Blocking of enhanced sensitivity to behavioral effects of naloxone induced by narcotic agonists in rats.
The present experiment evaluated whether prior treatment with naloxone could block the sensitization to opiate antagonist induced by single dose administration of pure agonist (morphine) or mixed agonist (buprenorphine). Food deprived male Wistar rats were trained to respond for food on a multiple-trial, fixed-interval 3 min schedule. Reinforcement was contingent upon a response within a 10-s limited hold period following a fixed-interval of 3 min. A trial consisted of three fixed interval of 3 min separated by a 10 min timeout period during which responses were not reinforced. The rate decreasing effects of the opioid antagonist naloxone was determined by cumulative dosing. Pretreatment with morphine (0.3 mg/ kg, SC) and buprenorphine (0.03 mg/kg, SC) resulted in an increase sensitivity to the rate decreasing effect of naloxone compared to saline pretreatment. Administration of naloxone (0.3 mg/kg) 10 min prior to pretreatment doses of buprenorphine (0.03 mg/kg; 1.0 mg/kg) and morphine (0.3 mg/kg) increased sensitization to naloxone. However, greater sensitization was observed at low dose of buprenorphine. The increased sensitivity was partially blocked at high dose of buprenorphine (1.0 mg/ kg) by naloxone pretreatment. These results suggest that the doses of naloxone used to block opioid induced sensitization might be different from those required in animals with normal sensitivity to opioid antagonists. Further agonist-induced sensitization to behavioral effects of opioid antagonist appears to be opioid receptor specific.


A brief look at model-based dose calculation principles, practicalities, and promise.
Model-based dose calculation algorithms (MBDCAs) have recently emerged as potential successors to the highly practical, but sometimes inaccurate TG-43 formalism for brachytherapy treatment planning. So named for their capacity to more accurately calculate dose deposition in a patient using information from medical images, these approaches to solve the linear Boltzmann radiation transport equation include point kernel superposition, the discrete ordinates method, and Monte Carlo simulation. In this overview, we describe three MBDCAs that are commercially available at the present time, and identify guidance from professional societies and the broader peer-reviewed literature intended to facilitate their safe and appropriate use. We also highlight several important considerations to keep in mind when introducing an MBDCA into clinical practice, and look briefly at early applications reported in the literature and selected from our own ongoing work. The enhanced dose calculation accuracy offered by a MBDCA comes at the additional cost of modelling the geometry and material composition of the patient in treatment position (as determined from imaging), and the treatment applicator (as characterized by the vendor). The adequacy of these inputs and of the radiation source model, which needs to be assessed for each treatment site, treatment technique, and radiation source type, determines the accuracy of the resultant dose calculations. Although new challenges associated with their familiarization, commissioning, clinical implementation, and quality assurance exist, MBDCAs clearly afford an opportunity to improve brachytherapy practice, particularly for low-energy sources.


Kiss and Run: Promoting Effective and Targeted Cellular Uptake of a Drug Delivery Vehicle Composed of an Integrin-Targeting Diketopiperazine Peptidomimetic and a Cell-Penetrating Peptide.
Cell-penetrating peptides (CPPs) have emerged as powerful tools in terms of drug delivery. Those short, often cationic peptides are characterized by their usually low toxicity and their ability to transport diverse cargos inside almost any kinds of cells. Still, one major drawback is their nonselective uptake making their application in targeted cancer therapies questionable. In this work, we aimed to combine the power of a CPP (sC18) with an integrin-targeting unit (c[DKP-f3-RGD]). The latter is composed of the Arg-Gly-Asp peptide sequence cyclized via a diketopiperazine scaffold and is characterized by its high selectivity toward integrin αvβ3. The two parts were linked via copper-catalyzed alkyne-azide click reaction (CuAAC), while the CPP was additionally functionalized with either a fluorescent dye or the anticancer drug daunorubicin. Both functionalities allowed a careful biological evaluation of these novel peptide-conjugates regarding their cellular uptake mechanism, as well as cytotoxicity in αvβ3 integrin receptor expressing cells versus cells that do not express αvβ3. Our results show that the uptake follows a "kiss-and-run"-like model, in which the conjugates first target and recognize the receptor, but translocate mainly by CPP mediation. Thereby, we observed significantly more pronounced toxic effects in αvβ3 expressing U87 cells compared to HT-29 and MCF-7 cells, when the cells were exposed to the substances with only very short contact times (15 min). All in all, we present new concepts for the design of cancer selective peptide-drug conjugates.


Benzodiazepines have no effect on fear-potentiated startle in humans.
Pre-clinical and clinical investigations have provided a great deal of evidence that the fear-potentiated startle paradigm represents a valid model for the objective assessment of emotional states of anxiety and fear. The four studies presented in this report sought to further validate the "threat of shock" paradigm as a human analogue to fear-potentiated startle in rats, by examining the effect of benzodiazepine administration on both baseline and fear-potentiated startle. Three studies, conducted at Utrecht University, evaluated the effects of oxazepam and of diazepam on baseline and fear-potentiated startle, whereas a fourth study, conducted at Yale University, evaluated the effect of diazepam on baseline, contextual and cue-specific fear-potentiated startle. The threat of shock paradigm consisted of verbal instruction about two visual cues (the threat cue predicted the possible administration of electric shock, the other predicted a safe period), followed by a series of presentations of these cues. During these conditions, acoustic startle stimuli were presented in order to elicit startle responses. The magnitude of the startle response was used to index the degree of fear or alarm experienced during the periods of threat and safety. The fourth study examined the effect of IV administration of diazepam in a similar threat of shock paradigm except that there were two additional context manipulations: electrode placement and darkness. None of the drug manipulations affected specific threat-cue potentiation of startle. However, reductions in baseline startle were observed. Further, startle potentiation by darkness was inhibited by diazepam. At least one type of fear-potentiated startle, i.e. potentiation by a cue-specific fear manipulation, is not susceptible to benzodiazepine treatment. In contrast, effects of manipulations more akin to anxiety (darkness, context) appear sensitive to benzodiazepines. Human experimental models differentiating between these cue specific and contextual responses are needed to shed more light on differences in the anatomy and pharmacology of anxiety disorders.


Testing a Method Based on an Improved UNet and Skeleton Thinning Algorithm to Obtain Branch Phenotypes of Tall and Valuable Trees Using Abies beshanzuensis as the Research Sample.
Sudden changes in the morphological characteristics of trees are closely related to plant health, and automated phenotypic measurements can help improve the efficiency of plant health monitoring, and thus aid in the conservation of old and valuable tress. The irregular distribution of branches and the influence of the natural environment make it very difficult to monitor the status of branches in the field. In order to solve the problem of branch phenotype monitoring of tall and valuable plants in the field environment, this paper proposes an improved UNet model to achieve accurate extraction of trunk and branches. This paper also proposes an algorithm that can measure the branch length and inclination angle by using the main trunk and branches separated in the previous stage, finding the skeleton line of a single branch via digital image morphological processing and the Zhang-Suen thinning algorithm, obtaining the number of pixel points as the branch length, and then using Euclidean distance to fit a straight line to calculate the inclination angle of each branch. These were carried out in order to monitor the change in branch length and inclination angle and to determine whether plant branch breakage or external stress events had occurred. We evaluated the method on video images of Abies beshanzuensis, and the experimental results showed that the present algorithm has more excellent performance at 94.30% MIoU as compared with other target segmentation algorithms. The coefficient of determination (R2) is higher than 0.89 for the calculation of the branch length and inclination angle. In summary, the algorithm proposed in this paper can effectively segment the branches of tall plants and measure their length and inclination angle in a field environment, thus providing an effective method to monitor the health of valuable plants.


Relationship between the Luscher Color Test and the MMPI.
Administered the short form of the Luscher Color Test and the booklet form of the MMPI to 42 graduate students in a counseling program. For every S a report that described personality was written from the test results, i.e., each S had two reports, one from the Color Test and one from the MMPI. These reports were written independently by two separate examiners. Two independent raters then read the reports on each S and noted the degree of agreement between the two reports. The overall results showed very little agreement between the Color Test and the MMPI. Reasons for the poor rate of agreement are discussed.


Estimated glomerular filtration rate in Korean patients exposed to long-term lithium maintenance therapy.
Lithium-induced nephrotoxicity has long been debated. However, it has been rarely explored in Asian populations. The aim of the present study was to assess the effect of lithium maintenance therapy on estimated glomerular filtration rate (eGFR) in Korean patients diagnosed with a psychiatric illness. This was a single-centered, retrospective study that included patients treated with lithium or comparator drug (valproate) in Samsung Seoul Medical Center between November 1994 and July 2020. Patients diagnosed with ICD codes F20-33 who had ≥ 6 months of exposure to lithium or valproate were included. Patients had to have ≥ 1 baseline and ≥ 2 post-baseline eGFR data with post-baseline data having an interval of at least 30 days. Chronic kidney disease (CKD) was defined as CKD stage 3 (eGFR < 60 mL/min/1.732). To be considered as CKD, the threshold had to be met at two consecutive post-baseline measurements. Those treated with both lithium and valproate, diagnosed with CKD stages 3-5, diagnosed with a renal disease, or received kidney transplantation were excluded. A total of 766 patients were included (242 treated with lithium and 524 with valproate). Two (0.8%) in the lithium group and 8 (1.5%) in the valproate group developed CKD stage 3. None developed CKD stages 4-5. Median yearly eGFR change was - 1.3 mL/min/1.732 (IQR: - 6.8, 1.7) for the lithium group and - 1.1 mL/min/1.732 (IQR: - 4.5, 1.5) for the valproate group, showing no significant difference between the two groups (p = 0.389). The rate of decline was more rapid for those with CKD in both groups. eGFR values of lithium and valproate groups did not show significant differences during a follow-up duration of 15 years or more. A significant negative correlation between baseline eGFR and yearly eGFR change was identified in a linear regression analysis. In Korean patients, treatment with lithium did not increase the risk of developing CKD compared to treatment with valproate. Prevalence of CKD was lower than those previously reported in western populations. Low baseline eGFR showed significant correlation with changes in renal function.


[Exposure assessment to harmful agents in workplaces in sewage plant workers].
The purpose of the study was to evaluate exposure to biological and chemical agents in a sewage treatment plant. Sampling was carried out in the summer and wintertime at the morning workshift. Ninety-nine sewage workers taking part in the study were divided into four occupational subgroups: mechanical treatment, biological treatment, sewage sludge treatment, and operation control workers. Exposure to: H2S, SO2, Pb, Cd, Cr3+, Cr6+, endotoxins, (1 --> 3)-beta-D glucans, and microorganisms was evaluated with special identification of Gram-negative rods. The concentrations of dust containing heavy metals and concentrations of gases from all stations did not exceed MAC values. Concentrations of endotoxins ranged from 0.08 to 223 ng/m3, and glucans from 0.00 to 163 ng/m3. The highest concentrations were found among sewage sludge treatment workers, in the summertime (geometric mean value = 37 ng/m3). In the winter, concentrations were almost ten times lower. Over sixty percent of all results exceeded the proposed reference value for airborne endotoxins (10 ng/m3). Concentrations of airborne bacteria in the sewage plant were at low level (10(2)( cfu/m3), except the sludge lagoon and sludge concentration building, where the results exceeded the proposed reference value for mesophilic bacteria (10(5) cfu/m3) "Environmental" bacteria (Pseudomonas, Burkholderia, Shewanella) predominated in the samples. There were also found enterobacteria genus (Enterococcus, family Enterobacteriaceae)--good indicators of hygienic cleanliness of the air. The study proved that the exposure varied and depended on the stage of sewage treatment. The sewage sludge treatment process was characterized by the highest emission of bioaerosols. All microorganisms found in the sewage plant belong to the second occupational risk group, under the ordinance of the Ministry of Health.


Class II Eplet Mismatch Modulates Tacrolimus Trough Levels Required to Prevent Donor-Specific Antibody Development.
Despite more than two decades of use, the optimal maintenance dose of tacrolimus for kidney transplant recipients is unknown. We hypothesized that HLA class II de novo donor-specific antibody (dnDSA) development correlates with tacrolimus trough levels and the recipient's individualized alloimmune risk determined by HLA-DR/DQ epitope mismatch. A cohort of 596 renal transplant recipients with 50,011 serial tacrolimus trough levels had HLA-DR/DQ eplet mismatch determined using HLAMatchmaker software. We analyzed the frequency of tacrolimus trough levels below a series of thresholds <6 ng/ml and the mean tacrolimus levels before dnDSA development in the context of HLA-DR/DQ eplet mismatch. HLA-DR/DQ eplet mismatch was a significant multivariate predictor of dnDSA development. Recipients treated with a cyclosporin regimen had a 2.7-fold higher incidence of dnDSA development than recipients on a tacrolimus regimen. Recipients treated with tacrolimus who developed HLA-DR/DQ dnDSA had a higher proportion of tacrolimus trough levels <5 ng/ml, which continued to be significant after adjustment for HLA-DR/DQ eplet mismatch. Mean tacrolimus trough levels in the 6 months before dnDSA development were significantly lower than the levels >6 months before dnDSA development in the same patients. Recipients with a high-risk HLA eplet mismatch score were less likely to tolerate low tacrolimus levels without developing dnDSA. We conclude that HLA-DR/DQ eplet mismatch and tacrolimus trough levels are independent predictors of dnDSA development. Recipients with high HLA alloimmune risk should not target tacrolimus levels <5 ng/ml unless essential, and monitoring for dnDSA may be advisable in this setting.


Treatment of secondary syphilis: an evaluation of 204 patients.
Our recommended treatment schedule for secondary syphilis is intramuscular benzathine penicillin G, 2.4 million units weekly for two consecutive weeks. If the patient is allergic to penicillin, we recommend that 2 gm of oral tetracycline be given each day for 12 days. Two hundred and four patients with secondary syphilis were treated with these schedules; 165 were given benzathine penicillin G and 39 received tetracycline. All of the patients were cured clinically and all achieved seronegativity within 24 months. There was a direct correlation between the duration of the rash and the secondary lesions that the patients exhibited. Patients who presented early in the course of illness tended to have macular and maculopapular lesions, whereas those who appeared later were more likely to have papular of pustular lesions. The serologic response to treatment was correlated with the duration of the rash and the appearance of the secondary lesions. Patients whose rash was of short duration and those with macular and maculopapular lesions became seronegative sooner than those patients whose rash was of longer duration and who had papular or pustular lesions.


A retrospective study of pathologic findings in cephalopods (extant subclasses: Coleoidea and Nautiloidea) under laboratory and aquarium management.
This retrospective study examines pathologic findings in 593 captive cephalopods (340 octopuses, 130 cuttlefish, 33 squid, and 90 nautiluses; 22 species in total) submitted to International Zoo Veterinary Group Pathology between May 2003 and August 2022. Common octopus, European common cuttlefish, hummingbird bobtail squid, and chambered nautilus were the most numerous species from the included orders of Octopoda, Sepiida, Sepiolida, and Nautilida, respectively. Commonly identified conditions included coccidiosis and renal dicyemid mesozoan infection in octopuses, amebiasis in squid, bacterial infections in cuttlefish, and idiopathic multisystemic inflammatory disease in nautiluses. Coccidiosis was most frequent in common octopuses, giant Pacific octopuses, and California 2-spot octopuses (present in 68.4%, 46.3%, and 23.8% of these species, respectively) and was the attributed cause of death in 32.3%, 36.0%, and 60.0% of such cases, respectively. Ulcerative dermatitis (UD) was common, affecting squid, cuttlefish, and octopuses, while many nautiluses exhibited black shell disease and/or UD. Notable differences in the prevalence of UD were detected between laboratory and aquaria-housed decapodiforms; 52.2% for laboratory squid versus 20.0% in aquaria; 51.3% in laboratory cuttlefish versus 11.0% in aquaria. All octopuses and nautiluses in the study were derived from aquaria. Semelparity-associated death in Coleoidea species was identified in 22.4% of octopuses, 11.5% of cuttlefish, and 6.1% of squid. This report aims to provide an overview and reassessment of species-specific disease patterns under aquarium and laboratory management as a starting point for future developments in husbandry and disease investigation.


Anemia and pregnancy outcomes: a longitudinal study.
To determine the prevalence of anemia at the first antenatal visit and at 32-34 weeks gestational age, and to evaluate perinatal and maternal outcomes. Venous blood samples were obtained for complete blood counts at both study visits. Maternal and perinatal morbidity and mortality were also recorded. The data were analyzed using SPSS (version 23). Two thousand pregnant women were recruited. The prevalence of anemia was 42.7% (n = 854/2000) at the first antenatal visit. Thirty-five percent had mild anemia and 68.9% had normocytic normochromic anemia. The prevalence of anemia in HIV infected women was higher than that in the noninfected group and 47.2% of the study population (n = 2000) was HIV infected. At the 32-34 weeks visit, hemoglobin (Hb) levels were available for 1433/2000 (71.7%) of the participants. The prevalence of anemia was 28.1% (n = 403/1433); 19.3% had mild anemia and 65.3% had normocytic normochromic anemia. There was a significant difference in Hb levels between that of the first visit and that at 32-34 weeks (42.7% vs. 28.1%; p = .001; 95% CI: 0.11-0.18). There were significant differences in prematurity, birth weight and hypertensive disorders of pregnancy between the anemic and nonanemic groups. The prevalence of anemia decreased from 42.7% (booking) to 28.1% (32 - 34 weeks). Normocytic normochromic anemia was the commonest type of anemia. Attention needs to be focused on detailed investigations to establish the exact cause of anemia.


Voltage-clamp predictions by gompertz kinetics model relating squid-axon Na+-gating and ionic currents.
Gompertz kinetics is a simple, realistic, accurate, and computationally parsimonious alternative for prediction of macroscopic changes in Na+ conductance during voltage clamp. Conductance delay and time course depend on initial amplitudes and decay rates of surrogates for the macroscopic gating currents. The model is tested by the fit to published data of other authors. The proposed physical basis for the model is that membrane potential perturbation triggers motion of charged "gating" components of the axon membrane at rapid (activating) and at slow (inactivating) rates. The resulting distortion increases and more slowly diminishes the probability that conduction channels will be open.


Induction of ferritin synthesis in human lung epithelial cells treated with crocidolite asbestos.
Crocidolite asbestos is a known human carcinogen containing 27% iron by weight. It has previously been shown that iron was mobilized intracellularly from crocidolite after treatment of human lung epithelial cells (A549) and that the toxicity of the fibers was directly related to how much mobilized iron was in the < 10,000 MW (low-molecular-weight, LMW) fraction [C. C. Chao, L.G. Lund, K. R. Zinn, and A. E. Aust (1994) Arch. Biochem. Biophys. 314, 384-391]. The data here show that iron mobilization from crocidolite began immediately after treatment of the A549 cells and increased linearly with time. However, the synthesis of ferritin, an iron storage protein, did not begin until after 4 h of treatment, reaching a sustained maximum after 12 h. Mobilized iron was preferentially incorporated into the nonferritin-protein fraction up to 7 h after treatment, when the amount of iron mobilized was low and before significant accumulation of newly synthesized ferritin had occurred. This suggested that these cultured cells needed additional iron for synthesis of iron-requiring proteins and that iron mobilized from crocidolite could be utilized directly for this purpose. Subsequent to this, additional mobilized iron was incorporated into newly synthesized ferritin. Even though iron from crocidolite was incorporated into newly synthesized ferritin or into other proteins, the amount of iron from crocidolite in the LMW fraction remained constant during the 24 h. Thus, it appeared that synthesis of ferritin may not have fully protected the cells from the toxic effects of iron mobilized from crocidolite.


The Diagnostic Yield of Brugada Syndrome After Sudden Death With Normal Autopsy.
Familial evaluation after a sudden death with negative autopsy (sudden arrhythmic death syndrome; SADS) may identify relatives at risk of fatal arrhythmias. This study aimed to assess the impact of systematic ajmaline provocation testing using high right precordial leads (RPLs) on the diagnostic yield of Brugada syndrome (BrS) in a large cohort of SADS families. Three hundred three SADS families (911 relatives) underwent evaluation with resting electrocardiogram using conventional and high RPLs, echocardiography, exercise, and 24-h electrocardiogram monitor. An ajmaline test with conventional and high RPLs was undertaken in 670 (74%) relatives without a familial diagnosis after initial evaluation. Further investigations were guided by clinical suspicion. An inherited cardiac disease was diagnosed in 128 (42%) families and 201 (22%) relatives. BrS was the most prevalent diagnosis (n = 85, 28% of families; n = 140, 15% of relatives). Ajmaline testing was required to unmask the BrS in 97% of diagnosed individuals. The use of high RPLs showed a 16% incremental diagnostic yield of ajmaline testing by diagnosing BrS in an additional 49 families. There were no differences of the characteristics between individuals and families with a diagnostic pattern in the conventional and the high RPLs. On follow-up, a spontaneous type 1 Brugada pattern and/or clinically significant arrhythmic events developed in 17% (n = 25) of the concealed BrS cohort. Systematic use of ajmaline testing with high RPLs increases substantially the yield of BrS in SADS families. Assessment should be performed in expert centers where patients are counseled appropriately for the potential implications of provocation testing.


Assessment and interpretation of aerobic fitness in children and adolescents.
Our understanding of the development of children and adolescents' aerobic fitness is limited by ethical considerations and methodological constraints. Protocols, apparatus, and criteria of maximal effort used with adults are often unsuitable for use with children. In normal children and adolescents, peak VO2 increases with growth and maturation, although there are indications that girls' peak VO2 may level off around 14 years of age. Males exhibit higher values of peak VO2 than females, and the sex difference increases as they progress through adolescence. The difference between males and females has been attributed to the boys' greater muscle mass and hemoglobin concentration. It appears that boys experience an adolescent growth spurt in peak VO2, which reaches a maximum gain near the time of PHV, but data are insufficient to offer any generalization for girls. Peak VO2 has usually been expressed in relation to body mass, and with this convention it appears that boys' values are consistent throughout the developmental period, whereas girls' values decrease as they get older. This type of analysis may, however, have clouded our understanding of growth and maturational changes in peak VO2, and scaling for differences in body size may provide further clarification. If differences are shown where none were previously thought to exist, then physiological explanations must be sought. Methodological issues have also hindered the understanding of how children's blood lactate responses to exercise develop. The actual lactate level recorded during an exercise test is influenced by the site of sampling and the blood handling and assay techniques. Valid interstudy comparisons can only be made where similar procedures have been employed. In general, children demonstrate lower blood lactate levels at peak VO2 than adults, although individual variation is wide. Therefore the use of blood lactate measures to confirm the attainment of peak VO2 cannot be supported. Exercise at the same relative submaximal intensity elicits a lower blood lactate in children than in adults, but interpretation and identification of developmental and maturational patterns of response are limited by the use of different testing conditions and reference points (e.g., lactate threshold and fixed level reference points). There is growing evidence that the 2.5 mM reference level should be used in preference to the 4.0 mM level, as the adult criterion occurs close to maximal exercise in many children and adolescents. Explanations for child-adult differences in blood lactate responses to exercise are difficult to elucidate.(ABSTRACT TRUNCATED AT 400 WORDS)


Erythropoietin-activated ERK/MAP kinase enhances GATA-4 acetylation via phosphorylation of serine 261 of GATA-4.
GATA-4, a zinc finger transcription factor, plays a critical role in heart development. Previous studies have shown that p300-targeted GATA-4 acetylation increases GATA-4 stability and transcriptional activity, which then stimulates hypertrophy of cardiomyocyte. Erythropoietin (EPO), an essential hypoxia-induced hormone for normal erythropoiesis, is known to exert cardioprotective effects against heart disease of either ischemic or non-ischemic origins. Although, various action mechanisms of EPO have been proposed in the diseased heart, its action mechanism in normal condition has not been investigated. In this study, we aimed to investigate the influence of EPO-induced ERK signaling on the regulation of GATA-4 protein action. EPO treatment increased the protein level of endogenous GATA-4 via ERK signaling pathway. Inhibition of ERK activity by U0126, suppressed EPO-induced expression of GATA-4 protein in rat cardiac myocytes. In addition, ERK activation by over-expression of constitutively active MEK1 strongly increased GATA-4 phosphorylation and subsequently enhanced its acetylation in P19 cells. EPO-induced ERK activation further increased the association of GATA-4 with p300. On the other hand, knock-down of p300 using siRNA diminished ERK-induced GATA-4 acetylation. As EPO-induced GATA-4 phosphorylation via ERK signaling pathway directly correlated with GATA-4 acetylation, we investigated to identify the ERK-dependent phosphorylation sites in GATA-4. Site-directed mutagenesis implicated that Ser-261 in GATA-4 played an important role for ERK-mediated GATA-4 acetylation. Taken together, these results indicated that EPO-induced ERK signaling activation increased GATA-4 phosphorylation and acetylation, partly via increase in the association between GATA-4 and p300, and these processes required the phosphorylation of GATA-4 at Ser-261 residue.


Challenges to promoting health for amateur athletes through anti-doping policy.
Anti-doping regulations are intended, at least in part, to promote the health of athletes. While most anti-doping efforts target elite and professional competitors, there have been recent moves by sport governing bodies to expand anti-doping testing to include amateur athletes. Drawing on previous critiques of anti-doping policies and illustrating cases, this article outlines five of the challenges to health promotion of applying the current detect and ban model to the amateur level of sport. I argue that the current approach is not effective and, in some ways, may undermine the goal of health promotion at the amateur level. In order to address these challenges, I propose alternative, health-centred strategies that focus on athlete empowerment and choice through critical awareness of a variety of substances, associated risks and rewards, and the role of expertise in decision-making.


[A brief history of traditional Chinese medicinal pills].
Traditional Chinese medicine pill, an archaic medicinal preparation form, is a kind of spherical or spherical-like preparation form produced by medicinal powders or extracts mixed with appropriate excipient or other accessories. It was originated in the Pre-Qin Dynasty, developed and enriched from the Han Dynasty to the Ming and Qing Dynasties. With the improvement of preparing process, honeyed pill, waxed pill, coating pill and wax-coating pill etc. appeared in succession. In modern times, with the progress of pharmaceutical machine, the medicinal pill is innovated constantly, and at present, it becomes the main form of Chinese patent medicine with batch production.


Nucleolar localization of the human telomeric repeat binding factor 2 (TRF2).
The telomeric repeat binding factor 2 (TRF2) specifically recognizes TTAGGG tandem repeats at chromosomal ends. Unexpectedly immunofluorescence studies revealed a prominent nucleolar localization of TRF2 in human cells, which appeared as discrete dots with sizes similar to those present in the nucleoplasm. The TRF2 dots did not overlap with dots stemming from the upstream binding factor (UBF) or the B23 protein. After treatment with a low concentration of actinomycin D (0.05 microg/ml), TRF2 remained in the nucleolus, although this condition selectively inhibited RNA polymerase I and led to a relocalization of UBF and B23. TRF2 was prominent in the nucleolus at G0 and S but seemed to diffuse out of the nucleolus in G2 phase. During mitosis TRF2 dispersed from the condensed chromosomes and returned to the nucleolus at cytokinesis. Treatment with low doses of actinomycin D delayed the release of TRF2 from the nucleolus as cells progressed from G2 phase into mitosis. With actinomycin D present TRF2 was detected in discrete foci adjacent to UBF in prophase, while in metaphase a complete overlap between TRF2 and UBF was observed. TRF2 was present in DNase-insensitive complexes of nucleolar extracts, whereas DNA degradation disrupted the protein-DNA complexes consisting of Ku antigen and B23. Following treatment with actinomycin D some of the mitotic cells displayed chromosome end-to-end fusions. This could be correlated to the actinomycin D-suppressed relocalization of TRF2 from the nucleolus to the telomeres during mitosis. These results support the view that the nucleolus may sequester TRF2 and thereby influences its telomeric functions.


Guillain-Barré syndrome triggered by influenza vaccination in a recipient of liver transplant on FK506.
Guillain-Barré syndrome (GBS) has been rarely reported after liver transplantation and generally has good outcome. We report a liver transplant patient on FK506 (tacrolimus) who developed GBS 6 months after liver transplantation. There was no evidence of liver rejection or active infection. Despite treatment with intravenous immunoglobulin, the patient expired. GBS occurred despite downregulation of T cells by FK506, suggesting that humoral dysfunction might be the predominant mechanism of GBS in this report.


The changing pattern of pediatric both-bone forearm shaft fractures among 86,000 children from 1997 to 2009.
Forearm fractures are common among children. Unlike most pediatric fractures, there is a risk of unsatisfactory results in forearm shaft fractures. The healing of a tubular bone is most unlikely in the diaphysis far away from the metaphyseal zones. The treatment of forearm shaft fractures is evolving. The purpose of the study was to analyze the pattern of forearm shaft fractures and their treatment in a population of children in recent years. All the children (from 0 to 16 years) with a both-bone forearm shaft fracture (AO-segment 22-D) during the years 1997 to 2009 in a catchment area of about 86,000 children were included in this population-based study. There were 291 fractures in all. The age-related annual incidences, background factors, seasonal variation, injury types, treatment, reoperations, and short-term outcome were determined. The incidence of all forearm shaft fractures increased threefold in 1997 to 2009 (p < 0.001). Boys predominated (70%) over the girls (p < 0.001). The mean age of the patients was 8.7 years (SD, +/- 3.8) among both genders. The fractures were most common in August and most uncommon in December (p < 0.001). A fall in the playground was the most common type of injury (34%). Ninety-two percent of all patients (N = 269) were treated in the operating room and 44% (N = 119) were invasively stabilized. The incidence of invasive surgery held stable. However, elastic stable intramedullary nailing (ESIN) increased from 10% in 1998-2000 to 30% in 2007-2009 (p = 0.043). There were 77 reoperations (26%); reoperation rate was 5% (6/119) and 41% (N = 71/172) in the invasive and non-invasive treatment groups, respectively. Twenty-three percent of the patients referred did not have better than "good" short-term results. The "excellent" short-term outcome was increasing (p = 0.031). We found two mega-trends in pediatric forearm shaft fractures in the period from 1997 to 2009: First, the number of fractures was increasing significantly. Second, the forearm shaft fractures were increasingly treated by an invasive intramedullary method. We also found a significant seasonal variation, but the reason for it is not clear. The findings are based on valuable population-based data and the results are certain. Pediatric trauma centres should prepare themselves for on-going changes in forearm shaft fractures.


Liver tumor promoting effect of omeprazole in rats and its possible mechanism of action.
Omeprazole (OPZ), a proton pump inhibitor, is a cytochrome P450 (CYP) 1A1/2 inducer. Some CYP1A inducers are known to have liver tumor promoting effects in rats and the ability to enhance oxidative stress. In this study, we performed a two-stage liver carcinogenesis bioassay in rats to examine the tumor promoting effect of OPZ (Experiment 1) and to clarify a possible mechanism of action (Experiment 2). In Experiment 1, male F344 rats were subjected to a two-third partial hepatectomy, and treated with 0, 138 or 276 mg/kg OPZ by oral gavage once a day for six weeks after an intraperitoneal injection of N-diethylnitrosamine (DEN). Liver weights significantly increased in the DEN+OPZ groups, and the number and area of glutathione S-transferase placental form (GST-P) positive foci significantly increased in the DEN+276 mg/kg OPZ group. In Experiment 2, the same experiment as Experiment 1 was performed, but the dosage of OPZ was 0 or 276 mg/kg. The number and area of GST-P positive foci as well as liver weights significantly increased in the DEN+276 mg/kg OPZ group. The number of proliferative cell nuclear antigen (PCNA)-positive cells also significantly increased in the same group. Real-time RT-PCR showed that the expression of AhR battery genes including Cyp1a1, Cyp1a2, Ugt1a6 and Nqo1, and Nrf2 battery genes including Gpx2, Yc2, Akr7a3, Aldh1a1 Me1 and Ggt1 were significantly upregulated in this group. However, the production of microsomal reactive oxygen species (ROS) and formation of thiobarbituric acid-reactive substances (TBARS) decreased, and 8-hydroxydeoxyguanosine (8-OHdG) content remained unchanged in this group. These results indicate that OPZ, CYP1A inducer, is a liver tumor promoter in rats, but oxidative stress is not involved in the liver tumor promoting effect of OPZ.


Therapeutic effect of Keap1-Nrf2-ARE pathway-related drugs on age-related eye diseases through anti-oxidative stress.
Age-related eye diseases, including cataract, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), are the leading causes of vision loss in the world. Several studies have shown that the occurrence and development of these diseases have an important relationship with oxidative stress in the eye. The Keap1-Nrf2-ARE pathway is a classical pathway that resists oxidative stress and inflammation in the body. This pathway is also active in the development of age-related eye diseases. A variety of drugs have been shown to treat age-related eye diseases through the Keap1-Nrf2-ARE (Kelch-like ECH-Associating protein 1- nuclear factor erythroid 2 related factor 2-antioxidant response element) pathway. This review describes the role of oxidative stress in the development of age-related eye diseases, the function and regulation of the Keap1-Nrf2-ARE pathway, and the therapeutic effects of drugs associated with this pathway on age-related eye diseases.


The reproducibility of the respiratory responses to maximum exercise.
In order to investigate the reproducibility of maximum progressive exercise we studied 6 healthy volunteers twice a day for 3 nonconsecutive days. The average within-subject coefficients of variation for the maximal ventilatory and heart rate (HR) responses ranged from 3.8% for HR to 12% for minute ventilation (Ve) and anaerobic threshold. Three-way analysis of variance revealed no significant variations in exercise parameters for the group as a whole except for the carbon dioxide output (VCO2) and respiratory exchange ratio (R) which was significantly greater in the afternoon (p less than 0.05). This was attributed to dietary effects of carbohydrate loading upon VCO2 and was associated in 1 subject with a significant increase in Ve (p less than 0.01). In another subject, morning values of Ve were consistently and significantly (p less than 0.05) greater than the afternoon values which could only be attributed to increased effort as indicated by an increased oxygen uptake. Tests of resting pulmonary mechanics (FEV1, FVC, FRC, RAW) measured before each exercise procedure showed no significant diurnal or day-to-day variations. Results indicate that while the maximal responses to progressive exercise are generally reproducible and the first exercise procedure can usually be considered representative, diurnal variations in R, VCO2 and Ve may occur which can be best avoided on repeated testing by exercising subjects at a standardized time of day.


Early breast cancer: significance and effectiveness of local control by conservative surgery and primary radiation therapy.
The significance of local-regional control in patients with early breast cancer is examined in the light of data from recent studies. Information from prospectively randomized studies assessing early detection, surgical and radiation therapy procedures, and adjuvant systemic therapies, supports the importance of achieving optimal local-regional control. In most patients effective local control can be achieved without removal of the breast. Wide excision of the primary tumor, axillary dissection and radiation therapy, result in good local control and survival rates that are equal to those achieved with radical mastectomy. The historical development of alternatives to mastectomy is described. Recent data from retrospective and prospective randomized studies evaluating the effectiveness of limited surgery and primary radiotherapy are reviewed and analyzed.


Tale of a wandering spleen: 1800 degree torsion with infarcted spleen and secondary involvement of liver.
Wandering spleen is a rare clinical entity characterized by splenic hypermobility resulting from laxity or maldevelopment of the suspensory splenic ligaments. The spleen can "wander" or migrate into various positions within the abdomen or pelvis due to this ligamentous laxity. It is usually detected between 20 and 40 years of age, and is more common in women. The clinical presentation of a wandering spleen is variable, it could present as an asymptomatic, incidentally detected, abdominal or pelvic mass, or as an acute abdomen secondary to splenic torsion. Diagnosis in an emergent setting can be challenging as it is a rare cause of acute abdomen and does not produce any symptoms until splenic torsion has occurred. We present and discuss a case of ectopic, torsed spleen resulting in complete infarction of the spleen and severe hepatic vascular compromise, diagnosed by ultrasound, confirmed by computed tomography and effectively managed by splenectomy.


Cardiometabolic risk management: insights from a European Society of Cardiology Cardiovascular Round Table.
Metabolic comorbidities are common in patients with cardiorenal disease; they can cause atherosclerotic cardiovascular disease (ASCVD), speed progression, and adversely affect prognosis. Common comorbidities are Type 2 diabetes mellitus (T2DM), obesity/overweight, chronic kidney disease (CKD), and chronic liver disease. The cardiovascular system, kidneys, and liver are linked to many of the same risk factors (e.g. dyslipidaemia, hypertension, tobacco use, diabetes, and central/truncal obesity), and shared metabolic and functional abnormalities lead to damage throughout these organs via overlapping pathophysiological pathways. The COVID-19 pandemic has further complicated the management of cardiometabolic diseases. Obesity, T2DM, CKD, and liver disease are associated with increased risk of poor outcomes of COVID-19 infection, and conversely, COVID-19 can lead to worsening of pre-existing ASCVD. The high rates of these comorbidities highlight the need to improve recognition and treatment of ASCVD in patients with obesity, insulin resistance or T2DM, chronic liver diseases, and CKD and equally, to improve recognition and treatment of these diseases in patients with ASCVD. Strategies to prevent and manage cardiometabolic diseases include lifestyle modification, pharmacotherapy, and surgery. There is a need for more programmes at the societal level to encourage a healthy diet and physical activity. Many pharmacotherapies offer mechanism-based approaches that can target multiple pathophysiological pathways across diseases. These include sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, selective mineralocorticoid receptor antagonists, and combined glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist. Non-surgical and surgical weight loss strategies can improve cardiometabolic disorders in individuals living with obesity. New biomarkers under investigation may help in the early identification of individuals at risk and reveal new treatment targets.


Preparation of glass solutions of three poorly water soluble drugs by spray drying, melt extrusion and ball milling.
The aim of this study was to investigate the influence of the manufacturing process on the physicochemical properties of three poorly water soluble compounds (carbamazepine, dipyridamole, and indomethacin) when processed with a polymer (polyvinylpyrrolidone K30 (PVP)) at a 1:2 drug to polymer ratio. Melt extrusion, spray drying, and ball milling techniques were used to prepare glass solutions. Product homogeneity, dissolution, physical stability, and drug/polymer interactions were investigated. Particular attention was paid to solid phase analysis using XRPD, modulated temperature DSC, optical microscopy, and Raman microscopy and the importance of using a combination of techniques was demonstrated. The latter technique when applied to freshly ball milled samples exhibited the presence of drug and polymer rich areas, indicating that complete glass solution formation had not occurred. The three compounds produced products with differing physical stability with indomethacin proving the most physically stable. These differences in physical stability were attributed to hydrogen bonding of drug and polymer. The manufacturing technique did not influence physical stability, but it did affect dissolution. The dissolution of the spray-dried material was generally poor, compared to melt extruded and ball milled products. This was probably due to rapid dissolution of PVP from the small particles of the spray-dried products.


[Cost-effectiveness of the treatment of acute and chronic rhinosinusitis at the IMSS].
Rhinosinusitis is one of the more common diseases encountered in outpatient visits to health care. The objective of this study was to determine the most cost-effective antibiotic treatment for patients with acute (RSA) and chronic rhinosinusitis (RSC) that is available at the Mexican Institute of Social Security (IMSS). Cost-effectiveness analysis of RSA and RSC treatment from an institutional perspective. Effectiveness outcome was defined as the percentage of cure. A decision tree with a Bayesian approach included the following therapeutic alternatives: ciprofloxacin, gatifloxacin, trimetoprim/sulfametoxazol (TMP/SMX), amoxicilin/clavulanic acid (AAC) and clindamicin. Treatment for RSA with AAC showed a mean cost per cured patient of $ 878 pesos. The remaining antibiotics had a higher cost per unit of success, and therefore the results showed that AAC was the best alternative considering this criterion. The therapy that showed a larger percentage of cured patients in RSC was clindamicin; however, the therapeutic alternative with the lowest cost per successful unit was the one based on ciprofloxacin, which dominates gatifloxacin and AAC. The most cost-effective alternative in the antibiotic treatment of patients with RSA was ACC while for RSC it was ciprofloxacin; sensitivity analysis showed the strength of the base study results.


The role of angiotensin receptor blockers in heart failure.
The effectiveness of ACE inhibitors in reducing morbidity and mortality in patients with heart failure is largely attributable to their suppression of angiotensin II production. Despite chronic therapy with ACE inhibitors, angiotensin II levels may be incompletely suppressed and contribute to the high mortality of patients with heart failure. Recently, angiotensin receptor blockers, which block the effects rather than the production of angiotensin II, have become available. Angiotensin receptor blockers have been evaluated as both monotherapy and in combination with ACE inhibitors. In short term studies, angiotensin receptor blocker monotherapy appears to share many of the hemodynamic and clinical features of ACE inhibitors. In a long-term study, the Losartan Heart Failure Survival Study, angiotensin receptor blockers failed to demonstrate any beneficial effect over that seen with ACE inhibitors. The addition of an angiotensin receptor blocker to an ACE inhibitor appears to exert favorable short term hemodynamic, clinical, and neurohormonal effects. Four ongoing trials, Valsartan Heart Failure Trial, Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity, Optimal Therapy in Myocardial Infarction with Angiotensin II Antagonist Losartan study, and Valsartan In Acute Myocardial Infarction study, are evaluating the role of angiotensin receptor blockers either alone or in combination with ACE inhibitors in the management of left ventricular dysfunction. (c)2000 by CHF, Inc.


Two-Dimensional Crystallization of Rylene Diimide Based n-Type Semiconductors Tuned by the Dimensions of the Aromatic Core at the Liquid-Solid Interface.
The investigation of semiconductors at the surface provides opportunities to observe and understand the mechanism of molecular interaction for the design of semiconductors so that organic electronics with good performance can be built. Herein, the 2D crystallization of rylene diimide based n-type semiconductors (i.e., 1-4) was explored at the liquid-highly oriented pyrolytic graphite interface by means of scanning tunneling microscopy. Rylene diimides 1-3 with increased aromatic dimensions show different surface crystallization behaviors and distinguished 2D patterns. The surface chirality was also found to be directly affected by the aromatic dimensions. The 2D patterns and the surface chirality could also be tuned by the nature of the solvent. In addition, molecular symmetry was found to be of great important for the formation of long-range ordered 2D monolayers. This investigation highlights the importance of the rational design of molecular dimensions and geometrical symmetry in achieving determined 2D nanopatterns on surfaces, especially for the rylene diimide based n-type semiconductors.


[FGF23 and the heart].
The prevalence of chronic kidney disease (CKD) has now reached epidemic proportions and it is very likely that it will continue to rise with the increasing prevalence of juvenile diabetes mellitus, hypertension and aging population. CKD is a risk factor for cardiovascular disease (CVD) and cardiovascular disease can lead to CKD. It is also well known that patients with CKD have a higher risk of death from CVD than of progressing to end-stage renal disease that requires renal replacement therapy. In patients with CKD, there is a higher mortality from sudden cardiac death and congestive heart failure than coronary artery disease, which is not the case in the general population. The high prevalence of congestive heart failure in CKD is due to cardiac remodeling which progresses from concentric remodeling to concentric and eccentric hypertrophy, leading to left ventricular hypertrophy with both systolic and diastolic dysfunction. Recent studies have suggested that, in patients with chronic kidney disease, common traditional risk factors for cardiovascular disease such as hypertension, hyperlipidemia and obesity may not be the main determinants of cardiovascular disease. Among the various non-traditional cardiovascular risk factors present in patients with chronic kidney disease, abnormalities of CKD related mineral and bone disorder, which includes elevated fibroblast growth factor 23 (FGF23) have been one of the most extensively studied. However, after many years of research, the debate over the exact pathways by which FGF23 may lead to increased CVD still continues. FGF23 may have both direct and indirect effects on the cardiovascular system. Better understanding of the most relevant pathophysiologic pathways for FGF23 may lead to therapeutic interventions against cardiovascular disease in patients with CKD.


Interaction of NBD-labelled fatty amines with liquid-ordered membranes: a combined molecular dynamics simulation and fluorescence spectroscopy study.
A complete homologous series of fluorescent 7-nitrobenz-2-oxa-1,3-diazol-4-yl-(NBD) labelled fatty amines of varying alkyl chain lengths, NBD-Cn, inserted in 1-palmitoyl, 2-oleoyl-sn-glycero-3-phosphocholine (POPC) or N-palmitoyl sphingomyelin (SpM) bilayers, with 50 mol% and 40 mol% cholesterol (Chol), respectively, was studied using atomistic molecular dynamics simulations. For all amphiphiles in both bilayers, the NBD fluorophore locates at the interface, in a more external position than that previously observed for pure POPC bilayers. This shallower location of the NBD group agrees with the lower fluorescent quantum yield, shorter fluorescence lifetime, and higher ionisation constants (smaller pKa) determined experimentally. The more external location is also consistent with the changes measured in steady-state fluorescence anisotropy from POPC to POPC/Chol (1 : 1) vesicles. Accordingly, the equilibrium location of the NBD group within the various bilayers is mainly dictated by bilayer compositions, and is mostly unaffected by the length of the attached alkyl chain. Similarly to the behaviour observed in POPC bilayers, the longer-chained NBD-Cn amphiphiles show significant mass density near the mixed bilayers' midplanes, and the alkyl chains of the longer derivatives, mainly NBD-C16, penetrate the opposite bilayer leaflet to some extent. However, this effect is quantitatively less pronounced in these ordered bilayers than in POPC. Similarly to POPC bilayers, the effects of these amphiphiles on the structure and dynamics of the host lipid were found to be relatively mild, in comparison with acyl-chain phospholipid analogues.


Vibrio cholerae 0139 'Bengal' in Singapore.
Vibrio cholerae 0139 was isolated from five patients with cholera-like illness. All were imported cases. Laboratory investigations found our five isolates in show similar morphological, biochemical and serological characteristics to the V. cholerae 0139 strains causing epidemics in Bangladesh and India. Our isolates were toxin producers resistant to streptomycin and co-trimoxazole. No local transmission was known to have occurred following introduction of these imported cases.


[The sequence of the alpha-amylase inhibitor Hoe-467 A (alpha-amylase inactivator Hoe-467 A) from Streptomyces tendae 4158].
An alpha-amylase inhibitor isolated from Streptomyces tendae, strain 4158 was re-purified by chromatography on CM- and DEAE-cellulose column. Two inhibitors could be characterized: alpha-amylase inhibitor Hoe-467 A (with aspartic acid as N-terminal residue), and alpha-amylase inhibitor Hoe-467 S (with serine as N-terminal residue). The primary structure was determined by automatic Edman-degradation procedures of the aziranized inhibitor and tryptic peptides, derived from digestions of the performic oxidized, aziranized and maleylated inhibitor, respectively. The alpha-amylase inhibitor Hoe-467 A consists of 74 residues and has a calculated molecular weight of 7958. It is composed of all common amino acids except methionine and phenylalanine. Digestion with pepsin was carried out to determine the disulfide bonds. Two fractions could be isolated, containing one cystine each giving information about the positions of the disulfide bridges. The possible clinical application of the inactivator (diabetes mellitus) is pointed out.


Tat, Tat-associated kinase, and transcription.
The HIV-1 Tat protein is an RNA-binding transcriptional transactivator. Recent findings suggest that Tat associates with a cellular kinase that phosphorylates the carboxyl-terminal domain of the largest subunit of RNA polymerase II. Here we review, in brief, the role of Tat-associated kinase in Tat-activated transcription. We discuss evidence that suggests involvement of TFIIH and/or P-TEFb.


Laparoscopic pyeloplasty for ureteropelvic junction obstruction in crossed fused ectopic pelvic kidney.
Crossed fused renal ectopia is a rare anomaly and may be associated with pelvic ureteric junction obstruction (PUJO). The L-shaped fusion variety is even rarer. We report such a case with a crossed fused ectopic pelvic kidney (L-type) with PUJO and its successful laparoscopic management. Through this report we emphasize the importance of adequate preoperative imaging and intraoperative details to avoid mishaps.


Perceptions and experiences of young Black South African women with obesity from a low socioeconomic community after following a 12-week structured exercise intervention.
Previous research has shown that Black South African (SA) women perceive a bigger body size to be acceptable and desirable, but nonetheless have shown interest in participating in community-based exercise programmes. This study aimed to investigate perceptions and experiences of participating in a 12-week exercise intervention designed to study the mechanisms of insulin sensitivity and secretion in young Black SA women with obesity. Qualitative data was collected from young (23 ± 2.9 years) Black SA women (n = 17) residing in a low-income setting in Cape Town, who took part in a 12-week structured exercise intervention. Focus group discussions (FGDs) and in-depth interviews (IDIs) were conducted 1-4 months after the completion of the intervention. These were all audio recorded and took between 45 and 60 min. The recordings were transcribed, translated and qualitative content analysis, entailing a systematic process of coding and identification of salient themes, was conducted using the ATLAS.ti software. Six broad themes were identified from participants' experiences and perceptions: motivational factors, acceptability of the programme, barriers, sustainability and influencing others, benefits of being physically active, definitions and perceptions of exercise. Anticipated weight loss and financial remuneration were identified as motivational factors for enrolment and retention in the exercise programme. Aspects of the training environment and feelings of wellness appeared in the acceptability, sustainability and benefits themes, whereas time scheduling and travel constraints were regarded as barriers. Exercise was perceived as the maintenance of a healthy body, and in some cases, only relevant for specific groups. Financial considerations played an important role in participants enrolling and staying in the 12-week exercise intervention. Participants liked many aspects of the intervention and identified physical and mental benefits that seemingly outweighed the barriers and disliked aspects of the programme. Optimizing the acceptability of exercise programmes and maximizing the opportunity for participants to experience improved mental well-being may contribute to attracting and retaining young Black SA women in exercise programmes.


A genomic perspective on the generation and maintenance of genetic diversity in herbivorous insects.
Understanding the processes that generate and maintain genetic variation within populations is a central goal in evolutionary biology. Theory predicts that some of this variation is maintained as a consequence of adapting to variable habitats. Studies in herbivorous insects have played a key role in confirming this prediction. Here, we highlight theoretical and conceptual models for the maintenance of genetic diversity in herbivorous insects, empirical genomic studies testing these models, and pressing questions within the realm of evolutionary and functional genomic studies. To address key gaps, we propose an integrative approach combining population genomic scans for adaptation, genome-wide characterization of targets of selection through experimental manipulations, mapping the genetic architecture of traits influencing fitness, and functional studies. We also stress the importance of studying the maintenance of genetic variation across biological scales-from variation within populations to divergence among populations-to form a comprehensive view of adaptation in herbivorous insects.


Selective operative cholangiography in the performance of laparoscopic cholecystectomy.
The objective of this prospective study was to evaluate the role of intraoperative cholangiography (IOC) for patients undergoing laparoscopic cholecystectomy (LC) to determine whether it could be safely omitted for all patients who fit standard criteria, namely normal liver function tests, no history of gallstone pancreatitis, common bile duct (CBD) diameter less than 10 mm or previous history of jaundice. Data were collected prospectively from 194 consecutive patients who had LC for symptomatic gall bladder disease. IOC was not performed in any patient. The conversion rate was 6.1% and one CBD injury occurred. Our experience demonstrates that LC performed without routine IOC does not result in an increased incidence of retained stones in selected patients who have no history of pancreatitis, normal liver function tests and CBD less than 10 mm diameter.


The QSEN Competency Legacy Threaded Through the Entry-Level AACN Essentials: Shaping the Future.
For the last 17 years, the Quality and Safety Education for Nurses (QSEN) prelicensure competencies and knowledge, skill, and attitude (KSA) statements were integrated into nursing curricula. With the publication of the competency-based American Association of Colleges of Nursing (AACN) Essentials, it is important to determine the overlap of the QSEN competencies. We developed a QSEN-AACN prelicensure crosswalk to help faculty map and integrate the 2021 AACN Essentials into their curriculum. The 6 QSEN competencies match to the 10 AACN Essentials domains except for evidence-based practice, which is listed as a concept. Fifty graduate-level QSEN KSAs were found to better align with prelicensure education and therefore important to integrate into the crosswalk. All but 1 of the original prelicensure QSEN KSA statements and all but 2 of the 50 transferred graduate-level QSEN KSAs were found in the AACN Essentials. Faculty implementing the QSEN framework can use the QSEN-AACN competency crosswalk and QSEN teaching strategies to guide their AACN Essentials journey.


Artificial pedicle screw reconstruction of the cervical spine after lateral paramedian transpedicular approach for lesions of the ventral cervical spinal canal.
We describe in detail the anatomic and surgical principles of a lateral cervical paramedian transpedicular approach, a novel technique that provides access to the ventral cervical spinal canal. We also describe single-stage posterior column reconstruction of the cervical spine in which traditional cervical lateral mass screws are used simultaneously to reconstruct the cervical pedicle and to allow for three-column stabilization in a continuous posterior screw-rod construct after this approach. This technique is a modification of traditional thoracic posterolateral extracavitary approaches and has been used by our group for the resection of intradural and extradural spinal lesions, as we illustrate. This approach is particularly useful in cases where significant pathological characteristics of the trachea or esophagus preclude an anterior approach to the cervical spine and in cases in which multiple levels are involved. Cervical spinal stability is enhanced, because all cervical levels are incorporated into the final screw-rod construct.


Scenedesmus obliquus metabolomics: effect of photoperiods and cell growth phases.
Environmental factors directly affect the growth and composition of microalgal biomass. Therefore, the present work analyzed the metabolomics (amino acids, organic acids, and fatty acids) of the microalga Scenedesmus obliquus cultivated in 24:0 and 12:12 (light:dark) photoperiods and different phases of cell growth. Furthermore, the metabolites were related to protein, lipid, and chlorophyll contents at the end of cultivation. The highest biomass concentration (4020 mg L- 1) and protein (47.3%) were obtained in culture under constant illumination. The cultivation 12:12 (light:dark) photoperiod triggered higher production of lipids (23.0%) and chlorophylls (26.4 mg g- 1) by S. obliquus. Microalgal metabolites were greatly affected by photoperiod and by phase of cell growth. Thus, metabolite production could be related to both the environmental conditions under which cultivation occurred and to the different concentrations of products (proteins, lipids, and chlorophylls) present in the S. obliquus biomass.


New molecular probes of vascular inflammation.
New molecular imaging approaches featuring the assessment of inflammatory processes in the vascular wall on top of existing anatomic and functional vessel imaging procedures could emerge as decisive tools for the understanding and prevention of cardiovascular events. In this respect imaging approaches addressing specific molecular and cellular targets in atherosclerosis are of high interest. This review summarizes the rationale and current status of nuclear imaging probes which possess high translational potential.


Links Between Reactive Attachment Disorder, Caregiving and Temperament: A Differential Susceptibility Perspective.
The links between Reactive Attachment Disorder (RAD) and temperament received relatively little research attention, in spite of their clinical and social relevance. Children with RAD sustain disproportionate burdens of early adversity related to their caregiving environment. However, there seem to be important individual differences in susceptibility to adversity, since only a small number of children show signs of RAD. Based on the work of Zeanah and Fox, this review aims to bring new insights to this relevant clinical issue in light of recent research. A differential susceptibility hypothesis will be considered as a promising and innovative approach toward a further understanding of the links between temperament and RAD.


Binding of exogenous cyanide reveals new active-site states in [FeFe] hydrogenases.
[FeFe] hydrogenases are highly efficient metalloenyzmes for hydrogen conversion. Their active site cofactor (the H-cluster) is composed of a canonical [4Fe-4S] cluster ([4Fe-4S]H) linked to a unique organometallic di-iron subcluster ([2Fe]H). In [2Fe]H the two Fe ions are coordinated by a bridging 2-azapropane-1,3-dithiolate (ADT) ligand, three CO and two CN- ligands, leaving an open coordination site on one Fe where substrates (H2 and H+) as well as inhibitors (e.g. O2, CO, H2S) may bind. Here, we investigate two new active site states that accumulate in [FeFe] hydrogenase variants where the cysteine (Cys) in the proton transfer pathway is mutated to alanine (Ala). Our experimental data, including atomic resolution crystal structures and supported by calculations, suggest that in these two states a third CN- ligand is bound to the apical position of [2Fe]H. These states can be generated both by "cannibalization" of CN- from damaged [2Fe]H subclusters as well as by addition of exogenous CN-. This is the first detailed spectroscopic and computational characterisation of the interaction of exogenous CN- with [FeFe] hydrogenases. Similar CN--bound states can also be generated in wild-type hydrogenases, but do not form as readily as with the Cys to Ala variants. These results highlight how the interaction between the first amino acid in the proton transfer pathway and the active site tunes ligand binding to the open coordination site and affects the electronic structure of the H-cluster.


A Cost-Benefit Analysis of School Nursing in One Large Urban School District.
This study is a cost-benefit analysis examining an urban district's partial school nurse coverage conversion to full-time coverage. Through a partnership with a health care system, the district received funding, resulting in the hiring of full-time nurses to cover all K-8 elementary schools. Researchers compared the cost of nursing services to the savings in teacher, secretary, principal, and parent productivity, reduced medical procedure costs, and grants nurses managed. The year before implementing additional nurses, the return on investment (ROI) to the community for nursing services was calculated to be $1.59 for every dollar invested in schools with full-time coverage and $1.29 for schools with partial coverage. After implementing full-time nurses in each school, there was an ROI of $1.50 during the 2015-2016 school year, $1.64 for 2016-2017, and $1.67 for 2017-2018. The analysis provides evidence that full-time coverage could result in a positive ROI for schools and the community.


Intermittent Hypoxia in Preterm Neonates and Its Effect on Neonatal Morbidity and Mortality: A Systematic Review.
The goal of the present systematic review was to investigate the occurrence patterns of intermittent hypoxemia in newborns throughout the early postnatal period as well as the link between neonatal intermittent hypoxemia exposure and harmful consequences such as neonatal morbidity and death. We collected data from 2014 to 2023 using several abstracting, referencing, and indexing database libraries in the field of medical sciences. A total of 715 papers were evaluated by both authors, and only seven articles met the specified review criteria after a thorough analysis. In preterm neonates with intermittent hypoxia (IH), severe morbidities such as bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), motor impairment, and cognitive delay were found. Only one study that extended to 18 months noted mortality. The length and occurrence of intermittent hypoxemia and the stage of premature neonates at the time of delivery are all closely associated with these morbidities. Therefore, it becomes important to continuously measure the patterns of occurrence of intermittent hypoxemia during early postnatal life to avoid its long-term morbidity and mortality impact.


A TEF-1 binding motif that interacts with a placental protein is important for the transcriptional activity of the hCS-B enhancer.
The transcriptional activity of the human placental lactogen genes (choriosomatomammotropic hormone, hCS) is controlled by tissue-specific enhancers located 4 kb downstream from their respective origins of transcription. The hCS-B enhancer is the strongest; its activity is mediated by synergism between two protein-binding sites (DF-3 and DF-4). The DF-4 site possesses a potential binding sequence for TEF-1, a known transcription factor. In this paper, we show by electrophoretic mobility-shift assays and antibody supershift experiments that TEF-1 does not bind to site DF-4. Mutations in the TEF-1-like binding motif of site DF-4 prevent formation of the DNA-protein complex, called complex f, in the presence of placental JEG-3 cell extracts. When HeLa cell extracts are used, another complex (complex c) is also affected. In transient expression experiments, TKCAT constructs linked to this mutated DF-4 site exhibit greatly reduced transcriptional activity when introduced into JEG-3 cells. Some cell lines contain both protein c and protein f (the proteins forming complexes c and f); when transfected, these lines display reduced DF-4-driven activity, suggesting that the two proteins could compete for the same DF-4 sequence. We conclude that protein f is important for the placenta-specific activity of the hCS-B enhancer. By UV cross-linking, we show that protein f is actually three polypeptides ranging in size from about 12 to 21 kD.


Seroprevalence of Toxoplasma gondii in Nazareth Town, Ethiopia.
To determine seroprevalence of toxoplasmosis, assess its zoonotic importance and identify factors associated with seroprevalence. Questionnaire survey and serological studies. Questionnaire survey and 65 serum samples from male and female urban and peri-urban residents aged between 15 days and 65 years. Feeding habits, purpose of keeping cats and association with family members, serologic evidence of toxoplasmosis by the Modified Direct Agglutination Test (MDAT), examination of HIV status using the HIV-Spot Test. Over 86% of the interviewed people had a history of consumption of raw or undercooked mutton and had close contact with cats. Of the serum samples analyzed by the MDAT 60% had serologic evidence of Toxoplasma infection. Significantly higher MDAT tiers were encountered both in pregnant and immunocompromised individuals. The risk factors associated with Toxoplasma infection, i.e. raw or undercooked mutton consumption and presence of cats appeared significant. The significance of toxoplasmosis as a disease of zoonotic importance was demonstrated. Close contact between family members and the consumption of raw or undercooked mutton were the major risk factors in the transmission of the disease. Considering the relatively high prevalence as revealed by this study it would be important to conduct studies on a wider scale. It would also be important to increase public awareness and upgrade the knowledge on congenital toxoplasmosis.


A multiple logistic regression analysis of risk factors in different subtypes of gastric ulcer.
To elucidate the relationship among disparate ulcer risk factors in 3 subtypes of gastric ulcer. One hundred and fifty-nine age-matched controls, 30 patients with ulcer craters in the gastric body (GU-I), 55 with coexistent gastroduodenal ulcer (GU-II), and 69 with ulcer craters in the prepyloric region (GU-III) were examined for potential risk factors. These included cigarette smoking, nonsteroidal anti-inflammatory drug use, Helicobacter pylori infection, gender and ABO blood group. Using multiple logistic regression analysis, Odds ratios of relevant risk factors associated with different subtypes of gastric ulcer were reported. Among all gastric ulcer subsets, cigarette smoking, nonsteroidal anti-inflammatory drugs use and H. pylori infection were independent ulcer risk factors. For GU-I, smoking (OR: 3.98; 95% CI: 1.44-11.0) and nonsteroidal anti-inflammatory drugs use (OR: 4.33; 95% CI: 1.10-17.1) raised the likelihood of ulceration. For GU-II and GU-III, smoking, nonsteroidal anti-inflammatory drug use and H. pylori infection were identified as risk factors. H. pylori infection carried the strongest association with gastroduodenal ulcer (OR: 9.29; 95% CI: 3.11-27.7) in GU-II, and nonsteroidal anti-inflammatory drug use generated the highest possibility of GU-III (OR: 11.3; 95% CI: 3.49-36.5). Nonsteroidal anti-inflammatory drug use also markedly raised the likelihood of multiple gastric ulcers (OR: 17.0; 95% CI: 4.21-68.9). Stratification analysis showed differential influences of risk factors on separate subtypes of gastric ulcer. These data support the hypothesis that peptic ulcer disease is heterogeneous in etiology and pathogenesis.


Revisiting the syntactic abilities of non-human animals: natural vocalizations and artificial grammar learning.
The domain of syntax is seen as the core of the language faculty and as the most critical difference between animal vocalizations and language. We review evidence from spontaneously produced vocalizations as well as from perceptual experiments using artificial grammars to analyse animal syntactic abilities, i.e. abilities to produce and perceive patterns following abstract rules. Animal vocalizations consist of vocal units (elements) that are combined in a species-specific way to create higher order strings that in turn can be produced in different patterns. While these patterns differ between species, they have in common that they are no more complex than a probabilistic finite-state grammar. Experiments on the perception of artificial grammars confirm that animals can generalize and categorize vocal strings based on phonetic features. They also demonstrate that animals can learn about the co-occurrence of elements or learn simple 'rules' like attending to reduplications of units. However, these experiments do not provide strong evidence for an ability to detect abstract rules or rules beyond finite-state grammars. Nevertheless, considering the rather limited number of experiments and the difficulty to design experiments that unequivocally demonstrate more complex rule learning, the question of what animals are able to do remains open.


Pseudo-hyperthyroidism: Biotin interference in a case with renal failure.
Biotin treatment causes false-low or false-high results in some immunoassays methods. This phenomenon is called as biotin interference. In the present article, a seven-month-old male, with renal failure and laboratory hyperthyroidism due to biotin interference is presented. High free T4 (fT4), free T3 (fT3), anti-thyroid peroxidase antibody (anti-TPO), anti-thyroglobulin antibody (anti-TG) and low thyroid stimulating hormone (TSH) levels were detected in a seven-month-old male patient who has metabolic acidosis, renal failure, and suspected of metabolic disease. Anti-thyroid drug therapy was started. However, when he was re-evaluated due to the absence of euthyroidism with anti-thyroid therapy (methimazole 0.8 mg/kg /day), it was found that the patient had been given 20 mg/day biotin for acidosis for two months. Biotin interference was considered in hormone measurement. Thyroid function tests were found to be normal 12 days after discontinuation of biotin therapy. Immunoassay measurements which use biotin should be done 2-7days after the last dose of biotin in patients under biotin treatment, but this time may need be much longer in renal failure patients. During this period or if the biotin therapy cannot be stopped, alternative methods should be preferred for analysis.


Histological analysis of the Ankylos peri-implant soft tissues in a dog model.
The importance of the soft tissue-implant interface is enhanced by the presence of a microgap between the implant and the abutment, which represents a contamination site for bacteria. The aim of this study was to investigate the interface between the Ankylos gap-free implant system and the surrounding soft tissues in a dog model. Six Labrador dogs were included in the study and two Ankylos implants were inserted per dog. The dogs were killed 6 months after abutment placement without functional loading and without plaque control. The implants were analysed histologically by scanning electron microscopy, light microscopy, and histomorphometry. Some sections exhibited histologic signs of a mild inflammation. The connective tissue between the most apical epithelial cells of the junctional epithelium and the alveolar crest was characterized by collagen fibers running from the periosteum and the alveolar crest toward the oral epithelium and, in front of the cone-shaped abutment, by a narrow zone of extracellular matrix with a few collagen fibers. Compared with results obtained in other studies using different types of implant (Astra, Bränemark, ITI), the Ankylos implant showed a higher length and a larger width of connective tissue contact as well as a shorter epithelial downgrowth. The absence of a microgap in the Ankylos system could explain the histologic mild inflammation in the connective tissue.


Reduced expression and proteolytic susceptibility of lubricin/superficial zone protein may explain early elevation in the coefficient of friction in the joints of rats with antigen-induced arthritis.
To investigate the effect of arthritis development and progression on the integrity and function of lubricin and the relationship of lubricin to cartilage damage in a rat antigen-induced arthritis model. Arthritis was induced in the right knee joints, using methylated bovine serum albumin and Freund's complete adjuvant. Whole joint friction measurements were performed ex vivo with a modified Stanton pendulum configuration, and coefficients of friction (mu) were determined. Levels of messenger RNA (mRNA) for lubricin, cathepsin B, and interleukin-1beta (IL-1beta) in synovial tissue from control and affected joints were determined by quantitative polymerase chain reaction. Lubricin staining in cartilage was performed using a lubricin-specific monoclonal antibody. The mu values in excised right joints following arthritis induction were significantly (P < 0.001) higher than those in excised left joints. Lubricin mRNA expression levels in synovial tissue on days 4 and 7 after arthritis induction were significantly (P < 0.001) lower in the right joints compared with the left joints, whereas levels of cathepsin B and IL-1beta mRNA expression on days 4, 7, and 14 were significantly (P < 0.001) higher in the right joints than the left joints. Lubricin staining was diminished in cartilage from the right joints compared with the left joints. Elevated coefficients of friction in arthritic joints occur concurrently with enhanced proteolytic degradation by up-regulated cathepsin B and other proteases, as well as decreased lubricin synthesis by synovial fibroblasts and superficial zone chondrocytes. Loss of joint lubrication is an early event in inflammatory arthropathy. Restoring chondroprotection and preventing potential wear-induced cartilage degradation may require lubricin supplementation in synovial fluid.


Ground reaction forces in Greyhounds with tibial nerve injury.
To measure ground reaction force variables during lameness resulting from impaired tibial nerve function and to determine whether these variables changed significantly as recovery progressed. 11 healthy Greyhounds of either sex, weighing between 22 and 39 kg. On 3 consecutive days before surgery, ground reaction forces were measured by force platform gait analysis at the trot. In dogs under general anesthesia, the left tibial nerve was crushed proximal to innervation of the gastrocnemius muscle. Gait analyses were repeated on days 8 to 10, 28 to 30, 43 to 45, 58 to 60, and 90 to 92 after surgery. Ground reaction force variables and stance time were compared among the 3-day clusters. 10 days after surgery, all dogs had weight-bearing lameness attributed to paralysis of muscles in the caudal compartment of the crus. Nerve regeneration resulted in functional recovery within 3 months. Decreases in vertical force were significant 10 days after surgery; thereafter, changes reflected gradual return of load bearing, with the most marked improvement between 10 and 45 days. At 90 days, vertical force variables were within 3% of presurgical values. Stance time for the left hind limb was significantly longer at 10, 30, and 45 days after surgery and was seen in all dogs, but returned to within 1 % of preoperative stance time at 90 days. The effect of tibial nerve dysfunction on braking or propulsive force was not significant. The significant changes in vertical ground reaction forces in hind limbs of dogs during lameness that resulted from impaired tibial nerve function are detectable, as is response during recovery, by use of force platform analysis.


Cu-Catalyzed Synthesis of Fluoroalkylated Isoxazoles from Commercially Available Amines and Alkynes.
A one-pot protocol for the construction of fluoroalkylated isoxazoles directly from commercially available amines and alkynes is described. The reaction is scalable, operationally simple, regioselective, mild, and tolerant of a broad range of functional groups. As such, it could be viewed as a "click synthesis" of fluoroalkylated isoxazoles. Preliminary mechanistic investigations reveal that the transformation involves an unprecedented Cu-catalyzed cascade sequence involving RfCHN2.


Acute flaccid paraparesis (cauda equina syndrome) in a patient with Bardet-Biedl syndrome.
Bardet-Biedl syndrome (BBS) is a rare, autosomal-recessive, debilitating genetic disorder, which can present with multitudinous systemic clinical features including rod-cone dystrophy, polydactyly, Frohlich-like central obesity, mental retardation, hypogonadism, and renal anomalies. Diverse neuromuscular manifestations in patients afflicted by this heterogeneous disorder include ataxia, cervical, and thoracic canal stenoses, presenting as spastic quadriparesis and other gait disturbances. We report a young patient with BBS, who had presented with acute flaccid paraparesis due to severe primary lumbar canal stenosis. She underwent immediate lumbar decompression and discectomy following which she recovered significantly. Acute cauda equina syndrome due to primary lumbar canal stenosis has not been reported as a clinical feature of BBS previously.


Dehydration Dynamics in Terrestrial Arthropods: From Water Sensing to Trophic Interactions.
Since the transition from water to land, maintaining water balance has been a key challenge for terrestrial arthropods. We explore factors that allow terrestrial arthropods to survive within a variably dry world and how they shape ecological interactions. Detection of water and hydration is critical for maintaining water content. Efficient regulation of internal water content is accomplished by excretory and osmoregulatory systems that balance water intake and loss. Biochemical and physiological responses are necessary as water content declines to prevent and repair the damage that occurs during dehydration. Desiccation avoidance can occur seasonally or daily via a move to more favorable areas. Dehydration and its avoidance have ecological impacts that extend beyond a single species to alter trophic interactions. As climate changes, evolutionary and ecological processes will be critical to species survival during drought.


The trajectory of cognitive development in males with fragile X syndrome.
The trajectory of cognitive development in males with fragile X syndrome was identified in a cross-sectional study of 56 males and in a smaller, longitudinal study of 10 fragile X males. Results from both studies indicated steady cognitive growth until late childhood and early adolescence (10 to 15 years of age), at which point mental age plateaued and IQ declined. Males with higher initial IQ scores manifested more IQ decline than those with initial lower levels of intelligence. The trajectories of IQ differ from those in other etiological groups and mixed groups of retarded individuals. Results have direct implications for intervention strategies with fragile X males. Parents and teachers should be informed about the possibility of an early plateau in mental age, the impact this may have on the child's academic performance, and that the plateau and IQ decline may not be apparent in the child's adaptive behaviors.


A newly invasive species may promote dissimilarity of pest populations between organic and conventional farming systems.
Insect taxa vary in their phenology across space creating dissimilar patterns of species abundance over time. The role of human disturbances and invasive species in these patterns of temporal dissimilarity (phenological differences) across space, however, remain largely unexplored. To dissect these patterns, we evaluated four common pests and one newly invasive species (Contarinia nasturtii; Swede midge) at 220 time points across 2 years on organic and conventional farms. We first summarized across time and evaluated differences in pest abundance between farm management (organic and conventional). We then used generalized additive models to describe temporal patterns of abundance, disentangling phenological differences across management systems. Last, we conducted a temporal beta diversity analysis to identify which species and management practices contribute most to dissimilarity. We found that aggregating pest abundance across time and species masked differences in pest phenology across management systems and concealed variation in pest abundance that was strongly driven by an invasive species, respectively. Overall, our results suggest that organic and conventional farms may be only superficially similar in pest abundance. Rather, by accounting for time, we demonstrate a more nuanced understanding of pest communities moving beyond abundance that may be particularly important for management of newly invasive species.


tRNAs in Trypanosoma brucei: genomic organization, expression, and mitochondrial import.
The mitochondrial genome of Trypanosoma brucei does not encode tRNAs. Consequently, all mitochondrial tRNAs are imported from the cytosol and originate from nucleus-encoded genes. Analysis of all currently available T. brucei sequences revealed that its genome carries 50 tRNA genes representing 40 different isoacceptors. The identified set is expected to be nearly complete since all but four codons are accounted for. The number of tRNA genes in T. brucei is very low for a eukaryote and lower than those of many prokaryotes. Using quantitative Northern analysis we have determined the absolute abundance in the cell and the mitochondrion of a group of 15 tRNAs specific for 12 amino acids. Except for the initiator type tRNA(Met), which is cytosol specific, the cytosolic and the mitochondrial sets of tRNAs were qualitatively identical. However, the extent of mitochondrial localization was variable for the different tRNAs, ranging from 1 to 7.5% per cell. Finally, by using transgenic cell lines in combination with quantitative Northern analysis it was shown that import of tRNA(Leu)(CAA) is independent of its 5'-genomic context, suggesting that the in vivo import substrate corresponds to the mature, fully processed tRNA.


Serum mannan-binding lectin in egyptian patients with chronic hepatitis C: its relation to disease progression and response to treatment.
Chronic hepatitis C virus (HCV) infection is a major worldwide public health problem. Egypt has the highest prevalence of adult HCV infection in the world, averaging 15%-25% in rural communities. Mannan-binding lectin (MBL) is a liver-derived pluripotent serum lectin that plays a role in the innate immune system of the host. It is an acute-phase protein that is involved in the activation of the classical complement pathway. MBL may play a defensive role in HCV infection. To investigate the relationship between MBL concentration and HCV infection in Egyptian patients suffering chronic hepatitis C. Serum samples obtained from 35 Egyptian hepatitis C patients and 30 normal controls were assayed for MBL. MBL concentrations were correlated to disease characteristics and treatment response. Serum MBL was significantly higher in HCV patients than in controls, but no relationship was found between MBL concentration and disease progression in terms of hepatic fibrosis and inflammation. Responders to interferon (INF)-based therapy had significantly higher serum MBL than non-responders. We found no association between serum MBL concentration and progression of HCV related liver disease. Responders to INF-based therapy had significantly higher serum MBL than non-responders.


External and internal hemipelvectomy: A retrospective analysis of 68 cases.
This study aims to investigate the factors that may be associated with surgical site infection and mortality in pelvic resection surgeries. A total of 68 patients (40 males, 28 females; mean age: 43±16.2 years; range, 11 to 70 years) who underwent internal or external hemipelvectomy between January 2010 and January 2020 were retrospectively analyzed. We reviewed data concerning histopathological diagnosis, surgical technique, pelvic resection type, tumor size, postoperative infection, duration of follow-up, and mortality. The mean follow-up was 45.5±42.2 months. Among 68 patients, 29 (42.6%) cases underwent external hemipelvectomy and 39 (57.4%) cases underwent internal hemipelvectomy. Reconstruction was performed in 14 (20.6%) patients who underwent internal hemipelvectomy. Of all patients, 61 had primary malignant pelvic tumors and two had metastatic pelvic tumors. Of the other five patients, two had a giant cell tumor, two had a pelvic hydatid cyst, and one had an aneurysmal bone cyst. The three most common pelvic tumors were chondrosarcoma (n=25, 36.7%), osteosarcoma (n=13, 19.1%), and Ewing sarcoma (n=8, 11.8%). Surgical site infections were observed in 34 (50.0%) patients. Of 34 patients, 15 (22.1%) had superficial infections and 19 (27.9%) had deep surgical infections. The superficial and deep infection rates were higher in the external hemipelvectomy group compared to internal hemipelvectomy (p=0.02). Patients with postoperative infection had a mean survival period of 36.0 months compared to 79.8 months in patients without infection (p=0.037). The patients treated with internal hemipelvectomy had a mean survival of 97.0 months compared to 25.7 months in patients treated with external hemipelvectomy (p<0.0001). The effect of Enneking stages of malignant pelvic tumors on survival was investigated using the Kaplan-Meier analysis. Cumulative survival decreased, as the stage progressed (p<0.0001). The type of surgical technique affects the possibility of postoperative infection. Postoperative infection, surgical method, and stage of the tumor are associated with survival.


Lipid profile disorders induced by long-term cessation of physical activity in previously highly endurance-trained subjects.
The objective of this study was to describe long-term detraining effects on lipid profile in previously highly endurance-trained athletes. The study design was longitudinal, with a 2-yr follow-up study of changes in lipid profile during hard training and detraining. Ten subjects trained for 2 yr (22 h/wk; two 47-wk training periods with a 5-wk recovery period), and the 10 others stopped training after wk 47. Main blood lipid profile parameters, energy intake, and body composition were measured at baseline (wk 1) and at wk 24, 47, 52, 76, and 99. Although food caloric intake was reduced (2411 +/- 256 vs. 5697 +/- 455 kcal/d, detraining vs. training), detraining induced a decrease in high density lipoprotein cholesterol and increases in fat mass (by 6.5 +/- 1.1 kg), body mass index, leptin, low density lipoprotein cholesterol, low density lipoprotein/high density lipoprotein ratio, and apolipoprotein B, although insulin resistance (determined by homeostasis model assessment) stabilization had previously occurred. Further disorders appeared in triglycerides (TG) metabolism during detraining, with a persistent increase in TG (from 1.0 +/- 0.3 to 1.4 +/- 0.3 mmol/liter), whereas glycerol decreased (from 88 +/- 9 to 73 +/- 8 micromol/liter), and very low density lipoprotein-TG, chylomicrons, and apolipoprotein C(3) remained stable. Plasma lipoprotein lipase activity decreased whereas hepatic lipase activity remained stable. As well as a rapid loss of endurance-training benefits for the cholesterolemic profile, detraining also induced disorders in TG metabolism, possibly as a result of the elevated TG turnover acquired with long-term hard training.


[Hypolipidemic effect of sulfated polysaccharides].
In experiments on hyperlipidemic rats it was observed the hypolipidemic effect of new sulfated polisaccharides-chitosan, lutelan and krilan sulfates, More pronounced decrease was established in VLDL and increase of HDL after sulfated polysaccharides treatment. The most distinct efficiency exhibites preparation with moledular mass of 20-40 x 10(3) D and the rate of sulfation 9-14%.


Immunity to adeno-associated virus-mediated gene transfer in a random-bred canine model of Duchenne muscular dystrophy.
Recombinant adeno-associated virus (rAAV)-mediated gene transfer has shown promise for treating diseases in various animal models including the mdx mouse model of Duchenne muscular dystrophy (DMD). In many cases, however, preclinical studies in inbred mice have not successfully predicted human clinical responses. To assess the potential clinical utility of treating human DMD patients by AAV-mediated gene delivery, we performed a series of direct intramuscular injections in random-bred wild-type dogs. AAV serotypes 2 and 6 carrying different promoter-transgene cassettes were produced as previously described for murine studies and administered intramuscularly. The injection sites were biopsied at various time points and analyzed for transgene expression and immunohistochemical analysis. In contrast to the generally nonimmunogenic nature of these vectors in murine studies, both AAV2 and AAV6 vectors elicited robust cellular immune responses regardless of the transgene expressed, the cellular specificity of the promoter, and the muscle type injected. Viral purification by various methods did not diminish T cell-mediated infiltration. Our data indicate that AAV2 and AAV6 capsid proteins can elicit primary cellular immune responses when injected into the skeletal muscle of random-bred dogs, and suggest the possibility of cellular immunity to AAV vectors in humans.


Experimental design and data analysis for array comparative genomic hybridization.
Array comparative genomic hybridization (aCGH) is a technique for measuring chromosomal aberrations in genomic DNA. With the availability of high-resolution microarrays, detailed characterization of the cancer genome has become possible. In this review, we discuss several issues in the generation and interpretation of aCGH data, including array platforms, experimental design, and data analysis. Due to the complexity of the data, application of appropriate statistical methods is crucial for avoiding false positive findings. We also describe integration of copy number data with other types of data to identify functional significance of observed aberrations.


Thyroidal modulation following hypo- and hyper-thermia in the soft-shelled turtle Lissemys punctata punctata Bonnoterre.
The aim of the current study was to investigate the effects of ambient temperature on thyroid activity of the soft-shelled turtle (Lissemys punctata pucntata). Turtles exposed to low ambient temperature (10 degrees C for 15 days) showed a significant decrease in relative thyroid weight, follicular cell size (cell became squamous from cuboidal type) and epithelial height in both the peripheral and central follicles of the gland, with the appearance of homogeneous colloid materials in the follicular lumen. Thyroid peroxidase activity declined significantly. In contrast, high ambient temperatures (32/34 degrees C for 15 days) caused reverse changes to those observed after exposure with low ambient temperature. No significant difference was marked in thyroid activity between 32 and 34 degrees C temperature treatments. The findings provide evidence that low ambient temperature inhibits thyroid activity and high ambient temperature stimulates the gland activity in soft-shelled turtles. Ambient temperature acts presumably via the hypothalamo-hypophysial (TRF-TSH) axis which in turn alters thyroid function in turtles.