Radical Chain Reduction of Alkylboron Compounds with Catechols

The conversion of alkylboranes to the corresponding alkanes is classically performed via protonolysis of alkylboranes. This simple reaction requires the use of severe reaction conditions, that is, treatment with a carboxylic acid at high temperature (>150 degrees C). We report here a mild radical procedure for the transformation of organoboranes to alkalies. 4-tert-Butylcatechol, a well-established radical inhibitor and antioxidant, is acting as a source of hydrogen atoms. An efficient chain reaction is observed due to the exceptional reactivity of phenoxyl radicals toward alkylboranes. The reaction has been applied to a wide range of organoboron derivatives such as B-alkylcatecholboranes, trialkylboranes, pinacolboronates, and alkylboronic acids. Furthermore, the so far elusive rate constants for the hydrogen transfer between secondary alkyl radical and catechol derivatives have been experimentally determined. Interestingly, they are less than 1 order of magnitude slower than that of tin hydride at 80 degrees C, making catechols particularly attractive for a wide range of transformations involving C-C bond formation.

A critical evaluation of secondary cancer risk models applied to Monte Carlo dose distributions of 2-dimensional, 3-dimensional conformal and hybrid intensity-modulated radiation therapy for breast cancer

The comparison of radiotherapy techniques regarding secondary cancer risk has yielded contradictory results possibly stemming from the many different approaches used to estimate risk. The purpose of this study was to make a comprehensive evaluation of different available risk models applied to detailed whole-body dose distributions computed by Monte Carlo for various breast radiotherapy techniques including conventional open tangents, 3D conformal wedged tangents and hybrid intensity modulated radiation therapy (IMRT). First, organ-specific linear risk models developed by the International Commission on Radiological Protection (ICRP) and the Biological Effects of Ionizing Radiation (BEIR) VII committee were applied to mean doses for remote organs only and all solid organs. Then, different general non-linear risk models were applied to the whole body dose distribution. Finally, organ-specific non-linear risk models for the lung and breast were used to assess the secondary cancer risk for these two specific organs. A total of 32 different calculated absolute risks resulted in a broad range of values (between 0.1% and 48.5%) underlying the large uncertainties in absolute risk calculation. The ratio of risk between two techniques has often been proposed as a more robust assessment of risk than the absolute risk. We found that the ratio of risk between two techniques could also vary substantially considering the different approaches to risk estimation. Sometimes the ratio of risk between two techniques would range between values smaller and larger than one, which then translates into inconsistent results on the potential higher risk of one technique compared to another. We found however that the hybrid IMRT technique resulted in a systematic reduction of risk compared to the other techniques investigated even though the magnitude of this reduction varied substantially with the different approaches investigated. Based on the epidemiological data available, a reasonable approach to risk estimation would be to use organ-specific non-linear risk models applied to the dose distributions of organs within or near the treatment fields (lungs and contralateral breast in the case of breast radiotherapy) as the majority of radiation-induced secondary cancers are found in the beam-bordering regions.

Prevention and Immunotherapy of Secondary Murine Alveolar Echinococcosis Employing Recombinant EmP29 Antigen

Alveolar echinococcosis (AE) is caused by infection with the larval stage of the tapeworm Echinococcus multilocularis. An increasing understanding of immunological events that account for the metacestode survival in human and murine AE infection prompted us to undertake explorative experiments tackling the potential of novel preventive and/or immunotherapeutic measures. In this study, the immunoprotective and immunotherapeutic ability of recombinant EmP29 antigen (rEmP29) was assessed in mice that were intraperitoneally infected with E. multilocularis metacestodes. For vaccination, three intraperitoneal injections with 20μg rEmP29 emulsified in saponin adjuvants were applied over 6 weeks. 2 weeks after the last boost, mice were infected, and at 90 days post-infection, rEmP29-vaccinated mice exhibited a median parasite weight that was reduced by 75% and 59% when compared to NaCl- or saponin-treated control mice, respectively. For immunotherapeutical application, the rEmP29 (20μg) vaccine was administered to experimentally infected mice, starting at 1 month post-infection, three times with 2 weeks intervals. Mice undergoing rEmP29 immunotherapy exhibited a median parasite load that was reduced by 53% and 49% when compared to NaCl- and saponin-treated control mice, respectively. Upon analysis of spleen cells, both, vaccination and treatment with rEmP29, resulted in low ratios of Th2/Th1 (IL-4/IFN-γ) cytokine mRNA and low levels of mRNA coding for IL-10 and IL-2. These results suggest that reduction of the immunosuppressive environment takes place in vaccinated as well as immunotreated mice, and a shift towards a Th1 type of immune response may be responsible for the observed increased restriction of parasite growth. The present study provides the first evidence that active immunotherapy may present a sustainable route for the control of AE.

Prognosis of Atrial Fibrillation in Patients with Symptomatic Peripheral Arterial Disease: Data from the REduction of Atherothrombosis for Continued Health (REACH) Registry

BACKGROUND: Atrial fibrillation (AF) is a significant risk factor for cardiovascular (CV) mortality. This study aims to evaluate the prognostic implication of AF in patients with peripheral arterial disease (PAD). METHODS: The International Reduction of Atherothrombosis for Continued Health (REACH) Registry included 23,542 outpatients in Europe with established coronary artery disease, cerebrovascular disease (CVD), PAD and/or >/=3 risk factors. Of these, 3753 patients had symptomatic PAD. CV risk factors were determined at baseline. Study end point was a combination of cardiac death, non-fatal myocardial infarction (MI) and stroke (CV events) during 2 years of follow-up. Cox regression analysis adjusted for age, gender and other risk factors (i.e., congestive heart failure, coronary artery re-vascularisation, coronary artery bypass grafting (CABG), MI, hypertension, stroke, current smoking and diabetes) was used. RESULTS: Of 3753 PAD patients, 392 (10%) were known to have AF. Patients with AF were older and had a higher prevalence of CVD, diabetes and hypertension. Long-term CV mortality occurred in 5.6% of patients with AF and in 1.6% of those without AF (p<0.001). Multivariable analyses showed that AF was an independent predictor of late CV events (hazard ratio (HR): 1.5; 95% confidence interval (CI): 1.09-2.0). CONCLUSION: AF is common in European patients with symptomatic PAD and is independently associated with a worse 2-year CV outcome.

Bilateral impairment of concurrent saccade programming in hemispatial neglect

When healthy observers make a saccade that is erroneously directed toward a distracter stimulus, they often produce a corrective saccade within 100ms after the end of the primary saccade. Such short inter-saccadic intervals indicate that programming of the secondary saccade has been initiated prior to the execution of the primary saccade and hence that the two saccades have been programmed concurrently. Here we show that concurrent saccade programming is bilaterally impaired in left spatial neglect, a strongly lateralized disorder of visual attention resulting from extensive right cerebral damage. Neglect patients were asked to make saccades to targets presented left or right of fixation while disregarding a distracter presented in the opposite hemifield. We examined those experimental trials on which participants first made a saccade to the distracter, followed by a secondary (corrective) saccade to the target. Compared to healthy and right-hemisphere damaged control participants the proportion of secondary saccades directing gaze to the target instead of bringing it even closer to the distracter was bilaterally reduced in neglect patients. In addition, the characteristic reduction of secondary saccade latency observed in both control groups was absent in neglect patients, whether the secondary saccade was directed to the left or right hemifield. This pattern is consistent with a severe, bilateral impairment of concurrent saccade programming in left spatial neglect.

In vitro detection of secondary caries associated with composite restorations on approximal surfaces using laser fluorescence

This study evaluated the performance of the DIAGNOdent pen laser fluorescence device (LFpen) in comparison with visual examination (VE), bitewing radiographs (BW) and visual examination combined with bitewing radiographs (VEBW) in detecting secondary approximal caries associated with composite restorations. In total, 60 approximal surfaces from 43 permanent molars with composite restorations were assessed twice by two examiners using the LFpen, VE, BW and VEBW. After histological preparation and hardness measurements, the sample was assigned to either a crown or root caries group, depending on the location of the lesions as the gold standard. For crown caries at D1, the highest values of specificity and sensitivity were observed for the LFpen at a cutoff value of 18 (1.00) and for the VEBW (0.89). At D3 (cutoff of 30), the LFpen showed the highest values of sensitivity and specificity. For root caries, the LFpen and VEBW showed the highest values of specificity (0.54), sensitivity (0.81) and accuracy (0.69). The Spearman rank correlation coefficients for crown/root caries with histology were 0.54/0.37 (LFpen), 0.29/0.10 (BW), 0.29/0.18 (VE) and 0.23/0.37 (VEBW). For the LFpen, the ICC varied from 0.80 (interexaminer) to 0.97 (intraexaminer B); the kappa value was 0.19 for BW and 0.35 for VE (interexaminer). Intraexaminer kappa values for BW were 0.25 (A) and 0.29 (B), and those for VE were 0.31 (A) and 0.32 (B). The LFpen device exhibited a performance comparable to that of conventional methods but with higher interexaminer reproducibility. Therefore, the LFpen should be considered an auxiliary method for the detection of secondary approximal caries associated with composite restorations.

Reduction of inappropriate medications among older nursing-home residents: a nurse-led, pre/post-design, intervention study

Background: Medication-related problems are common in the growing population of older adults and inappropriate prescribing is a preventable risk factor. Explicit criteria such as the Beers criteria provide a valid instrument for describing the rate of inappropriate medication (IM) prescriptions among older adults. Objective: To reduce IM prescriptions based on explicit Beers criteria using a nurse-led intervention in a nursing-home (NH) setting. Study Design: The pre/post-design included IM assessment at study start (pre-intervention), a 4-month intervention period, IM assessment after the intervention period (post-intervention) and a further IM assessment at 1-year follow-up. Setting: 204-bed inpatient NH in Bern, Switzerland. Participants: NH residents aged ≥60 years. Intervention: The intervention included four key intervention elements: (i) adaptation of Beers criteria to the Swiss setting; (ii) IM identification; (iii) IM discontinuation; and (iv) staff training. Main Outcome Measure: IM prescription at study start, after the 4-month intervention period and at 1-year follow-up. Results: The mean±SD resident age was 80.3±8.8 years. Residents were prescribed a mean±SD 7.8±4.0 medications. The prescription rate of IMs decreased from 14.5% pre-intervention to 2.8% post-intervention (relative risk [RR] = 0.2; 95% CI 0.06, 0.5). The risk of IM prescription increased nonstatistically significantly in the 1-year follow-up period compared with post-intervention (RR = 1.6; 95% CI 0.5, 6.1). Conclusions: This intervention to reduce IM prescriptions based on explicit Beers criteria was feasible, easy to implement in an NH setting, and resulted in a substantial decrease in IMs. These results underscore the importance of involving nursing staff in the medication prescription process in a long-term care setting.

An education and training programme for radiological institutes: impact on the reduction of the CT radiation dose

To establish an education and training programme for the reduction of CT radiation doses and to assess this programme's efficacy.

Effects of adherence to guidelines for the control of major cardiovascular risk factors on outcomes in the REduction of Atherothrombosis for Continued Health (REACH) Registry Europe

To examine the impact of cardiovascular risk factor control on 3-year cardiovascular event rates in patients with stable symptomatic atherothrombotic disease in Europe.

Role of catechol in the radical reduction of B-alkylcatecholboranes in presence of methanol

Mechanistic investigations on the previously reported reduction of B-alkylcatecholboranes in the presence of methanol led to the disclosure of a new mechanism involving catechol as a reducing agent. More than just revising the mechanism of this reaction, we disclose here the surprising role of catechol, a chain breaking antioxidant, which becomes a source of hydrogen atoms in an efficient radical chain process

The design of artificial nestboxes for the study of secondary hole-nesting birds: a review of methodological inconsistencies and potential biases

The widespread use of artificial nestboxes has led to significant advances in our knowledge of the ecology, behaviour and physiology of cavity nesting birds, especially small passerines Nestboxes have made it easier to perform routine monitoring and experimental manipulation of eggs or nestlings, and also repeatedly to capture, identify and manipulate the parents However, when comparing results across study sites the use of nestboxes may also Introduce a potentially significant confounding variable in the form of differences in nestbox design amongst studies, such as their physical dimensions, placement height, and the way in which they are constructed and maintained However, the use of nestboxes may also introduce an unconsidered and potentially significant confounding variable clue to differences in nestbox design amongst studies, such as their physical dimensions, placement height, and the way in which they are constructed and maintained Here we review to what extent the characteristics of artificial nestboxes (e g size, shape, construction material, colour) are documented in the 'methods' sections of publications involving hole-nesting passerine birds using natural or excavated cavities or artificial nestboxes for reproduction and roosting Despite explicit previous recommendations that authors describe in detail the characteristics of the nestboxes used, we found that the description of nestbox characteristics in most recent publications remains poor and insufficient We therefore list the types of descriptive data that should be included in the methods sections of relevant manuscripts and justify this by discussing how variation in nestbox characteristics can affect or confound conclusions from nestbox studies We also propose several recommendations to improve the reliability and usefulness of research based on long-term studies of any secondary hole-nesting species using artificial nestboxes for breeding or roosting.

Mechanisms of failure and outcome of secondary surgical interventions after thoracic endovascular aortic repair (TEVAR)

We evaluated mechanisms of failure and outcome of secondary surgical interventions after thoracic endovascular aortic repair (TEVAR).

Celecoxib enhances radiation response of secondary bone tumors of a human non-small cell lung cancer via antiangiogenesis in vivo

Cyclooxygenase-2 (COX-2) inhibitors mediate a systemic antitumor activity via antiangiogenesis and seem to enhance the response of primary tumors to radiation. Radiosensitizing effects of COX-2 inhibition have not been reported for bone metastases. Therefore, the aim of this study was the investigation of the radiosensitizing effects of the selective COX-2 inhibitor celecoxib in secondary bone tumors of a non-small cell lung carcinoma in vivo.

Early antiretroviral therapy during primary HIV-1 infection results in a transient reduction of the viral setpoint upon treatment interruption

Long-term benefits of combination antiretroviral therapy (cART) initiation during primary HIV-1 infection are debated.