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A diverse range of biochemical and cellular assays are used by medicinal chemists to guide compound optimization. The data collected from these assays influence decisions taken on structure-activity relationship (SAR) campaigns. Therefore, it is paramount that medicinal chemists have a solid understanding of the strengths and limitations of each assay being used to characterize synthesized analogs. For the successful execution of a medicinal chemistry campaign, it is our contention that an early partnership among assay biologists, informaticians, and medicinal chemists must exist. Their combined skill sets are necessary to not only design and develop robust assays but also implement an effective screening cascade in which multiple orthogonal and counter assays are selected to validate the activity and target(s) of the synthesized compounds. We review multiple cases of drug and chemical probe discovery from collaborative National Center for Advancing Translational Sciences/National Institutes of Health projects and published scientific literature in which the evaluation of compounds in secondary or orthogonal assays led to the discovery of unexpected activities, forcing a reconsideration of the original assay design that was used to discover the biological activity of the compound. Using these retrospective case studies, the goal of this Perspective is to hedge toward the development of physiologically relevant assays that are able to capture the true bioactivity of compounds being developed in a medicinal chemistry campaign.

An efficient palladium-free Stille cross-coupling reaction of allylic bromides and functionalized organostannylfuran using catalytic copper halide has been developed. The coupling reaction was optimized using CuI and low catalyst loading (down to 5 mol %). The reaction was conveniently carried out at ambient temperature in the presence of inorganic base to afford the coupling product in good-to-excellent yields. The utility of this reaction was demonstrated in the synthesis of a furan with sensitive functionalities. A sulfolene moiety was utilized as a masking group for the sensitive diene. Noyori asymmetric reduction, Achmatowicz reaction, and Kishi reduction steps converted sulfolene to a highly substituted tetrahydropyran intermediate used in the synthesis of the highly potent antitumor agents, spliceostatins, and their derivatives.

Background: Pulmonary infection with SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2; COVID-19) has rapidly spread worldwide to become a global pandemic. Objective: To collect paediatric COVID-19 cases worldwide and to summarize both clinical and imaging findings in children who tested positive on polymerase chain reaction testing for SARS-CoV-2. Materials and methods: Data were collected by completion of a standardised case report form submitted to the office of the European Society of Paediatric Radiology from March 12 to April 8, 2020. Chest imaging findings in children younger than 18 years old who tested positive on polymerase chain reaction testing for SARS-CoV-2 were included. Representative imaging studies were evaluated by multiple senior paediatric radiologists from this group with expertise in paediatric chest imaging. Results: Ninety-one children were included (49 males; median age: 6.1 years, interquartile range: 1.0 to 13.0 years, range: 9 days–17 years). Most had mild symptoms, mostly fever and cough, and one-third had coexisting medical conditions. Eleven percent of children presented with severe symptoms and required intensive unit care. Chest radiographs were available in 89% of patients and 10% of them were normal. Abnormal chest radiographs showed mainly perihilar bronchial wall thickening (58%) and/or airspace consolidation (35%). Computed tomography (CT) scans were available in 26% of cases, with the most common abnormality being ground glass opacities (88%) and/or airspace consolidation (58%). Tree in bud opacities were seen in 6 of 24 CTs (25%). Lung ultrasound and chest magnetic resonance imaging were rarely utilized. Conclusion: It seems unnecessary to perform chest imaging in children to diagnose COVID-19. Chest radiography can be used in symptomatic children to assess airway infection or pneumonia. CT should be reserved for when there is clinical concern to assess for possible complications, especially in children with coexisting medical conditions. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Background: Human trafficking is a global problem and results in deleterious psychological, social, and physical effects on the lives of those who are trafficked; however, it is not clear how to best intervene with survivors. The purpose of this review was to synthesize the evidence of exit and postexit intervention programs for survivors of human trafficking to inform practice and research. Method: Systematic review methods were used to search, select, and extract data from published and unpublished experimental, quasi-experimental, and preexperimental studies that assessed the effects of any exit or postexit interventions for victims of human trafficking. The authors searched eight databases, reviewed bibliographies, and conducted forward citation searches from relevant reports and prior reviews to find studies authored between 2005 and 2015. Results: The search yielded six eligible studies that included 155 female and 6 male survivors from four countries. Interventions were diverse, with three using a trauma-informed approach. Authors measured a myriad of outcomes, including mental health, social network, community reintegration, and employment; however, the quality of most studies was poor. Discussion: Evidence of effects of exit and postexit interventions is sparse, and much of the research is poorly designed and executed; however, the needs of trafficking survivors are complex and effective interventions are desperately needed. Implications for practice and research are discussed.

Enantioselective syntheses of hexacyclic aspidoalbidine alkaloids (+)-fendleridine (2) and (+)-acetylaspidoalbidine (3) are described. These syntheses feature an asymmetric decarboxylative allylation and photocyclization of a highly substituted enaminone. Also, the synthesis highlights the formation of the C19 hemiaminal ether via a reduction/condensation/intramolecular cyclization cascade with the C21-alcohol. The present synthesis provides convenient access to the aspidoalbidine hexacyclic alkaloid family in an efficient manner.

Background: The purpose of this study was to review the outcomes associated with different surgical treatments in the management of suppurative flexor tenosynovitis (SFT). Methods: Patients treated by open drainage (OD) through a single incision and closed catheter irrigation (CCI) of the tendon sheath were evaluated from 2003 to 2009 at a single institution. Variables examined included culture results, time to surgery, duration of hospitalization and antibiotic therapy, pain, reoperation, and functional outcomes were recorded. Statistical analyses used included parametric and nonparametric t tests. Results: Twenty-four patients were treated for SFT with a mean follow-up of 3 ± 2 years. There were 13 (100%) males in the OD group compared to 8 (72%) males within the CCI group. Ninety-two percent of patients who underwent OD and 100% who underwent CCI reported none or mild pain. There were no differences between the 2 groups with regard to functional outcome scores. Factors leading to worse functional outcomes included prolonged time to receiving antibiotics and Staphylococcus aureus infection. Smokers required prolonged antibiotic treatment compared to nonsmokers. Accounting for planned returns to the operating room, there was no difference in reoperation rates between the OD or CCI groups. Conclusions: Surgical treatment of SFT with either OD or CCI resulted in similar outcomes for pain, function, and need for reoperation. Factors that lead to poor outcomes include S aureus culture, prolonged time to antibiotics, and smoking.

Purpose To evaluate and compare two adjustable femoral cortical suspensory fixation devices used for anterior cruciate ligament reconstruction through a novel, direct computed tomography (CT) analysis metric and biomechanical laxity testing in a matched cadaveric human knee study. Methods Anterior cruciate ligament reconstructions with bovine tendon grafts were performed using two adjustable femoral cortical suspensory fixation devices (RigidLoop Adjustable [DePuy Synthes Mitek, Raynham, MA] and TightRope [Arthrex, Naples, FL]) in 12 knees (6 matched pairs). A mechanical testing series was used to determine each knee's laxity in the intact condition. After reconstruction, each specimen was again tested for laxity and also imaged with CT. The laxity testing and CT imaging were then repeated after 1,000 cycles of anteroposterior loading on each knee to compare changes in laxity for the two fixation devices and to visualize changes in button-to-graft distance migration through a three-dimensional CT imaging method. Results No significant differences were found between the two fixation groups' laxity measures after reconstruction (all P values ≥ .620) or after cycling (all P values ≥ .211) at any flexion angle. In addition, no significant differences were found between the two groups regarding button-to-graft distance migration ( P = .773; mean, 0.61 ± 0.6 mm [95% confidence interval, −0.1 to 1.3 mm] in RigidLoop Adjustable group and 0.53 ± 0.6 mm [95% confidence interval, −0.1 to 1.2 mm] in TightRope group). Conclusions There were no significant differences between the two femoral cortical suspensory adjustable-loop devices regarding laxity outcomes or loop displacement as measured by button-to-graft distance migration. Clinical Relevance Use of either of the adjustable-loop cortical suspensory devices in our analysis would appear to produce similar, acceptable laxity outcomes and minimal effects in terms of device-related loop displacement.

Case: A seventy-three-year-old woman who had been given the tentative diagnosis of spontaneous osteonecrosis presented to our clinic for a second opinion. Additional imaging and evaluation revealed the lesion to be a subchondral metastasis consistent with breast cancer. She received proper oncologic treatment and subsequent total knee arthroplasty. Conclusion: Orthopaedic surgeons should be aware of the possibility of metastatic disease manifesting itself in the form of an isolated subchondral lesion about the knee. For patients with such lesions, treatment in the form of total knee arthroplasty is a viable option that can provide excellent pain relief and function.

Background— It has been proposed that under hypoxic conditions, nitrite may release nitric oxide, which causes potent vasodilation. We hypothesized that nitrite would have a greater dilator effect in capacitance than in resistance vessels because of lower oxygen tension and that resistance-vessel dilation should become more pronounced during hypoxemia. The effect of intra-arterial infusion of nitrite on forearm blood flow and forearm venous volumes was assessed during normoxia and hypoxia. Methods and Results— Forty healthy volunteers were studied. After baseline infusion of 0.9% saline, sodium nitrite was infused at incremental doses from 40 nmol/min to 7.84 μmol/min. At each stage, forearm blood flow was measured by strain-gauge plethysmography. Forearm venous volume was assessed by radionuclide plethysmography. Changes in forearm blood flow and forearm venous volume in the infused arm were corrected for those in the control arm. The peak percentage of venodilation during normoxia was 35.8±3.4% (mean±SEM) at 7.84 μmol/min ( P P P Conclusions— Nitrite is a potent venodilator in normoxia and hypoxia. Arteries are modestly affected in normoxia but potently dilated in hypoxia, which suggests the important phenomenon of hypoxic augmentation of nitrite-mediated vasodilation in vivo. The use of nitrite as a selective arterial vasodilator in ischemic territories and as a potent venodilator in heart failure has therapeutic implications.

Hintergrund: Studien zum Einsatz von Schulterarthroplastiken erzielten gute Resultate bezuglich der Wiederherstellung der Schulterfunktion. Der kurzfristige Rehabilitationsverlauf ist bisher jedoch kaum untersucht. Ziel: Primares Ziel war die Untersuchung objektiver und subjektiver Ergebnisse innerhalb der ersten 6 Monate nach Implantation einer Schulterarthroplastik, sekundares Ziel die Evaluation der individuellen Heilungsverlaufe von Patienten mit anatomischer versus inverser Arthroplastik. Methode: Prospektiv wurden 19 Patienten nach Schulterarthroplastik mit einem Durchschnittsalter von 72 Jahren eingeschlossen. Die Erhebung subjektiver Parameter mithilfe des Shoulder Pain and Disability Index (SPADI) und objektiver Parameter mit dem Constant Murley Score erfolgte praoperativ, nach 6 Wochen sowie nach 3 und 6 Monaten. Ergebnisse: Alle Patienten verbesserten sich bezuglich aller Parameter signifikant zwischen der praoperativen Untersuchung und dem Follow-up nach 6 Monaten (p ≤ 0,05). Patienten mit einer inversen Schulterarthroplastik zeigten praoperativ eine deutlich bzw. teilweise signifikant schlechtere Funktion als die mit einer anatomischen Arthroplastik. Nach 6 Monaten waren jedoch keine funktionellen Unterschiede zwischen den beiden Gruppen feststellbar (p ≥ 0,05). Schlussfolgerung: Die Heilungsverlaufe von Patienten mit anatomischer versus inverser Schulterarthroplastik unterscheiden sich in den ersten Monaten. Nach einem halben Jahr sind ahnliche Ergebnisse zu erwarten.

Any hypothesis for arterial thrombosis must be able to account for the following facts: (1) thrombi do not form in normal arteries; (2) thrombi form in atherosclerotic arteries; (3) arterial thrombi consist initially of aggregated platelets; (4) atherosclerosis increases slowly, whereas thrombosis occurs rapidly and is individually unpredictable. Therefore, atherosclerotic arteries must be subject to sudden, unpredictable events capable of initiating platelets aggregation; (5) most occlusive thrombi are associated with fissures in underlying atheromatous placques.

A quench-precipitated sample of highly syndiotactic polypropylene (s-PP) (with 86% fully syndiotactic pentads), which shows an X-ray spectrum near that calculated for an ideal orthorhombic C-centered structural model of packing as proposed by Corradini et al. (with chains in a helical (TTGG) n conformation), has been analyzed by high-resolution solid-state 13 C-NMR spectroscopy. The 13 C-NMR CP MAS spectra of this sample, in addition to the resonances already reported in the literature for s-PP (in the B-centered structure), exhibit additional peaks in the regions of the methyl (at 18.9 and 22.4 ppm) and methylene (at 44.9 ppm) groups. It is established that these additional resonances belong indeed to nuclei in well-defined conformational environments fixed in rigid structures placed at the interface of the crystallites and within the strained or disordered area of the crystallites themselves. In particular, the peak at 44.9 ppm in assigned to CH 2 carbon atoms in a TX.YG conformational environment, whereas the resonance at 18.9 ppm is assigned to CH 3 in trans-planar portions of the chain (γ-gauche effect). This indicates local disorder in the C-centered crystalline s-PP sample, due to the presence of conformationally disordered chains. Models of s-PP chains comprising defective but energetically feasible portions of chains in a trans-planar conformation (disturbing the (TTGG) n dominating conformation) are imagined as packed according to a C-pseudocentered structure. In order to keep the methyl groups in a crystalline register and the chains well interdigitated, the defects should be clustered on planes which cross 3D ordered portions in the crystals. The chemical shifts of the carbon atoms in the regions comprising the defect for model chains have been calculated on an ab initio level through the IGLO method, and the results are compared with the experiments. The calculations provide a good explanation of the peculiarities of the experimental 13 C-NMR spectra of the s-PP sample under study. Thus, detailed information on chain defects can be obtained by combining X-ray scattering, solid-state NMR, and computer simulations.

An electrochemical method for the deposition of calcium phosphate phases on titanium surfaces using the galvanostatic mode is presented. Deposition was performed in a (Ca(2+) / H(x)PO(4) ((3-x)-))-containing electrolyte near physiological conditions with regard to pH (6.4) and temperature (36 degrees C). Cathodic alkalization leads first to the formation of a thin homogeneous layer that shows a nanoscale surface topography of alternating wall-like elevations and channels. It is thought that these channels in the calcium phosphate prelayer are formed as pathways for hydroxyl ions and hydrogen. Upon this layer, spheres of amorphous calcium phosphate (ACP) are formed as indicated by Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy. According to transmission electron microscopy images, these spheres consist of small clusters of calcium phosphate (approximately 30 nm) and can grow up to 300 nm in diameter. Characteristic for this ACP is a high water content as seen by FTIR. As a function of current density, the ACP is then transformed into crystalline hydroxyapatite (HAP), which was identified using FTIR and X-ray diffraction. The morphology of the HAP crystals can be described as needles with dimensions of

The effects of long-term low-dose treatment with reserpine on plasma lipoproteins and arterial cholesterol were determined in cholesterol-fed rabbits. Hepatic low-density lipoprotein (LDL) receptors; uptake of LDL by liver, heart, and kidneys; plasma fibrinogen; blood pressure; and heart rate were also determined. Reserpine at 43 μg/kg . d was continuously infused subcutaneously via implanted minipumps for 6 weeks into conscious unrestrained male New Zealand White rabbits (n = 5) fed a 0.2% cholesterol-enriched diet. Compared with controls, reserpine (n = 4) significantly reduced the elevated levels of plasma total cholesterol and esterified and unesterified cholesterol throughout the study, and at 6 weeks of treatment these reductions were 42, 41, and 49%, respectively. The increased cholesterol in the aortic walls (n = 5) produced by the atherogenic diet was reduced by 73% (p < 0.004) and 125 I-tyramine cellobiose-labeled LDL by 67 to 86% (0.05 < p

This article gives an account of the life of Max Born, one of the founders of quantum mechanics and the author's father, in the context of his forebears, family and descendants. It traces the family's history from Martin Luther to the present day, ranging as far afield as Ben Elton and Olivia Newton–John.

Reconstruction of the multiligament-injured knee often involves extended surgical and tourniquet use times and often is performed in patients who have sustained concomitant fractures as well as vascular injuries, all of which would appear to predispose the patient to the potentially serious complications of deep vein thrombosis and perhaps pulmonary embolism, yet little is known about the frequency of venous thromboembolic (VTE) events after multiligamentous knee reconstruction.The purposes of this study were to (1) determine the frequency of symptomatic VTE after multiligamentous knee reconstruction at a single institution; and (2) to determine associated risk factors for VTE in these patients.The records of 134 (63% of the 213 consented individuals in our longitudinal database) patients who underwent primary (129 [96%]) or revision (five [4%]) multiligamentous knee reconstruction at a single institution between 1992 and 2013 were retrospectively reviewed. With two patients undergoing procedures bilaterally, this resulted in a total of 136 multiligamentous knee reconstructions. VTE for which clinical symptoms were evident and confirmed by imaging within 3 months after the reconstructive procedure was noted. Pre- and perioperative data were collected with respect to demographics, associated injuries, medical history, smoking status, and surgical data. Standard rehabilitation and thromboprophylaxis protocols were used in all patients.Three cases of symptomatic VTE (three deep vein thromboses) occurred after the 136 reconstructions (2%; 95% confidence interval, 0.53%-7.3%). Two of the three patients were obese and the remaining patient smoked and abused alcohol. However, as a result of a low frequency of VTE, no risk factors could be identified in this series.Symptomatic VTE occurred in 2% of multiligamentous knee reconstructions at our institution while receiving thromboprophylaxis. This is similar to rates documented after anterior cruciate ligament reconstruction without thromboprophylaxis. Further multicenter research is required to identify the true frequency of and risk factors for developing VTE in patients undergoing multiligamentous knee reconstruction after knee dislocation.Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

The effects were determined in rats of single injections of reserpine at increasing doses (0.5, 1.58, and 5.0 mg/kg) on low-density lipoprotein (LDL) and cholesterol in aortic wall, heart, liver, kidney, and adrenal gland. Catecholamine levels in plasma, heart, and liver, arterial blood pressure, and heart rate were also monitored. Reserpine was injected intraperitoneally, followed immediately by the administration of [3H]cholesterol by gavage. Twelve hours later, homologous 125I-tyramine cellobiose-labeled LDL (125I-TC-LDL) was injected intravenously. Twenty-four hours later, the rats were killed, and the radioactivities of aortic walls, heart, liver, kidney, and adrenal glands were determined. The results showed that after reserpine treatment the accumulation of both the 125I-TC label derived from LDL and total [3H]cholesterol was significantly reduced in aortic wall and heart, increased in liver, and unchanged in the kidney and adrenal gland. At higher doses (1.58 and 5.0 mg/kg), reserpine significantly accelerated the plasma clearance of radiolabelled LDL. Plasma noradrenaline in reserpine-treated animals decreased maximally (86%) by 12 h and by 61-71% at 36 h compared with the control. Plasma adrenaline increased transiently after injection of reserpine and then returned to the basal levels. Reserpine greatly decreased noradrenaline and adrenaline levels in heart and liver. Arterial blood pressure was decreased significantly (0.001 < p < 0.05) at 12 h by the two lower doses of reserpine and then returned to normal values over the next 24 h. The results indicate that reserpine decreases LDL cholesterol in artery wall and heart and increases it in liver. These findings suggest that reserpine could find a new use as a cholesterol-lowering drug for the prevention of atherosclerosis.

Background —Antiplatelet agents are widely recognized for their efficacy in reducing the occurrence of vascular events in patients with atherothrombotic disease. Aspirin is currently considered to be the “reference standard” antiplatelet agent and is recommended by the American Heart Association for use in patients with a wide range of manifestations of cardiovascular disease on the basis of its high benefit-to-risk and benefit-to-cost ratios. Recently, clopidogrel (Plavix, Bristol-Myers Squibb Co), another antiplatelet agent, was approved by the Food and Drug Administration for many of the same indications as aspirin. Summary of Review —Because physicians will be faced with deciding whether to switch from the well-established practice of recommending aspirin for use in patients with atherothrombotic disease, both aspirin and clopidogrel are compared with respect to the primary factors that influence such decisions (ie, their relative efficacy, safety, cost, and convenience of use). Conclusions —Based on the available evidence, aspirin is preferred for the majority of stroke or myocardial infarction patients at risk of recurrent atherothrombotic events. Clopidogrel may, however, provide valuable therapeutic benefit over aspirin in patients with peripheral arterial disease and in stroke or myocardial infarction patients for whom aspirin treatment is contraindicated or for whom aspirin fails to achieve the desired therapeutic effect.

The on-line detection of emulsion polymerization processes by means of solid-state NMR spectroscopy is demonstrated for the first time using poly(butyl acrylate) as a model system. Relatively short time intervals are accessible via 1H detection while the use of 13C NMR spectroscopy results in an increased spectral resolution. Details of sample preparation and experimental techniques are given, while remaining artifacts of the preliminary results will be addressed in further investigations.

Objective To evaluate the effect of different 4-week doses of deoxycorticosterone acetate (DOCA), together with 0.9% sodium chloride in the drinking water (DOCA-salt) on the blood pressure and on the accumulation of low-density lipoprotein (LDL) and fibrinogen in artery walls and other tissues in conscious, unrestrained, normotensive Wistar-Kyoto rats. Methods The accumulation of LDL labelled with 125 I via the adduct tyramine cellobiose ([ 125 I]-TC-LDL) and of fibrinogen similarly labelled with 131 I ([ 131 I]-TC-fibrinogen) was compared in aortic walls, heart, liver, kidney, lung, skeletal muscle, and adrenal gland tissues during the final 24 h of a 4-week administration of DOCA-salt, with vehicle-salt and saline as controls. Results In control and vehicle rats the blood pressure did not change significantly during the last 5 days of treatment. Administration of DOCA-salt produced a dose-dependent increase in blood pressure during the same period. DOCA-salt administration increased LDL accumulation in the aorta and the heart and decreased LDL accumulation in the adrenal gland compared with those in rats of the control and vehicle groups. DOCA-salt administration did not affect fibrinogen accumulation significantly. Conclusion DOCA-salt treatment produces an increase in arterial blood pressure accompanied by an increase in LDL accumulation by the aortic wall and heart and a decrease in LDL accumulation by the adrenal gland. These observations raise the possibility that one mechanism by which hypertension affects atherosclerosis is through increased LDL accumulation in arterial walls.

Hypertension, low-density lipoprotein (LDL), and fibrinogen are risk factors for atherosclerosis. We investigated the effect of reducing blood pressure, by blocking the renin-angiotensin system (RAS), on the accumulation of these atherogenic proteins in arterial walls and other tissues in conscious, unrestrained, normotensive and hypertensive rats. The accumulation of LDL and fibrinogen, labeled respectively with 125 I and 131 I via the adduct tyramine cellobiose ([ 125 I]-TC-LDL and [ 131 I]-TC-fibrinogen) was compared in aortic walls, heart, lung, skeletal muscle, liver, kidney, and adrenal gland during the final 24 h of treatment with either the angiotensin-converting enzyme (ACE) inhibitor captopril or the angiotensin Il-receptor I (AT 1 ) antagonist losartan. In normotensive rats, the blood pressure was decreased only by losartan. In spontaneously hypertensive rats (SHRs), the blood pressure was decreased by both losartan and captopril. Captopril had no significant effect on the accumulation of LDL or fibrinogen by the aortic wall. Losartan significantly increased the accumulation of LDL by the aortic wall of SHRs. Neither agent produced any change in LDL or fibrinogen accumulation in any of the other tissues. These results indicate that although blocking the RAS at either the enzymic or receptor level produces significant decrease of blood pressure in hypertensive animals, only losartan has any affect on LDL accumulation by the aortic wall.

A new system for external counter pulsation is presented. The leg muscles are stimulated periodically by textile electrodes which produce diastolic extra-flows into the peripheral vascular system. In an initial clinical experiment advanced peripheral perfusion and reduced systematic vascular resistance could be demonstrated. Therefore the use in chronic heart failure therapy is suggested.

The inhomogeneous broadening of solid state 13 C spectra of glassy polymers and the configurational splitting observed in solution spectra are analyzed by a unifying approach. The method combines conformational statistics and ab initio IGLO calculations to obtain simulated solid state and solution spectra. A number of polymers of different structural classes are investigated, including poly(ethylene), atactic poly(propylene), poly(vinyl chloride), and poly(methyl methacrylate). For most systems a remarkable degree of agreement between simulation and experiment is achieved for both the solid state NMR and the configurational splitting. Furthermore, the influence of geometric parameters on the chemical shift, the validity of the γ-gauche effect, an MO analysis, and the role of the anisotropic part of the chemical shift tensor as a source of structural information are considered.

Recently, 31P two-dimensional (2D) NMR has been proposed as a powerful tool for direct investigations of the connectivities between the Qn units in glasses, i.e. the medium-range order. In this paper, the principles of these experiments and applications to both polycrystalline Mg2P2O7 and a Na2O-P205 glass are demonstrated, including a theoretical description and modelling of the polarization transfer between the two inequivalent phosphorus sites in the magnesium pyrophosphate.

31 P two-dimensional (2D) nuclear magnetic resonance (NMR) is proposed a powerful tool for direct investigation of the connectivities between like or different Q n units in glasses or the medium-range order. The entire experiment was carried out under conditions of fast magic angle sample spinning (MAS). The magnetization transfer was obtained by recoupling of the dipole-dipole interaction despite the fast MAS. The mixing time dependence of the 2D spectra for a binary Na 2 OP 2 O 5 glass suggests an almost regular alternation of Q 2 and Q 3 units for that glass.

The spread in 13 C-NMR chemical shifts in solid amorphous polymers is considered as a source of structural information. To this end, 13 C chemical shifts are calculated on an ab initio level for the central carbons of a tetramer model molecule, employing the IGLO method. Remarkable agreement between experimental and simulated spectra is obtained for polyisobutylene using the conformational statistics as obtained by Vacatello and Yoon. The observed experimental spread of ≃20 ppm for the CH 2 resonance is quantitatively reproduced in the calculations as is the γ-gauche effect. Correlations of the chemical shift with specific geometrical aspects as C-C bond lengths are established

Purpose For patients with purulent flexor tenosynovitis, our purpose was to (1) calculate the diagnostic accuracy of white blood count (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) for those who underwent surgical drainage, (2) to correlate these markers for those treated with antibiotics alone, and (3) to evaluate the accuracy of diagnosis for surgical patients. Methods A total of 82 consecutive patients (71 surgical and 11 nonsurgical) with flexor tenosynovitis were identified from orthopedic databases at 2 academic centers. We evaluated inflammatory markers (WBC, ESR, and CRP), radiographs, descriptions of surgical findings, and intraoperative cultures for all patients. For nonsurgical patients, we evaluated inflammatory markers for possible correlation with the presumed diagnosis of purulent flexor tenosynovitis. For surgical patients, sensitivity, specificity, positive predictive value, and negative predictive value were calculated individually for inflammatory markers. Results For nonsurgical patients, WBC, ESR, and CRP were elevated in 3 of 11 patients (27%), 6 of 8 patients (75%), and 6 of 7 patients (86%), respectively. For surgical patients, the intraoperative findings or cultures were consistent with infection in 69 of 71 cases (97%), whereas calcific tendinitis was diagnosed in 2 cases. Cultures were positive in 56 patients (79%). All 3 markers had a specificity and positive predictive value of 100%. For WBC, ESR, and CRP, respectively, the sensitivity was 39%, 41%, and 76% and the negative predictive value was 4%, 3%, and 13%. Conclusions Commonly used inflammatory blood markers (WBC, ESR, and CRP) may be helpful in diagnosing purulent flexor tenosynovitis. If the levels of any of these markers are elevated in patients suspected of having the diagnosis, the likelihood of infection is extremely high. However, with low negative predictive values, these markers cannot reliably rule out infection. Type of study/level of evidence Diagnostic III.

Cisplatin-resistant mouse fibrosarcoma cells, SSK-R, were isolated after short and low-dose drug treatment of the sensitive SSK cells in vitro. These SSK-R sublines exhibit up to sevenfold cisplatin resistance and are characterized mainly by an increased metallothionein content. Loss of drug resistance after about 140-180 cell divisions in drug-free medium coincides with loss of metallothionein content. The glutathione level is the same in the sensitive and resistant sublines; inhibition of glutathione synthesis by buthionine sulphoximine enhances the sensitivity in both cells lines by a factor of 2.7. The resistant sublines are not cross-resistant to radiation; a radiation exposure followed immediately by cisplatin treatment results in an additive effect. The cellular cisplatin content is slightly reduced in SSK-R2 cells and it remains at this level also upon loss of drug sensitivity.

AIMS: This work investigates the role of myoglobin in mediating the vascular relaxation induced by nitrite. Nitrite, previously considered an inert by-product of nitric oxide metabolism, is now believed to play an important role in several areas of pharmacology and physiology. Myoglobin can act as a nitrite reductase in the heart, where it is plentiful, but it is present at a far lower level in vascular smooth muscle-indeed, its existence in the vessel wall is controversial. Haem proteins have been postulated to be important in nitrite-induced vasodilation, but the specific role of myoglobin is unknown. The current study was designed to confirm the presence of myoglobin in murine aortic tissue and to test the hypothesis that vascular wall myoglobin is important for nitrite-induced vasodilation. METHODS AND RESULTS: Aortic rings from wild-type and myoglobin knockout mice were challenged with nitrite, before and after exposure to the haem-protein inhibitor carbon monoxide (CO). CO inhibited vasodilation in wild-type rings but not in myoglobin-deficient rings. Restitution of myoglobin using a genetically modified adenovirus both increased vasodilation to nitrite and reinstated the wild-type pattern of response to CO. CONCLUSION: Myoglobin is present in the murine vasculature and contributes significantly to nitrite-induced vasodilation.

Reduced endothelial surface charge markedly increases the rate of LDL uptake into blood vessels. Previous work in the streptozotocin diabetic rat reported reduced endothelial surface charge. We compared endothelial surface charge density in internal mammary artery rings from patients with type 2 diabetes (n = 12) and from non diabetic patients undergoing coronary artery bypass grafting, and observed a substantial (52%) reduction in the former. This was associated with higher plasma sialic acid levels suggesting loss of sialic acid residues from the glycocalyx as a possible mechanism.

Skeletal muscle is rarely a site of malignant metastasis; the molecular and cellular basis for this rarity is not understood. We report that myogenic cells exert pronounced effects upon co-culture with metastatic melanoma (B16-F10) or carcinoma (LLC1) cells including conversion to the myogenic lineage in vitro and in vivo, as well as inhibition of melanin production in melanoma cells coupled with cytotoxic and cytostatic effects. No effect is seen with non-tumorigenic cells. Tumor suppression assays reveal that the muscle-mediated tumor suppressor effects do not generate resistant clones but function through the down-regulation of the transcription factor MiTF, a master regulator of melanocyte development and a melanoma oncogene. Our findings point to skeletal muscle as a source of therapeutic agents in the treatment of metastatic cancers.