suggest that selective attention and sensory monitoring seem to be separable neural processes.

Health-related quality of life among individuals with long-standing spinal cord injury: a comparative study of veterans and non-veterans.

BACKGROUND: Spinal cord-injured (SCI) patients experience poor health-related quality of life (HRQOL) and they usually report lower HRQOL than the general population or population subgroups in Iran and elsewhere. The aim of this study was to compare HRQOL between veterans and non-veterans with SCI in Iran. METHODS: This was a cross-sectional study. HRQOL was measured using the 36-item Short Form Health Survey (SF-36). Thirty-nine male veterans and 63 non-veteran males with SCI were included in the study. Regression analyses were applied to determine the variables affecting physical and mental health-related quality of life among the patients. RESULTS: The male veterans had a lower HRQOL than the non-veterans with SCI. The differences were significant for all measures except for physical and social functioning. The greatest difference was observed for bodily pain (P = 0.001). The regression analysis results indicated that a longer time since injury was associated (P = 0.01) with better physical health-related quality of life (PCS), while being a veteran (P < 0.001) and having a spinal lesion in the cervical region (P = 0.001) were associated with poorer PCS. Older age (P < 0.001) and higher education (P = 0.01) were associated with better mental health-related quality of life (MCS), while being a veteran and having a spinal lesion in the cervical region (P = 0.02) were associated with poorer MCS. CONCLUSION: The study findings showed that veterans with SCI experienced lower HRQOL than their non-veteran counterparts. A qualitative study is recommended to evaluate why HRQOL was lower in veterans than in non-veterans with SCI although veterans had higher incomes as a result of their pensions and increased access to equipment, and medications. To improve quality of life in both veterans and non-veterans with spinal cord injuries, policy changes or implementation of new interventions may be essential so that veterans could receive additional support (e.g. counseling, recreation therapy, vocational therapy, etc.) and non-veterans could meet their basic needs.

Synthesis of 4,4-Dimethyl-1,6-heptadiyne and Alcyopterosin O.

A four-step synthesis of 4,4-dimethyl-1,6-heptadiyne and an associated five-step synthesis of alcyopterosin O, an illudalane sesquiterpene natural product, are described starting from commercially available dimedone. The process features C-C bond-cleaving fragmentation and elimination methods for making alkynes, and it proceeds by way of nonsymmetrical diynes that are themselves valuable synthetic building blocks, as exemplified by the synthesis of alcyopterosin O.

Induction of Chondrogenic Differentiation in Human Mesenchymal Stem Cells Cultured on Human Demineralized Bone Matrix Scaffold under Hydrostatic Pressure.

BACKGROUND: Articular cartilage damage is still a troublesome problem. Hence, several researches have been performed for cartilage repair. The aim of this study was to evaluate the chondrogenicity of demineralized bone matrix (DBM) scaffolds under cyclic hydrostatic pressure (CHP) in vitro. METHODS: In this study, CHP was applied to human bone marrow mesenchymal stem cells (hBMSCs) seeded on DBM scaffolds at a pressure of 5 MPa with a frequency of 0.5 Hz and 4 h per day for 1 week. Changes in chondrogenic and osteogenic gene expressions were analyzed by quantifying mRNA signal level of Sox9, collagen type I, collagen type II, aggrecan (ACAN), Osteocalcin, and Runx2. Histological analysis was carried out by hematoxylin and eosin, and Alcian blue staining. Moreover, DMMB and immunofluorescence staining were used for glycosaminoglycan (GAG) and collagen type II detection, respectively. RESULTS: Real-time PCR demonstrated that applying CHP to hBMSCs in DBM scaffolds increased mRNA levels by 1.3-fold, 1.2-fold, and 1.7-fold (p < 0.005) for Sox9, Col2, and ACAN, respectively by day 21, whereas it decreased mRNA levels by 0.7-fold and 0.8-fold (p < 0.05) for Runx2 and osteocalcin, respectively. Additionally, in the presence of TGF-ß1 growth factor (10 ng/ml), CHP further increased mRNA levels for the mentioned genes (Sox9, Col2, and ACAN) by 1.4-fold, 1.3-fold and 2.5-fold (p < 0.005), respectively. Furthermore, in histological assessment, it was observed that the extracellular matrix contained GAG and type II collagen in scaffolds under CHP and CHP with TGF-ß1, respectively. CONCLUSION: The osteo-inductive DBM scaffolds showed chondrogenic characteristics under hydrostatic pressure. Our study can be a fundamental study for the use of DBM in articular cartilage defects in vivo and lead to production of novel scaffolds with two different characteristics to regenerate both bone and cartilage simultaneously.

Enhancing the Ecological Validity of fMRI Memory Research Using Virtual Reality.

Functional magnetic resonance imaging (fMRI) is a powerful research tool to understand the neural underpinnings of human memory. However, as memory is known to be context-dependent, differences in contexts between naturalistic settings and the MRI scanner environment may potentially confound neuroimaging findings. Virtual reality (VR) provides a unique opportunity to mitigate this issue by allowing memories to be formed and/or retrieved within immersive, navigable, visuospatial contexts. This can enhance the ecological validity of task paradigms, while still ensuring that researchers maintain experimental control over critical aspects of the learning and testing experience. This mini-review surveys the growing body of fMRI studies that have incorporated VR to address critical questions about human memory. These studies have adopted a variety of approaches, including presenting research participants with VR experiences in the scanner, asking participants to retrieve information that they had previously acquired in a VR environment, or identifying neural correlates of behavioral metrics obtained through VR-based tasks performed outside the scanner. Although most such studies to date have focused on spatial or navigational memory, we also discuss the promise of VR in aiding other areas of memory research and facilitating research into clinical disorders.

Transcranial Alternating Current Stimulation (tACS) Mechanisms and Protocols.

Perception, cognition and consciousness can be modulated as a function of oscillating neural activity, while ongoing neuronal dynamics are influenced by synaptic activity and membrane potential. Consequently, transcranial alternating current stimulation (tACS) may be used for neurological intervention. The advantageous features of tACS include the biphasic and sinusoidal tACS currents, the ability to entrain large neuronal populations, and subtle control over somatic effects. Through neuromodulation of phasic, neural activity, tACS is a powerful tool to investigate the neural correlates of cognition. The rapid development in this area requires clarity about best practices. Here we briefly introduce tACS and review the most compelling findings in the literature to provide a starting point for using tACS. We suggest that tACS protocols be based on functional brain mechanisms and appropriate control experiments, including active sham and condition blinding.

Prevalence and severity of depression in chronic viral hepatitis in Iran.

AIM: The aim of this study was to compare the prevalence and severity of depression in chronic hepatitis B (CHB) patients, chronic hepatitis C (CHC) patients, and healthy participants. METHODS: Two hundred and fifty-three persons participated in this cross-sectional study between 2011 and 2012 in Imam Khomeini Hospital. The prevalence and severity of depression were assessed using the Hamilton Scale. RESULTS: There was significantly higher prevalence of depression in CHC patients (35.9%) than in healthy participants (11.3%) and CHB patients (19.8%) (both P < 0.01). However, CHB and CHC patients did not differ significantly in their depression prevalence after excluding inactive hepatitis B surface antigen (HBsAg) carriers (29.3% vs. 35.9%; P > 0.05). Inactive HBsAg carriers differed significantly from CHB patients-excluding inactive HBsAg carriers-in depression prevalence (10.0% vs. 29.3%; P < 0.05). No statistically significant difference was found in depression severity between all groups (P > 0.05). CONCLUSION: Depression screening in chronic hepatitis B and chronic hepatitis C patients may be beneficial in disease management.

Construction of Plasmid Insulin Gene Vector Containing Metallothionein IIA (pcDNAMTChIns) and Carbohydrate Response Element (ChoRE), and Its Expression in NIH3T3 Cell Line.

BACKGROUND: Type 1 diabetes mellitus is one of the metabolic diseases that cause insulin-producing pancreatic ß cells be destroyed by immune system self-reactive T cells. Recent-ly, new treatment methods have been developed including use of the stem cells, ß islet cells transplantation and gene therapy by viral and non-viral gene constructs. OBJECTIVES: The aim of this project was preparing the non-viral vector containing the glucose inducible insulin gene and using it in the NIH3T3 cell line. MATERIALS AND METHODS: Cloning was carried out by standard methods. Total RNA was extracted from pancreatic tissue, RNA was converted to cDNA using RT-PCR reaction and preproinsulin gene was amplified using specific primers. PNMTCH plasmid was extract-ed and digested by NotI, HindIII, and MTIIA and ChoRE genes were purified and cloned into pcDNA3.1 (-) plasmid and named pcDNAMTCh. Finally, the preproinsulin genes were cloned into pcDNA3.1 (-) plasmid and pcDNAMTChIns was built. RESULTS: The cloned gene constructs were evaluated by restriction enzyme digestion and RT-PCR. The NIH3T3 cells were transfected by plasmid naked DNA containing preproinsu-lin gene and expression was confirmed by Reverse Transcriptase PCR and Western Blot-ting Techniques. CONCLUSIONS: Gel electrophoresis of PCR products confirmed that cloning was per-formed correctly. The expression of preproinsulin gene in recombinant plasmid in NI-H3T3 cell line was observed for the first time. The findings in this study can be the basis of further research on diabetes mellitus type 1 gene therapy on animals.