Hemodynamics of the oral mucosa during cooling: A crossover clinical trial.

Objective: Oral cryotherapy is used to prevent the onset of oral mucositis, a common and debilitating adverse effect following cancer chemotherapy. A protective mechanism associated with oral cooling is thought to be mediated through reduced tissue microcirculation. The aim of the present study was to examine the underlying mechanism associated with oral mucosal cooling by measuring oral microcirculation and tissue oxygen saturation after cooling with ice chips (IC) and an intraoral cooling device (ICD). Study design: In a single-center randomized crossover study, 10 healthy volunteers were assigned (1:1) randomly to the order in which the two intraoral cooling procedures (IC/ICD) were to be commenced. On day 1, half of the study participants started with IC and then crossed over to intraoral cooling with the ICD on day 2, while the other half of the participants undertook the same two procedures in the reverse order. Total and functional capillary density (T/FCD) and tissue oxygen saturation (StO2) measurements were obtained at baseline and 30 min following oral cooling. Results: Following 30 min of oral cooling, a statistically significant difference was found for FCD between IC and ICD (percentage points; +2 vs. -13; p < 0.05). A statistically significant decrease in StO2 was observed with both IC and ICD (%; 13 vs. 10) after 30 min of cooling as compared to baseline (p < 0.05). As for the participants' preference the ICD was preferred over IC by 9 out of 10 participants (p = 0.021). Conclusions: Both microcirculation parameters and tissue oxygen saturation are altered in conjunction with oral cooling, indicating their potential mechanistic contribution towards cryoprevention of oral mucositis.

Outcome of a rabbit model for late irradiation effects in mandibular oral mucosa and bone: A pilot study.

BACKGROUND/AIM/OBJECTIVE: Late side effects of radiotherapy (RT) in the treatment for head and neck (HN) malignancies involve an inadequate healing response of the distressed tissue due to RT-induced hypovascularity. The aim of this study was to develop a pilot model in which vascular alterations associated with the onset of late irradiation (IR) injury could be measured in rabbit oral mucosa and mandibular bone. MATERIALS AND METHODS: Eight male New Zealand white rabbits were divided over four treatment groups. Group I-III received four fractions of RT (5.6 Gy, 6.5 Gy, and 8 Gy, respectively) and Group IV received 1 fraction of 30 Gy. Oral microcirculatory measurements were performed at baseline (before RT) and once a week during 11 consecutive weeks after RT assessing perfusion parameters, that is, total vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV), and microvascular flow index (MFI). Post-mortem histopathology specimens were analyzed. RESULTS: Five weeks after RT, TVD, and PVD in all groups showed a decrease of >10% compared to baseline, a significant difference was observed for Groups I, II, and IV (P<0.05). At T11, no lasting effect of decreased vessel density was observed. PPV and MFI remained unaltered at all-time points. Group IV showed a marked difference in scattered telangiectasia such as microangiopathies, histological necrosis, and loss of vasculature. CONCLUSION: No significant lasting effect in mucosal microcirculation density due to IR damage was detected. Observed changes in microcirculation vasculature and histology may align preliminary tissue transition towards clinical pathology in a very early state associated with late IR injury in the oral compartment. RELEVANCE FOR PATIENTS: Enhancing knowledge on the onset of late vascular IR injury in the HN region could help the development, monitoring, and timing of therapies that act on prevention, discontinuation, or repair of radiation pathology.

Effects of sterilization on the mechanical properties of poly(methyl methacrylate) based personalized medical devices.

BACKGROUND: Nowadays, personalized medical devices are frequently used for patients. Due to the manufacturing procedure sterilization is required. How different sterilization methods affect the mechanical behavior of these devices is largely unknown. MATERIALS AND METHODS: Three poly(methyl methacrylate) (PMMA) based materials (Vertex Self-Curing, Palacos R+G, and NextDent C&B MFH) were sterilized with different sterilization methods: ethylene oxide, hydrogen peroxide gas plasma, autoclavation, and γ-irradiation. Mechanical properties were determined by testing the flexural strength, flexural modulus, fracture toughness, and impact strength. RESULTS: The flexural strength of all materials was significantly higher after γ-irradiation compared to the control and other sterilization methods, as tested in a wet environment. NextDent C&B MFH showed the highest flexural and impact strength, Palacos R+G showed the highest maximum stress intensity factor and total fracture work. CONCLUSION: Autoclave sterilization is not suitable for the sterilization of PMMA-based materials. Ethylene oxide, hydrogen peroxide gas plasma, and γ-irradiation appear to be suitable techniques to sterilize PMMA-based personalized medical devices.

Assessment of obstructive sleep apnoea treatment success or failure after maxillomandibular advancement.

Maxillomandibular advancement (MMA) is an alternative therapeutic option that is highly effective for treating obstructive sleep apnoea (OSA). MMA provides a solution for OSA patients that have difficulty accepting lifelong treatments with continuous positive airway pressure or mandibular advancement devices. The goal of this study was to investigate the different characteristics that determine OSA treatment success/failure after MMA. The apnoea-hypopnoea index (AHI) was used to determine the success or failure of OSA treatment after MMA. Sixty-two patients underwent MMA for moderate and severe OSA. A 71% success rate was observed with a mean AHI reduction of 69%. A statistically significant larger neck circumference was measured in patients with failed OSA treatments following MMA (P=0.008), and older patients had failed OSA treatments with MMA: 58 vs. 53 years respectively (P=0.037). Cephalometric analysis revealed no differences between successful and failed OSA treatment outcomes. There was no difference in maxillary and mandibular advancements between success and failed MMA-treated OSA patients. The complications most frequently reported following MMA were sensory disturbances in the inferior alveolar nerve (60%) and malocclusion (24%). The results suggest that age and neck girth may be important factors that could predict susceptibility to OSA treatment failures by MMA.

Is pelvic organ prolapse associated with altered microcirculation of the vaginal wall?

AIMS: Vascularisation of the vagina is necessary for optimal function and support of the surrounding organs. We evaluated whether vaginal microcirculation, as representative of vascularisation, differs between women with and without pelvic organ prolapse (POP). METHODS: In 17 women with POP-Q stage ≥2 and 10 women without POP measurements were performed using sidestream dark-field imaging (groups were not matched). POP and non-POP sites were compared in women with a single compartment prolapse (n = 7). Morphology of the microvessels was scored using the microcirculatory architecture and capillary tortuosity scores at four regions of the vaginal wall. Capillary density measurements were performed and microvascular flow was assessed according to the microvascular flow index (MFI) score. RESULTS: Architecture and tortuosity scores were similar for each anatomical region between women with and without POP and between the POP and non-POP site. A statistically significant difference in capillary density in the left vaginal wall between women with and without POP was observed (25.8 vs. 34.0, P = 0.049). No significant differences in capillary density were observed between the POP and non-POP site. Average MFI scores revealed a continuous flow for all four regions in patients with and without POP. CONCLUSIONS: Vaginal microcirculatory architecture, capillary density, and microvascular flow are similar in women with and without POP. Our method to assess the microcirculation of the vaginal wall is consistent in women with POP, which generates an opportunity to assess vaginal microcirculation in the (surgical) treatments of POP. Neurourol. Urodynam. 35:764-770, 2016. © 2015 Wiley Periodicals, Inc.

Patient discomfort and other side effects after bilateral sagittal split osteotomy or distraction osteogenesis of the mandible: a randomized clinical trial.

A randomized clinical trial was conducted to compare bilateral sagittal split osteotomy (BSSO) with distraction osteogenesis (DO) for the advancement of the mandible, with a focus on patient discomfort, postoperative pain, the need for analgesics, and occurrence of infection. All patients were non-syndromal, had a class II hypoplastic mandible, and had not undergone previous mandibular surgery. A total of 66 patients were allocated randomly to the BSSO group (32 patients) or the DO group (34 patients). Sixty-three patients were eligible for evaluation, 29 in the BSSO group and 34 in the DO group. Patients in the DO group experienced more pain after 6 days postoperative, and were administered more analgesics after 5 days postoperative than patients in the BSSO group (P=0.030 and P=0.045, respectively). The operating time was significantly shorter for the BSSO group than for the DO group (78 min vs. 100 min, P=0.024). All postoperative infections (12 in total) emerged in the DO group (P=0.005). All patients in the DO group had a second surgery in day care to remove the distractor, while two patients in the BSSO group needed plate removal. It is concluded that patients experienced more pain after DO, needed more analgesics postoperatively, and had more infections in comparison to the BSSO group.

Catalytic, oxidant-free, direct olefination of alcohols using Wittig reagents.

Reported here is the catalytic, acceptorless coupling of alcohols with in situ generated, non-stabilized phosphonium ylides to form olefins as major products. The reaction uses low catalyst loadings and does not require added oxidants. Hydrogenation of the product is minimized and the reaction leads to Z (aliphatic) or E (benzylic) stereospecificity.

A candidate gene survey of quantitative trait loci affecting chemical composition in tomato fruit.

In tomato, numerous wild-related species have been demonstrated to be untapped sources of valuable genetic variability, including pathogen-resistance genes, nutritional, and industrial quality traits. From a collection of S. pennellii introgressed lines, 889 fruit metabolic loci (QML) and 326 yield-associated loci (YAL), distributed across the tomato genome, had been identified previously. By using a combination of molecular marker sequence analysis, PCR amplification and sequencing, analysis of allelic variation, and evaluation of co-response between gene expression and metabolite composition traits, the present report, provides a comprehensive list of candidate genes co-localizing with a subset of 106 QML and 20 YAL associated either with important agronomic or nutritional characteristics. This combined strategy allowed the identification and analysis of 127 candidate genes located in 16 regions of the tomato genome. Eighty-five genes were cloned and partially sequenced, totalling 45,816 and 45,787 bases from S. lycopersicum and S. pennellii, respectively. Allelic variation at the amino acid level was confirmed for 37 of these candidates. Furthermore, out of the 127 gene-metabolite co-locations, some 56 were recovered following correlation of parallel transcript and metabolite profiling. Results obtained here represent the initial steps in the integration of genetic, genomic, and expressional patterns of genes co-localizing with chemical compositional traits of the tomato fruit.

Advances in metal chemistry of quinonoid compounds: new types of interactions between metals and aromatics.

This Account presents an overview of current research activities that focus on novel types of interactions between cationic transition metal complexes and arene systems and on unprecedented quinonoid complexes which result from such interactions. When a negatively charged phenoxy group is present in a position para to the metal in a high oxidation state, intramolecular charge transfer occurs, giving the corresponding metallaquinones or quinone methide complexes. In addition, two types of interactions involving low-valent metal compounds have been observed: methylene arenium complexes which result from positive charge transfer to the aromatic ring and sigma-bonded C-H and C-C agostic complexes of cationic metals. These sigma-complexes are proposed as intermediates in metal-based bond activation processes.

Comparison of steric and electronic requirements for C-C and C-H bond activation. Chelating vs nonchelating case.

C-H bond activation was observed in a novel PCO ligand 1 (C(6)H(CH(3))(3)(CH(2)OCH(3))(CH(2)P(t-Bu)(2))) at room temperature in THF, acetone, and methanol upon reaction with the cationic rhodium precursor, [Rh(coe)(2)(solv)(n)()]BF(4) (solv = solvent; coe = cyclooctene). The products in acetone (complexes 3a and 3b) and methanol (complexes 4a and 4b) were fully characterized spectroscopically. Two products were formed in each case, namely those containing uncoordinated (3a and 4a) and coordinated (3b and 4b) methoxy arms, respectively. Upon heating of the C-H activation products in methanol at 70 degrees C, C-C bond activation takes place. Solvent evaporation under vacuum at room temperature for 3-4 days also results in C-C activation. The C-C activation product, ((CH(3))Rh(C(6)H(CH(3))(2)(CH(2)OCH(3))(CH(2)P(t-Bu)(2))BF(4)), was characterized by X-ray crystallography, which revealed a square pyramidal geometry with the BF(4)(-) anion coordinated to the metal. Comparison to the structurally similar and isoelectronic nonchelating Rh-PC complex system and computational studies provide insight into the reaction mechanism. The reaction mechanism was studied computationally by means of a two-layer ONIOM model, using both the B3LYP and mPW1K exchange-correlation functionals and a variety of basis sets. Polarization functions significantly affect relative energetics, and the mPW1K profile appears to be more reliable than its B3LYP counterpart. The calculations reveal that the electronic requirements for both C-C and C-H activation are essentially the same (14e intermediates are the key ones). On the other hand, the steric requirements differ significantly, and chelation appears to play an important role in C-C bond activation.

Solvent-stabilized alkylrhodium(III) hydride complexes: a special mode of reversible C-H bond elimination involving an agostic intermediate

Reaction of the complex [Rh(coe)2(solv)n]BF4 (coe=cyclooctene) with the phosphane 1-di-tert-butylphosphinomethyl-2,4,6-trimethylbenzene (1) results in selective C-H bond activation, yielding the spectroscopically characterized solvento complexes [(solv)nRhH(CH2C6H2(CH3)2[CH2P(tBu)2]]]BF4 (solv = acetone, 2a; THF, 2b; methanol, 2c). The stability of these complexes is solvent dependent, alcohols providing significant stabilization. Although cis-alkylrhodium hydride complexes containing labile ligands are generally unstable, 2a-c are stable at room temperature. Complex [ (acetone)(ketol)RhH[CH2C6H2(CH3)2[CH2P(t-Bu)2]]]BF4 (2d, ketol 4-hydroxy-4-methyl-2-pentanone, the product of acetone aldol condensation), crystallized from a solution of 2a in acetone and was structurally characterized. Unusual solvent- and temperature-dependent selectivity in reversible C-H bond elimination of these complexes, most probably controlled by a special mode of strong agostic interactions, is observed by spin saturation transfer experiments.

A novel approach towards intermolecular stabilization of para-quinone methides. First complexation of the elusive, simplest quinone methide, 4-methylene-2,5-cyclohexadien-1-one

A novel approach towards the intermolecular stabilization of "simple" (i.e. methylene-unsubstituted) p-quinone methides (QMs) by their coordination to a transition-metal center is described. 4-Bromomethyl phenols, protected by a silyl group, were employed as the QM precursors and cis-chelating diphosphine Pd0 complexes were chosen as the metal precursors, since they have strong back-bonding interactions with the electron-poor QM moiety. Removal of the silyl protecting-group from the corresponding [LPd(benzyl)Br] complex (L=bisphosphine) with fluoride results in the spontaneous rearrangement of the unobserved zwitterionic Pd(II) complex into the QM-Pd0 complex. The feasibility of this approach was demonstrated in the synthesis of the structurally characterized Pd0 complex of BHT-QM (4), a biologically relevant metabolite of 2,6-di-tert-butyl-p-cresol, and the synthesis of the complex of 4-methylene-2,5-cyclohexadien-1-one (11), the simplest, and so far unobserved QM molecule. These complexes exhibit a remarkable thermal stability and do not react with alcohol or water. In both cases, the use of an appropriate incoming ligand allowed the release of the coordinated QM into the reaction media in which it was effectively trapped by added nucleophiles.

Radiation-induced tumors in irradiated stage I testicular seminoma: results of a 25-year follow-up (1968-1993).

BACKGROUND AND OBJECTIVES: Testicular seminoma is a very radiosensitive and curable cancer, with survival rates following radiation therapy within the range of 90-98% without apparent severe side effects. However, long-term survival following exposure to moderate-dose radiation therapy can result in radiation-induced tumors. METHODS: The incidence of radiation-induced tumors was determined in 81 irradiated stage I testicular seminoma patients treated at the Northern Israel Oncology Center (NIOC) from 1968 through 1993. RESULTS: Three (4%) patients developed second cancers within the high-dose volume. Indeed, those patients received a higher than usual dose to the para-aortic and pelvic regions. One patient, who developed inoperable pancreatic carcinoma, was treated with "hockey stick" field and mediastinal irradiation, plus, as a result of relapses, multiple cisplatin and VP-16 based regimens. CONCLUSIONS: The elimination of causative factors through lower total doses and field size reduction may reduce the, albeit very low, incidence of radiation-induced cancer in cured testicular seminoma.

Impact of molecular order in langmuir-blodgett films on catalysis

Catalytically active Langmuir-Blodgett films of a rhodium complex were prepared and characterized to determine the possible effect of the molecular order of metal complexes on catalytic activity. The hydrogenation of carbon-oxygen double bonds was used as a model reaction. The complex in solution exhibited low catalytic activity, whereas it was highly active in the film. The catalytic activity was found to be highly dependent on the orientation of the complex within the film. The reactions were also highly selective with regard to the substrate. These observations and the observed rate dependence on temperature strongly implicate the molecular order of a metal complex as an important dimension in catalysis.

Evidence for Direct trans Insertion in a Hydrido-Olefin Rhodium Complex-Free Nitrogen as a Trap in a Migratory Insertion Process.

Reduction of the hydrido chloride complex [Rh(H)Cl{CH3 C(CH2 CH2 -P(tBu)2 )2 }] (4) with NaH under a nitrogen atmosphere results in formation of two products: the dinitrogen complex [Rh(N2 )-{CH3 C(CH2 P(tBu)2 )2 }] (2) and the unusual low-valent hydrido-olefin complex, [RhH{CH2 C(CH2 CH2 P(tBu)2 )2 }] (3). In the presence of N2 , complexes 2 and 3 are in equilibrium in solution; 2 is about 2.9kcalmol(-1) more stable than 3 + N2 . Both complexes co-crystallize in the solid state; they occupy the same crystallographic site in the crystal lattice (P2-(1)/c; Z = 4; a = 12.173(2), b = 14.121 (3), c = 15.367 (3); α = 90, ß = 106.50(3), γ = 90°). The mechanism of the reversible interconversion of 2 and 3 has been studied in detail. Complex 3 undergoes rapid olefin insertion/ß-hydrogen elimination processes. The insertion rates were measured at different temperatures by saturation transfer NMR experiments, providing evidence for a highly organized late transition state (δS≠≈︂ - 40 e.u.), which can be caused by a concerted "trans migration". This theoretically unfavorable process is assisted by a distortion from the ideal square-planar configuration, including a decrease of the P-Rh-P angle and some bias of the double bond toward the hydride as indicated by the X-ray crystal structure of 3. Under a nitrogen atmosphere, the intermediate formed upon olefin insertion is slowly trapped by free dinitrogen to form complex 2. The dinitrogen dissociation from 2 was found to be the rate-determining step for the overall interconversion of 2 and 3 (δG≠298 = 24.1 kcalmol(-1) ).

Preoperative concurrent chemoradiotherapy for unresectable Stage III nonsmall cell lung cancer.

PURPOSE: We carried out a Phase II trial in an attempt to improve resectability and survivability of inoperable Stage III A and III B nonsmall cell lung cancer (NSCLC) patients by implementing a neoadjuvant chemoradiotherapy treatment program. METHODS AND MATERIALS: Thirty-six patients with locally advanced Stage III NSCLC received neoadjuvant therapy consisting of 50.4 Gy in 5.5 weeks concurrent with two cycles of chemotherapy, using cisplatin and etoposide. No postsurgical consolidation therapy was given. RESULTS: Assessment at 3 to 6 weeks after treatment suggested that 26 (72%) patients had been rendered resectable. Toxicities were common but usually tolerable; however, one toxic death occurred. Of 24 patients who proceeded to thoracotomy, complete resection was achieved in 20 (56%). There were two surgically related deaths. Surgical-pathological staging showed downstaging in 18 patients, including complete sterilization of the tumor in 3 (8%). The median survival for all 36 patients is 15 months, but at the time of analysis, median survival of resectable patients had not been reached. The actuarial 2-year survival is 39% for all study groups, 57% for resectable patients, and 16% for the remaining (p < 0.005). CONCLUSIONS: While this preoperative neoadjuvant appears to improve survival of patients with Stage III NSCLC, comparison with previous reports of other similar trials indicate a superior survival advantage in association with higher doses of radiotherapy.