Sprouty2 is involved in male sex organogenesis by controlling fibroblast growth factor 9-induced mesonephric cell migration to the developing testis.
Fibroblast growth factor 9 (FGF9) signal has a role in organogenesis of the mammalian testis by controlling migration of mesonephric cells to the XY gonad, but neither it nor the FGF receptors is expressed sex-specifically. Of the Sprouty genes encoding antagonists of receptor tyrosine kinases including FGFr, mSprouty2 expression was confined to the developing testis and mesonephros. Gain of SPROUTY2 function in the male genital ridge and mesonephros malformed the vas deferens and epididymis, and diminished the number of seminiferous tubules and interstitium associating with reduced mesonephric cell migration and Fgf9 expression in embryonic testis, whereas exogenous FGF9 signaling recovered mesonephric cell migration inhibited by SPROUTY2. These phenotypes associated also with the decreased expression of Sox9, Desert hedgehog, Hsd3beta, Platelet/endothelial cell adhesion molecule, and alpha-smooth muscle actin, which are markers of the Sertoli, Leydig, endothelial, and peritubular myoid cells of the developing testis. Based on these data, we propose that the Sprouty proteins are involved normally in mediating the sexually dimorphic signaling of FGF9 and controlling cell migration from the mesonephros during testis development.


Primary Peritonitis-A Forgotten Entity.
Primary peritonitis is a rare phenomenon in modern antibiotic era. A case of pediatric primary peritonitis is presented here, in which a child presented with complaints of abdominal pain, vomiting for one day. Abdominal examination showed marked tenderness and guarding, diagnosis of appendicitis was made and laparoscopic appendectomy done. Later, ascitic fluid analysis and appendix histopathology proved it to be a case of primary peritonitis.


Purification and Partial Characterization of Potato (Solanum tuberosum) Invertase and Its Endogenous Proteinaceous Inhibitor.
Invertase plays an important role in the hydrolysis of sucrose in higher plants, especially in the storage organs. In potato (Solanum tuberosum) tubers, and in some other plant tissues, the enzyme seems to be controlled by interaction with an endogenous proteinaceous inhibitor. An acid invertase from potato tubers (variety russet) was purified 1560-fold to electrophoretic homogeneity by consecutive use of concanvalin A-Sepharose 4B affinity chromatography, DEAE-Sephadex A-50-120 chromatography, Sephadex G-150 chromatography, and DEAE-Sephadex A-50-120 chromatography. The enzyme contained 10.9% carbohydrate, had an apparent molecular weight of 60,000 by gel filtration, and was composed of two identical molecular weight subunits (M(r) 30,000). The enzyme had a K(m) for sucrose of 16 millimolar at pH 4.70 and was most stable and had maximum activity around pH 5. The endogenous inhibitor was purified 610-fold to homogeneity by consecutive treatment at pH 1 to 1.5 at 37 degrees C for 1 hour, (NH(4))(2)SO(4) fractionation, Sephadex G-100 chromatography, DEAE-Sephadex G-50-120 chromatography, and hydroxylapatite chromatography. The inhibitor appears to be a single polypeptide (M(r) 17,000) without glyco groups. The purified inhibitor was stable over the pH range of 2 to 7 when incubated at 37 degrees C for 1 hour.


Propofol in a modified cyclodextrin formulation: first human study of dose-response with emphasis on injection pain.
A new lipid-free preparation of propofol has been developed containing the drug, sulfobutylether ß-cyclodextrin and water. The primary objective of this study was to compare the effects of propofol in the lipid formulation with those of the new cyclodextrin formulation, particularly with regard to pain on injection. We hypothesized that the propofol in cyclodextrin would be associated with less pain on injection than propofol in lipid. The study was a single-center, double-blind, 2-period, randomized, dose-escalating study using a completely balanced cross-over design in healthy volunteers. Pain on injection was compared between propofol in cyclodextrin and propofol in lipid using subject and observer assessments of pain rated at several different time points. Five response variables to pain were analyzed. Propofol in cyclodextrin had significantly higher pain scores for all 5 variables. Other endpoints, including sedation, showed no difference. The propofol in cyclodextrin formulation failed to reduce the pain on injection associated with propofol.


Folding of the cerebral cortex in mammals. A scaling model.
A model of cortical folding in mammals is presented. The model consists of a cube, superimposed on which are straight close-packed gyri, running the length of the cube. The cortex is represented by a thin layer of constant thickness. It proves possible, by adjusting the length, height, and width of the 'gyri' and the thickness of the 'cortex', to obtain a reasonable fit to the available empirical data (which extend over three to four orders of magnitude in brain weight). The model directs attention to possible features of the macroscopic organization of the mammalian brain which are novel and hitherto unremarked.


Elucidation of the molecular mechanisms of anaplastic thyroid carcinoma by integrated miRNA and mRNA analysis.
To elucidate the complex molecular mechanisms of anaplastic thyroid carcinoma (ATC), the mRNA and miRNA expression profiles of ATC were systematically explored. A total of 55 common differentially expressed genes (DEGs) were obtained from two mRNA expression datasets including 23 ATC samples and 24 paired normal samples. Gene expression levels of three randomly selected DEGs, VCAN, COL5A1 and KCNJ16, were examined using RT-PCR in 10 ATC samples. Notably, the ATC and normal samples were clearly classified into two groups based on their common DEGs. Moreover 23 common DEGs, such as TG, NKX2-1, KCNJ16 and CTHRC1, were predicted to be the potential targets of 17 identified miRNAs in ATC. Meanwhile, several miRNA target genes were associated with biological processes related to tumor progression such as angiogenesis, cell migration or growth and potassium channel regulation. In summary, the poor prognosis of ATC is possibly caused via complex biological processes. Firstly, angiogenesis was activated by the high expression of CTHRC1, VCAN and POSTN, providing necessary nutrition for tumor cells. Then tumor distant metastasis was induced via stimulation of cell migration and cell growth or regulation of cell-cell interaction. Moreover, intracellular potassium concentration changes promoted ATC progression indirectly. Hence, identification of these critical DEGs was valuable in understanding the molecular mechanisms of ATC.


Combination of Inferior Vena Cava Diameter, Hepatic Venous Flow, and Portal Vein Pulsatility Index: Venous Excess Ultrasound Score (VEXUS Score) in Predicting Acute Kidney Injury in Patients with Cardiorenal Syndrome: A Prospective Cohort Study.
Fluid overload is deleterious in critically ill patients. It can lead to venous congestion, thereby increasing venous pressure, theoretically increasing the backpressure, and thereby reducing renal blood flow. Venous congestion thus can be an important contributor to acute kidney injury (AKI), with no validated tools to objectively identify venous congestion bedside. Patients above 18 years admitted in ICU with a provisional diagnosis of cardiorenal syndrome were included in the study. Those with inadequate window, inferior vena cava (IVC) thrombus, and known case of cirrhosis with portal hypertension were excluded from the study. Patients underwent ultrasound examination with serial determination till AKI resolved or patient is initiated on dialysis. Venous excess ultrasound score (VEXUS) comprising inferior vena cava, hepatic vein waveform, and portal vein pulsatility was assessed. Thirty patients were enrolled for the study. The mean age was 59.53 ± 16.47 with 21 (70%) males. Mean sequential organ failure assessment (SOFA) score was 5.03 ± 1.97. Fourteen patients (46.7%) were in AKI stage 1, while eight patients (26.7%) were in AKI stage 2 and stage 3 each. Twenty patients (66.7%) had VEXUS grade III. Resolution of AKI injury showed significant correlation with improvement in VEXUS grade (p value 0.003). Similarly, there was significant association between changes in VEXUS grade and fluid balance (p value 0.006). There was no correlation between central venous pressure (CVP), left ventricular function, and right ventricular function with change in VEXUS grade. The study shows that a combined grading of IVC, hepatic vein, and portal vein might reliably demonstrate venous congestion and aid in the clinical decision to perform fluid removal. Bhardwaj V, Vikneswaran G, Rola P, Raju S, Bhat RS, Jayakumar A, et al. Combination of Inferior Vena Cava Diameter, Hepatic Venous Flow, and Portal Vein Pulsatility Index: Venous Excess Ultrasound Score (VEXUS Score) in Predicting Acute Kidney Injury in Patients with Cardiorenal Syndrome: A Prospective Cohort Study. Indian J Crit Care Med 2020;24(9):783-789.


Characterization of Bacillus phage-K2 isolated from chungkookjang, a fermented soybean foodstuff.
An investigation of a virulent Bacillus phage-K2 (named Bp-K2) isolated from chungkookjang (a fermented soybean foodstuff) was made. Bp-K2 differed in infectivity against a number of Bacillus subtilis strains including starter strains of chungkookjang and natto, being more infectious to Bacillus strains isolated from the chungkookjang, but much less active against a natto strain. Bp-K2 is a small DNA phage whose genome size is about 21 kb. Bp-K2 is a tailed bacteriophage with an isometric icosahedral head (50 nm long on the lateral side, 80 nm wide), a long contractile sheath (85-90 nm × 28 nm), a thin tail fiber (80-85 nm long, 10 nm wide), and a basal plate (29 nm long, 47 nm wide) with a number of spikes, but no collar. The details of the structures of Bp-K2 differ from natto phage ϕBN100 as well as other known Bacillus phages such as SPO1-like or ϕ 29-like viruses. These data suggest that Bp-K2 would be a new member of the Myoviridae family of Bacillus bacteriophages.


The epileptology of William Aldren Turner.
William Aldren Turner (1864-1945), in his day Physician to the National Hospital, Queen Square, and to King's College Hospital, London, was one of the major figures in the world of epileptology in the period between Hughlings Jackson in the latter part of the 19th century and the advent of electroencephalography in the 1930s. Although he also made contributions to knowledge in other areas of neurology, and with Grainger Stewart wrote a competent textbook on that subject, Turner's main professional interest throughout his career seems to have been epilepsy. On the basis of a series of earlier, rather heavily statistical, personal publications dealing with various aspects of the disorder, he authored what became a well-accepted monograph entitled Epilepsy - a study of the idiopathic disorder, which appeared in 1907, and he also gave the 1910 Morison lectures in Edinburgh on the topic. His writings on epilepsy over a period of three decades consolidated knowledge rather than led to significant advances, but helped maintain interest in the disorder during a rather long fallow phase in the development of the understanding of its nature.


Gene expression patterns, and protein metabolic and histological analyses for muscle development in Peking duck.
In this study, we aimed to use duck breast muscle and leg muscle, the 2 main productive muscle organs, as a model to elucidate the molecular mechanism controlling how the 2 muscles have different deposition capabilities, and to analyze the mechanisms facilitating duck muscle development posthatching. Peking duck breast muscle and leg muscle were collected 3, 7, and 16 wk posthatching. The morphology of the myofibers was observed by paraffin sectioning the muscles. The expression of genes involved in protein metabolism [mammalian target of rapamycin (mTOR), RPS6-p70-protein kinase (S6K), forkhead box O1 (FoxO1), muscle RING finger 1 (MuRF1), and atrogin-1 (MAFbx)] was detected using real-time quantitative PCR and Western blot assays, and the results indicated that breast muscle had a stronger capacity for both protein synthesis and protein degradation compared with leg muscle. Satellite cell frequency declined during muscle development in both tissues, and the expression of Pax3/7, satellite cell marker genes, was not significantly different between breast muscle and leg muscle. No notable apoptosis was observed in either tissue. The results of this study suggest that protein metabolism signaling is the main reason promoting duck skeletal muscle mass gain.


Assessing Injury and Violence Prevention in North Carolina's Local Health Departments.
Injury and violence-related morbidity and mortality present a major public health problem in North Carolina. However, the extent to which local health departments (LHDs) engage in injury and violence prevention (IVP) has not been well described. One objective of the current study is to provide a baseline assessment of IVP in the state's LHDs, describing capacity, priorities, challenges, and the degree to which programs are data-driven and evidence-based. The study will also describe a replicable, cost-effective method for systematic assessment of regional IVP. This is an observational, cross-sectional study that was conducted through a survey of North Carolina's 85 LHDs. Representatives from 77 LHDs (91%) responded. Nearly one-third (n = 23; 30%) reported that no staff members were familiar with evidence-based interventions in IVP, and over one-third (n = 29; 38%) reported that their LHD did not train staff in IVP. Almost one-half (n = 37; 48%) had no dedicated funding for IVP. On average, respondents said that about half of their programs were evidence-based; however, there was marked variation (mean, 52%; standard deviation = 41). Many collaborated with diverse partners including law enforcement, hospitals, and community-based organizations. There was discordance between injury and violence burden and programming. Overall, 53% of issues listed as top local problems were not targeted in their LHDs' programs. Despite funding constraints, North Carolina's LHDs engaged in a broad range of IVP activities. However, programming did not uniformly address state injury and violence priorities, nor local injury and violence burden. Staff members need training in evidence-based strategies that target priority areas. Multisector partnerships were common and increased LHDs' capacity. These findings are actionable at the state and local level.


The protective effects of zinc in lead-induced testicular and epididymal toxicity in Wistar rats.
The aim of this study was to investigate the beneficial effects of zinc (Zn) in preventing lead (Pb)-induced reproductive toxicity in Wistar rats. The rats were divided into four groups, namely, control group, Pb group, Zn group, and Pb + Zn group. Animals were exposed to Pb (819 mg of Pb/L) or Zn (71 mg of Zn/L) or both through drinking water for 65 days. Rats exposed to Pb showed decreased weights of testes and accessory sex organs. Significant decrease in the testicular daily sperm production, epididymal sperm count, motility, viability, and number of hypoosmotic tail coiled sperm was observed in Pb-exposed rats. Testicular 3β- and 17β-hydroxysteroid dehydrogenase activity levels and circulatory testosterone levels were also decreased significantly in Pb-exposed rats. A significant increase in the lipid peroxidation products with a significant decrease in the activities of catalase and superoxide dismutase were observed in the testes and epididymis of Pb-exposed rats. Moreover, the testicular architecture showed lumens devoid of sperm in Pb-exposed rats. Supplementation of Zn mitigated Pb-induced oxidative stress and restored the spermatogenesis and steroidogenesis in Pb-exposed rats. In conclusion, cotreatment of Zn is effective for recovering suppressed spermatogenesis, steroidogenesis, elevated oxidative status, and histological damage in the testis of rats treated with Pb.


Near-infrared fluorescence imaging of murine atherosclerosis using an oxidized low density lipoprotein-targeted fluorochrome.
The aim of this study was to explore the feasibility of detecting plaques using an NIR797 fluorochrome-labeled, anti-oxLDL antibody (anti-oxLDL-NIR797) and near-infrared fluorescence (NIRF) imaging in a murine model of atherosclerosis. Anti-mouse oxLDL polyclonal antibodies were conjugated to NIR797 dyes to synthesis oxLDL-targeted NIRF probe. In situ and ex vivo NIRF imaging of the high-cholesterol diet-induced atherosclerotic lesions of apoE-/- mice (baseline) as well as ex vivo NIRF imaging in the progression and regression group (without or with atorvastatin treatment for another 8 weeks) were performed 24 h after an intravenous injection of 1 mg/kg of anti-oxLDL-NIR797, while phosphate-buffered saline (PBS) was used for the controls. The plaque areas were investigated using Oil Red O (ORO) staining. Aortas isolated from the apoE-/- mice 24 h post-injection exhibited a selective, strong, heterogeneous NIRF signal enhancement in the aortic root, arch, and bifurcation, whereas the PBS and competitive inhibition groups had limited NIRF signal changes (p < 0.05). There was a significant correlation between ORO staining and NIRF in the atherosclerotic aortas that received anti-oxLDL-NIR797. Immunofluorescence studies confirmed the colocalization of the oxLDL/macrophages and NIR797 fluorochromes. Furthermore, the atherosclerotic lesions of atorvastatin-treated mice showed reduced anti-oxLDL-NIR797 uptake and oxLDL expression. These results indicate that NIRF plaque imaging is feasible with an oxLDL-targeted NIRF probe. Thus, oxLDL-based molecular imaging of atherosclerotic plaques is feasible and may provide important methods for characterizing vulnerable plaques and monitoring the response to therapeutic interventions for atherosclerosis.


[Extraovarian peritoneal serous papillary carcinoma: studies of clinical and pathological features].
To study the clinicopathological features of extraovarian peritoneal serous papillary carcinoma (EPSPC). The clinical pictures and pathological characteristics of 10 cases of EPSPC admitted to our hospital from 1980 through 1994 were studied retrospectively. Meanwhile, control studies were performed for 5 cases of ovarian serous papillary carcinoma and 4 cases of malignant peritoneal methothelioma. The ages of the 10 patients were between 44 and 77. The bilateral overies and fallopian tubes were all normal. The histomorphology as examined by photomicroscope and ultrastructural electromicroscope, the histochemistry determined by periodic acid-schiff (PAS) and Alcian blue stain and the immuno-histochemistry detected by carcinoembryonic antigen (CEA), AE1 and AE3 monoclonal antibody assays all revealed no difference between EPSPC and ovarian serous papillary carcinoma. The same is true for those between EPSPC and malignant methothelioma of peritonium except that the Alcian blue stain result would turned to be negative from positive after digesting with hyaluronidase and the micro-villi are longer for malignant peritoneal methothelioma as compared with EPSPC. The pathohistogenicity of EPSPC is not from ovaries but the methothelium of peritoneum, so called the secondary Müllarian system.


Vapor-liquid nucleation of argon: exploration of various intermolecular potentials.
The homogeneous vapor-liquid nucleation of argon has been explored at T=70 and 90 K using classical nucleation theory, semiempirical density functional theory, and Monte Carlo simulations using the aggregation-volume-bias algorithm with umbrella sampling and histogram-reweighting. In contrast with previous simulation studies, which employed only the Lennard-Jones intermolecular potential, the current studies were carried out using various pair potentials including the Lennard-Jones potential, a modified Buckingham exponential-six potential, the Barker-Fisher-Watts pair potential, and a recent ab initio potential developed using the method of effective diameters. It was found that the differences in the free energy of formation of the critical nuclei between the potentials cannot be explained solely in terms of the difference in macroscopic properties of the potentials, which gives a possible reason for the failure of classical nucleation theory.


Clinical aspects of the use of dental adhesive materials in patients with chronic xerostomia.
Adhesives are commonly used by denture wearers to increase the retention and stability of the complete denture, to improve the chewing and masticatory abilities and to psychologically support the patient to make the complete denture more acceptable. Denture fixatives can be especially recommended for use and to aid retention for patients with dryness of the mouth, poor secretion of saliva and xerostomia (e.g. diabetes mellitus). Dental adhesives may be contaminated with bacteria, yeast and fungi during the manufacturing process, and they have been shown to initiate and promote microbial growth. Some products have been shown to release formaldehyde, which is cytotoxic to cell culture and fibroblasts and is a potent allergen. Patients with chronic xerostomia may use denture adhesives during the course of the treatment and disease. These patients are often immunocompromised, and microorganisms they are exposed to must be considered potential pathogens.


Agrochemical characterization of vermicomposts produced from residues of Palo Santo (Bursera graveolens) essential oil extraction.
Fruits of Palo Santo (Bursera graveolens) are used for essential oil extraction. The extraction process is very efficient, because up to 3% of the fresh fruits can be transformed into essential oil; however, a considerable amount of waste is concurrently produced (>97% of the fresh biomass). Recent developments in Ecuadorian policies to foster environmentally friendly agroforestry and industrial practices have led to widespread interest in reusing the waste. This study evaluated the application of four vermicomposts (VMs), which are produced from the waste of the Palo Santo fruit distillation in combination with other raw materials (kitchen leftovers, pig manure, goat manure, and King Grass), for agrochemical use and for carbon (C) and nitrogen (N) decomposition in two soils with different textures. The results showed that the vermicompost mixtures (VMM) were valuable for agricultural utilisation, because total N (min. 2.63%) was relatively high and the C/N ratio (max. 13.3), as well as the lignin (max. 3.8%) and polyphenol (max. 1.6%) contents were low. In addition, N availability increased for both soil types after the application of the VMM. In contrast, N became immobile during decomposition if the VM of the pure waste was added. This likely occurred because of the relatively low total N (1.16%) content and high C/N ratio (35.0). However, the comparatively low C decomposition of this VM type makes its application highly recommendable as a strategy to increase the levels of organic matter and C, as well as for soil reclamation. Overall, these results suggest that the residues of the Palo Santo essential oil extraction are a potential source for vermicompost production and sustainable agriculture.


A systematic review of complications in thoracic spine surgery for ossification of the posterior longitudinal ligament.
To answer two questions: (1) what are the common complications associated with surgery for thoracic myelopathy caused by ossification of the posterior longitudinal ligament, and (2) which surgical approach is safer with regard to the incidence of post-operative complications. Relevant literature searches were performed using the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, KoreaMed, and the Japan CentraRevuoMedicina. 15 studies met the inclusion criteria and were retrieved. They included a total of 595 patients, 39 % of whom were male and 61 % female. The mean patient age ranged from 52.6 to 60.9 years. The mean recovery rate from each individual study varied between 24.7 and 77.6 % and the pooled neurologic function recovery rate was 50.4 %. From these 15 studies, the mean complication rate was 39.4 %. By far, two complications were more common than the others: cerebrospinal fluid leakage (incidence rate 22.5 %) and post-operative neurologic deficit (incidence rate 13.9 %). 7.7 % of patients from the indirect decompression group experienced cerebrospinal fluid leakage, while it was reported in 25.6 % of those in the direct decompression group. Neurologic deficit was reported in 8.4 % of patients undergoing indirect decompression and 19.8 % of those undergoing direct decompression. Cerebrospinal fluid leakage and neurologic deficit were the two most common complications following surgical decompression of the thoracic spine with ossification of the posterior longitudinal ligament. Patients undergoing indirect decompression surgeries had significantly lower complication rates compared with those undergoing direct decompression surgeries.


Glucose conjugation of anthranilate by the Arabidopsis UGT74F2 glucosyltransferase is required for tryptophan mutant blue fluorescence.
Plant mutants with defects in intermediate enzymes of the tryptophan biosynthetic pathway often display a blue fluorescent phenotype. This phenotype results from the accumulation of the fluorescent tryptophan precursor anthranilate, the bulk of which is found in a glucose-conjugated form. To elucidate factors that control fluorescent tryptophan metabolites, we conducted a genetic screen for suppressors of blue fluorescence in the Arabidopsis trp1-100 mutant, which has a defect in the second enzymatic step of the tryptophan pathway. This screen yielded loss-of-function mutations in the UDP-glucosyltransferase gene UGT74F2. The bacterially expressed UGT74F2 enzyme catalyzed a conjugation reaction, with free anthranilate and UDP-glucose as substrates, that yielded the same fluorescent glucose ester compound as extracted from the trp1-100 mutant. These results indicate that sugar conjugation of anthranilate by UGT74F2 allows its stable accumulation in plant tissues. A highly related Arabidopsis enzyme UGT74F1 could also catalyze this reaction in vitro and could complement the ugt74F2 mutation when overexpressed in vivo. However, the UGT74F1 gene is expressed at a lower level than the UGT74F2 gene. Therefore, even though UGT74F1 and UGT74F2 have redundant conjugating activities toward anthranilate, UGT74F2 is the major source of this activity in the plant.


Spontaneous Rupture of the Gravid Uterus in a Postmenopausal Woman Receiving Fertility Treatment.
Uterine rupture is an uncommon obstetric emergency that is potentially fatal to the mother and fetus. Spontaneous rupture of the unscarred gravid uterus in postmenopausal women who achieve pregnancy through in vitro fertilization (IVF) has been infrequently described in the literature. We present the case of a 72-year-old postmenopausal woman, gravida 1 para 0, who conceived by donor oocyte IVF in Europe and subsequently suffered uterine rupture at 22 weeks gestation with large hemoperitoneum. The patient underwent emergent laparotomy, with successful repair of the uterine wall defects. Postmenopausal women face an increased risk of spontaneous uterine rupture and life-threatening bleeding, which is likely due to uterine atrophy and limited uterine capacity. Further research is needed to establish age-appropriate guidelines for selecting treatment candidates.


Differential mechanisms underlying responses of soil bacterial and fungal communities to nitrogen and phosphorus inputs in a subtropical forest.
Atmospheric nitrogen (N) deposition and phosphorus (P) addition both can change soil bacterial and fungal community structure with a consequent impact on ecosystem functions. However, which factor plays an important role in regulating responses of bacterial and fungal community to N and P enrichments remains unclear. We conducted a manipulative experiment to simulate N and P inputs (10 g N · m-2 · yr-1 NH4NO3 or 10 g P · m-2 · yr-1 NaH2PO4) and compared their effects on soil bacterial and fungal species richness and community composition. The results showed that the addition of N significantly increased NH4 + and Al3+ by 99.6% and 57.4%, respectively, and consequently led to a decline in soil pH from 4.18 to 3.75 after a 5-year treatment. P addition increased Al3+ and available P by 27.0% and 10-fold, respectively, but had no effect on soil pH. N addition significantly decreased bacterial species richness and Shannon index and resulted in a substantial shift of bacterial community composition, whereas P addition did not. Neither N nor P addition changed fungal species richness, Shannon index, and fungal community composition. A structural equation model showed that the shift in bacterial community composition was related to an increase in soil acid cations. The principal component scores of soil nutrients showed a significantly positive relationship with fungal community composition. Our results suggest that N and P additions affect soil bacterial and fungal communities in different ways in subtropical forest. These findings highlight how the diversity of microbial communities of subtropical forest soil will depend on future scenarios of anthropogenic N deposition and P enrichment, with a particular sensitivity of bacterial community to N addition.


Accumulation and autofluorescence of phagocytized rod outer segment material in macrophages and microglial cells.
To explore the ability of macrophages and microglial cells to phagocytize rod outer segments (ROSs) in a cell culture and characterize the resulting lipofuscin-like autofluorescence (LLAF). Either regular or modified ROSs or ROS components (11-cis-retinal, all-trans-retinal, lipids) were fed to macrophages and microglial cells for 4 days. Afterwards, autofluorescence was detected by fluorescence-activated cell sorting (FACS) at two different wavelengths (533 nm and 585 nm), and the cells were imaged by confocal and electron microscopy. Fluorescein isothiocyanate (FITC)-labeled ROSs were added to macrophage and microglial cell cultures for 1-24 h to determine the kinetics of phagocytosis in these cell lines. Feeding with different ROSs or ROS components led to a significant increase in LLAF in both microglia and macrophages. The 4-hydroxynonenal (HNE)-modified ROSs gave rise to the highest increase in LLAF at both 533 nm and 585 nm. Application of 11-cis-retinal or all-trans-retinal resulted in higher LLAF at 585 nm, compared to application of 9-cis-retinal or liposomes. Fluorescein isothiocyanate-labeled ROSs co-localized well with lysosomes in both types of cells. HNE-modified ROSs were phagocytized more rapidly by both types of cells, compared to unmodified ROSs. Electron microscopy demonstrated inclusion bodies containing whorls of membranes in all types of cells fed with ROSs. Both macrophages and microglia have the ability to phagocytize ROSs, and this results in increased autofluorescence. Oxidation of ROSs results in faster phagocytosis, higher levels of LLAF, and the appearance of more inclusion bodies inside the cells. Results from the present study suggest that both types of cells accumulate lipofuscin-like material under physiologically relevant conditions. Such accumulation could interfere with their ability to clear cellular debris and could be part of the pathogenetic mechanism for age-related macular degeneration and other lipofuscinopathies.


Patterns of compliance with once versus twice daily antihypertensive drug therapy in primary care: a randomized clinical trial using electronic monitoring.
To evaluate patterns of compliance with once versus twice daily administration of antihypertensive therapy (primary-outcome measure) and relevance of partial compliance for blood pressure control (secondary outcome measure). Multicentre, nonblinded, parallel group randomized design. Nonacademic primary care practices across Canada. Patients with mild essential hypertension (diastolic blood pressure 95 to 110 mmHg) of either sex (40% women), age 18 to 80 years (average 55 years). One hundred and ninety-eight patients were randomized to active treatment; 14 patients discontinued the study because of side effects. After a four-week placebo run-in period, patients were randomized to amlodipine 5 mg once-a-day or diltiazem slow release formulation (SR) 90 mg twice daily. Doses were increased to 10 mg and 180 mg to achieve sitting diastolic blood pressure of 90 mmHg or less. During 20 weeks on active treatment, compliance was assessed by pill counts and medication event monitoring system (MEMS), assessing percentage of prescribed doses taken, percentage days correct doses taken, percentage prescribed doses taken on time and blood pressure control as determined by office blood pressure measurement. The percentage prescribed doses taken (by either pill count of MEMS) showed a high degree of compliance, similar for the two treatments. However, other parameters of compliance were significantly better with once versus twice daily therapy. Partial compliance (less than 80% by pill count) led to less blood pressure control with the short acting diltiazem, but did not affect blood pressure control for the long acting amlodipine. Side effects profiles did not differ between the two treatments. Within the constraints of a clinical trial, hypertensive patients in primary care show a high degree of overall compliance with once or twice daily pill-taking, but patterns of pill-taking are more erratic with twice versus once daily medication, particularly in men. The results suggest that the negative consequences of partial compliance for blood pressure control can be offset by choosing agents with a duration of action well beyond the dosing interval.


Population analysis on the microcomputer: a system of software packages.
"This paper describes a system of versatile software packages that has been developed by the author for population analysis on IBM-compatible microcomputers using PC or MS DOS. The series includes programs for the production of life tables, the analysis of spatial patterns and temporal trends in mortality, population projections, stationary-state population simulations and demographic planning, cohort survival estimates of net migration, and the analysis of migration matrices. Each of the programs in the series is discussed in terms of its principal analytical features, associated conceptual and methodological issues, and potential applications. The programs are intended for use both as basic research and planning tools and as instructional aids in university-level-courses. The programs and related documentation are available on a set of four 360K diskettes." (SUMMARY IN FRE)


Oxide nanowire microfluidics addressing previously-unattainable analytical methods for biomolecules towards liquid biopsy.
Nanowire microfluidics using a combination of self-assembly and nanofabrication technologies is expected to be applied to various fields due to its unique properties. We have been working on the fabrication of nanowire microfluidic devices and the development of analytical methods for biomolecules using the unique phenomena generated by the devices. The results of our research are not just limited to the development of nanospace control with "targeted dimensions" in "targeted arrangements" with "targeted materials/surfaces" in "targeted spatial locations/structures" in microfluidic channels, but also cover a wide range of analytical methods for biomolecules (extraction, separation/isolation, and detection) that are impossible to achieve with conventional technologies. Specifically, we are working on the extraction technology "the cancer-related microRNA extraction method in urine," the separation technology "the ultrafast and non-equilibrium separation method for biomolecules," and the detection technology "the highly sensitive electrical measurement method." These research studies are not just limited to the development of biomolecule analysis technology using nanotechnology, but are also opening up a new academic field in analytical chemistry that may lead to the discovery of new pretreatment, separation, and detection principles.


The 6th nationwide anthropological survey of children and adolescents in the Czech Republic in 2001.
The 6th nationwide anthropological survey (NAS) of children and adolescents was carried out in the Czech Republic in 2001 to continue the series of surveys repeated at 10-year intervals since 1951 (with the participation of the Slovak Republic up to 1991). The major objective was to find out the following body measurements of children and adolescents: body height and weight, and head, arm, waist and hip circumferences. Questionnaires were used to find out the body measurements of parents (body height and weight) and some socio-economic characteristics of the child's family (number of siblings, education of parents, breast feeding duration, birth weight and length, child's physical activities, TV watching time, computer gaming time, etc.). A school children questionnaire focused on eating habits was also part of the survey in 2001. A total of 59,000 children aged 0.00 to 18.99 years, i.e. about 3% of the population of the same age range, were enrolled in the survey in 2001. The results obtained presented in diagrammatic and tabular forms are reference standards for monitoring growth of the Czech children and adolescents from birth to the age of 19 years. The survey revealed a substantial slowdown in the long-term trend in body height increase for both boys and girls. The most marked increase in the mean body height is currently recorded in boys at the prepubescent age while the pubescent girls show a practically zero increase for this parameter. A more marked increase in body height at the adult age is not expected any more, but the increase in body height and weight at the prepubescent age is likely to continue for some time. The 6th NAS showed a marked slow down to a stop in the trend in the mean body weight increase. No increase in the mean body weight has been recorded in pubescent girls since the 1970's and in pubescent and postpubescent boys since 1991. Nevertheless, the younger age groups, namely those of preschool and primary school children, continue to show increase in the mean body weight. The secular trend in body weight has been less pronounced compared to that in body height. The rates of overweight and obese children (as assessed by body mass index, BMI) have risen in most age groups of school children compared to those reported in 1991. In contrast, a slight decrease in the rate of overweight children can be seen in boys starting from the age of 16 years and in girls starting from the age of 13 years. The obesity prevalence rate is significantly higher in boys than girls. Statistical analysis confirmed a correlation between the BMI values in children and education of parents (the higher the education, the lower the rate of overweight children) and between the BMI values and the population size of the community where the child lives (the higher the population, the lower the prevalence rates of overweight and obesity). Single children suffer more frequently from overweight and obesity than those with siblings.


Hemodynamic assessment of the development and rupture of intracranial aneurysms using computational simulations.
Intracranial aneurysms manifest themselves as sacculations within a weakened region of the vessel wall and pose substantial neurological risks upon rupture. A primary factor in the development and rupture stages of an aneurysm is hemodynamics and its degrading effects on the aneurysm wall. Wall dynamics and hemodynamics within a fully developed aneurysm were investigated using computational simulation techniques. To study wall dynamics, the aneurysm was modeled as a thing spherical shell with linearly elastic and plastic (viscoelastic) wall behavior. The sensitivity of this model to the biophysical parameters which describe it will assist in the quantitative assessment of factors predisposing to aneurysm rupture and subarachnoid hemorrhage. Flow dynamics simulations were performed for spherical aneurysms with rigid walls. We observed the development and motion of an annular vortex within the lateral sacculation. We also simulated a ruptured aneurysm by placing a tear near the neck of the aneurysm. Flow patterns showed blood flowing out during the initial stages of the flow, but displayed an inflow of blood soon thereafter, as the internal pressure dropped. These results are substantiated by the clinical observations that turbulent flow is observed within the aneurysm as evidenced by reduced bruits.


Feasibility study of bioremediation of a drilling-waste-polluted soil: stimulation of microbial activities and hydrocarbon removal.
The objective of this study was to determine the feasibility of bioremediation as a treatment option for an aged and chronically polluted drilling waste soil located at the Southeast of Mexico. The polluted drilling-waste site with a mean total petroleum hydrocarbon concentration (TPHs) of 39,397 +/- 858 mg/kg was treated with one dose of a nutrient-surfactant commercial product at 40 mg/kg soil and two doses of H2O2 (50 and 100 mg H2O2/kg soil). In this study, the parameters that were monitored include soil respiration, heterotrophic and hydrocarbon-degrading bacteria as biological indicators, catalase and dehydrogenase activities, and TPHs degradation as decontamination parameters. The results demonstrated that the microbial activities can be stimulated in a polluted drilling-waste site by the addition of H2O2 and commercial product, thereby resulting in increasing TPHs degradation. These aspects must be taken into account when biodegradation studies involve the application of a commercial product.


Regulation of bone remodeling by vasopressin explains the bone loss in hyponatremia.
Although hyponatremia is known to be associated with osteoporosis and a high fracture risk, the mechanism through which bone loss ensues has remained unclear. As hyponatremic patients have elevated circulating arginine-vasopressin (AVP) levels, we examined whether AVP can affect the skeleton directly as yet another component of the pituitary-bone axis. Here, we report that the two Avp receptors, Avpr1α and Avpr2, coupled to Erk activation, are expressed in osteoblasts and osteoclasts. AVP injected into wild-type mice enhanced and reduced, respectively, the formation of bone-resorbing osteoclasts and bone-forming osteoblasts. Conversely, the exposure of osteoblast precursors to Avpr1α or Avpr2 antagonists, namely SR49059 or ADAM, increased osteoblastogenesis, as did the genetic deletion of Avpr1α. In contrast, osteoclast formation and bone resorption were both reduced in Avpr1α(-/-) cultures. This process increased bone formation and reduced resorption resulted in a profound enhancement of bone mass in Avpr1α(-/-) mice and in wild-type mice injected with SR49059. Collectively, the data not only establish a primary role for Avp signaling in bone mass regulation, but also call for further studies on the skeletal actions of Avpr inhibitors used commonly in hyponatremic patients.


Constraint-led changes in internal variability in running.
We investigated the effect of a one-time application of elastic constraints on movement-inherent variability during treadmill running. Eleven males ran two 35-min intervals while surface EMG was measured. In one of two 35-min intervals, after 10 min of running without tubes, elastic tubes (between hip and heels) were attached, followed by another 5 min of running without tubes. To assess variability, stride-to-stride iEMG variability was calculated. Significant increases in variability (36 % to 74 %) were observed during tube running, whereas running without tubes after the tube running block showed no significant differences. Results show that elastic tubes affect variability on a muscular level despite the constant environmental conditions and underline the nervous system's adaptability to cope with somehow unpredictable constraints since stride duration was unaltered.


Evaluation of a bone substitute covered with a collagen membrane for ridge preservation after tooth extraction. Clinical and tomographic randomized controlled study in humans.
To evaluate the use of a synthetic bone substitute covered with a collagen membrane for ridge preservation after tooth extraction, by clinical and tomographic analysis. Fifteen patients, presenting at least two maxillary anterior teeth indicated for extraction, were selected: in the test group (TG), post-extraction sockets were filled by a synthetic bone substitute; in the control group (CG), by blood clot. In both groups, the sockets were covered by a collagen membrane. Cone-beam computerized tomography (CBCT) scans were acquired immediately after and 6 months post-surgically, and horizontal and vertical dimensional bone changes were quantified. Transurgical clinical analysis presented no statistically significant differences between TG and CG (p > .05). CBCT intragroup evaluation presented statistically significant reduction for the buccal alveolar measurement (TG = 1.58 mm or 21.82%, and CG = 1.66 mm or 24.08%) and horizontal cervical measurement (TG = 0.55 mm or 8.30% and CG = 1.30 mm or 17.68%), and not significant for palatal alveolar measurement (TG = 0.44 mm or 3.42% and CG = 0.26 mm or 3.89%). For alveolar height and horizontal apical measurements, this decrease was significant only for the CG, with reductions of 1.03 mm and 0.50 mm, respectively, compared to a decrease of 0.57 mm and 0.19 mm for the TG. The intergroup analysis showed significant difference for cervical horizontal measurement after 6 months (p < .05). The results showed that the use of the bone substitute covered with a collagen membrane resulted in less changes in vertical and horizontal alveolar ridge dimensions than the collagen membrane alone.


Upregulation of cytosolic NADP+-dependent isocitrate dehydrogenase by hyperglycemia protects renal cells against oxidative stress.
Hyperglycemia-induced oxidative stress is widely recognized as a key mediator in the pathogenesis of diabetic nephropathy, a complication of diabetes. We found that both expression and enzymatic activity of cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) were upregulated in the renal cortexes of diabetic rats and mice. Similarly, IDPc was induced in murine renal proximal tubular OK cells by high hyperglycemia, while it was abrogated by co-treatment with the antioxidant N-Acetyl-Cysteine (NAC). In OK cells, increased expression of IDPc by stable transfection prevented hyperglycemia-mediated reactive oxygen species (ROS) production, subsequent cellular oxidative stress and extracellular matrix accumulation, whereas these processes were all stimulated by decreased IDPc expression. In addition, production of NADPH and GSH in the cytosol was positively correlated with the expression level of IDPc in OK cells. These results together indicate that upregulation of IDPc in response to hyperglycemia might play an essential role in preventing the progression of diabetic nephropathy, which is accompanied by ROS-induced cellular damage and fibrosis, by providing NADPH, the reducing equivalent needed for recycling reduced glutathione and low molecular weight antioxidant thiol proteins.


Influence of dyslipidemia and smoking on redox markers in humans--a critical study.
Experimental research indicates that oxidative processes play a role in susceptibility to a large number of diseases. A better understanding of the parameters affecting redox balance could delay and even prevent such processes. The present study aims to investigate blood parameters associated with antioxidant systems in a Portuguese population for the first time, taking into consideration gender, age range, lipid profile and smoking habits as influencing factors. One hundred and eighty-three healthy Portuguese subjects of both genders were recruited from the metropolitan area of Lisbon. The group consisted of individuals aged from 20 to 70 years, who gave their informed consent before participating in the study. All subjects were screened to determine eligibility, which was based on a clinical report. Subjects were considered eligible if they had no acute or chronic illness and were not taking any drugs or dietary supplements that could compromise the values of the studied parameters. The subjects were then divided into different subgroups according to gender, age range, lipid profile and smoking habits. Whole blood glutathione peroxidase activity and serum albumin, transferrin and uric acid were determined using commercially available kits. Superoxide dismutase activity in erythrocytes and thiobarbituric acid reactive substances in serum were measured using methods published elsewhere. Glutathione peroxidase activity was not affected by any of the studied variables, but superoxide dismutase activity decreased with smoking. Albumin levels remained unchanged under all conditions. Hyperlipidemia was associated with higher lipid peroxidation as well as higher uric acid levels. Gender was the strongest predictor for transferrin, total iron binding capacity and uric acid variations. Finally, a multivariate statistical model clearly separated genders and lipid profile and genders and smoking. The present study suggests that hyperlipidemia and smoking should be considered important selection criteria in epidemiological studies focusing on oxidative stress and on the atherosclerotic process.


Activation of bone marrow cells treated with Canova in vitro.
Canova is a Brazilian complex homeopathic medication produced from Aconitum, Thuya, Bryonia, Lachesis and Arsenicum. Previous studies demonstrated that Canova induces up-regulation in numbers of leukocytes. The bone marrow microenvironment is composed of growth factors, stromal cells, extracellular matrix, and progenitor cells that differentiate into mature blood cells. As it is the major site of blood cell formation, we studied in vitro Canova effects on bone marrow cells of mice. Swiss mouse femurs were dissected, cleaned, and the marrow was flushed. The cells were plated, treated or not, incubated for different times and processed for light, scanning electron, and confocal microscopy, and also flow cytometry. The treatment did not modify the expression of the analyzed surface markers or cytokine production. All microscopy techniques showed that a monocytic lineage (CD11b(+)) and stromal cells (adherent cells) were activated by treatment. Canova also increased cell clusters over adherent cells, suggesting proliferation areas.


Operation for acute peripheral arterial occlusion: is it still the gold standard?
Acute arterial ischemia secondary to peripheral arterial occlusion has been shown to cause severe morbidity and mortality. Debate continues about the best mode for initial therapy of patients presenting with acute limb ischemia (ALI). Surgery traditionally has been used as the sole mode of therapy. Since the introduction of catheter-directed thrombolysis (CDT), role of surgery as the "gold standard" has been questioned. In this report the authors review the role of surgery compared with CDT. They discuss the role of prompt diagnosis on the outcome of the intervention and the results of CDT compared with the surgical standard. The best therapy for ALI is the one that is instituted early; intervention should be tailored based on the initial clinical presentation, and surgery remains the gold standard with CDT, an adjunctive tool for the vascular surgeon dealing with acute peripheral arterial occlusion (PAO).


[SOP-surgical operation planning].
Our active research project DFG Eu-49/1-2 strives to the reconstruction of bone defects basing on the individual craniofacial implants prefabricated within the TICC-processing-chain. In cases of disease of the bone the defect is to plan and the bone has to be resected. The planning of the defect is done on CT- and CAD-data. The common visualisation of this different data-types (CT-data as pixel- or voxel-data on the one hand and CAD-data as geometry-data on the other hand) was not possible in the used application. The development of "Surgical Operation Planning" (SOP) results in an application between CT-visualisation and CAD-application and allows the common visualisation and planning for defect reconstructions.


Clinical, radiographic and functional efficacy of abatacept in routine care for rheumatoid arthritis patients: Abatacept Leading Trial for RA on Imaging Remission (ALTAIR) study.
To investigate the efficacy and safety of abatacept for treating patients with rheumatoid arthritis (RA) in routine clinical practice and to determine the prognostic factors affecting clinical outcomes. We performed a retrospective study of 194 RA patients treated with abatacept. Clinical outcomes at 1 year after the treatment were assessed. Joint damage was assessed by the van der Heijde-modified total Sharp score (mTSS). Of the 194 patients, abatacept was discontinued in 51 patients, resulting in a retention rate at week 52 of 73.7%. At week 52, 23.7% of patients achieved clinical remission (SDAI ≤3.3). Lower SDAI and higher RF titre at baseline were the prognostic factor for SDAI at 52 weeks. Structural remission (ΔmTSS ≤0.5) was achieved in 73.4% of patients. However, clinical relevant radiographic progression which was defined as an increase in ΔmTSS >3 in a year, occurred in 7.6% of patients. Likewise, rapid radiological progression, which was defined as an increase in ΔmTSS >5 in a year, was observed in 6.4% of patients. 16.5% of patients achieved comprehensive disease remission, which was defined as SDAI ≤3.3, HAQ-DI ≤0.5, ΔmTSS ≤0.5, while 22.4% of patients achieved comprehensive disease control (CDC), which was defined as SDAI ≤11.0, HAQ-DI ≤0.5, ΔmTSS ≤0.5. The present results confirm that abatacept is effective and safe in routine clinical practice. It is possible that abatacept is more effective in seropositive RA patients with significant immunological abnormality.


Hydrogen bond dynamics in heavy water studied with quantum dynamical simulations.
The structure and dynamics of the hydrogen-bond network in heavy water (D(2)O) is studied as a function of the temperature using quantum dynamical simulations. Our approach combines an ab initio-based representation of the water interactions with an explicit quantum treatment of the molecular motion. A direct connection between the calculated linear and nonlinear vibrational spectra and the underlying molecular dynamics is made, which provides new insights into the rearrangement of the hydrogen-bond network in heavy water. A comparison with previous calculations on liquid H(2)O suggests that tunneling does not effectively contribute to the dynamics of the water hydrogen-bond network above the melting point. However, the effects of nuclear quantization are not negligible at all temperatures and become increasingly important near the melting point, which is in agreement with recent experimental analysis of the structural properties of liquid water as well as of the proton momentum distribution in supercooled water.


Inhibition of cdk2 activating phosphorylation by mevastatin.
Phosphorylation of cdk2 on threonine 160 is essential for kinase activity. Mevastatin, an inhibitor of cholesterol synthesis, inhibits cell growth through inhibition of cdk2 and this has been suggested to be due to enhancement of p21 levels. In a prostate cancer cell line, PC3, mevastatin treatment led to elevated levels of p21 and caused a small increase in the p21 associated with cdk2. However, this increase in the associated p21 appeared out of proportion with the resulting dramatic inhibition of kinase activity. Using RNA interference we show that mevastatin inhibits cdk2 activity despite lack of induction of p21, p27, and p57. Instead the kinase was inhibited due to a decrease in activating phosphorylation. Phosphorylation of cdk2 from mevastatin-treated cells with exogenous cyclin-dependent kinase (cdk)-activating enzymes restored its functional activity. The only known mammalian cyclin H.cdk7.mat1 complex (cdk2-activating kinase, Cak), was not inhibited by mevastatin, suggesting either that a different CAK is responsible for cdk2 phosphorylation in vivo or that the regulation is at the level of substrate accessibility or of cdk2 dephosphorylation. These results suggest that mevastatin inhibits cdk2 activity in PC3 cells through the inhibition of Thr-160 phosphorylation of cdk2, providing a novel example of regulation of cdk2 at this level.


Delay in Seeking Health Care Services After Onset of Urethritis Symptoms in Men.
Symptom awareness, behavioral factors, and other barriers associated with timely sexually transmitted infection (STI) health care provision in men is not well studied. Men attending an STI clinic answered a questionnaire regarding their symptoms, sexual behavior, and sociodemographic and behavioral characteristics. Characteristics of symptomatic men were compared between those who did and did not delay seeking health care services. Delayed care seeking was defined as clinic attendance longer than 7 days after symptoms, whereas early care seeking was defined as clinic attendance of 7 days or less. Over a quarter (n = 43 [27.7%]) of men with urethritis symptoms (urethral discharge or dysuria) delayed seeking care for more than 7 days. Compared with men who sought treatment within 7 days, those that delayed care worried for longer periods that their symptoms were STI-related, were more likely to attempt self-treatment of STI symptoms, were more likely to continue engaging in sexual activity, and were less likely to use a condom during their last sexual encounter. Conversely, men that delayed care seeking were less likely to have urethral discharge on physical examination, to have 5 or more polymorphonuclear leukocytes, and to test positive for Neisseria gonorrhoeae. When compared with men that sought care earlier, men that delayed care seeking had fewer overall and new partners in the past 30 days. Our data suggest that over a quarter of men aware of STI symptoms delay seeking health services. Interventions that promote better patient understanding of the importance of symptom recognition and that facilitate timely access to care may provide new opportunities to reduce STI transmission.


Diffusion tensor imaging can be used to detect lesions in peripheral nerves in patients with chronic inflammatory demyelinating polyneuropathy treated with subcutaneous immunoglobulin.
Magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) has shown that fractional anisotropy (FA) is lower in peripheral nerves in chronic inflammatory demyelinating polyneuropathy (CIDP). We examined whether DTI correlates to muscle strength or impairment. MRI of sciatic and tibial nerves was performed on 3-T MR scanner by obtaining T2- and DTI-weighted sequences with fat saturation. On each slice of T2-weighted (T2w) and DTI, the tibial and sciatic nerves were segmented and served for calculation of signal intensity. On DTI images, pixel-by-pixel calculation of FA and apparent diffusion coefficient (ADC) was done. Muscle strength at knee and ankle was determined by isokinetic dynamometry and severity of CIDP by neuropathy impairment score (NIS). Fourteen CIDP patients treated with subcutaneous immunoglobulin were compared to gender- and age-matched controls. T2w values expressed as a nerve/muscle ratio (nT2w) were unchanged in CIDP versus controls 0.93 ± 0.21 versus 1.02 ± 0.21 (P = 0.10). FA values were lower in CIDP compared to controls 0.38 ± 0.07 versus 0.45 ± 0.05 (P < 0.0001), and ADC values were higher in CIDP versus controls 1735 ± 232 versus 1593 ± 116 × 10(-6) mm(2)/s (P = 0.005). In CIDP, FA values correlated to clinical impairment (NIS) (r = -0.57, P = 0.03), but not to muscle strength. FA value in the sciatic nerve distinguishes CIDP from controls with a sensitivity and a specificity of 92.9 %. CIDP patients have unchanged nT2w values, lower FA values, and higher ADC values of sciatic and tibial nerves compared to controls. FA values correlated to NIS but were unrelated to muscle strength. DTI of sciatic nerves seems promising to differentiate CIDP from controls.


Blue light-induced Absorbance Changes in Membrane Fractions from Corn and Neurospora.
Blue light-induced absorbance changes were measured from differentially centrifuged membrane fractions from dark-grown coleoptiles of Zea mays L., and mycelia from an albino mutant of Neurospora crassa. Actinic irradiation caused changes in absorbance consistent with a flavinmediated reduction of a b-type cytochrome. Both corn and Neurospora showed similar light-minus-dark difference spectra, dose response curves, and kinetics of dark recovery after irradiation. The photoreducible cytochrome system from Neurospora showed the same distribution as the activity of a sodium-stimulated adenosine triphosphatase, thought to be a plasma membrane marker, in differential centrifugation experiments. The fraction showing the absorbance change did not co-sediment with the mitochondria, nor with the endoplasmic reticulum. Comparison of absorption spectra of fully oxidized, partially reduced, and fully reduced preparations showed that approximately a 30% reduction of the cytochromes involved with the process was needed to obtain the light-induced absorbance changes.


Pyridine analogues of the antimetastatic Ru(III) complex NAMI-A targeting non-covalent interactions with albumin.
A series of pyridine-based derivatives of the antimetastatic Ru(III) complex imidazolium [trans-RuCl(4)(1H-imidazole)(DMSO-S)] (NAMI-A) have been synthesized along with their sodium-ion compensated analogues. These compounds have been characterized by X-ray crystallography, electron paramagnetic resonance (EPR), NMR, and electrochemistry, with the goal of probing their noncovalent interactions with human serum albumin (hsA). EPR studies show that the choice of imidazolium ligands and compensating ions does not strongly influence the rates of ligand exchange processes in aqueous buffer solutions. By contrast, the rate of formation and persistence of interactions of the complexes with hsA is found to be strongly dependent on the properties of the axial ligands. The stability of noncovalent binding is shown to correlate with the anticipated ability of the various pyridine ligands to interact with the hydrophobic binding domains of hsA. These interactions prevent the oligomerization of the complexes in solution and limit the rate of covalent binding to albumin amino acid side chains. Electrochemical studies demonstrate relatively high reduction potentials for these complexes, leading to the formation of Ru(II) species in aqueous solutions containing biological reducing agents, such as ascorbate. However, EPR measurements indicate that while noncovalent interactions with hsA do not prevent reduction, covalent binding produces persistent mononuclear Ru(III) species under these conditions.


A laser tracking and ranging system.
An engineering model of a pulsed optical radar was developed for NASA to monitor continually the position of an astronaut on the lunar surface. The system tracks and measures range to a cooperative target (retroreflector) up to a distance of 700 m with a range accuracy of +/-1 m and an angular accuracy of +/-1 mrad. The system also directs a TV camera at the astronaut. An optical radar was used because it does not require the large complex antenna system and target reflector of conventional rf radars. The system design, which features GaAs injection laser, small retroreflector target, and silicon photodiode receiver, was directed toward providing a compact, rugged, lightweight system with high accuracy and low power consumption.


Studies on the aminotransferases participating in the glycolate metabolism of the alga mougeotia.
Microbodies from Mougeotia spec., Strain 168.80 contain aminotransferases for conversion of glyoxylate to glycine and serine to hydroxypyruvate. Formation of glycine is possible at highest rates with alanine and glutamate as amino donors, whereas for deamination of serine, pyruvate and glyoxylate are the most convenient substrates. A serine hydroxymethyl-transferase was found exclusively in the mitochondrial fraction. There are indications that this enzyme is bound to the mitochondrial membranes. The activities of all transferases are increased under culture conditions stimulating the synthesis of glycolate.


ETV6-ARNT fusion in a patient with childhood T lymphoblastic leukemia.
The ETS variant gene 6 (ETV6) gene is located at 12p13, and is frequently involved in translocations in various human neoplasms, resulting in the expression of fusion proteins consisting of the amino-terminal part of ETV6 and unrelated transcription factors or protein tyrosine kinases. Leukemia with t(1;12)(q21;p13) was previously described in a 5-year-old boy with acute myeloblastic leukemia (AML-M2) who exhibited a novel ETV6-aryl hydrocarbon receptor nuclear translocator (ARNT) fusion protein. We herein report the case of a 2-year-old boy with T-cell lymphoblastic leukemia (T-ALL) harboring t(1;12)(q21;p13). Fluorescence in situ hybridization (FISH) with a ETV6 dual-color DNA probe revealed that the split signals of the ETV6 gene in 96.7% of bone marrow cells, indicating rearrangement of the ETV6 gene. Therefore, we performed a FISH analysis with bacterial artificial chromosome (BAC) probes containing the ARNT, BCL9, and MLLT11 genes located at 1q21, and these results indicated that the ARNT gene might be involved in the t(1;12)(q21;p13). Reverse transcriptase-polymerase chain reaction analysis disclosed the existence of a ETV6-ARNT fusion gene. To our knowledge, the current report is novel in its report of the ETV6-ARNT fusion in childhood T-ALL. The ETV6-ARNT fusion is associated not only with AML but also with T-ALL.


[Thrombolysis in Madrid: is there improvement in the 4 years temporal analysis?].
Thrombolysis in acute ischemic stroke (IS) is limited by the short time window. However, this can be improved with adequate coordination of all the professionals and procedures involved in acute stroke treatment. A multicenter, observational, prospective study conducted in IS patients treated with intravenous recombinant tissue plasminogen activator between January 2003 and May 2007 was performed. A descriptive analysis of epidemiologic and clinical variables was conducted. Temporal analysis of safety, efficacy and quality parameters was carried out with the Auto-Regressive Integrated Moving Average (ARIMA) (p, d, q) models. From January 2003 to 2007, 324 patients were included (56% males; median age: 65.6). A total of 53.6 % became independent at 3 months (score 0-2 on the Modified Rankin Scale). Mortality rate 3 months after treatment was 15.7% and 3.7% suffered symptomatic intracranial bleeding. The temporal analysis showed a significant increase of thrombolysis, from a mean of 2 procedures per month to 20 (p<0.0001). There was a significant increase in the percentage of 3-month independent patients (0.83% [ARIMA] (1, 0, 1) p<0.0001). Intravenous thrombolysis is a safe and effective procedure for the treatment of IS in the clinical practice. As the experience of all the professionals involved in IS treatment increases, the number of patients who receive iv rtPA increases, with better outcome. Temporal analysis by ARIMA models is useful in planning health policies.


Klebsiella oxytoca Complex: Update on Taxonomy, Antimicrobial Resistance, and Virulence.
Klebsiella oxytoca is actually a complex of nine species-Klebsiella grimontii, Klebsiella huaxiensis, Klebsiella michiganensis, K. oxytoca, Klebsiella pasteurii, Klebsiella spallanzanii, and three unnamed novel species. Phenotypic tests can assign isolates to the complex, but precise species identification requires genome-based analysis. The K. oxytoca complex is a human commensal but also an opportunistic pathogen causing various infections, such as antibiotic-associated hemorrhagic colitis (AAHC), urinary tract infection, and bacteremia, and has caused outbreaks. Production of the cytotoxins tilivalline and tilimycin lead to AAHC, while many virulence factors seen in Klebsiella pneumoniae, such as capsular polysaccharides and fimbriae, have been found in the complex; however, their association with pathogenicity remains unclear. Among the 5,724 K. oxytoca clinical isolates in the SENTRY surveillance system, the rates of nonsusceptibility to carbapenems, ceftriaxone, ciprofloxacin, colistin, and tigecycline were 1.8%, 12.5%, 7.1%, 0.8%, and 0.1%, respectively. Resistance to carbapenems is increasing alarmingly. In addition to the intrinsic blaOXY, many genes encoding β-lactamases with varying spectra of hydrolysis, including extended-spectrum β-lactamases, such as a few CTX-M variants and several TEM and SHV variants, have been found. blaKPC-2 is the most common carbapenemase gene found in the complex and is mainly seen on IncN or IncF plasmids. Due to the ability to acquire antimicrobial resistance and the carriage of multiple virulence genes, the K. oxytoca complex has the potential to become a major threat to human health.


Comparative Analysis of Transcriptomes of Macrophage Revealing the Mechanism of the Immunoregulatory Activities of a Novel Polysaccharide Isolated from Boletus speciosus Frost.
The mechanism of the immunoregulatory activities of polysaccharide is still not clear. Here, we performed the B-cell, T-cell, and macrophage cell proliferation, the cell cycle analysis of macrophage cells, sequenced the transcriptomes of control group macrophages, and Boletus speciosus Frost polysaccharide (BSF-1) group macrophages using Illumina sequencing technology to identify differentially expressed genes (DEGs) to determine the molecular mechanisms of immunomodulatory activity of BSF-1 in macrophages. These results suggested that BSF-1 could promote the proliferation of B-cell, T-cell, and macrophages, promote the proliferation of macrophage cells by abolishing cell cycle arrests in the G0/G1 phases, and promote cell cycle progression in S-phase and G2/M phase, which might induce cell division. A total of 12,498,414 and 11,840,624 bp paired-end reads were obtained for the control group and BSF-1 group, respectively, and they corresponded to a total size of 12.5 G bp and 11.8 G bp, respectively, after the low-quality reads and adapter sequences were removed. Approximately 81.83% of the total number of genes (8,257) were expressed reads per kilobase per million mapped reads (RPKM ≥1) and more than 1366 genes were highly expressed (RPKM >60) in the BSF-1 group. A gene ontology-enrichment analysis generated 13,042 assignments to cellular components, 13,094 assignments to biological processes, and 13,135 assignments to molecular functions. A Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the mitogen-activated protein kinase (MAPK) signaling pathways are significantly enriched for DEGs between the two cell groups. An analysis of transcriptome resources enabled us to examine gene expression profiles, verify differential gene expression, and select candidate signaling pathways as the mechanisms of the immunomodulatory activity of BSF-1. Based on the experimental data, we believe that the significant antitumor activities of BSF-1 in vivo mainly involve the MAPK signaling pathways. Boletus speciosus Frost-1 (BSF-1) could promote the proliferation of B-cell, T-cell, and macrophages, promote the proliferation of macrophage cells by abolishing cell cycle arrests in the G0/G1 phases, and promote cell cycle progression in S-phase and G2/M phase, which might induce cell divisionApproximately 81.83% of the total number of genes (8257) were expressed (reads per kilobase per million mapped reads [RPKM] =1) and more than 1366 genes were highly expressed (RPKM >60) in the BSF-1 groupA gene ontology-enrichment analysis generated 13,042 assignments to cellular components, 13,094 assignments to biological processes, and 13,135 assignments to molecular functionsA Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the mitogen-activated protein kinase signaling pathways are significantly enriched for DEGs between the two cell groups. Abbreviations used: BSF-1: Boletus speciosus Frost polysaccharide.


[Medicine and industry learning from each other].
This paper presents a comparative review of the quality control methods in the industry and health care system with emphasis placed on hospitals. These standards were applied for the first time in the medical sector in 1995 in German hospital, which then was given the quality certificate. According to experience the application of standards ISO 9000, 9001 and 9002 in the hospital requires certain modification because the quality control in the health care is targeted on the process of production and not only on the outcome of the provided service. Unfortunately in the countries of former Yugoslavia there is no greater interest yet.


CsRAV1 induces sylleptic branching in hybrid poplar.
• Sylleptic branching in trees may increase significantly branch number, leaf area and the general growth of the tree, particularly in its early years. Although this is a very important trait, so far little is known about the genes that control this process. • This article characterizes the Castanea sativa RAV1 gene, homologous to Arabidopsis TEM genes, by analyzing its circadian behavior and examining its winter expression in chestnut stems and buds. Transgenic hybrid poplars over-expressing CsRAV1 or showing RNA interference down-regulated PtaRAV1 and PtaRAV2 expression were produced and analyzed. • Over-expression of the CsRAV1 gene induces the early formation of sylleptic branches in hybrid poplar plantlets during the same growing season in which the lateral buds form. Only minor growth differences and no changes in wood anatomy are produced. • The possibility of generating trees with a greater biomass by manipulating the CsRAV1 gene makes CsRAV1 transgenic plants promising candidates for bioenergy production.


Prediction of fetal sex by amplification of fetal DNA present in cow plasma.
The aim of the present study was to predict fetal sex at different time points of gestation in cattle by detecting the fetal SRY gene in cow plasma. Plasma DNA was extracted from the blood samples of 110 pregnant cows during the gestational period of 30 to 242 days. Nested PCR was employed to detect the fetal SRY, which the male fetus carries exclusively, in cow plasma. The cows positive for SRY were predicted to carry male fetuses. The results showed that the fetal DNA from cow plasma was successfully amplified and that fetuses could be sexed with an overall accuracy rate of 100% (43/43) for males and 91.0% (61/67) for females and with accuracy rates of 100% (3/3) for males and 85.7% (12/14) for females at 30 EN 59 days of gestation and 100% (40/40) for males and 92.5% (49/53) for females at more than 2 months of gestation, respectively. This suggests that the molecular method developed here could be used in sex prediction for fetuses.


[A case of microscopic polyangitis presented with acute pericarditis].
We report a case of microscopic polyangitis presenting with acute pericarditis. A 75-year-old man, who had recurrent acute pericarditis, was referred by a cardiologist because of bilateral infiltrates in the chest radiograph, microhematuria and progressive renal failure. The test for MPO-ANCA was positive. Transbronchial and renal biopsies were compatible with microscopic polyangitis, showing alveolar hemorrhage and crescentic glomerulonephritis. After 3 days, intravenous methylpredonisolone was given, followed by oral prednisolone 40 mg/day, and the patient's radiographic infiltrates cleared and renal dysfunction improved. However, he died from opportunistic infection 109 days after the onset of treatment.


Considerations in compound database preparation--"hidden" impact on virtual screening results.
Structure-based virtual screening (SBVS) utilizing docking algorithms has become an essential tool in the drug discovery process, and significant progress has been made in successfully applying the technique to a wide range of receptor targets. In silico validation of virtual screening protocols before application to a receptor target using a corporate or commercially available compound collection is key to establishing a successful process. Ultimately, retrieval of a set of active compounds from a database of inactives is required, and the metric of enrichment (E) is habitually used to discern the quality of separation of the two. Numerous reports have addressed the performance of docking algorithms with regard to the quality of binding mode prediction and the issue of postprocessing "hit lists" of docked ligands. However, the impact of ligand database preprocessing has yet to be examined in the context of virtual screening and prioritization of compounds for biological evaluation. We provide an insight into the implications of cheminformatic preprocessing of a validation database of compounds where multiple protonated, tautomeric, stereochemical, and conformational states have been enumerated. Several commonly used methods for the generation of ligand conformations and conformational ensembles are examined, paired with an exhaustive rigid-body algorithm for the docking of different "multimeric" compound representations to the ligand binding site of the human estrogen receptor alpha. Chemgauss, a shapegaussian scoring function with intrinsic chemical knowledge, was combined with PLP as a consensus-scoring scheme to rank output from the docking protocol and enrichment rates calculated for each screen. The overheads of CPU consumption and the effect on relative database size (disk requirement) for each of the protocols employed are considered. Assessment of these parameters indicates that SBVS enrichments are highly dependent on the initial cheminformatic treatment(s) used in database construction. The interplay of SMILES representations, stereochemical information, protonation state enumeration, and ligand conformation ensembles are critical in achieving optimum enrichment rates in such screening.


Duration of sodium amytal effect: behavioral and EEG measures.
In performance of an intracarotid sodium amytal test duration of action is a critical factor since measurements obtained after cessation of action are invalid. Duration of action is often monitored by measuring handstrength contralateral to injection or by visual inspection of amytal-induced EEG slow waves ipsilateral to injection. We describe new objective methods of monitoring drug effect: quantified EEG and sensory discrimination. In a first study of patients with scalp electrodes, the two traditional and the two new measures were compared in 40 injections. Results indicated that the two EEG measures did not differ significantly and estimated a shorter drug effect than the two behavioral measures, which were also not significantly different. The two new measures had a smaller SD, indicating that they may be less erratic. In a second study of 14 patients, using intracerebral electrodes, we showed that slow waves in the frontocentral region lasted as long as the motor and sensory effects, but also that slow waves in the medial temporal region dissipated earlier than the motor and sensory deficits. Our results suggest that motor and sensory measures may overestimate the time in which valid testing can occur if hippocampal function is at issue.


A rare and particular form of goiter to recognize.
Dyshormonogenetic goiter is a rare cause of congenital hypothyroidism occurring due to a lack of enzymes necessary for the synthesis of thyroid hormones. It is morphologically characterized by architectural and cellular pleomorphism that may mimic thyroid malignancy and cause difficulties in differential diagnosis. We report a new case occurring in a 37-year-old male with history of hypothyroidism since the age of 6 years treated by L-thyroxin. He developed a progressively slow growing multinodular goiter and consulted for recent dyspnea. Computed tomography scan showed a multinodular plunging goiter with compression of the trachea and vessels in the left side. A total thyroidectomy was performed. Gross examination revealed an enlarged and multinodular thyroid gland, presenting hemorrhagic changes in the larger nodules. Histologically, the features were consistent with dyshormonogenetic goiter. The literature on the histopathology of dyshormonogenetic goiter is reviewed and clues to avoid inappropriate overdiagnosis of malignancy are given.


Detecting factor XIa in immune globulin products: Commutability of international reference materials for traditional and global hemostasis assays.
Activated coagulation factor XIa (FXIa) is an impurity and primary source of procoagulant activity in thrombosis-implicated immune globulin (IG) products. Several assays, of varying quality and precision are used to assess FXIa-like procoagulant activity in units relevant to their respective principles. To advance unified reporting, we sought to employ the World Health Organization reference reagents (RRs) to present the results of differing methodologies in units of FXIa activity and rank the sensitivity and robustness of these methodologies. RR 11/236 served as a calibrator in several FXIa-sensitive blood coagulation tests: two commercial chromogenic FXIa assays (CAs); a nonactivated partial thromboplastin time (NaPTT); an in-house fibrin generation (FG) assay; an in-house thrombin generation (TG) assay; and an assay for FXIa- and kallikrein-like proteolytic activities based on cleavage of substrate SN13a. Some assays were tested in either normal or FXI-deficient plasma. Each method demonstrated a sigmoidal dose-response to RRs. NaPTT was the least sensitive to FXIa and the least precise; our in-house TG was the most sensitive; and the two CAs were the most precise. All methods, except for SN13a, which is less specific for thrombotic impurities, gave comparable (within 20% difference) FXIa activity assignments for IG lots. Purified FXIa reference standards support quantitation of FXIa levels in IG products in all tested assay methodologies. This should help to standardize the measurement of thrombotic potentials in IG products and prevent products exhibiting high procoagulant activity from distribution for patient use. Further research is needed to address the effect of IG product-specific matrixes on assay performance.


Inhibition of phosphorus and water passage across intact roots by polyethylene glycol and phenylmercuric acetate.
Application of polyethylene glycol or phenylmercuric acetate to intact bean (Phaseolus vulgaris L., cv. Red Wade) roots inhibited passage of phosphorus across the roots to the xylem. The same results occurred for foliar application of phenylmercuric acetate when time was allowed for absorption and distribution of the chemical in the plant. For both chemicals the inhibition of phosphorus was proportional to or greater than any accompanying restriction on water flow across the root.


In vivo selection of randomly mutated retroviral genomes.
Darwinian evolution, that is the outgrowth of the fittest variants in a population, usually applies to living organisms over long periods of time. Recently, in vitro selection/amplification techniques have been developed that allow for the rapid evolution of functionally active nucleic acids from a pool of randomized sequences. We now describe a modification of the nucleic acid-evolution protocol in which selection and amplification take place inside living cells by means of a retroviral-based replication system. We have generated a library of HIV-1 DNA genomes with random sequences in particular domains of the TAR element, which is the binding site for the Tat trans-activator protein. This mixture of HIV genomes was transfected into T cells and outgrowth of the fittest viruses was observed within two weeks of viral replication. The results of this in vivo selection analysis are consistent with the notion that primary sequence elements in both TAR bulge and loop domains are critical for Tat-mediated trans-activation and viral replication.


A method for three-dimensional quantification of vascular smooth muscle orientation: application in viable murine carotid arteries.
When studying in vivo arterial mechanical behaviour using constitutive models, smooth muscle cells (SMCs) should be considered, while they play an important role in regulating arterial vessel tone. Current constitutive models assume a strictly circumferential SMC orientation, without any dispersion. We hypothesised that SMC orientation would show considerable dispersion in three dimensions and that helical dispersion would be greater than transversal dispersion. To test these hypotheses, we developed a method to quantify the 3D orientation of arterial SMCs. Fluorescently labelled SMC nuclei of left and right carotid arteries of ten mice were imaged using two-photon laser scanning microscopy. Arteries were imaged at a range of luminal pressures. 3D image processing was used to identify individual nuclei and their orientations. SMCs showed to be arranged in two distinct layers. Orientations were quantified by fitting a Bingham distribution to the observed orientations. As hypothesised, orientation dispersion was much larger helically than transversally. With increasing luminal pressure, transversal dispersion decreased significantly, whereas helical dispersion remained unaltered. Additionally, SMC orientations showed a statistically significant (p < 0.05) mean right-handed helix angle in both left and right arteries and in both layers, which is a relevant finding from a developmental biology perspective. In conclusion, vascular SMC orientation (1) can be quantified in 3D; (2) shows considerable dispersion, predominantly in the helical direction; and (3) has a distinct right-handed helical component in both left and right carotid arteries. The obtained quantitative distribution data are instrumental for constitutive modelling of the artery wall and illustrate the merit of our method.


Microbial alkaloid staurosporine induces formation of nanometer-wide membrane tubular extensions (cytonemes, membrane tethers) in human neutrophils.
In the present work, we demonstrate that microbial alkaloid staurosporine (STS) and Ro 31-8220, structurally related to STS protein kinase C inhibitor, caused development of membrane tubular extensions in human neutrophils upon adhesion to fibronectin-coated substrata. STS-induced tubular extensions interconnected neutrophils in a network and bound serum-opsonized bacteria Salmonella enterica serovar Typhimurium. The diameter of STS-induced extensions varied in the range 160-200 nm. The extensions were filled with cytoplasm and covered with membrane, as they included fluorescent cytoplasmic and lipid dyes. Neither protein kinase C inhibitors H-7 and bisindolylmaleimide VII, nor tyrosine protein kinase inhibitors tyrphostin AG 82 and genistein caused such extensions formation. Supposedly, STS induces membrane tubular extension formation promoting actin cytoskeleton depolymerization or affecting NO synthesis.


Efficacy of ketotifen in corticosteroid-dependent idiopathic anaphylaxis.
To assess the potential benefit of ketotifen in the treatment of patients with corticosteroid-dependent idiopathic anaphylaxis, ketotifen was administered in an open trial to nine patients with idiopathic anaphylaxis who required maintenance prednisone for control of their disease. A double-blind trial was not done for reasons of patient safety. After a period of management with prednisone and establishment of the minimal dose of prednisone that controlled idiopathic anaphylaxis, ketotifen was initiated and cautious reduction of prednisone was attempted. The prednisone requirement was not altered in two patients, but prednisone was either substantially reduced or terminated in seven patients. Of these seven, three patients developed recurrent symptoms of idiopathic anaphylaxis after tapering and discontinuation of ketotifen, and ketotifen had to be resumed. The statistical analysis of prednisone reduction was highly significant (P less than .004) and we conclude ketotifen was of significant benefit in seven of nine patients with corticosteroid-dependent idiopathic anaphylaxis.


Synthesis and magnetic behavior of the tetrahedral cage complex [(cyclen)4V4(CN)6]6+.
Reaction of [(cyclen)V(CF(3)SO(3))(2)](CF(3)SO(3)) with 4 equiv. of Et(4)N(CN) in DMF generates the seven-coordinate complex [(cyclen)V(CN)(3)], while a reaction employing just 1.5 equiv. produces a tetrahedral cage complex, [(cyclen)(4)V(4)(CN)(6)](6+), in which antiferromagnetic coupling leads to an S= 0 ground state.


Update: the radiographic features of pulmonary tuberculosis.
Pulmonary tuberculosis produces a broad spectrum of radiographic abnormalities. During the primary phase of the disease these include pulmonary consolidation (50%), which often involves the middle or lower lobes or the anterior segment of an upper lobe; cavitation (29%) or pneumatocele formation (12%); segmental or lobar atelectasis (18%); pleural effusion (24%); hilar and mediastinal lymphadenopathy (35%); disseminated miliary disease (6%); and a normal chest radiograph (15%). During the postprimary phase of the disease, common abnormalities include exudative and/or fibroproductive parenchymal densities (100%), predominantly in the apical and posterior segments of the upper lobes (91%); cavitation (45%) with bronchogenic spread of disease (21%); marked fibrotic response in the lungs (29%); and pleural effusion, empyema, and fibrosis (18%, 4%, and 41%, respectively). Upper-lobe masslike lesions are seen occasionally (7%); spontaneous pneumothorax and intrathoracic lymphadenopathy are rare (5% each). Common causes of a missed diagnosis of tuberculosis are (1) failure to recognize hilar and mediastinal lymphadenopathy as a manifestation of primary disease in adults, (2) exclusion of tuberculosis because disease predominates in or is limited to the anterior segment of an upper lobe or the basilar segment of a lower lobe, (3) overlooking of minimal fibroproductive lesions or reporting them as inactive, (4) failure to recognize that an upper-lobe mass surrounded by satellite fibroproductive lesions might be tuberculous, and (5) failure to consider healed sequelae of primary disease or a positive purified protein derivative skin test as contributory to identifying the patient's pulmonary disease.


A metronome for controlling the mean velocity during the bench press exercise.
Lifting velocity may have a great impact on strength training-induced adaptations. The purpose of this study was to validate a method including a metronome and a measurement tape as inexpensive tools for the estimation of mean lifting velocity during the bench press exercise. Fifteen subjects participated in this study. After determining their one repetition maximum (1RM) load, we estimated the maximum metronome rhythm (R) that each subject could maintain in the concentric phase for loads of 40 and 60% of 1RM. To estimate R, the 3 repetitions with highest concentric power, as measured by means of a linear encoder, were selected, and their average duration was calculated and converted to lifting rhythm in beats per minute (bpm) for each subject. The range of motion was measured using a regular tape and kept constant during all exercises. Subjects were instructed to begin with the barbell at arm lengths and lower it in correspondence with the metronome beep. They subsequently performed 5 repetitions at 3 different rhythms relative to R (50, 70, and 90% R) for each training load (40 and 60% of 1RM). A linear encoder was attached to the bar and used as a criterion to measure the vertical displacement over time. For each rhythm, the mean velocity was calculated with the metronome (time) and the reference distance and compared with that recorded by the linear encoder. The SEM for velocity between both testing methods ranged from 0.02 to 0.05 m.s (coefficient of variation, 4.0-6.4%; Pearson's correlation, 0.8-0.95). The present results showed that the use of a metronome and a measurement tape may be a valid method to estimate the mean velocity of execution during the bench press exercise. This simple method could help coaches and athletes achieve their strength training goals, which are partly determined by lifting velocity.


[Prenatal diagnosis of de novo complex balanced rearrangements in chromosomes 3,4, and 13] ].
A case of apparently balanced de novo complex chromosome rearrangement with three breaks found in foetus by amniotic fluid examination is described. Amniocentesis was indicated because of low AFP in maternal serum during the first pregnancy of 25-year-old healthy woman. Her family anamnesis as well as her husbands on was insignificant, chromosomes were normal. Fetal karyotype was 46,XY,t(3;13;4)(q26.2;q21.3;q12). To eliminate further cryptic aberrations the multicolor FISH technique was employed. The risk of serious inborn malformation in complex rearrangement with three breaks was estimated on the basis of literary data to be 10.5% (3.5% per each break). The couple decided to terminate the pregnancy. No distinct anomaly was found in the fetus. Only 12 prenatal diagnoses of the complex balanced chromosome rearrangements formed de novo can be found in the literature. Total risk of the serious malformation relating to that small group of described cases is rather high. Only substantial enlargement of the clinic may enable to use prenatal evaluation of each individual case according to the number of chromosomal breaks or according to other criteria with more accurate results.


Carbohydrate-deficient transferrin in serum in patients with liver diseases.
Carbohydrate-deficient transferrin (CDT) in serum was analyzed by isocratic microanion exchange chromatography at pH 5.65 followed by a transferrin radioimmunoassay in 102 patients with biopsy-verified liver diseases. CDT values were normal in all of the 87 nonalcohol-abusing patients irrespective of type or degree of liver disease. Thirteen of the 15 alcoholic patients (87%) with current abuse showed elevated CDT values while in abstaining alcoholics with remaining liver disease the values were normal. No correlations were found between CDT level and volume density of liver fibrosis or steatosis or values of a number of clinicochemical liver tests. The only significant correlation demonstrated was between CDT concentration and the level of present daily alcohol consumption in the alcoholic patients. These results indicate that CDT can be used as a marker of present but not previous alcohol abuse, even in patients with various liver diseases.


How are model protein structures distributed in sequence space?
The figure-to-structure maps for all uniquely folding sequences of short hydrophobic polar (HP) model proteins on a square lattice is analyzed to investigate aspects considered relevant to evolution. By ranking structures by their frequencies, few very frequent and many rare structures are found. The distribution can be empirically described by a generalized Zipf's law. All structures are relatively compact, yet the most compact ones are rare. Most sequences falling to the same structure belong to "neutral nets." These graphs in sequence space are connected by point mutations and centered around prototype sequences, which tolerate the largest number (up to 55%) of neutral mutations. Profiles have been derived from these homologous sequences. Frequent structures conserve hydrophobic cores only while rare ones are sensitive to surface mutations as well. Shape space covering, i.e., the ability to transform any structure into most others with few point mutations, is very unlikely. It is concluded that many characteristic features of the sequence-to-structure map of real proteins, such as the dominance of few folds, can be explained by the simple HP model. In analogy to protein families, nets are dense and well separated in sequence space. Potential implications in better understanding the evolution of proteins and applications to improving database searches are discussed.


The mentally retarded infant. Is placement feasible?
A 1968 questionnaire about placement resources for mentally retarded infants that was sent to public agencies in all 58 California counties showed:* Resources for counseling, placement, and financial aid for out-of-home placement are not uniformly available to all groups within the population.* Financial help with out-of-home placement of a member of a family that is not medically indigent may be available in less than one-fourth of the counties of the state.* Knowledge of resources is often inadequate. A family could be referred inappropriately from one agency to another.


[Hypertensive crises: prevalence and clinical aspects].
To analyze the prevalence and characteristics of patients with hypertensive crises and to know the clinical differences between patients with hypertensive urgencies and patients with hypertensive emergencies. Three-months prospective study in which all patients attended at the Emergency Department with an hypertensive crisis (arterial blood pressure of at least 210/120 mmHg) were included. From each patient, a clinical history, physical examination, eye fundus examination, blood analysis, electrocardiogram, and a chest X-ray were obtained. A total of 118 patients were included in the study, representing 0.65% of all attended emergencies. Twenty-two percent of them had an emergency hypertensive crisis. Coronary heart disease was the most common cause for this emergency crisis. Hypertension was unknown to 12.7% of patients and 12.6% of patients aware of their condition were not taking any medication. Twenty-four percent of patients were diabetic. Patients with hypertensive emergencies had more involvement of target organs. Twenty-four percent of crises resolved with no therapy, and captopril was the most commonly used drug. Hypertensive crises accounted for 0.65% of attended emergencies at our institution. Coronary heart disease was the most common condition for hypertensive emergencies. Patients with hypertensive emergencies had a more severe involvement of target organs. Twenty four percent of crisis resolved with rest alone.