Association between the oxidative status, Vitamin D levels and respiratory function in asthmatic children.

AIM: We studied the relationship between plasma concentrations of oxidative system markers, vitamin D, and respiratory functions in children with asthma. MATERIALS AND METHODS: Ninety one children aged 6-17 years with stable asthma seen in the clinic had the serum concentrations of oxidative system markers [total antioxidant capacity (TAC), total oxidative status (TOS), paraoxonase-1 activity (PON-1), and 25-hydroxyvitamin D3] and respiratory functions were measured. RESULTS: There was no statistical correlation between TAC and age and FEV1. There was a significant positive correlation between TAC and 25(OH)D3 (r = 0.214, P = 0.021), TAC and TOS (r = 0.218, P = 0.007), TAC and PON-1 (r = 0.230, P = 0.028), TAC and IgE (r = 0.194, P = 0.033), and inverse correlation between TAC and PEF (r = -0.208, P = 0.024). In the backward multiple regression analysis, 25(OH)D3 (t = 2.613, P = 0.011), age (t = -2.158, P = 0.034), TOS (t = 2.158, P = 0.000), and OSI index (t = -13.859 P = 0.000) maintained an independent relationship with TAC (r = 0.858, r2 = 0.737, F = 21.436, P = 0.000). CONCLUSION: Oxidative stress correlates with the serum vitamin D concentrations. Clinical trials are required to confirm that increasing serum 25OHD may improve asthma control, as measured by clinical and oxidative stress markers.

Modern approaches to therapeutic oligonucleotide manufacturing.

Therapeutic oligonucleotides are a powerful drug modality with the potential to treat many diseases. The rapidly growing number of therapies that have been approved and that are in advanced clinical trials will place unprecedented demands on our capacity to manufacture oligonucleotides at scale. Existing methods based on solid-phase phosphoramidite chemistry are limited by their scalability and sustainability, and new approaches are urgently needed to deliver the multiton quantities of oligonucleotides that are required for therapeutic applications. The chemistry community has risen to the challenge by rethinking strategies for oligonucleotide production. Advances in chemical synthesis, biocatalysis, and process engineering technologies are leading to increasingly efficient and selective routes to oligonucleotide sequences. We review these developments, along with remaining challenges and opportunities for innovations that will allow the sustainable manufacture of diverse oligonucleotide products.

The convergence of computing and telecommunications systems.

Since we do not know of any completely workable solutions to the problems we have considered, we shall settle for a few general observations: 1) The public availability of socially useful computer communications services is and has been held back by legal battles that are now under way between the potential suppliers. 2) No simple resolution of these issues in the near future seems likely in view of the past conceptual separation of computers and communications doctrines. 3) The current policy is to determine whether the nation shall or shall not have certain computer communications services, by the adversary process. In this process, often only the voices of the loudest adversary suppliers are heard. 4) Although there can be no certainty that better alternatives cannot be devised, we believe that such a possibility assumes a higher probability if the key actors come from the technical community sectors more representative of the future consumers. 5) If we are to have the new services that are possible, we need an approach that makes better use of the technologists' dreams and goals rather than have future prospects excessively bound by lawyers paid to preserve the interests of their clients, irrespective of any secondary consequences. 6) We cannot be sanguine about this possibility, as technological statesmanship is too easily corrupted by the same forces that have placed us in this predicament. Furthermore, even if not corrupted, beneficial cooperation can too readily be regarded as simply collusion. 7) Although we do not have any clear answer, we do know that present approaches are not taking us where we want to go very rapidly and that alternative approaches should at least be considered.

Aqueous V(V)-peroxo-amino acid chemistry. Synthesis, structural and spectroscopic characterization of unusual ternary dinuclear tetraperoxo vanadium(V)-glycine complexes.

Vanadium participation in cellular events entails in-depth comprehension of its soluble and bioavailable forms bearing physiological ligands in aqueous distributions of binary and ternary systems. Poised to understand the ternary V(V)-H(2)O(2)-amino acid interactions relevant to that metal ion's biological role, we have launched synthetic efforts involving the physiological ligands glycine and H(2)O(2). In a pH-specific fashion, V(2)O(5), glycine, and H(2)O(2) reacted and afforded the unusual complexes (H(3)O)(2)[V(2)(O)(2)(mu(2):eta(2):eta(1)-O(2))(2)(eta(2)-O(2))(2)(C(2)H(5)NO(2))] x 5/4 H(2)O (1) and K(2)[V(2)(O)(2)(mu(2):eta(2):eta(1)-O(2))(2)(eta(2)-O(2))(2)(C(2)H(5)NO(2))] x H(2)O (2). 1 crystallizes in the triclinic space group P1, with a = 7.805(4) A, b = 8.134(5) A, c = 12.010(7) A, alpha = 72.298(9) degrees, beta = 72.991(9) degrees, gamma = 64.111(9) degrees, V = 641.9(6) A(3), and Z = 2. 2 crystallizes in the triclinic space group P1, with a = 7.6766(9) A, b = 7.9534(9) A, c = 11.7494(13) A, alpha = 71.768(2) degrees, beta = 73.233(2) degrees, gamma = 65.660(2) degrees, V = 610.15(12) A(3), and Z = 2. Both complexes 1 and 2 were characterized by UV/visible, LC-MS, FT-IR, Raman, NMR spectroscopy, cyclic voltammetry, and X-ray crystallography. The structures of 1 and 2 reveal the presence of unusual ternary dinuclear vanadium-tetraperoxo-glycine complexes containing [(V(V)=O)(O(2))(2)](-) units interacting through long V-O bonds and an effective glycinate bridge. The latter ligand is present in the dianionic assembly as a bidentate moiety spanning both V(V) centers in a zwitterionic form. The collective physicochemical properties of the two ternary species 1 and 2 project the chemical role of the low molecular mass biosubstrate glycine in binding V(V)-diperoxo units, thereby stabilizing a dinuclear V(V)-tetraperoxo dianion. Structural comparisons of the anions in 1 and 2 with other known dinuclear V(V)-tetraperoxo binary anionic species provide insight into the chemical reactivity of V(V)-diperoxo species in key cellular events such as insulin mimesis and antitumorigenicity, potentially modulated by the presence of glycinate and hydrogen peroxide.

Free propagation phase-contrast breast CT provides higher image quality than cone-beam breast-CT at low radiation doses: a feasibility study on human mastectomies.

In this study we demonstrate the first direct comparison between synchrotron x-ray propagation-based CT (PB-CT) and cone-beam breast-CT (CB-CT) on human mastectomy specimens (N = 12) including different benign and malignant lesions. The image quality and diagnostic power of the obtained data sets were compared and judged by two independent expert radiologists. Two cases are presented in detail in this paper including a comparison with the corresponding histological evaluation. Results indicate that with PB-CT it is possible to increase the level of contrast-to-noise ratio (CNR) keeping the same level of dose used for the CB-CT or achieve the same level of CNR reached by CB-CT at a lower level of dose. In other words, PB-CT can achieve a higher diagnostic potential compared to the commercial breast-CT system while also delivering a considerably lower mean glandular dose. Therefore, we believe that PB-CT technique, if translated to a clinical setting, could have a significant impact in improving breast cancer diagnosis.

Propagation-based x-ray phase-contrast tomography of mastectomy samples using synchrotron radiation.

PURPOSE: Propagation-based phase-contrast computed tomography (PB-CT) is a method for three-dimensional x-ray imaging that utilizes refraction, as well as absorption, of x rays in the tissues to increase the signal-to-noise ratio (SNR) in the resultant images, in comparison with equivalent conventional absorption-only x-ray tomography (CT). Importantly, the higher SNR is achieved without sacrificing spatial resolution or increasing the radiation dose delivered to the imaged tissues. The present work has been carried out in the context of the current development of a breast CT imaging facility at the Australian Synchrotron. METHODS: Seven unfixed complete mastectomy samples with and without breast cancer lesions have been imaged using absorption-only CT and PB-CT techniques under controlled experimental conditions. The radiation doses delivered to the mastectomy samples during the scans were comparable to those approved for mammographic screening. Physical characteristics of the reconstructed images, such as spatial resolution and SNR, have been measured and compared with the results of the radiological quality assessment of the complete absorption CT and PB-CT image stacks. RESULTS: Despite the presence of some image artefacts, the PB-CT images have outperformed comparable absorption CT images collected at the same radiation dose, in terms of both the measured objective image characteristics and the radiological image scores. The outcomes of these experiments are shown to be consistent with predictions of the theory of PB-CT imaging and previous reported experimental studies of this imaging modality. CONCLUSIONS: The results presented in this paper demonstrate that PB-CT holds a high potential for improving on the quality and diagnostic value of images obtained using existing medical x-ray technologies, such as mammography and digital breast tomosynthesis (DBT). If implemented at suitable synchrotron imaging facilities, PB-CT can be used to complement existing imaging modalities, leading to more accurate breast cancer diagnosis.

Optimization of propagation-based x-ray phase-contrast tomography for breast cancer imaging.

The aim of this study was to optimise the experimental protocol and data analysis for in-vivo breast cancer x-ray imaging. Results are presented of the experiment at the SYRMEP beamline of Elettra Synchrotron using the propagation-based phase-contrast mammographic tomography method, which incorporates not only absorption, but also x-ray phase information. In this study the images of breast tissue samples, of a size corresponding to a full human breast, with radiologically acceptable x-ray doses were obtained, and the degree of improvement of the image quality (from the diagnostic point of view) achievable using propagation-based phase-contrast image acquisition protocols with proper incorporation of x-ray phase retrieval into the reconstruction pipeline was investigated. Parameters such as the x-ray energy, sample-to-detector distance and data processing methods were tested, evaluated and optimized with respect to the estimated diagnostic value using a mastectomy sample with a malignant lesion. The results of quantitative evaluation of images were obtained by means of radiological assessment carried out by 13 experienced specialists. A comparative analysis was performed between the x-ray and the histological images of the specimen. The results of the analysis indicate that, within the investigated range of parameters, both the objective image quality characteristics and the subjective radiological scores of propagation-based phase-contrast images of breast tissues monotonically increase with the strength of phase contrast which in turn is directly proportional to the product of the radiation wavelength and the sample-to-detector distance. The outcomes of this study serve to define the practical imaging conditions and the CT reconstruction procedures appropriate for low-dose phase-contrast mammographic imaging of live patients at specially designed synchrotron beamlines.

The compromise of dynamic disulfide/thiol homeostasis as a biomarker of oxidative stress in trichloroethylene exposure.

In this study, we aimed to investigate disulfide/thiol homeostasis in trichloroethylene (TCE) exposure. The study was carried out in 30 nonsmoker TCE-exposed workers with a variety of occupations. Additionally, 30 healthy nonsmoker volunteers were recruited as the control group. TCE exposure was determined by measuring urinary trichloroacetic acid (TCA) concentration. Median urinary TCA levels of exposed workers (20.5 mg/L) were significantly higher than control subjects (5 mg/L). Thiol and disulfide concentrations were determined using a novel automated method. Disulfide/thiol ratio was significantly higher in the exposed group (p < 0.001). Thiol/disulfide homeostasis was found to be disturbed in TCE-exposed workers. We predict that in TCE-exposed workers this disturbance can be a therapeutic target, and the efficiency of the treatment can easily be monitored by the novel method we used.

Low airloss hydrotherapy versus standard care for incontinent hospitalized patients.

OBJECTIVE: To determine whether low airloss hydrotherapy reduces the incidence of new skin lesions associated with incontinence in hospitalized patients and results in more rapid healing of existing pressure sores compared with standard care. To assess subjectively patient and nursing satisfaction related to using low airloss hydrotherapy beds. DESIGN: Randomized, prospective, unblinded study. SETTING: Acute and chronic hospital wards. PARTICIPANTS: A total of 116 newly admitted, incontinent, hospitalized patients with and without existing pressure sores. INTERVENTION: Low airloss hydrotherapy compared with treatment on hospital beds and mattresses ordered by the patient's attending physician. MEASUREMENTS: Incidence rates of new skin lesion development, e.g., pressure sores, candidiasis, and chemical irritation; improvement in existing pressure sore size, volume, and status; subjective assessment of patient and nursing satisfaction. RESULTS: Possible hypothermia was identified in two patients during the first week of the study, and patient and nursing dissatisfaction with low airloss hydrotherapy remained high throughout the first months of the study. Therefore, two major modifications in the initial protocol were made: (1) increased patient temperature monitoring for hypothermia was initiated in Week 2 of the study and (2) increased staff resources for in-service training on bed use began in Week 18 of the study. After the latter change, 58 subjects were randomized to low airloss hydrotherapy and 58 to standard care. Subjects were old (median age > or = 80 years), and almost all were bedbound or nonambulatory. The median (range) length of follow-up for subjects in the treatment group was significantly shorter than for those in the control group (4 (1-60) days versus 6 (1-62) days, respectively, P = .017) because there were more dropouts from the treatment group (24 (36%) of 58 versus 2 (3%) of 58, P = .0001). The major reasons dropout occurred were patient or family dissatisfaction (12 (21%)), new or worsened skin lesions thought to be related to bed use (4 (7%)), and hypothermia < 97 degrees F (4 (7%)). The total cumulative incidence of new truncal skin lesions within 9 days of enrollment was greater in the treatment than in the control group (48% versus 14%, respectively, P < 0.01). Too few patients with existing pressure sores were treated for too short a period of time to assess the effect of low airloss hydrotherapy on pressure sore healing. Because only 10 patients treated on low airloss hydrotherapy beds were able to complete satisfaction surveys meaningfully, interpretation of these data is difficult. Only nine (21%) of 44 nurses subjectively reported overall satisfaction using the low airloss hydrotherapy bed. CONCLUSIONS: This study shows the value of a rigorously designed clinically based evaluation of a new product developed for older patients. The results of the study led to re-engineering of the prototype low airloss hydrotherapy bed as well as a change in marketing strategy. Studies of products targeted to the prevention and treatment of pressure sores in older patients should be undertaken before generalized marketing begins.

Novel strategies to construct the gamma-hydroxy lactone moiety of the CP molecules. Synthesis of the CP-225,917 core skeleton.

[formula: see text] The array of challenging structural lineaments embodied in the CP molecules (1 and 2, Figure 1) offers synthetic chemists uncharted realms of exploration and discovery. In this communication, we focus on the chemical hurdies posed by the gamma-hydroxy lactone moiety of these exciting targets. Thus, the examination of the general reactivity of these systems, the development of a novel tandem oxidation sequence to construct the gamma-hydroxy lactone moiety, and the successful construction of the complete polycyclic core of 2 (compound 28, Scheme 5) is enumerated within.

New synthetic technology for the synthesis of hindered alpha-diazoketones via acyl mesylates.

[formula: see text] A mild and reliable one-pot protocol for the elaboration of sterically demanding carboxylic acids into alpha-diazoketones via acyl mesylates has been developed. Aside from delineating the reaction parameters which render this strategy quite general for hindered carboxylic acids, we have directly proven the existence of the fleeting acyl mesylate group as the reactive species in these reactions and shed light onto the differing mechanisms which are operative in the activation of hindered and simple carboxylic acids with methanesulfonyl chloride.

[Abortion in relation to reproductive behavior and the outcome of the subsequent pregnancy]. / Interrupce ve vztahu k reprodukcnímu chování a výsledku bezprostredne následujícího tehotenství.

PIP: The authors submit the results of an analysis of a group of 6166 spontaneous abortions from the Gottwaldov district (1981-83). The abortions are frequently the result of an uncontrolled reproductive cycle, in particular its onset. A total of 33.1% of the abortions recorded in the history of those women studied was an interruption of their 1st pregnancy. Very often after the abortion there is an interval of less than 6 months followed by a conception -- 47.6% in women aged 18-19 years. An increased ratio of a new pregnancy within 6 months was recorded as well in women with abortions occurring in the 3rd pregnancy. In the group of women who did not plan for the birth of another child, 61.2% of the couples did not use contraceptives, 13.2% of the women became pregnant because of failed contraception, 16.3% admitted that they had failed to use contraception, and 9.3% reported ignorance with regard to contraception. Interruption of a previous pregnancy closely before the subsequent one increased the rate of complications in the latter (although to a lesser extent than reported in some sources). The risk is more marked in some defined age groups. Results do not advocate abortion as a means to regulate fertility but should spur experts to provide better education for parenthood and more intense effort directed towards development of better contraception. (author's modified)^ieng

[Spontaneous disintegration of the IUD in the uterus]. / Spontánní rozpad IUD in utero.

PIP: A 30 year old woman who had had 2 normal pregnancies and no abortions came to a clinic 4 years after the insertion of a DANA Super 2 IUD. During her last menstrual period, she found 2 pieces of plastic on her sanitary pad. She believed them to be pieces of her IUD, and X-ray examination of the lower abdomen confirmed that the IUD had fractured within her uterus. The remaining pieces of the IUD were removed, and the patient suffered no sustained damage or injury. The IUD probably shattered because of defects in the microstructure of the plastic used to make the device. The plastic is stressed during insertion and perhaps further stressed by uterine movements when in place. The suspected defects may have caused the device to shatter when exposed to these repeated stresses.^ieng

[The occupation of the pregnant woman in relation to the course and outcome of pregnancy]. / Zamestnání tehotné zeny ve vztahu k prubehu a výsledku tehotenství.

Some occupations are associated with an extra risk during pregnancy. Intensive action is not involved (the relative risk does not exceed the value of 2,000) but with regard to the number of women in these categories it is a significant extensive factor. Based on the results of an analysis of a group of all naturally terminated pregnancies in the district of Gottwaldov in 1981-1983 (6166 pregnancies), as compared with the mean an increased ratio of reproductive losses was recorded in charwomen, hairdressers, teachers, engineers with university education. Prematurity was recorded in particular in waitresses, shop-assistants, nurses, other health workers and women doctors. Workers on the whole have relatively favourable results, however, the risk in these occupation more frequently develops into actual failure of pregnancy (haemorrhage in the 1st trimester, imminent premature child birth). These workers are also more protected by legal leave after a previous childbirth, as compared with other occupations.

[Adverse effects of the work process in relation to pregnancy]. / Nekteré nepríznivé momenty pracovního procesu ve vztahu k tehotenství.

Some characteristics of the working activity of pregnant women were investigated during statistical analysis of data pertaining to 6166 naturally terminated pregnancies in the Gottwaldov district (1981-1983). The threatening element from the aspect of spontaneous abortions in the first trimester is work done during most of the shift in a standing position without movement. There also the highest incidence of small-for-age and hypotrophic foetuses was found. Work involving constant movement is a risk and may lead to premature delivery. Manipulation with loads threatens pregnancy by reproductive losses (in particular a higher incidence of haemorrhage during the first trimester) and by prematurity. Social tension at the place of work also threatens pregnancy - at conflict in work places a significantly increased risk was proved. It was also proved that it is important to respect medical recommendation to transfer pregnant women to other work. As to associated factors, commuting was investigated and its adverse effect is particularly apparent when the distance is more than 25 km.

[Position of patient-relevance to isotope nephrography in second half of pregnancy (author's transl)]. / Uber den Einfluss der Lage der Patientin bei Isotopennephrographie in der zweiten Hälfte der Schwangerschaft.

Diagnostic isotope nephrography of 63 women in the second half of pregnancy is reported in this paper. Positioning was changed for control checks, and major deviations were found to occur to the ING curve with patients in lateral position. There was, above all, an improvement in the excretion phase on the relieved side. Less variation was recorded from the secretion phase. Those findings should be taken into due consideration, particularly for diagnosis of ureter obstructions in advanced pregnancy. Lateral positioning is recommended for the above reasons also in cases of late gestosis, gestational cystopyelitis, and suspicion of intra-uterine retardation of foetal growth. Lateral positioning proved to be superior to genupectoral positioning. -- The above findings appear to provide additional evidence in support of a hypothetic proposition according to which mechanical factors are of sizeable importance to the genesis of urinary retention in advanced pregnancy. Therefore, no publication should be made without data on patient positioning.

[Our experiences with Mayer-Ringpessary in the prevention of premature labor (author's transl)]. / Uber unsere Erfahrungen mit dem Mayer-Ringpessar in der Prävention der frühzeitigen Geburt

After very good results with a new model of the Mayer-Ringpessary made of organic glass the authors used this "unbloody cerclage" as a method of choice with all patients in their district (180 000 inhabitants) with partus praematurus imminens. It is necessary controls to apply the method in stage of this complication in good-time. There were below 10% of immature children in 405 high risk patients and only 1,2% to 1500 g. They succeded to delay the delivery in more favourable time to shorten the hospitalisation and unability considerably. Perinatal mortality was also favourably influenced. The details are in tables.

[Isotope nephrography in the 2d half of pregnancy]. / Isotopennephrographie in der zweiten Hälfte der Schwangerschaft

166 Women were investigated after 26 weeks of pregnancy, divided into 4 groups (normal pregnancy, after urinary tract infection, with cystopyelitis and with toxemia). Renography is a very sensitive method. Only 6,6% women had bilateraly normal function. Unilateral pathology was detected more often on the right side (17,6% versus 2,9%) and the damage was on the right side also more intensive (30% versus 8%), and present as early as in the 7. to 8. month of pregnancy. The damage of the secretion phase of the renogram in pregnancy is mostly sequal of the disturbed drainage following compression of the ureter trough varicosal veins and the pregnant uterus.

[Interruption of second-trimester pregnancy through the extraovular instillation of hypertonic NaCl]. / Prerusení tehotenství druhého trimestru extraovulární instilací hypertonického NaCl

PIP: 30 women in the 12th week of pregnancy underwent abortion by means of an extraovular instillation of 200 ml of 20% NaC1. No grave complications were encountered. 1 woman suffered prolonged fever for 3 days, most likely caused by a slight endometritis, and another underwent failure of the method. It is recommended that abortion be undertaken as soon as possible, and should not be put off past the 16th week.^ieng