Association of Urinary N-Acetyl-β-D-Glucosaminidase with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes Mellitus without Nephropathy.
Cardiovascular autonomic neuropathy (CAN) is a common microvascular complication of diabetes and related to albuminuria in diabetic nephropathy (DN). Urinary N-acetyl-β-D-glucosaminidase (uNAG) is a renal tubular injury marker which has been reported as an early marker of DN even in patients with normoalbuminuria. This study evaluated whether uNAG is associated with the presence and severity of CAN in patients with type 1 diabetes mellitus (T1DM) without nephropathy. This cross-sectional study comprised 247 subjects with T1DM without chronic kidney disease and albuminuria who had results for both uNAG and autonomic function tests within 3 months. The presence of CAN was assessed by age-dependent reference values for four autonomic function tests. Total CAN score was assessed as the sum of the partial points of five cardiovascular reflex tests and was used to estimate the severity of CAN. The correlations between uNAG and heart rate variability (HRV) parameters were analyzed. The association between log-uNAG and presence of CAN was significant in a multivariate logistic regression model (adjusted odds ratio, 2.39; 95% confidence interval [CI], 1.08 to 5.28; P=0.031). Total CAN score was positively associated with loguNAG (β=0.261, P=0.026) in the multivariate linear regression model. Log-uNAG was inversely correlated with frequency-domain and time-domain indices of HRV. This study verified the association of uNAG with presence and severity of CAN and changes in HRV in T1DM patients without nephropathy. The potential role of uNAG should be further assessed for high-risk patients for CAN in T1DM patients without nephropathy.


Failure of lactoperoxidase to iodinate specifically the plasma membrane of cucurbita tissue segments.
An attempt has been made to use lactoperoxidase-catalyzed iodination of excised Cucurbita hypocotyl hooks to monitor the distribution of plasma membrane fragments relative to that of phytochrome in particulate fractions from this tissue. Upon fractionation, the iodinated tissue yields a 20,000g pellet which contains 58% of the trichloroacetic acid-precipitable (125)I at a specific radioactivity 12 times that of the proteins in the supernatant. On sucrose gradients, the labeled fraction has a mean isopycnic density of 1.15 g . cm(-3). The distribution profile is distinct from that of the total particulate protein and does not coincide with either mitochondrial or endoplasmic reticulum markers. These observations satisfy operational criteria commonly accepted in other systems as indices of selective labeling of the cell surface. The sucrose gradient profiles of the phytochrome and (125)I in the 20,000g pellets are noncoincident. In the absence of more direct evidence, this is readily interpreted to indicate a lack of association of the pigment with the plasma membrane.Autoradiographic analysis indicates, however, that the (125)I is almost exclusively associated with an amorphous film (possibly phloem-exudate protein) overlying the cut cells at the point of prelabeling excision and along the outer physical surface of the hypocotyl cuticle. No evidence of plasma membrane labeling is apparent. The observed membrane-like behavior of the iodinated material upon cell fractionation is attributed to the preferential posthomogenization association of this material with a particular membrane fraction(s). These data indicate that in addition to the well recognized potential for spurious labeling of the internal cytoplasmic proteins of leaky cells, a further source of ambiguity in surface-labeling experiments should be considered. That is, the potential for labeling extracellular proteins of nonplasma membrane origin but with a capacity to become associated with membranes upon homogenization.


Free proximal cortical ulnar autograft for the treatment of distal radial osteosarcoma in a dog.
This report describes the use of a non-vascularized proximal cortical autograft from the ipsilateral ulna in limb-sparing surgery for the treatment of distal radial osteosarcoma. A pancarpal arthrodesis was performed to stabilize the site. Construct failure and probable local tumor recurrence were observed. The total survival time was 282 days.


A Circadian Rhythm in the Number of Daughter Cells in Synchronous Chlorella fusca var vacuolata.
Chlorella fusca var vacuolata cells were transferred to continuous darkness or weak light (0.07 watts per square meter) (both were called waiting time, WT) after a 12-hour light and 12-hour dark schedule. A daily dilution is performed at the end of the light/dark schedule, resulting in always the same average production of 18 autospores per mother cell. After 12 and 24 hours of WT in darkness, the production of autospores in a subsequent light/dark schedule was 50 and 100%, respectively. If the WT was performed in weak light (0.07 watts per square meter) the lowest production was obtained, independently of the length of WT. However, an interruption of this weak light by dark pulses (3 hours) increased the autospore production by an amount that depends upon the phase of the circadian rhythm, and varied up to 70% of the control (WT in permanent darkness). If the WT (total darkness) was interrupted by light pulses of 0.5 hour (white, same as used for growth), a phase response curve of productivity resulted. Pulses between the 12th and 18th hour of WT in darkness gave a 3-hour delay of maximum; later on pulses shifted the maximum autospore production 3 hours ahead.


The management of acute myocardial infarction--practical problems in implementing the evidence.
Cardiovascular disease is the leading cause of death in Europe. Acute myocardial infarction (AMI) is among the most common of its manifestations. Women and older patients are under-represented in most trials of treatment for AMI, as are those with significant co-morbidities. These patients also have a worse long term outcome after AMI. We sought to evaluate the management of AMI in a small non-academic general hospital. A review was performed of cases of AMI during 2000. Ninety-two cases were analysed, 69% were male. The mean age was 70 years. In-hospital mortality was 12%; 30-day mortality was 14%. There was no gender or age difference in mortality. Of thirty eligible patients, twenty-eight were thrombolysed (93%). Aspirin (81%) and beta-blocker (41%) prescription on discharge were below published European and American rates. Females were significantly less likely to receive aspirin or beta-blockers on discharge. Those aged 70 years or more were less likely to receive beta-blockers, statins or ACE inhibitors on discharge. Those with co-morbidities were less likely to receive beta-blockers or statins on discharge. This study highlights the difficulty in realising evidence based guidelines optimal management of AMI in clinical practice. While the outcome with regard to mortality is similar to national figures, there is a need to enhance care, with particular emphasis on secondary pharmacological measures prescribed on discharge.


Genome-wide identification and expression analysis of CIPK genes in diploid cottons.
Calcineurin B-like protein-interacting protein kinase (CIPK) plays a key regulatory role in the growth, development, and stress resistance of plants by combining with phosphatase B subunit-like protein. In the present study, CIPK genes were identified in the whole genomes of diploid cottons and their sequences were subjected to bioinformatic analyses. The results demonstrated that the CIPK gene family was unevenly distributed in two diploid cotton genomes. Forty-one CIPKs were identified in the D genome, mainly located on chromosomes 9 and 10, whereas thirty-nine CIPKs were identified in the A genome, mainly located on chromosomes 8 and 11. Based on the gene structures, CIPKs in cotton could be classified into two types: one that is intron-rich and the other that has few introns. Phylogenetic analysis revealed that the CIPK gene family members in cotton had close evolutionary relationships with those of the dicotyledonous plants, such as Arabidopsis thaliana and poplar. The analysis of transcriptome sequence data demonstrated that there were differences in gene expression in different tissues, indicating that the expression of the CIPKs in cotton had spatio-temporal specificity. The expression analysis of CIPKs under abiotic stresses (drought, salt, and low temperature) in different tissues at trefoil stage demonstrated that these stresses induced the expression of CIPKs.


Meiotic sex chromosome inactivation in male mice with targeted disruptions of Xist.
X chromosome inactivation occurs twice during the life cycle of placental mammals. In normal females, one X chromosome in each cell is inactivated early in embryogenesis, while in the male, the X chromosome is inactivated together with the Y chromosome in spermatogenic cells shortly before or during early meiotic prophase. Inactivation of one X chromosome in somatic cells of females serves to equalise X-linked gene dosage between males and females, but the role of male meiotic sex chromosome inactivation (MSCI) is unknown. The inactive X-chromosome of somatic cells and male meiotic cells share similar properties such as late replication and enrichment for histone macroH2A1.2, suggesting a common mechanism of inactivation. This possibility is supported by the fact that Xist RNA that mediates somatic X-inactivation is expressed in the testis of male mice and humans. In the present study we show that both Xist RNA and Tsix RNA, an antisense RNA that controls Xist function in the soma, are expressed in the testis in a germ-cell-dependent manner. However, our finding that MSCI and sex-body formation are unaltered in mice with targeted mutations of Xist that prevent somatic X inactivation suggests that somatic X-inactivation and MSCI occur by fundamentally different mechanisms.


What a few hairs can tell us about the resource use of giant armadillos.
Understanding of resource requirements of vulnerable species is key for conservation planning. Here, we used stable carbon (δ13 C) and nitrogen isotopes (δ15 N) of hair from giant armadillos (Priodontes maximus) to understand individual resource use. We collected hair from 19 giant armadillos analyzing 34 samples from the Brazilian Pantanal and compared the resource use between sexes and age classes. We also assessed the relationship of isotopic values with individuals' body mass and the habitat type used. We observed a wide variation in resource use by giant armadillos, showing that individuals consume prey that feeds on distinct resources and occupies different habitat types, indicating that there is individual variation in foraging behavior. Most giant armadillos presented a mixed diet (C3 /C4 resources, forests/open areas), but a quarter of individuals had strictly C4 diets (open areas). Males are more prone to forage on C4 resources, presenting an isotopic niche 2.6-times larger than that of females. Subadults presented diets more associated with habitats with high arboreal cover (C3 resources, forests), while adults foraged more in open areas (C4 resources). This result is mirrored by the positive relationship between δ13 C values and body mass, suggesting that larger giant armadillos tend to feed more in open areas. We observed that δ13 C values decreased as individuals increased the use of habitats with high arboreal cover. We stress the importance of conserving the natural mosaic in the Pantanal landscape for the species persistence, given that giant armadillos require all habitat types to fulfill their dietary, spatial, and developmental needs.


Satellite telemetry informs PCB source apportionment in a mobile, high trophic level marine mammal: the ringed seal (Pusa hispida).
Marine mammals are typically poor indicators of point sources of environmental contaminants as a consequence of their often complex feeding ecologies and extensive movements, all of which mask the contributions of specific inputs. The release of polychlorinated biphenyls (PCBs) by a military radar station into Saglek Bay, Labrador (Canada) has contaminated marine sediments, bottom-feeding fish, seabirds, and some ringed seals, but attributing the PCBs in the latter highly mobile animals to this source is exceedingly difficult. In addition to the application of such tools as stable isotopes (δ(15)N and δ(13)C) and univariate and multivariate statistical exploration of contaminant patterns and ratios, we used satellite telemetry to track the movements of 13 seals in their transient use of different feeding areas. Reduced size of home range and core area (i.e., areas of concentrated use), as well as increased time in coastal inlets, were important determinants of increased PCB concentrations in seals reflecting the contribution of Saglek Bay. Seals were classified into the same feeding groups using both space use and their contaminant burdens 85% of the time, highlighting the link between feeding ecology and exposure to PCBs. While the PCB source at Saglek provided a strong local signal in a remote environment, this first use of satellite telemetry demonstrates the utility of evaluating space-use strategies to better understand contaminant exposure, and more specifically the contribution of contaminant hotspots to mobile predators.


Phosphorylation of pRb: mechanism for RB pathway inactivation in MYCN-amplified retinoblastoma.
A small, but unique subgroup of retinoblastoma has been identified with no detectable mutation in the retinoblastoma gene (RB1) and with high levels of MYCN gene amplification. This manuscript investigated alternate pathways of inactivating pRb, the encoded protein in these tumors. We analyzed the mutation status of the RB1 gene and MYCN copy number in a series of 245 unilateral retinoblastomas, and the phosphorylation status of pRb in a subset of five tumors using immunohistochemistry. There were 203 tumors with two mutations in RB1 (RB1-/- , 83%), 29 with one (RB1+/- , 12%) and 13 with no detectable mutations (RB1+/+ , 5%). Eighteen tumors carried MYCN amplification between 29 and 110 copies: 12 had two (RB1-/- ) or one RB1 (RB1+/- ) mutations, while six had no mutations (RB1+/+ ). Immunohistochemical staining of tumor sections with antibodies against pRb and phosphorylated Rb (ppRb) displayed high levels of pRb and ppRb in both RB1+/+ and RB1+/- tumors with MYCN amplification compared to no expression of these proteins in a classic RB1-/- , MYCN-low tumor. These results establish that high MYCN amplification can be present in retinoblastoma with or without coding sequence mutations in the RB1 gene. The functional state of pRb is inferred to be inactive due to phosphorylation of pRb in the MYCN-amplified retinoblastoma without coding sequence mutations. This makes inactivation of RB1 by gene mutation or its protein product, pRb, by protein phosphorylation, a necessary condition for initiating retinoblastoma tumorigenesis, independent of MYCN amplification.


Low-risk metastatic gestational trophoblastic disease.
Low-risk metastatic gestational trophoblastic disease is almost uniformly curable with chemotherapy if the diagnosis is correct. Recent clinical investigations have focused on reducing the toxicity and cost of chemotherapy. This article discusses the diagnosis and current management.


Enhanced secretion of heterologous proteins in Pichia pastoris following overexpression of Saccharomyces cerevisiae chaperone proteins.
In Pichia pastoris, secretory proteins are folded and assembled in the endoplasmic reticulum (ER). However, upon introduction of foreign proteins, heterologous proteins are often retained in the cytoplasm or in the ER as a result of suboptimal folding conditions, leading to protein aggregation. The Hsp70 and Hsp40 chaperone families in the cytoplasm or in ER importantly regulate the folding and secretion of heterologous proteins. However, it is not clear which single chaperone is most important or which combination optimally cooperates in this process. In the present study we evaluated the role of the chaperones Kar2p, Sec63, YDJ1p, Ssa1p, and PDI from Saccharomyces cerevisiae. We found that the introduction of Kar2p, Ssa1p, or PDI improves protein secretion 4-7 times. In addition, we found that the combination chaperones of YDJ1p/PDI, YDJ1p/Sec63, and Kar2p/PDI synergistically increase secretion levels 8.7, 7.6, and 6.5 times, respectively. Therefore, additional integration of chaperone genes can improve the secretory expression of the heterologous protein. Western blot experiments revealed that the chaperones partly relieved the secretion bottleneck resulting from foreign protein introduction in P. pastoris. Therefore, the findings from the present study demonstrate the presence of a network of chaperones in vivo, which may act synergistically to increase recombinant protein yields.


Infectious Etiologies of Stroke.
Central nervous system (CNS) infections are a frequently underappreciated potential etiology of cerebrovascular disease. Highlighted in this review are a selection of infectious agents that lead to cerebrovascular complications through various mechanisms including multifocal vasculopathy, focal infiltrative vasculitis and vasospasm, and direct vessel wall invasion and thrombus formation. Diagnosis of stroke due to underlying CNS infection requires a high index of clinical suspicion and careful consideration of neuroimaging, serum, and cerebrospinal fluid studies in addition to a detailed history and neurologic examination. Prompt and targeted treatment is essential in these conditions, which frequently herald a poor prognosis. Specifically, cerebrovascular complications associated with varicella zoster virus, syphilis, tuberculosis, aspergillosis, and acute bacterial meningitis are addressed here in detail.


[Removal of SO2 from flue gas by water vapor DC corona discharge].
The influence of several factors on removal rate of SO2 from flue gas in unsaturated water vapor DC corona discharge was researched. Furthermore, the experiments of the removal rate of SO2 in pulsed discharge increased by water vapor DC corona discharge plasma were conducted. The experiment system is supplied with multi-nozzle-plate electrodes and the flow of simulated flue gas is under 70 m3/h. The results show that removal rate of SO2 can be improved by increasing the concentration of water vapor, intensity of electric field or decreasing flow of simulated flue gas. In unsaturated water vapor DC corona discharge, removal rate of SO2 can be improved by 10%, when NH3 is added as NH3 and SO2 is in a mole ratio of two to one, it can reach 60%. The removal rate of SO2 can be increased by 5% in pulsed corona discharge and reach above 90%.


[Evaluation of pharmacodynamic equivalence of glycerol trinitrate-containing sprays for oral administration with or without chlorofluorocarbons ].
Evaluation of Pharmacodynamic Equivalence of Glyceryl Trinitrate Sprays for Oral Application with or without Fluorochlorohydrocarbons. The pharmacodynamic equivalence of a fluorochlorohydrocarbons(FCH)-free vs a FCH-containing glyceryl trinitrate (NTG, CAS 55-63-0) spray was investigated. Three oral sprays were administered at 24 h intervals to 9 male and 6 female healthy subjects in a double-blind placebo-controlled period-balanced 3-way cross-over study design: treatment NT (FCH-free, NTG-containing spray, dose of 0.8 mg NTG), treatment NR (FCH- and NTG-containing spray, dose of 0.8 mg NTG) and treatment PL (placebo: FCH- and NTG-free spray, dose of 2 puffs). The treatments were administered after suitable preparation and under strict standardisation. Subsequently digital plethysmography (systolic a-wave, dicrotic b-wave and the c-incisura) was monitored for 2 h. After administration of the NTG-containing sprays (NR and NT) the median a-wave increased rapidly, the median c-incisura deepened and the median b-wave rose slightly. The time courses of these changes and those of the resulting b/a- and c/a-ratios were superimposable and clearly distinct from those after PL. On the basis of the analysis of variance of the response variables (Rmin: maximum drop, and A(0-60): the area under the time course during the first hour after dosing) of the c/a-ratio as change from the predosing baseline, the following point estimates and 90% confidence intervals (CI) were calculated for the true ratio of treatments NT/NR: 104.4%, CI: 88.3 to 120.5% for Rmin, and 101.4%, CI: 79.3 to 123.5% for A(0-60).(ABSTRACT TRUNCATED AT 250 WORDS)


Postoperative Pain Management in Pediatric Spinal Fusion Surgery for Idiopathic Scoliosis.
This article reviews and summarizes current evidence and knowledge gaps regarding postoperative analgesia after pediatric posterior spine fusion for adolescent idiopathic scoliosis, a common procedure that results in severe acute postoperative pain. Inadequate analgesia may delay recovery, cause patient dissatisfaction, and increase chronic pain risk. Despite significant adverse effects, opioids are the analgesic mainstay after scoliosis surgery. However, growing emphasis on opioid minimization and enhanced recovery has increased adoption of multimodal analgesia (MMA) regimens. While opioid adverse effects remain a concern, MMA protocols must also consider risks and benefits of adjunct medications. We discuss use of opioids via different administration routes and elaborate on the effect of MMA components on opioid/pain and recovery outcomes including upcoming regional analgesia. We also discuss risk for prolonged opioid use after surgery and chronic post-surgical pain risk in this population. Evidence supports use of neuraxial opioids at safe doses, low-dose ketorolac, and methadone for postoperative analgesia. There may be a role for low-dose ketamine in those who are opioid-tolerant or have chronic pain, but the evidence for preoperative gabapentinoids and intravenous lidocaine is currently insufficient. There is a need for further studies to evaluate pediatric-specific optimal MMA dosing regimens after scoliosis surgery. Questions remain regarding how best to prevent acute opioid tolerance, opioid-induced hyperalgesia, and chronic postsurgical pain. We anticipate that this timely update will enable clinicians to develop efficient pain regimens and provide impetus for future research to optimize recovery outcomes after spine fusion.


Whole-body magnetic resonance imaging.
Whole-body magnetic resonance imaging is a fast and accurate modality for the detection of disease throughout the entire body. Technical improvements including the availability of different high image quality MR sequences, the remote movement of the imaging table, and the use of specialized surface coils have rendered whole-body screening with MRI a feasible method. In this article we describe underlying techniques and report on first clinical experiences of whole-body magnetic resonance imaging as a staging and screening method. Furthermore, advantages and limitations compared with whole-body imaging based on computed tomography are discussed.


Micro-CLC as an interface between SLM extraction and CZE for enhancement of sensitivity and selectivity in bioanalysis of drugs.
This work demonstrates the high selectivity and sensitivity obtainable in bioanalysis using the supported liquid membrane (SLM) technique coupled on line with capillary zone electrophoresis (CZE) through a micro-column liquid chromatography (CLC) interface. The system utilizes two selective, sequential enrichment steps before the third analyte focusing and separation step with double-stacking CZE. The enantiomers of bambuterol in human plasma can be concentrated about 40,000 times (approx. 6 times by the SLM treatment, approx. 17 times by micro-CLC focusing, and approx. 400 times by double-stacking CZE) on their way through the system, and extremely high selectivity is obtained. Determinations in the subnanomolar region are achievable for the enantiomers despite relatively weak UV absorbance. Good performance of the entire procedure is demonstrated and a method to increase the sample throughput is presented.


Stem cell factor and stromal cell co-culture prevent apoptosis in a subculture of the megakaryoblastic cell line, UT-7.
The megakaryoblastic cell line, UT-7, is dependent for its growth upon interleukin-3 (IL-3), erythropoietin, or granulocyte-macrophage colony stimulating factor (GM-CSF). A subculture of this line can be maintained in recombinant human c-kit ligand [stem cell factor (SCF)] at 100 ng/ml without requirement for other growth factors. Removal of this subculture from SCF results in rapid loss of viability and decreased proliferation. Cells grown in SCF also can be maintained in GM-CSF but not vice versa. In this work, we have characterized the SCF dependence of this UT-7 subculture. Stem cell factor removal results in apoptosis and a decline in viability which can be restored partially by re-addition of SCF, GM-CSF, or co-culture with adherent marrow stromal cells. Apoptosis in the factor-starved UT-7 population has been documented by light microscopy, electron microscopy and DNA analysis, showing the typical 180 base pair laddering characteristic of apoptosis. To quantitate the degree of apoptosis in the cell populations, and to assess whether apoptosis decreased with re-exposure of starved cells to growth factors or stroma, we utilized flow cytometry. This confirmed that exposure of previously factor-starved cells to stroma decreased the percentage of cells undergoing apoptosis. Co-culture with an SCF-deficient murine stromal cell line was also able to prevent apoptosis, suggesting contribution of other stromal cell factors. Experiments performed using trans-well inserts which do not allow cell passage, showed greatest viability of cells in contact with stroma, but viability was also improved in cells cultured in the presence of, but not in contact with, stromal cells compared to those cultured above plastic, suggesting a role for soluble stroma-produced substances. These data demonstrate that SCF alone can prevent apoptosis in cells dependent upon its presence for proliferation. Also, marrow stromal cells can serve as a partial substitute for growth factor in the prevention of apoptosis in these cells, probably due to constitutive presentation of SCF and other hematopoietic growth factors in both soluble and surface-bound forms.


Leisure-time physical exercise: prevalence, attitudinal correlates, and behavioral correlates among young Europeans from 21 countries.
Increasing leisure time physical exercise is a major target of public health programs throughout the developed world, but few international comparisons of exercise habits among people from diverse cultures have been published. The objectives of this study were to assess the prevalence of exercise among young adults from 21 European countries, to analyze associations with health beliefs and risk awareness, and to investigate relationships among exercise, other health-related behaviors, and emotional well-being. The European Health and Behaviour Survey, a questionnaire survey of 7,302 male and 9,181 female university students ages 18-30 years from 21 countries, was analyzed. Age-adjusted prevalence of physical exercise in the past 2 weeks averaged 73.2% among men and 68.3% among women, but varied markedly from more than 80% to less than 60% across country samples. Beliefs in the health benefits of exercise were consistently associated with physical exercise, as was desire to lose weight. Awareness of the influence of exercise on heart disease averaged 52% among men and 54% among women, but was not strongly associated with engagement in exercise. Associations among exercise, lack of smoking, and sleep time were observed, but results for alcohol consumption were inconsistent. Social support and depression were independently associated with physical exercise. Physical exercise levels are highly variable across samples of relatively privileged young Europeans from different countries. Associations with other health behaviors and with emotional well-being suggest that regular physical exercise is consistent with a healthy lifestyle. Links with health beliefs are consistent despite sociocultural differences, but deficient knowledge of the health consequences of a sedentary lifestyle remains a cause for concern.


Star-shaped poly(styrene)-block-poly(4-vinyl-N-methylpyridiniumiodide) for semipermanent antimicrobial coatings.
Goal of the present work is to develop an antimicrobial coating that can be applied from an aqueous solution and resists short washing cycles, but can be rinsed off by thorough washing. To this end, a series of star-shaped polystyrene-block-poly(4-vinyl-N-methylpyridinium iodide) polymers are synthesized by anionic polymerization using a core-first approach. The optimal resulting polymers are applied as coatings on glass slides, showing high antimicrobial efficiency against Staphylococcus aureus as well as Escherichia coli. The coatings, characterized by atomic force microscopy and transmission electron microscopy, stay at the surface even after at least 20 flush-like washings with water, and retain their antimicrobial activity.


Anti-angiogenic therapies for children with cancer.
Tumor angiogenesis, i.e. the development of neovascularisation in and around solid tumors, plays a key role in the local and distant growth of cancer and anti-angiogenic treatments are now established strategies to treat cancer patients. Specific inhibitors of angiogenesis such as bevacizumab or receptor tyrosine kinase inhibitors targeting VEGFR or PDGFR are now in clinical trials and are being increasingly validated for the treatment of poor prognostic cancers. Other anti-angiogenic strategies such as cilengitide or metronomic chemotherapy (low-dose anti-angiogenic chemotherapy) have been developed to treat certain types of adult cancer. In children, the clinical potential of anti-angiogenic approach is still in an early stage of investigation. This review will focus on the role of angiogenesis in pediatric solid tumors and will describe the pre-clinical and clinical experience with several anti-angiogenic compounds as a potential treatment for children with cancer.


Thermography of the cardiovascular system.
The identification of vulnerable plaque is one of the primary goals in cardiology during the last years. Several techniques have been developed for the anatomic and functional assessment of atherosclerotic plaques. Thermography is a new method for the evaluation of the inflammatory process locally within the atherosclerotic plaque. Several animal and clinical studies demonstrated the value of thermography not only for the detection of inflamed atherosclerotic plaques, but its use in new fields like in the evaluation of inflammation in the coronary vascular bed and the cardiovascular system. This article reviews the developments and the clinical implications of thermography.


Full-frequency GW without frequency.
Efficient computer implementations of the GW approximation must approximate a numerically challenging frequency integral; the integral can be performed analytically, but doing so leads to an expensive implementation whose computational cost scales as O(N6), where N is the size of the system. Here, we introduce a new formulation of the full-frequency GW approximation by exactly recasting it as an eigenvalue problem in an expanded space. This new formulation (1) avoids the use of time or frequency grids, (2) naturally obviates the need for the common "diagonal" approximation, (3) enables common iterative eigensolvers that reduce the canonical scaling to O(N5), and (4) enables a density-fitted implementation that reduces the scaling to O(N4). We numerically verify these scaling behaviors and test a variety of approximations that are motivated by this new formulation. The new formulation is found to be competitive with conventional O(N4) methods based on analytic continuation or contour deformation. In this new formulation, the relation of the GW approximation to configuration interaction, coupled-cluster theory, and the algebraic diagrammatic construction is made especially apparent, providing a new direction for improvements to the GW approximation.


Validity and reliability of dental age estimation of teeth root translucency based on digital luminance determination.
In forensic anthropological casework, estimating age-at-death is key to profiling unknown skeletal remains. The aim of this study was to examine the reliability of a new, simple, fast, and inexpensive digital odontological method for age-at-death estimation. The method is based on the original Lamendin method, which is a widely used technique in the repertoire of odontological aging methods in forensic anthropology. We examined 129 single root teeth employing a digital camera and imaging software for the measurement of the luminance of the teeth's translucent root zone. Variability in luminance detection was evaluated using statistical technical error of measurement analysis. The method revealed stable values largely unrelated to observer experience, whereas requisite formulas proved to be camera-specific and should therefore be generated for an individual recording setting based on samples of known chronological age. Multiple regression analysis showed a highly significant influence of the coefficients of the variables "arithmetic mean" and "standard deviation" of luminance for the regression formula. For the use of this primer multivariate equation for age-at-death estimation in casework, a standard error of the estimate of 6.51 years was calculated. Step-by-step reduction of the number of embedded variables to linear regression analysis employing the best contributor "arithmetic mean" of luminance yielded a regression equation with a standard error of 6.72 years (p < 0.001). The results of this study not only support the premise of root translucency as an age-related phenomenon, but also demonstrate that translucency reflects a number of other influencing factors in addition to age. This new digital measuring technique of the zone of dental root luminance can broaden the array of methods available for estimating chronological age, and furthermore facilitate measurement and age classification due to its low dependence on observer experience.


The US National Cancer Institute's natural products repository; origins and utility.
The US National Cancer Institute's natural products collection program has been running since 1986 and over the years the materials collected and processed have been stored in a repository that as a result of initial planning, has permitted the establishment of a national resource that is now being utilized as a drug discovery tool for any disease of interest to the NIH by researchers world-wide. This paper describes the history of the program.


Are Future Doctors Taught to Respond to Intimate Partner Violence? A Study of Australian Medical Schools.
Intimate partner violence (IPV) is a leading cause of morbidity and mortality among women of childbearing age. This study aimed to describe delivery of IPV education in Australian pre-vocational medical degrees, and barriers and facilitators influencing this delivery. Eighteen Australian medical schools offering pre-vocational medical degrees were identified. Two were excluded as they had not finalized new curricula. One declined to participate. At least one staff member from each of the remaining 15 schools completed a telephone survey. Main outcome measures included whether IPV education was delivered within the degree, at what stage, and whether it was compulsory; mode and number of hours of delivery; and barriers and facilitators to delivery. Twelve of the medical schools delivered IPV education (median time spent per course = 2 hr). IPV content was typically included as part of Obstetrics and Gynecology or General Practice curriculum. Barriers included time constraints and lack of faculty commitment, resources, and funding. The two schools that successfully implemented a comprehensive IPV curriculum used an integrated, advocacy-based approach, with careful forward planning. Most Australian pre-vocational medical students receive little or no IPV education. The need remains for a more consistent, comprehensive approach to IPV education in medical degrees.


Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association.
Congenital abnormalities of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease and they are the most frequent cause of end-stage renal disease in children in the US. However, its genetic etiology remains mostly elusive. VACTERL association is a rare disorder that involves congenital abnormalities in multiple organs including the kidney and urinary tract in up to 60% of the cases. By homozygosity mapping and whole-exome resequencing combined with high-throughput mutation analysis by array-based multiplex PCR and next-generation sequencing, we identified recessive mutations in the gene TNF receptor-associated protein 1 (TRAP1) in two families with isolated CAKUT and three families with VACTERL association. TRAP1 is a heat-shock protein 90-related mitochondrial chaperone possibly involved in antiapoptotic and endoplasmic reticulum stress signaling. Trap1 is expressed in renal epithelia of developing mouse kidney E13.5 and in the kidney of adult rats, most prominently in proximal tubules and in thick medullary ascending limbs of Henle's loop. Thus, we identified mutations in TRAP1 as highly likely causing CAKUT or VACTERL association with CAKUT.


Does lactobionic acid affect the colloidal structure and skin moisturizing potential of the alkyl polyglucoside-based emulsion systems?
Moisturizing creams are the most prescribed products in dermatology, essential in maintaining healthy skin as well as in the topical treatment of some diseases. The irritation potential of commonly used emulsifiers and moisturizing ingredients, but also their mutual interactions, could affect the functionality and safety of those dermopharmaceutics. The aim of this study was to promote moisturizing alkyl polyglucoside (APG)-based emulsion as vehicle for lactobionic acid (LA), advantageous representative of the alphahydroxyacids (AHAs)-multifunctional moisturizers, assessing the safety for use (in vitro acute skin irritation test using cytotoxicity assay compared with in vivo data obtained using skin bioengineering methods) and in vivo moisturizing capacity (bioengineering of the skin). In order to investigate possible interactions between APG mild natural emulsifier-based emulsion and LA, a deeper insight into the colloidal structure of the placebo and the emulsion with LA was given using polarization and transmission electron microscopy, rheology, thermal and texture analysis. This study showed that APG-based emulsions could be promoted as safe cosmetic/dermopharmaceutical vehicles and carriers for extremely acidic and hygroscopic AHA class of actives (specifically LA); prospective safety for human use of both APG and LA with the correlation between in vivo and in vitro findings was shown. However, it was revealed that LA strongly influenced the colloidal structure of the emulsion based on APGs and promoted the formation of lamellar structures which reflects onto the mode of water distribution within the cream. The advantageous skin hydrating potential of LA-containing emulsion vs. placebo was unlikely to be achieved, pointing that emulsions stabilized by lamellar liquid crystalline structures probably are not satisfying carriers for highly hygroscopic actives in order to reach the full moisturizing potential. Safe and effective use on dry skin is presumed.


[Advances in mechanism of autophagy in renal tubular injury].
Autophagy is a lysosome-dependent degradation process that eliminates damaged macromolecular proteins and aging organelles to maintain intracellular homeostasis. Autophagy is observed in almost all eukaryotic cells and plays important roles in many cellular physiological processes, including the cell proliferation and growth, cellular functional alteration and phenotypical transition. Renal tubule is an important target for renal injury under different pathological conditions. Following the discoveries of the molecular basis of autophagy, accumulated lines of evidence have indicated that autophagy dysfunction in tubule is involved in the pathogenesis of many renal diseases. This review will summarize the recent progress in molecule mechanism of autophagy and its roles in renal tubular injury.


Survival of long nerve allografts following donor antigen pretreatment: a pilot study.
In this study, the authors evaluated whether the pretransplant portal venous administration of UV-B irradiated donor alloantigen would induce tolerance to long peripheral nerve allografts in a swine model. They completed nerve allograft transplantation between four swine of separate lineages. Regeneration across the nerve allografts was followed for 10 months postoperatively. Sequential IN VITRO assays demonstrated the successful and prolonged suppression of the recipient immune response to donor antigen following antigen inoculation. Histomorphometric analysis demonstrated successful regeneration across the long nerve allografts in the pretreated recipients, but not across allografts in unimmunosuppressed recipients. A single pretransplant antigen delivery protocol has the potential to replace chronic medicinal immunosuppressant therapy and its associated morbidities. Furthermore, tolerance to long nerve allografts has immediate applicability to clinical requirements for bridging multiple, complex, long nerve gaps.


Recombinant protein CPSIT_0846 induces protective immunity against Chlamydia psittaci infection in BALB/c mice.
Chlamydia psittaci is an obligate intracellular bacteria that causes respiratory disease in poultry and humans. Currently, there are no licensed vaccines against chlamydial infection in humans. The transmembrane head protein CPSIT_0846 of C. psittaci is a putative member of the larger Inc protein family. In this study, we investigated immunogenicity and protective efficacy of the recombinant CPSIT_0846 protein in BALB/c mice. Mice immunized with CPSIT_0846 developed strong T-lymphocyte responses that were recalled by the immunogen CPSIT_0846 in an in vitro restimulation assay. These T cells displayed a strong Th1-biased cytokine profile with high levels of IFN-γ. At the same time, a strong humoral immune response was also detected in the immunized mice with high titers of Chlamydia psittaci-specific serum IgG antibodies. More importantly, the robust immune responses correlated well with significantly reduced chlamydial burden and inflammatory pathology in the mouse lungs upon an airway challenge infection. The above results together suggest that the CPSIT_0846 protein may be a potential vaccine candidate antigen for inducing protection against C. psittaci infection and disease in the airway.


Prevalence of anthelmintic resistant nematodes in sheep in south-east England.
The prevalence of anthelmintic resistant nematodes among 52 commercial flocks in south-east England was investigated by comparing the faecal egg counts of groups of lambs before, and seven days after, treatment with thiabendazole and levamisole. Evidence of thiabendazole resistance was found on seven farms. in each case Haemonchus contortus was the only species of nematode involved. In vitro egg hatch assays carried out for isolates from these farms gave ED50 estimates of 0.065 to 0.332 micrograms thiabendazole/ml compared with estimates of 0.027 to 0.031 micrograms thiabendazole/ml for a known susceptible strain of H contortus assayed at the same time. In a series of slaughter trials, there was a 17 to 85 per cent reduction, as compared with controls, in the mean worm burdens of groups of lambs infected with these isolates and killed seven days after treatment with thiabendazole, confirming their resistance to this anthelmintic.


[Adult-to-adult living-related donor liver transplantation: report of 2 cases].
To investigate the feasibility and safety of adult-to-adult living-related donor liver transplantation using a right lobe graft. The clinical data of 2 cases of living-related donor liver transplantation performed between July, 2010 and November, 2010 were analyzed. Liver transplantation was performed using a right lobe graft including the middle hepatic vein in one case and a right lobe graft without the middle hepatic vein in the other. The ratio of graft volume to standard liver volume was 46.2% and 47.3% in the two cases, with GR/WR of 0.83 and 0.80, and donor residue liver of 42.1% and 39.5%, respectively. The donor operation lasted for 6.5 h and 5 h in the two cases with blood loss of about 200-250 ml without blood transfusion. The donors recovered uneventfully without any surgical complications, whose liver function was normal 7 days after the operation, and were discharged 14 days and 16 days after the surgery, respectively. The recipient operation lasted for 8 h and 7 h with blood loss of about 800-1000 ml. The right hepatic vein, hepatic artery, portal vein and bile duct reconstruction were performed by end-to-end anastomoses in the 2 recipients. Bile duct anastomosis stricture occurred in the first recipient 2 months after transplantation and was treated with percutaneous transhepatic cholangiography and drainage. The second recipient recovered smoothly without any complications. The recipients have so far survived 9 months and 5 months, respectively. Adult-to-adult living-related donor liver transplantation is a safe and effective option for treatment of end-stage liver diseases in the context of cadaveric liver graft shortage.


Direct evidence for methylation of arginine residues in high molecular weight forms of basic fibroblast growth factor.
Basic fibroblast growth factor (bFGF) is a heparin-binding angiogenic polypeptide mitogen. Protein sequence analysis of bFGF isolated from tissue sources initially established that it is composed of 146 amino acids (apparent Mr 18,000). More recently larger apparent molecular weight forms have been identified and partially characterized. In addition, these high molecular weight forms (apparent Mr 22,000 and 25,000) have been shown to localize preferentially to nuclear fractions of transfected cells. In this report we demonstrate that the higher molecular weight, amino terminally extended forms of bFGF contain methylated arginine residues. The demonstration is based on 1) amino acid sequence analysis of a protein known to contain methylated arginine (myelin basic protein) and a comparison with amino acid sequence analysis of trypsin-derived fragments of the high molecular weight bFGF purified from guinea pig brain and 2) the ability to label in vivo the high molecular weight forms of bFGF with S-adenosyl-L-(methyl-3H)-methionine, the substrate of arginine-protein methylase I. These results are suggestive of a role of arginine methylation in directing nuclear localization of certain forms of bFGF.


[Use of three-dimensional ultrasound visualization in differential diagnosis of pancreatic head diseases].
Retrospective analysis of 3D-reconstruction of ultrasound images is discussed with reference to the diagnosis of pancreatic disorders, such as pseudotumorous pancreatitis and pancreatic head neoplasm, based on the data extracted from case records collected in the Central Clinical Hospital No 1, OJSC RZhD, for the period of 2004-2008. In addition, comparative analysis is presented of different beam diagnostics methods for the examination of hepatobiliary system (classical ultrasound, 3D-reconstruction of ultrasound images, CT, endoscopic techniques, e.g. retrograde cholangiopancreatography). Control group comprised 20 patients without signs of gastrointestinal pathology, group 2 included 24 patients with pseudotumorous pancreatitis, group 3 54 patients with pancreatic head neoplasm (up to 3 cm). It was shown that 3D-images facilitate detection of pathologic processes in the pancreas. Minimal slice thickness permits to visualize small objects, segmentation of irregularly shaped tumorous foci and their volume. This method gives better idea of the relationship between the tumour and other tissues and vessels than other diagnostic tools and thereby makes easier the choice of treatment strategy and prognosis of its outcome. Also, it improves the quality of information about arterial and venous circulation and permits to differentiate between benign and malignant tumours.


Surgical treatment of a 72-year-old patient with headache, hyponatremia and oculomotor nerve palsy: a case report and literature review.
Pituitary apoplexy is a life-threatening syndrome caused by acute infarction of the pituitary gland. The most common symptoms associated with pituitary apoplexy are headache, nausea, vomiting, visual symptoms, hypopituitarism, and altered mental status. Both oculomotor nerve palsy and hyponatremia are relatively rare complications of pituitary apoplexy. The treatment of pituitary apoplexy is controversial. We report a case of a 72-year-old man with severe headache, nausea, vomiting, confusion and left oculomotor nerve palsy, who was initially considered as posterior communicating artery aneurysm (PCOAA) based on the presenting symptoms. Initial biochemical evaluation showed severe hyponatremia, hormonal evaluation identified multiple pituitary hormone deficiency and enhanced magnetic resonance imaging showed a large pituitary adenoma with signs of hemorrhage. A diagnosis of pituitary apoplexy and secondary hypopituitarism was finally made. The patient was treated with intravenous hydrocortisone 100 mg twice daily and oral levothyroxine 100 mg once daily. Appropriate venous transfusion with sodium was also used concomitantly to correct hyponatremia. After seven days of treatment, the patient's serum electrolytes normalized and he gradually recovered alertness. Then, the patient underwent transsphenoidal surgery for tumor removal. Left ptosis and oculomotor nerve palsy completely recovered three months after surgery. Postoperatively, hormone replacement therapy was essential for the patient with 20 mg hydrocortisone and 50 mg levothyroxine once daily. During the last follow up 4 years later, the patient was still on hormonal replacement and in good condition. So, for patients with pituitary apoplexy, we have shown that a semi-elective surgery after conservative treatment when the patient becomes clinically stable and hypopituitarism has been corrected is a good approach.


Abscisic Acid and the Photoperiodic Induction of Dormancy in Salix viminalis L.
A series of growth room experiments was carried out aiming to establish the role of abscisic acid on dormancy of Salix viminalis L. The inhibitor content and abscisic acid levels of extracts from roots, sap, leaves, and apical tissues of willow were measured using biological assay and gas-liquid chromatography.No evidence was obtained that photoperiodically mediated dormancy is associated with changes in abscisic acid levels or beta-inhibitor activity.


Personalized computational heart models with T1-mapped fibrotic remodeling predict sudden death risk in patients with hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is associated with risk of sudden cardiac death (SCD) due to ventricular arrhythmias (VAs) arising from the proliferation of fibrosis in the heart. Current clinical risk stratification criteria inadequately identify at-risk patients in need of primary prevention of VA. Here, we use mechanistic computational modeling of the heart to analyze how HCM-specific remodeling promotes arrhythmogenesis and to develop a personalized strategy to forecast risk of VAs in these patients. We combine contrast-enhanced cardiac magnetic resonance imaging and T1 mapping data to construct digital replicas of HCM patient hearts that represent the patient-specific distribution of focal and diffuse fibrosis and evaluate the substrate propensity to VA. Our analysis indicates that the presence of diffuse fibrosis, which is rarely assessed in these patients, increases arrhythmogenic propensity. In forecasting future VA events in HCM patients, the imaging-based computational heart approach achieved 84.6%, 76.9%, and 80.1% sensitivity, specificity, and accuracy, respectively, and significantly outperformed current clinical risk predictors. This novel VA risk assessment may have the potential to prevent SCD and help deploy primary prevention appropriately in HCM patients.


Determination of dicumyl peroxide in workplace air.
A method for the determination of dicumyl peroxide in workplace air was developed and applied. Micro-impinger bottles and personal air sampling pumps were used for the sampling. Gas chromatography/mass spectrometry was used for the analytical separation and quantitative determination. The technique makes it possible to monitor peroxide concentrations down to 5 micro g/m(3) in air.


Epstein-Barr virus in the pathogenesis of oral cancers.
Epstein-Barr virus (EBV) is a ubiquitous gamma-herpesvirus that establishes a lifelong persistent infection in the oral cavity and is intermittently shed in the saliva. EBV exhibits a biphasic life cycle, supported by its dual tropism for B lymphocytes and epithelial cells, which allows the virus to be transmitted within oral lymphoid tissues. While infection is often benign, EBV is associated with a number of lymphomas and carcinomas that arise in the oral cavity and at other anatomical sites. Incomplete association of EBV in cancer has questioned if EBV is merely a passenger or a driver of the tumorigenic process. However, the ability of EBV to immortalize B cells and its prevalence in a subset of cancers has implicated EBV as a carcinogenic cofactor in cellular contexts where the viral life cycle is altered. In many cases, EBV likely acts as an agent of tumor progression rather than tumor initiation, conferring malignant phenotypes observed in EBV-positive cancers. Given that the oral cavity serves as the main site of EBV residence and transmission, here we review the prevalence of EBV in oral malignancies and the mechanisms by which EBV acts as an agent of tumor progression.


Mechanisms of kin discrimination inferred from pedigrees and the spatial distribution of mates.
Where animals avoid inbreeding, different mechanisms of kin discrimination can leave different 'signatures' in the patterns of observed mate relationship. For example, consider a species with no paternal care. If a female avoids mating with familiar individuals, one would expect a deficit of offspring whose parents are maternal half-siblings, but paternal half-siblings would be unfamiliar with each other and thus have offspring at the frequency expected by chance. If spatial cues are used to avoid inbreeding, a female would be expected to produce few offspring with males (even unrelated males) living near her birth site. We searched for these and other signatures with data from a long-term study of banner-tailed kangaroo rats, Dipodomys spectabilis, in Arizona, USA, using a combination of intensive censusing, mapping of available dens, microsatellite-based parentage determination, and a randomization routine that determines the numbers of offspring expected if females in the population mate indiscriminately among the males available to them. The data are consistent with the hypothesis that kangaroo rats discriminate kin by familiarity developed via association early in life, rather than by using spatial cues or self-referential phenotype matching. Our approach should be widely applicable as a means of assessing the degree to which kin discrimination exists (in contexts like nepotism as well as inbreeding avoidance) and in inferring what cues animals use to assess categories of relationship.


[Urbanization and aspects of cancer epidemiology].
In a large industrial Povolzhje region-Kuibyshev Province, within a 15-year period according to standardized indices the incidence of malignancies increased by 71.9% (1956-133,7; 1973-229,9; Pt = 0.95) It prevailed among urban population in relation to cancer of the breast and other organs; no reliable differences were found in relation to cancer of the lung, larynx, esophagus, stomach and skin. The incidence of cancer of the lower lip and female genitalia was higher in rural population. In the central industrial complex, where all cities and industrial enterprises are concentrated, the incidence rate among the rural population is higher than the average provincial one (100), so cancer of the upper respiratory tract is 129.5, esophagus--118, stomach-114, breast-115. The incidence rate is mostly high in cities with machine, petrochemical, electrical industry enterprises and aged population.


Effectiveness of nutrition education in improving fruit and vegetable consumption among selected college students in urban Puducherry, South India. A pre-post intervention study.
World Health Organization (WHO) suggests intake of five servings (400 g) of fruits and vegetables (F&V) per day to ensure an adequate dietary fibre and to reduce the risk of non-communicable diseases. Risk factor survey of Non-Communicable Diseases (2007-08), reports that only 1% population in Tamil Nadu, South India consumed more than five servings a day. So we aimed to assess the effectiveness of nutrition education in improving the daily intake of fruit and vegetable servings and stage of behaviour change among college students. A pre-post intervention study was conducted among undergraduate students from two selected women's colleges in urban Puducherry, South India during September-October 2019. The two English departments were randomly allocated into intervention group (IG), control group (CG) and 75 students in each group were chosen by systematic random sampling. IG received 30 min of nutrition education programme; which includes importance and minimum daily intake of fruits & vegetables, local availability, cost and awareness about myths and misconceptions. CG received pamphlets regarding healthy dietary intake. Knowledge regarding portion sizes, average daily servings of fruit & vegetable intake and stage of behaviour change were assessed at baseline and after one month of intervention. There was a significant increase in knowledge regarding portion sizes (28- 64%) after intervention in IG (p<0.001) compared to CG (24- 40%). The knowledge regarding the required number of servings of fruits (27-56%) and vegetables (15-58%) also increased significantly (p<0.001) in the IG. Intake of fruits, vegetables and juices in the last 24 h were significantly increased in IG compared to CG (p<0.001). There was a significant increase (p=0.002) in contemplation and preparation stage (13-34%) in IG after intervention. A well designed nutrition education programme is an effective tool in promoting healthy eating habits among adolescents. It enabled a significant increase in knowledge regarding portion sizes of F&V and daily intake of fruits and vegetables.


Understanding the Role of Metakaolin towards Mitigating the Shrinkage Behavior of Alkali-Activated Slag.
This research investigates the mechanism of metakaolin for mitigating the autogenous and drying shrinkages of alkali-activated slag with regard to the activator parameters, including concentration and modulus. The results indicate that the incorporation of metakaolin can decrease the initial viscosity and setting time. Increasing activator concentration can promote the reaction process and shorten the setting time. An increase in the metakaolin content induces a decrease in compressive strength due to reduced formation of reaction products. However, increasing activator dosage and modulus can improve the compressive strength of alkali-activated slag containing 30% metakaolin. The inclusion of metakaolin can mitigate the autogenous and drying shrinkage of alkali-activated slag by coarsening the pore structure. On the other hand, increases in activator concentration and modulus result in an increase in magnitude of the autogenous and drying shrinkage of alkali-activated slag containing metakaolin. The influence of the activator modulus on the shrinkage behavior of alkali-activated slag-metakaolin binary system should be further investigated.


The sexual habits of males who molest.
To gain better understanding into the causes of molesting behaviour in males, we examined a prison cohort of molesters and compared them with a control group comprising thieves. The molesters were older, had attained a higher educational level and were more likely to be married. They had their initial sexual intercourse at an older age but tended to have multiple sexual relationships and were less likely to report having viewed pornographic material. Three months prior to committing their offences, molesters seemed to engage in less sexual activity. The implications are that molesters had a need for more explicit sexual contact but were unable to sustain ongoing, stable, intimate sexual relationships.


[A multicentric study on clinical characteristics and antibiotic sensitivity in children with methicillin-resistant Staphylococcus aureus infection].
Objective: To investigate the clinical characteristics of pediatric methicillin-resistant Staphylococcus aureus (MRSA) infection and the antibiotic sensitivity of the isolates. Methods: The clinical data of children with MRSA infection and antibiotic sensitivity of the isolates from 11 children's hospitals in Infectious Diseases Surveillance of Paediatrics (ISPED) group of China between January 1, 2018 and December 31, 2018 were collected retrospectively. The children's general condition, high-risk factors, antimicrobial therapy and prognosis, differences in clinical disease and laboratory test results between different age groups, and differences of antibiotic sensitivity between community-acquired (CA)-MRSA and hospital-acquired (HA)-MRSA were analyzed. The t test and Wilcoxon rank sum test were used for statistical analysis of the quantitative data and Chi-square test were used for comparison of rates. Results: Among the 452 patients, 264 were males and 188 were females, aged from 2 days to 17 years. There were 233 cases (51.5%) in the ≤1 year old group, 79 cases (17.5%) in the>1-3 years old group, 29 cases (6.4%) in the >3-5 years old group, 65 cases (14.4%) in the >5-10 years old group, and 46 cases (10.2%) in the>10 years old group. The main distributions of onset seasons were 55 cases (12.2%) in December, 47 cases (10.4%) in February, 46 cases (10.2%) in November, 45 cases (10.0%) in January, 40 cases (8.8%) in March. There were 335 cases (74.1%) CA-MRSA and 117 (25.9%) cases HA-MRSA. Among all cases, 174 cases (38.5%) had basic diseases or long-term use of hormone and immunosuppressive drugs. During the period of hospitalization, 209 cases (46.2%) received medical interventions. There were 182 patients (40.3%) had used antibiotics (β-lactams, glycopeptides, macrolides, carbapenems, oxazolones, sulfonamides etc) 3 months before admission. The most common clinical disease was pneumonia (203 cases), followed by skin soft-tissue infection (133 cases), sepsis (92 cases), deep tissue abscess (42 cases), osteomyelitis (40 cases), and septic arthritis (26 cases), suppurative meningitis (10 cases). The proportion of pneumonia in the ≤1 year old group was higher than the >1-3 years old group,>3-5 years old group,>5-10 years old group,>10 years old group (57.5% (134/233) vs. 30.4% (24/79), 31.0% (9/29), 38.5% (25/65), 23.9% (11/46), χ(2)=17.374, 7.293, 7.410, 17.373, all P<0.01) The proportion of skin and soft tissue infections caused by CA-MRSA infection was higher than HA-MRSA (33.4% (112/335) vs. 17.9% (21/117), χ(2)=10.010, P=0.002), and the proportion of pneumonia caused by HA-MRSA infection was higher than CA-MRSA (53.0% (62/117) vs. 42.1% (141/335), χ(2)=4.166, P=0.041). The first white blood cell count of the ≤1 year old group was higher than that children > 1 year old ((15±8)×10(9)/L vs. (13±7)×10(9)/L, t=2.697, P=0.007), while the C-reactive protein of the ≤1 year old group was lower than the 1-3 years old group,>5-10 years old group,>10 years old group (8.00 (0.04-194.00) vs.17.00 (0.50-316.00), 15.20 (0.23-312.00), 21.79(0.13-219.00) mg/L, Z=3.207, 2.044, 2.513, all P<0.05), there were no significant differences in procalcitonin (PCT) between different age groups (all P>0.05). After the treatment, 131 cases were cured, 278 cases were improved, 21 cases were not cured, 12 cases died, and 10 cases were abandoned. The 452 MRSA isolates were all sensitive to vancomycin (100.0%), linezolid (100.0%), 100.0% resistant to penicillin, highly resistant to erythromycin (85.0%, 375/441), clindamycin (67.7%, 294/434), less resistant to sulfonamides (5.9%, 23/391), levofloxacin (4.5%, 19/423), gentamicin (3.2%, 14/438), rifampicin (1.8%, 8/440), minocycline (1.1%, 1/91). The antimicrobial resistance rates were not significantly different between the CA-MRSA and HA-MRSA groups (all P>0.05). Conclusions: The infection of MRSA is mainly found in infants under 3 years old. The prevalent seasons are winter and spring, and MRSA is mainly acquired in the community. The main clinical diseases are pneumonia, skin soft-tissue infection and sepsis. No MRSA isolate is resistant to vancomycin, linezolid. MRSA isolates are generally sensitive to sulfonamides, levofloxacin, gentamicin, rifampicin, minocycline, and were highly resistant to erythromycin and clindamycin. To achieve better prognosis. clinicians should initiate anti-infective treatment for children with MRSA infection according to the clinical characteristics of patients and drug sensitivity of the isolates timely and effectively.


TTK predicts triple positive breast cancer prognosis and regulates tumor proliferation and invasion.
This study was conducted to investigate the expression of the spindle assembly checkpoint kinase tyrosine/threonine kinase (TTK) in triple positive breast cancer (TPBC) and its effect on TPBC cells. We analyzed the status of TTK in 69 TPBC samples using immunohistochemistry. The correlation between TTK and clinicopathological parameters was analyzed using a chi-squared test. The prognostic value of TTK was evaluated using Kaplan-Meier survival curves. We analyzed the role of TTK in the invasion and proliferation of TPBC cells in vitro and in vivo. The mean age of the 69 patients with TPBC enrolled in this study was 53 years (range: 29-86 years). TTK expression was positively correlated with tumor size (p=0.034), p53 status (p=0.023), TNM stage ([p=0.023), and Ki-67 index (p<0.001). The Kaplan-Meier curves revealed that TTK expression was correlated with poor disease-free survival (p=0.001) and overall survival (p=0.050). Multivariate proportional hazard regression analyses showed that TTK and TNM staging were significant independent predictors of disease-free survival (p=0.007 and p=0.034, respectively). Additionally, TTK knockdown inhibited the invasion and proliferation of the BT474 TPBC cell line. The findings of this study indicate that TTK overexpression is associated with cancer progression and prognosis in patients with TPBC, whereas TTK knockdown inhibits the invasion and proliferation of TPBC cells. Thus, TTK might serve as a prognostic marker for TPBC.


Effects of surgical sympathetic denervation on myo-inositol trisphosphate production and contraction in the dilator and sphincter smooth muscles of the rabbit iris: evidence for interaction between the cyclic AMP and calcium signaling systems.
The effects of norepinephrine (NE), carbachol (CCh), NaF, 3-isobutyl-1-methylxanthine (IBMX), and high K+ concentration (80 mM) depolarization on inositol trisphosphate (IP3) accumulation, cyclic AMP (cAMP) formation, and contraction were investigated in the dilator and sphincter smooth muscles of the sympathetically denervated as well as the normal rabbit eye. (a) In the denervated dilator muscle, NE-stimulated IP3 production and contraction are enhanced. (b) In the sphincter muscle of rabbits that have undergone sympathetic denervation. CCh-stimulated IP3 production and contraction are attenuated. (c) The increase in tension by a maximal effective dose of NaF (209 mM) in the dilator was 12.5 and 18 mg of tension/mg wet weight in normal and denervated tissue, respectively, and in the sphincter was 33.8 and 15.2 mg of tension/mg wet weight in normal and denervated tissue, respectively. NaF had no effect on cAMP formation. (d) Addition of NE had no effect on cAMP formation in both the normal and denervated dilator, whereas basal and IBMX-induced cAMP formation increased. in the denervated sphincter over that of the normal tissue by 15 and 60%, respectively. (e) Isoproterenol (5 microM) increased cAMP formation in the normal and denervated sphincter by 47 and 91%, respectively. (f) Whereas CCh inhibits cAMP formation in the normal sphincter, it lost its inhibitory effect in the sphincter with denervation. (g) IBMX (0.1 mM) attenuated the CCh-stimulated IP3 production and contraction of the sphincter by approximately 30% of their respective controls. (h) High K+ concentration depolarization attenuated contraction in both dilator and sphincter muscles with denervation. These observations suggest that an increase in the level of cAMP in the iris sphincter due to sympathetic denervation could lead to inhibition of phospholipase C (or other target sites, such as phosphorylation of the muscarinic receptor, Gp protein itself, myosin light chain kinase, or the IP3 receptor), IP3 production, and contraction. In conclusion, we suggest that the supersensitivity and subsensitivity observed after surgical sympathetic denervation of the iris dilator and sphincter muscles, respectively, are caused by alterations in the efficiency of coupling, probably through the Gp proteins, between their respective receptors and the breakdown of polyphosphoinositides by phospholipase C. In addition, we propose that the sympathetic nervous system can regulate, through alterations in cAMP levels, the muscarinic stimulation of IP3 accumulation and contraction in the iris sphincter. These findings add further support to the hypothesis that there are reciprocal interactions between the cAMP and IP3-Ca2+ signaling systems and the contractile response in the iris smooth muscle.


Effect of buspirone on the behavioral regulation of rats in low versus high anxiety conditions.
Buspirone (CAS 33386-08-2) is reported to have anxiolytic effects in humans and is mostly described for mild anxiety. To further explore the effects of buspirone on different levels of anxiety, the effect of buspirone was evaluated in two different conditions of the open field which were distinguished as low and high anxiety (enclosed and exposed open field, respectively). Twenty-eight albino Wistar rats (350-400 g) were tested in two different arena settings, an enclosed and an exposed open field. Fourteen animals were initially injected with 1 ml saline while the others (n = 14) received buspirone 3 mg/kg. The data showed clear differences in the two open-field settings, suggesting a higher anxiety level in the exposed open field. In addition, correlation analysis showed that the two anxiety tests measure different aspects of anxiety. Buspirone treatment reduced the behavioral activity in both the enclosed and exposed open-field, which is generally interpreted as an anxiogenic effect. However, buspirone increased the time in the center areas and decreased the frequencies in the outer regions. These behavioral changes are generally seen as an anxiolytic effect. Correlation analysis showed that buspirone treatment disrupted the relation between indices of anxiety. These results showed that in an open-field setting buspirone appears to have a dual effect. The reduced activity and increase in time spent in the center areas are indicative of both an anxiogenic and an anxiolytic effect, respectively. This was found in both open-field settings, suggesting that the effects of buspirone are independent of the anxiety level.


Homogeneous and heterogeneous catalytic oxidation of sulfides by H2O2 over zinc(II) compounds.
It has been recently shown that zinc compounds are effective catalysts for the oxidation of alkyl aryl sulfides to the corresponding sulfoxides in the presence of hydrogen peroxide. In this paper, we have investigated homogeneous and heterogeneous catalytic oxidation of sulfides by H(2)O(2) over Zn(NO(3))(2) x 6 H(2)O and the metal-organic porous material [Zn(2)(bdc)(L-lac)(dmf)] x DMF (where H(2)bdc = p-benzenedicarboxylic acid, H(2)lac = lactic acid), respectively. The experimental data can be explained by the proposed catalytic cycle which includes the activation of H(2)O(2) via coordination to Zn(II) ions followed by oxygen transfer step. In homogeneous conditions, the presence of a large amounts of H(2)O(2) results in the coordination of two molecules of hydrogen peroxide to Zn(II), so that sulfone is formed via transfer of two oxygen atoms from Zn(H(2)O)(4)(H(2)O(2))(2)(2+) active species. Contrary to the homogeneous system, the use of [Zn(2)(bdc)(L-lac)(dmf)] x DMF as catalyst does not lead to the formation of sulfone in the initial period of reaction. This is consistent with the proposed catalytic cycle of sulfoxidation as each Zn(II) center in the crystalline framework is able to activate only one H(2)O(2) molecule. Our investigations indicate that the sorption and activation of H(2)O(2) molecules by microporous framework [Zn(2)(bdc)(L-lac)(dmf)] occur faster than sulfide sorption and oxygen transfer.


[Etiopathogenesis of diabetic neuropathy].
The cause of diabetic neuropathy remains unclear but several mechanisms have been considered. Hyperglycemia with all its metabolic and vascular consequences probably plays the main role. Metabolic consequences of hyperglicemia including increased level of sorbitol and fructose, myoinositol deficiency and Na+/K+ adenosine triphosphate deficiency alter the function of peripheral nerves and lead to an oxidative stress, which changes fatty acid metabolism. Chronic hyperglycemia is also responsible for abnormalities in microcirculation that could lead to local ischemia evoking many endothelial changes. There are also some genetic factors, impaired neurotrophic support and autoimmune damage that influence sensitivity to peripheral nerve damage in diabetes mellitus.


Prognostic Score of Long-Term Survival After Surgery for Malignant Pleural Mesothelioma: A Multicenter Analysis.
Despite ongoing efforts to improve therapy in malignant pleural mesothelioma, few patients undergoing extrapleural pneumonectomy experience long-term survival (LTS). This study aims to explore predictors of LTS after extrapleural pneumonectomy and to define a prognostic score. From January 2000 to December 2010, we retrospectively reviewed clinicopathologic and oncological factors in a multicenter cohort of 468 malignant pleural mesothelioma patients undergoing extrapleural pneumonectomy. LTS was defined as survival longer than 3 years. Associations were evaluated using χ(2), Student's t, and Mann-Whitney U tests. Logistic regression, Cox regression hazard model, and bootstrap analysis were applied to identify outcome predictors. Survival curves were calculated by the Kaplan-Meier method. Receiver operating characteristic analyses were used to estimate optimal cutoff and area under the curve for accuracy of the model. Overall, 107 patients (22.9%) survived at least 3 years. Median overall, cancer-specific, and disease-free survival times were 60 (95% confidence interval [CI], 51 to 69), 63 (95% CI, 54 to 72), and 49 months (95% CI, 39 to 58), respectively. At multivariate analysis, age (odds ratio, 0.51; 95% CI, 0.31 to 0.82), epithelioid histology (odds ratio, 7.07; 95% CI, 1.56 to 31.93), no history of asbestos exposure (odds ratio, 3.13; 95% CI, 1.13 to 8.66), and the ratio between metastatic and resected lymph nodes less than 22% (odds ratio, 4.12; 95% CI, 1.68 to 10.12) were independent predictors of LTS. According to these factors, we created a scoring system for LTS that allowed us to correctly predict overall, cancer-specific, and disease-free survival in the total sample, obtaining two different groups with favorable or poor prognosis (area under the curve, 0.74; standard error, 0.04; p < 0.0001). Our prognostic model facilitates the prediction of LTS after surgery for malignant pleural mesothelioma and can help to stratify the outcome and, eventually, tailor postoperative treatment.


Gender differences in cognitive ability associated with genetic variants of NLGN4.
Neuroligin-4 (NL4), encoded by the NLGN4 gene on the X chromosome, is a neuronal-specific brain membrane protein which plays an important role in the formation of functional presynaptic elements and axon specialization. The genetic variants of NLGN4 affect the biological function of NL4, resulting in the manifestation of different psychiatric disorders. The present study investigates the influence of these genetic variants on cognitive performance. The cognitive abilities of 351 subjects were evaluated using the Chinese Wechsler Intelligence Scale Children. The haplotypes were assigned with the PHASE program. The ANOVA method was applied to investigate the relationship between single SNP, the identified target haplotypes and cognitive performance in a random sample. We observed that the X(C) allele of rs5916271 and X(A) allele of the re6638575 carriers had significantly higher cognitive ability performances than the noncarrier boys (p < 0.05). The target haplotype composed of 2 allele (X(CA+)) carriers also displayed a higher cognitive performance than that of the noncarriers boys. The genetic polymorphism of NLGN4 also had a significant effect on the boys' cognitive ability and other intelligence factors. Future research will involve determining the relationship between NLGN4 and personal cognitive ability.


3 V omni-directionally stretchable one-body supercapacitors based on a single ion-gel matrix and carbon nanotubes.
Stretchable supercapacitors often have laminated structures consisting of electrode, electrolyte, and supporting layers. Since the layers are likely to be composed of different materials, delamination is a major cause of failure upon stretching. In this study, we demonstrate delamination-free stretchable supercapacitors where all the component layers are prepared with a single matrix, which is composed of a polymer, poly(vinylidene fluoride-hexafluoropropylene) and an ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide. Since the ionic liquid in the composite plays a role as both an electrolyte and a plasticizer, this composite can be used as an electrolyte and a supporting layer in the stretchable supercapacitor. The electrode layer can be fabricated by incorporating carbon nanotubes in the common matrix. Then, all the layers can be seamlessly fused into one body by dissolving the surface of the composite with acetone, which evaporates after the integration, leaving no borders between the layers. This one-body stretchable supercapacitor not only has high durability against repetitive stretches but also is stretchable in all directions. This feature clearly distinguishes them from conventional stretchable supercapacitors fabricated using buckled structures, which are stretchable only in one or two directions. Moreover, this supercapacitor has high cell voltage (∼3 V) owing to the ionic liquid-based gel electrolytes. Our demonstration of isotropically stretchable high-durability supercapacitors may have a great implication in the development of stretchable energy storage devices for real applications.


Development of sex cord stromal tumors after heterotopic transplantation of cryopreserved ovarian tissue in rats.
Chemoradiotherapy has substantially improved life expectancy in young women with cancer, but these treatments often cause infertility. One method of preserving fertility is to cryopreserve ovarian tissue, with subsequent autotransplantation of the tissue after successful anticancer therapy. This study examined the long-term effect of heterotopic transplantation of cryopreserved ovarian tissue on the histology. Ovarian tissue from rats was cryopreserved using a slow-freezing protocol. After thawing, the tissue pieces were transplanted under the splenic capsule in 14 rats of the same inbred strain and remained there for 210 or 300 days. Sex cord stromal tumors, consisting mainly of granulosa cells, were found in all of the rats. Although the hormonal situation in rats cannot be directly compared to that in humans, the development of sex cord stromal tumors in this animal model may be worth considering when cryopreserved ovarian tissue is transplanted heterotopically in fertility-preserving programs for cancer patients.


Sizing up the competition: quantifying the influence of the mental lexicon on auditory and visual spoken word recognition.
Much research has explored how spoken word recognition is influenced by the architecture and dynamics of the mental lexicon (e.g., Luce and Pisoni, 1998; McClelland and Elman, 1986). A more recent question is whether the processes underlying word recognition are unique to the auditory domain, or whether visually perceived (lipread) speech may also be sensitive to the structure of the mental lexicon (Auer, 2002; Mattys, Bernstein, and Auer, 2002). The current research was designed to test the hypothesis that both aurally and visually perceived spoken words are isolated in the mental lexicon as a function of their modality-specific perceptual similarity to other words. Lexical competition (the extent to which perceptually similar words influence recognition of a stimulus word) was quantified using metrics that are well-established in the literature, as well as a statistical method for calculating perceptual confusability based on the phi-square statistic. Both auditory and visual spoken word recognition were influenced by modality-specific lexical competition as well as stimulus word frequency. These findings extend the scope of activation-competition models of spoken word recognition and reinforce the hypothesis (Auer, 2002; Mattys et al., 2002) that perceptual and cognitive properties underlying spoken word recognition are not specific to the auditory domain. In addition, the results support the use of the phi-square statistic as a better predictor of lexical competition than metrics currently used in models of spoken word recognition.


Breathing retraining with chest wall mobilization improves respiratory reserve and decreases hyperactivity of accessory breathing muscles during respiratory excursions: A randomized controlled trial.
The aim of this paper was to evaluate the effects of breathing retraining with chest wall mobilization on the onset of accessory breathing muscle recruitment and respiratory reserve in individuals with chronic neck pain. Thirty-two participants with non-specific chronic neck pain were randomly assigned into intervention and control groups. The intervention group received 30 minutes of breathing retraining with chest wall mobilization and the control group was assigned to rest for 30 minutes. Electromyography (EMG) of upper trapezius (UT), scalene (SC), and sternocleidomastoid (SCM) muscles were recorded during respiratory excursions by cycling for 12 minutes. Measurement of maximum voluntary ventilation (MVV), chest expansion, and pain intensity were taken during normal breathing. The immediate effects within each group and between two groups were analyzed. Significant improvement in respiratory reserve was observed in the intervention group compared to control group through prolonged EMG onset of accessory breathing muscles. Moreover, increase of MVV, chest expansion and decrease in pain intensity were observed. This research suggests that breathing patterns and chest expansion should be considered within the physical assessment of breathing retraining, and that chest wall mobilization offers clinically important improvements in patients with chronic neck pain.


Potential of neural stem cells for the treatment of brain tumors.
Neural stem cells (NSCs) are self-renewing multipotent cells that generate the main phenotypes of the nervous system, neurons, astrocytes and oligodendrocytes. As such they hold the promise to treat a broad range of neurological diseases and injuries. Neural progenitor and stem cells have been isolated and characterized in vitro, from adult, fetal and post-mortem tissues, providing sources of material for cellular therapy. However, NSCs are still elusive cells and remain to be unequivocally identified and characterized, limiting their potential use for therapy. Neural progenitor and stem cells, isolated and cultured in vitro, can be genetically modified and when transplanted migrate to tumor sites in the brain. These intrinsic properties of neural progenitor and stem cells provide tremendous potential to bolster the translation of NSC research to therapy. It is proposed to combine gene therapy and cellular therapy to treat brain cancers. Hence, neural progenitor and stem cells provide new opportunities for the treatment of brain cancers.


Analgesic activity of cynaropicrinon on post-inflammatory irritable bowel syndrome visceral hypersensitivity in a rat model.
Visceral hypersensitivity is one of the most common symptoms in patients with post-inflammatory-irritable bowel syndrome (PI-IBS). Enterochromaffin (EC) cells and 5-hydroxytryptamine (5-HT) are important in the development of visceral hyperalgesia, and EC cells are influenced by helper T-cell subtype 1 or 2 cytokine predominant environments. In the present study, the analgesic effect of cynaropicrin and its underlying mechanism on the treatment of trinitrobenzene sulfonic (TNBS)-induced PI-IBS visceral hyperalgesia rats was investigated. The results from the abdominal withdrawal reflex tests and electromyography recordings indicated that treatment with cynaropicrin significantly and dose-dependently alleviated the visceral hyperalgesia of PI-IBS rats (P<0.05). In addition, the increased colonic 5-HT content, colonic tryptophan hydroxylase expression, EC cell number and the cytokine levels, including tumor necrosis factor-α and interleukin-6 in PI-IBS rats were significantly alleviated by cynaropicrin (P<0.05). These data demonstrate that the analgesic activity of cynaropicrin on TNBS-induced PI-IBS visceral hypersensitive rats was mediated via reduction of cytokines levels. Thus, cynaropicrin as a bioactive natural product may offer promising therapeutic avenues for visceral hypersensitivity in IBS.


Poly[aqua-{μ(3)-5-[(pyridin-2-ylmeth-yl)amino]-isophthalato-κN,N':O,O:O}cobalt(II)].
In the title polymer, {[Co(C(14)H(10)N(2)O(4))(H(2)O)]·3.5H(2)O}(n), the Co(2+) ion is coordinated by three carboxyl-ate O atoms from two 5-[(pyridin-2-ylmeth-yl)amino]-isophthalate anions, two N atoms from a (pyridin-2-ylmeth-yl)amino group and an O atom from a water mol-ecule, furnishing a distorted CoO(4)N(2) octa-hedral geometry. Each anion acts as a μ(3)-bridge, linking cobalt ions into a two-dimensional layer parallel to (100). The asymmetric unit also contains three and a half solvent water mol-ecules, which could not be modeled. Therefore, the diffraction contribution of the solvent water mol-ecules was removed by the subroutine SQUEEZE in PLATON [Spek (2009). Acta Cryst. D65, 148-155]. The crystal structure is stabilized by O-H⋯O hydrogen bonds in which the coordinated water mol-ecule acts as donor and the carboxyl-ate O atoms as acceptors.


Respiration and Gas Exchange in Stem Tissue of Opuntia basilaris.
Respiration and gas exchange in the light were studied manometrically with tissue slices from stem material of Opuntia basilaris Engelm. and Bigel. Dark respiration rates were greater in young stems than in mature stems. The timing of the experiment in the day/night cycle influences the magnitude and pattern of respiration and gas exchange in the light. Net dark respiration has a temperature optimum between 35 and 40 C, and is maintained at 60% of the control rate in tissue equilibrated with experimental osmotic potentials of -25 bars. Net gas exchange in the light is regulated by the titratable acidity of the tissue and by the tissue temperature. Increased rates of net CO(2) evolution and net O(2) consumption occur in the light with high levels of titratable acidity and high temperatures. An efflux of CO(2) and influx of O(2) occur following light/dark transitions. These patterns are reversed following dark/light transitions. Similar results were demonstrated at 15, 25, and 35 C, and are interpreted as a mechanism of adaptation to desert environments.


The effect of dimerization and ligand binding on the dynamics of Kaposi's sarcoma-associated herpesvirus protease.
The Kaposi's sarcoma-associated herpesvirus protease is essential for virus maturation. This protease functions under allosteric regulation that establishes its enzymatic activity upon dimerization. It exists in equilibrium between an inactive monomeric state and an active, weakly associating, dimeric state that is stabilized upon ligand binding. The dynamics of the protease dimer and its monomer were studied using the Gaussian network model and the anisotropic network model , and its role in mediating the allosteric regulation is demonstrated. We show that the dimer is composed of five dynamical domains. The central domain is formed upon dimerization and composed of helix five of each monomer, in addition to proximal and distal domains of each monomer. Dimerization reduces the mobility of the central domains and increases the mobility of the distal domains, in particular the binding site within them. The three slowest ANM modes of the dimer assist the protease in ligand binding, motion of the conserved Arg142 and Arg143 toward the oxyanion, and reducing the activation barrier for the tetrahedral transition state by stretching the bond that is cleaved by the protease. In addition, we show that ligand binding reduces the motion of helices α1 and α5 at the interface and explain how ligand binding can stabilize the dimer.


The disulfide folding pathway of tick anticoagulant peptide (TAP), a Kunitz-type inhibitor structurally homologous to BPTI.
The pathway of oxidative folding of tick anticoagulant peptide (TAP, 60 amino acids and three disulfides) has been analyzed by characterization of the acid and iodoacetate trapped folding intermediates. The results reveal a high degree of heterogeneity of the one- and two-disulfide intermediates and the presence of three-disulfide scrambled species along the folding pathway. The picture of TAP folding differs significantly from the well-documented case of bovine pancreatic trypsin inhibitor (BPTI), despite the fact that both proteins share close structural homology in term of 3-D conformation and disulfide pattern.


Holoprosencephaly: an antenatally-diagnosed case series and subject review.
Holoprosencephaly (HPE) is an uncommon congenital failure of forebrain development. Although the aetiology is heterogeneous, chromosomal abnormalities or a monogenic defect are the major causes, accounting for about 40% to 50% of HPE cases. At least 7 genes have been positively implicated, including SHH, ZIC2, SIX3, TGIF, PTCH1, GLI2, and TDGF1. Twelve antenatally- and 1 postnatally-diagnosed cases are presented in this study. These comprised 6 amniotic fluid, 3 chorionic villus, 2 fetal blood, 1 peripheral blood, and 1 product of conception. The total chromosome abnormality rate was 92.3%, comprising predominantly trisomy 13 (66.7%). There was 1 case of trisomy 18, and 3 cases of structural abnormalities, including del13q, del18p, and add4q. Despite the poor outcome of an antenatally-diagnosed HPE and the likely decision by parents to opt for a termination of pregnancy, karyotyping and/or genetic studies should be performed to determine if a specific familial genetic or chromosomal abnormality is the cause. At the very least, a detailed chromosome analysis should be carried out on the affected individual. If the result of high resolution karyotyping is normal, Fluorescence in situ hybridisation (FISH) and/or syndrome-specific testing or isolated holoprosencephaly genetic testing may be performed. This information can be useful in making a prognosis and predicting the risk of recurrence.


An immunologically anomalous luteinizing hormone variant in a healthy woman.
An investigation was undertaken to characterize an immunological LH variant in a 31-yr-old healthy woman whose serum LH was either poorly or not at all recognized by two monoclonal antibodies. The two antibodies recognize epitopes present on the intact LH dimer, but not on the free subunits. It was found that the immunologically aberrant LH of the subject was bioactive, as evidenced by an in vitro bioassay for LH. Nothing in the personal history of the subject or in the results from a number of hormone analyses revealed any endocrine abnormalities. In a GnRH stimulation test, the increase in immunoreactive LH using two reference immunometric assays for LH was less than 10% of the mean response of five control subjects. In relative terms, the maximal increase in LH in the subject was only 60-100%, in contrast to 340-560% for the control subjects. The bio/immuno ratio of the LH in the subject was high and was further increased in the GnRH stimulation test. A low proportion of acid LH isoforms in basal and stimulated samples from the subject was in agreement with the high bio/immuno ratio. Gel filtration studies showed the presence of molecular species of apparently lower molecular size than the intact LH, but different from the free beta-subunit. The results suggest the presence of fragments of the alpha-beta-dimer where at least part of the beta-subunit has been lost. A pedigree analysis involving the parents, siblings, and children of the subject strongly suggests a genetic origin of the LH variant described with an autosomal mode of inheritance. This report on an immunological variant of LH illustrates the potential dangers of using monoclonal based immunoassays where a protein hormone with fully maintained biopotency may be partially or totally missed due to the monospecificity of the immunoreagent. This possibility should be kept in mind when inappropriately low levels of gonadotropins are detected in diagnostic routine.


Changes in Physicochemical and Microbiological Properties, Fatty Acid and Volatile Compound Profiles of Apuseni Cheese during Ripening.
The evolution during ripening on the quality of Apuseni cheese was studied in this research. The cheese samples were controlled and evaluated periodically (at 4 months) during 16 months of storage (at 2-8 °C) for physicochemical parameters (pH, moisture, fat, fat in dry matter, total protein, ash, NaCl), microbiological (total combined yeasts and molds count (TYMC), total viable count (TVC), Escherichia coli, Staphylococcusaureus, Salmonella, lactic acid bacteria (LAB)), fatty acids (FA) and volatile compounds. For better control of the quality of the cheese, the storage space was evaluated for TYMC and TVC. The ripening period showed improved effects on the quality of the cheese, showing lower values for moisture and pH and an increase in macronutrients. Both the cheese samples and the storage space were kept within the allowed microbiological limits. Lipids are predominant, the predominant FAs being saturated fatty acids (SFAs), which decrease, while monounsaturated fatty acids (MUFAs) increase. During ripening, the microbiological and chemical changes result in the development of flavor. Major volatile compounds such as 2-heptanone show accumulations, while acetophenone, limonene, or thymol show a decrease. In conclusion, Apuseni ripening cheese clearly involves a complex series of transformations, leading to a ripening cheese with improved nutritional and aromatic characteristics.


[A study of hypoplastic myelodysplastic syndrome].
To distinguish hypoplastic myelodysplastic syndrome (MDS) from aplastic anemia (AA), morphological abnormalities of bone marrow hematopoietic cells in 8 patients with MDS and 39 patients with AA were studied. All the patients with MDS and AA showed prolonged plasma iron disappearance time, (PIDT1/2) > 120 min. Five hundred erythroid and myeloid cells, as well as 20 megakaryocytes were counted. Dysplastic changes were defined if morphological changes were present in more than 1.0% cells with only one lineage, or in more than 0.6% cells with more than two lineages. Twenty six of 39 patients with AA showed morphological abnormalities. In MDS cases, morphological abnormalities were prominent in trilineage cells in some cases, in bilineage (erythroid and megakaryocytic or myeloid and megakaryocytic cells), in others, or solely in myeloid cells or in megakaryocytic cells in other cases. Morphological abnormalities seen solely in erythroid cells, especially those with segmented nuclei were considered to be less significant for the diagnosis of MDS. The findings were considered to be useful to distinguish hypoplastic MDS from AA.


Activation of acetyl-CoA carboxylase. Purification and properties of a Mn2+-dependent phosphatase.
Acetyl-CoA carboxylase was isolated from rat liver by polyethylene glycol precipitation and avidin affinity chromatography. Sodium dodecyl sulfate electrophoresis of the enzyme gives one protein band (Mr 250,000). Phosphate analysis of the carboxylase showed the presence of 8.3 mol of phosphate/mol of subunit (Mr 250,000). The purified carboxylase has low activity in the absence of citrate (specific activity = 0.3 units/mg). However, addition of 10 mM citrate activates the carboxylase 10-fold, with half-maximal activation observed at 2 mM citrate, well above the physiological citrate level. Using this carboxylase as a substrate, we have isolated from rat liver a protein that activates the enzyme about 10-fold. This protein has been purified to near homogeneity (Mr 90,000). Incubation of this protein with 32P-labeled acetyl-CoA carboxylase results in a time-dependent activation of carboxylase with concomitant release of 32Pi, indicating that this protein is a phosphoprotein phosphatase. Both activation and dephosphorylation are dependent on Mn2+, but not citrate. This phosphatase does not hydrolyze p-nitrophenyl phosphate but does show high affinity for acetyl-CoA carboxylase (Km = 0.2 microM) as compared to its action on phosphorylase a (Km = 5.5 microM) and phosphohistone (Km = 20 microM). Activated acetyl-CoA carboxylase was isolated after dephosphorylation by the phosphatase. Such preparations contain about 5 mol of phosphate/mol of subunit and have specific activities of 2.6-3.0 units/mg in the absence of citrate. These activities are comparable to those of the phosphorylated carboxylase in the presence of 10 mM citrate. Thus, dephosphorylation by the Mn2+-dependent phosphatase renders the carboxylase citrate-independent, as compared to the phosphorylated form, which is citrate-dependent. To our knowledge this is the first report of a preparation of animal acetyl-CoA carboxylase that has substantial catalytic activity independent of citrate.