Oxygen-derived free radical scavengers for amelioration of reperfusion damage in heart transplantation.
In this study we tried to define the possible benefits of the oxygen-derived free radical scavengers after 3 hours of cold myocardial global ischemia, as required in the setting of cardiac transplantation. Twenty-one pig hearts were harvested after preservation with a cold cardioplegic solution (St. Thomas' Hospital solution) and topical cooling. Normothermic reperfusion with blood was achieved with a special heart-lung machine preparation, which allows the heart to beat in a working or nonworking mode. Twelve hearts served as control hearts (group I), and nine (group II) were subjected to superoxide dismutase and catalase. Superoxide dismutase was applied at a dose of 40 U/ml of cardioplegic solution and 1500 U/kg body weight with the start of reperfusion. Catalase was added to the cardioplegic solution in a dose of 100 U/kg and 3500 U/kg body weight with the start of reperfusion. After 15 minutes of retrograde reperfusion, both left ventricular developed pressure and its first derivative were significantly higher in group II (137 +/- 7.6 mm Hg, 2467 +/- 162 mm Hg/sec) than in group I (105 +/- 6 mm Hg, 1676 +/- 231 mm Hg/sec, p less than 0.05 for each). In addition, a considerably higher coronary blood flow was observed in group II throughout the 180-minute period of reperfusion (p = 0.047). We therefore conclude that the combined administration of superoxide dismutase and catalase during the initial period of cardioplegic arrest and during early reperfusion of donor hearts submitted to 3 hours of cold ischemia has a beneficial effect on myocardial performance.


Combined use of algorithms for peak picking, peak tracking and retention modelling to optimize the chromatographic conditions for liquid chromatography-mass spectrometry analysis of fluocinolone acetonide and its degradation products.
A strategy for rapid optimization of liquid chromatography column temperature and gradient shape is presented. The optimization as such is based on the well established retention and peak width models implemented in software like e.g. DryLab and LC simulator. The novel part of the strategy is a highly automated processing algorithm for detection and tracking of chromatographic peaks in noisy liquid chromatography-mass spectrometry (LC-MS) data. The strategy is presented and visualized by the optimization of the separation of two degradants present in ultraviolet (UV) exposed fluocinolone acetonide. It should be stressed, however, that it can be utilized for LC-MS analysis of any sample and application where several runs are conducted on the same sample. In the application presented, 30 components that were difficult or impossible to detect in the UV data could be automatically detected and tracked in the MS data by using the proposed strategy. The number of correctly tracked components was above 95%. Using the parameters from the reconstructed data sets to the model gave good agreement between predicted and observed retention times at optimal conditions. The area of the smallest tracked component was estimated to 0.08% compared to the main component, a level relevant for the characterization of impurities in the pharmaceutical industry.


Epigenetic response to environmental stress: Assembly of BRG1-G9a/GLP-DNMT3 repressive chromatin complex on Myh6 promoter in pathologically stressed hearts.
Chromatin structure is determined by nucleosome positioning, histone modifications, and DNA methylation. How chromatin modifications are coordinately altered under pathological conditions remains elusive. Here we describe a stress-activated mechanism of concerted chromatin modification in the heart. In mice, pathological stress activates cardiomyocytes to express Brg1 (nucleosome-remodeling factor), G9a/Glp (histone methyltransferase), and Dnmt3 (DNA methyltransferase). Once activated, Brg1 recruits G9a and then Dnmt3 to sequentially assemble repressive chromatin-marked by H3K9 and CpG methylation-on a key molecular motor gene (Myh6), thereby silencing Myh6 and impairing cardiac contraction. Disruption of Brg1, G9a or Dnmt3 erases repressive chromatin marks and de-represses Myh6, reducing stress-induced cardiac dysfunction. In human hypertrophic hearts, BRG1-G9a/GLP-DNMT3 complex is also activated; its level correlates with H3K9/CpG methylation, Myh6 repression, and cardiomyopathy. Our studies demonstrate a new mechanism of chromatin assembly in stressed hearts and novel therapeutic targets for restoring Myh6 and ventricular function. The stress-induced Brg1-G9a-Dnmt3 interactions and sequence of repressive chromatin assembly on Myh6 illustrates a molecular mechanism by which the heart epigenetically responds to environmental signals. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.


Pattern of paediatric malignancies seen at the Radiotherapy Department of the University College Hospital, Ibadan, Nigeria.
Paediatric tumours are seen by the radiotherapist following referral from other specialists. Patients seen by the radiotherapists may not conform to the full spectrum seen in the hospital. To review the pattern of presentation of paediatric malignancies seen at the radiotherapy department of the UCH, Ibadan. Retrospective study of all patients below the age of 12 seen in Radiotherapy Department of UCH, Ibadan over a 19-year period was undertaken. Data were collected from the case files and the radiotherapy treatment cards. 244 cases were evaluated with age ranged between 4 months and 12 years. Male to female ratio was 1.15 to 1.0. 23 tumour types were seen with retinoblastoma accounting for about 45% of all the patients reviewed. Burkitt's lymphoma accounted for only about 2.5%. Retinoblastoma, nephroblastoma, intracranial malignancies and rhabdomyosarcoma are the tumours most commonly seen at the Radiotherapy Department of the UCH, Ibadan.


[Cluster size polymorphism of active human ribosomal genes and simulation of the conditions of its stability through generations].
Based on selective silver nitrate staining of active ribosomal gene (AcRG) clusters in nucleolus organizer regions (NORs) of human metaphase chromosomes, a technique was developed earlier to estimate the AcRG dosage in individual genomes as a sum of arbitrary units (0-3) ascribed to the silver precipitate (AgNOR) on ten NORs. The AcRG dosage was considered to be an additive quantitative trait determined by five polymorphic autosomal loci (with for allelic forms for each locus). A database was created to contain the data on AcRG cluster variants for more than 1000 individual human genomes. In this study, the population frequencies of AcRG cluster variants were determined. The results agreed with the hypothesis that stabilizing selection acts at the zygotic and/or early embryogenetic stage to restrain the AcRG genomic dosage (copy number) within a range from 14.9 to 23.7 arbitrary units (the cell is unviable when the trait is beyond this range). The average zygotic losses due to selection were estimated at 9.1-9.9% for a real population. A computer model where the AcRG dosage of a progeny results from a random combination of the AgNORs of the five acrocentric chromosome pairs of the parents was developed and used to simulate the formation of a certain AcRG genomic dosage through generations in a human panmictic population with nonoverlapping generations. A combination of stabilizing selection by total AcRG copy number and a certain spontaneous mutation rate (the probability of changes in the cluster size of a NOR as a result of unequal crossingover in meiotic prophase) was shown to be a sufficient condition for the restrain of equilibrium population frequencies of AgNOR size variants in a human panmictic population. Using the model, the most probable spontaneous mutation frequency was predicted to be (2.1-2.3) x 10(-2) per NOR per generation for human AgNORs. The predicted frequency was within the 95% confidence interval of the experimental rate, which was determined by studying the inheritance of AgNOR variants in real families.


Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma.
Previous study has shown that chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 4 (CMTM4) can bind and maintain programmed cell death ligand 1 (PD-L1) expression to promote tumor progression by alleviating the suppression of tumor-specific T cell activity, suggesting its potential role in tumor immunotherapy. However, the role of CMTM4 in tumor immunity has not been well clarified, especially in hepatocellular carcinoma (HCC). The protein expression of CMTM4/PD-L1/CD4/CD8 was detected by immunohistochemistry (IHC) detection in 90 cases of HCC tissues. The mRNA expression profiles and related prognosis data were obtained from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC). Two immune therapy cohorts were from Imvigor210 and GSE176307. Though the single protein expression of CMTM4, PD-L1, CD4 or CD8 in HCC tissues by IHC detection didn't show a significant relationship with the prognosis of HCC patients, we found that high co-expression of CMTM4/PD-L1/CD4 showed a good prognosis of HCC patients. Further Timer 2.0 analysis identified that HCC patients with high expression of CMTM4/PD-L1 and high infiltration of CD4+ T cells had a better overall survival than those with low infiltration of CD4+ T cells. Moreover, a series of bioinformatics analyses revealed that CMTM4-related genes posed important effects on prognosis and immunity in HCC patients, and CMTM4 had a positive correlation with infiltration of CD4+ and CD8+ T cells in HCC. At last, we used two immunotherapy cohorts to verify that the combination of CMTM4 with PD-L1 could improve the prognosis of tumor patients underwent immunotherapy. CMTM4 and PD-L1 co-expression with T cell infiltration shows prognostic significance in HCC, suggesting combined effect from multiple proteins should be considered in HCC treatment.


[Computer-assisted EEG in epileptic patients treated with intermittent normobaric hypoxic therapy in combined treatment of epilepsy].
The article presents an analysis of bioelectrical brain activity in patients with epilepsy during adaptation to intermittent normobaric hypoxia. Before adaptation and after the 1st, 4th, 20th adaptation sessions, resting EEG and EEG during hyperventilation were registered. By the end of the hypoxic trainings, a significant increase of spectral power of the EEG bands was found in resting EEG. At comparing bioelectrical activity in the resting condition and during hyperventilation, the difference between these indices decreased towards the end of hypoxic therapy course. This evidence argues for brain functions normalization during hypoxic therapy.


An introduction to critical points for biophysicists; observations of compositional heterogeneity in lipid membranes.
Scaling laws associated with critical points have the power to greatly simplify our description of complex biophysical systems. We first review basic concepts and equations associated with critical phenomena for the general reader. We then apply these concepts to the specific biophysical system of lipid membranes. We recently reported that lipid membranes can contain composition fluctuations that behave in a manner consistent with the two-dimensional Ising universality class. Near the membrane's critical point, these fluctuations are micron-sized, clearly observable by fluorescence microscopy. At higher temperatures, above the critical point, we expect to find submicron fluctuations. In separate work, we have reported that plasma membranes isolated directly from cells exhibit the same Ising behavior as model membranes do. We review other models describing submicron lateral inhomogeneity in membranes, including microemulsions, nanodomains, and mean field critical fluctuations, and we describe experimental tests that may distinguish these models.


Combination of Lipofilling With Liposuction in the Correction of Pseudo Genu Varus Deformity.
The combined use of lipofilling and liposuction has not been reported for the correction of pseudo genu varus deformity. The aim of this study was to evaluate the utility of combined liposuction and lipofilling for a bilateral correction of pseudo genu varus deformity based on a single-center experience over a 13-year period. A total of 72 patients with pseudo genu varus deformity treated with combined liposuction and lipofilling were included. Data on postoperative complications, the need for additional rounds of lipofilling, and aesthetic outcomes over an average of 5 years (range, 1-9 years) were recorded. Fat harvested from the upper medial portion of the knee was sufficient for lipofilling in 12 (16.7%) patients, and additional donor sites were used in 60 (83.3%) patients. A second round of lipofilling (average, 20 mL; range, 15-50 mL) was required in 17 (23.6%) patients within 6 months to 1 year after the operation. The need for additional lipofilling or liposuction was not noted for any other patients. None of the patients developed major complications such as fat necrosis, infections, contour deformities, or medial concavities during knee flexion. The current findings strongly suggest that the combined use of liposuction and lipofilling for the correction of pseudo genu varus deformity is a feasible, effective, and safe alternative that seems to offer additional benefits compared with fat grafting alone, including a fast recovery, a low risk of complications, and an increased likelihood of a long-lasting correction of the calf contour.


A systematic review and meta-analysis on the association between CD36 rs1761667 polymorphism and cardiometabolic risk factors in adults.
The cluster of differentiation 36 (CD36) is one of the main receptors implicated in the pathogenesis of the cardiovascular disease. This study aimed to assess the association between CD36 rs1761667 polymorphism and cardiometabolic risk factors including body mass index (BMI), waist circumference (WC), total cholesterol (TC), triglyceride, HDL-C, LDL-C, blood pressure and fasting blood glucose (FBG). PubMed, EMBASE, Scopus, web of science, and Google Scholar were searched up to December 2021. Subgroup and meta-regression analyses were conducted to explore sources of heterogeneity. Eighteen eligible studies (6317 participants) were included in the study. In the overall analysis, a significant association was found between rs1761667 polymorphism of CD36 and TG in allelic (p < 0.001), recessive (p = 0.001) and homozygous (p = 0.006) models. A relationship between this polymorphism and HDL-C and FBG level was observed in the recessive genetic model. In the subgroup analysis, the A allele was associated with impaired lipid profiles (TC, LDL-C and HDL-C) in the Asian population. The influences of health status, design of the study, confounders, and other sources of heterogeneity should be considered when interpreting present findings. Cohort studies with large sample size and in different ethnicities are needed to confirm the relationship between rs1761667 SNP and cardiometabolic risk factors.


Particle size, surface hydrophobicity and interaction with serum of parenteral fat emulsions and model drug carriers as parameters related to RES uptake.
Fat emulsions for parenteral nutrition, stabilized by egg lecithin, were characterized in terms of parameters relevant to uptake by the reticuloendothelial system (RES), e.g. size distribution, surface hydrophobicity and adsorption of serum components as a measure of the degree of opsonization. Adsorption of serum components was quantified by zeta potential measurement. Fat emulsions for nutrition were compared with emulsions used for drug delivery and model drug carries for intravenous injection. The emulsions for drug delivery were stabilized by the blockcopolymers Poloxamer 188 and 407 (Pluronic F68 and F127) and Poloxamine 908. Model drug carriers were hydrophobic and hydrophilic polystyrene latex particles. Hydrophilic particles were prepared by adsorption of Poloxamine 908 (coating) onto the particle surface. The hydrophobicity and serum protein adsorption decreased from hydrophobic latex particles to egg lecithin emulsions and blockcopolymer emulsions and particles. The data correlated with that in the literature concerning liver uptake in vivo showing complete RES clearance of hydrophobic latex particles, reduced uptake of egg lecithin emulsions and avoidance of RES uptake by Poloxamine 908 coated particles.


Cross-sectional study on the etiological diagnosis of the patients with chronic prostatitis-like symptoms by application of the urine-prostate-semen test.
The prostatic secretion was considered to be the most important and even only specimen in diagnosis and differential diagnosis of chronic prostatitis like symptoms, but little attention has been paid to other genital organ infections. A urine-prostate-semen test (U-EPS-S test) was used to investigate the microbial flora of internal genital organs in patients with chronic prostatitis-like symptoms and their influence on the diagnosis and treatment of the patients. We randomly selected the patients with chronic prostatitis-like symptoms for this study and used a U-EPS-S test to collect urine, prostatic secretion, and semen specimens. The specimens were inoculated respectively into a suitable culture medium for bacteriological/fungal detection, and the number and distribution of colonies in each isolation culture were observed before and after the therapy. All of the specimens from the internal genital organs of these patients were shown as microbe-positive isolation and the infection rate was 100%. Of these, prostatic secretion with microbe-positive isolation was obtained in 66 cases (33%), semen with microbe-positive isolation was obtained in 34 cases (17%), and both prostatic secretion and semen with microbe-positive isolation were obtained in 100 cases (50%). In the isolates, Gram-positive microbes were shown as the most common pathogens, accounting for 91.1%. In 200 patients, 95 patients were infected with one microbial species infection, of them 36 were prostatic secretion positive-isolation (18%), 20 were semen sample positive-isolation (10%), and 39 were positive-isolation both prostatic secretion and semen samples (19.5%); 104 patients were infected with two microbial species, of them 30 were prostatic secretion positive-isolation (15%), 14 were semen sample positive-isolation (7%), and 60 were positive-isolation both prostatic secretion and semen samples (30%); one patient was infected with three microbial species and them were isolated from the semen sample (0.5%). In the patients with chronic prostatitis-like symptoms, the multiple microbial infection (MMI) was accounted for 53.5%, and the multiorgan infection (MOI) was accounted for 67%. The U-EPS-S test is not only helpful to accurately identify the pathogens and contaminants in the culture isolates, but also the diagnosis and differential diagnosis and also evaluation of the treatment efficacy of the infection in different genital organs. In the patients with chronic prostatitis symptoms, Gram-positive microbes were the most common causative agents, and MMI and MOI caused by resistant strains of different microbial species have a high incidence.


GABAergic regulation of cell proliferation within the adult mouse spinal cord.
Manipulation of neural stem cell proliferation and differentiation in the postnatal CNS is receiving significant attention due to therapeutic potential. In the spinal cord, such manipulations may promote repair in conditions such as multiple sclerosis or spinal cord injury, but may also limit excessive cell proliferation contributing to tumours such as ependymomas. We show that when ambient γ-aminobutyric acid (GABA) is increased in vigabatrin-treated or decreased by GAD67 allele haplodeficiency in glutamic acid decarboxylase67-green fluorescent protein (GAD67-GFP) mice of either sex, the numbers of proliferating cells respectively decreased or increased. Thus, intrinsic spinal cord GABA levels are correlated with the extent of cell proliferation, providing important evidence for manipulating these levels. Diazepam binding inhibitor, an endogenous protein that interacts with GABA receptors and its breakdown product, octadecaneuropeptide, which preferentially activates central benzodiazepine (CBR) sites, were highly expressed in spinal cord, especially in ependymal cells surrounding the central canal. Furthermore, animals with reduced CBR activation via treatment with flumazenil or Ro15-4513, or with a G2F77I mutation in the CBR binding site had greater numbers of Ethynyl-2'-deoxyuridine positive cells compared to control, which maintained their stem cell status since the proportion of newly proliferated cells becoming oligodendrocytes or astrocytes was significantly lower. Altering endogenous GABA levels or modulating GABAergic signalling through specific sites on GABA receptors therefore influences NSC proliferation in the adult spinal cord. These findings provide a basis for further study into how GABAergic signalling could be manipulated to enable spinal cord self-regeneration and recovery or limit pathological proliferative activity.


Sarcomatoid renal carcinoma.
Sarcomatoid renal carcinoma made up 1 per cent of renal parenchymal tumors resected from 1967 to 1980. The majority of patients with this aggressive type of renal carcinoma were symptomatic and had a palpable renal mass at the time of diagnosis. Only 2 of 13 patients had tumor confined within the renal capsule at the time of operation. One of these patients survived and 12 of 13 died rapidly of metastatic renal carcinoma, with a median survival of 6.3 months from the time of diagnosis. This distinctive histologic variant of renal carcinoma has a highly malignant biological behavior and, as effective adjuvant treatment for renal carcinoma becomes available, should be one of the tumor types treated vigorously.


Intramuscular injection of mesenchymal stem cells activates anabolic and catabolic systems in mouse skeletal muscle.
Skeletal muscle mass is critical for good quality of life. Mesenchymal stem cells (MSCs) are multipotent stem cells distributed across various tissues. They are characterized by the capacity to secrete growth factors and differentiate into skeletal muscle cells. These capabilities suggest that MSCs might be beneficial for muscle growth. Nevertheless, little is known regarding the effects on muscle protein anabolic and catabolic systems of intramuscular injection of MSCs into skeletal muscle. Therefore, in the present study, we measured changes in mechanistic target of rapamycin complex 1 (mTORC1) signaling, the ubiquitin-proteasome system, and autophagy-lysosome system-related factors after a single intramuscular injection of MSCs with green fluorescence protein (GFP) into mouse muscles. The intramuscularly-injected MSCs were retained in the gastrocnemius muscle for 7 days after the injection, indicated by detection of GFP and expression of platelet-derived growth factor receptor-alpha. The injection of MSCs increased the expression of satellite cell-related genes, activated mTORC1 signaling and muscle protein synthesis, and increased protein ubiquitination and autophagosome formation (indicated by the expression of microtubule-associated protein 1 light chain 3-II). These results suggest that the intramuscular injection of MSCs activated muscle anabolic and catabolic systems and accelerated muscle protein turnover.


Glycolipid biosynthesis in rainbow trout: characterization of a beta 1----4galactosyltransferase independent from regulation by alpha-lactalbumin.
1. Rainbow trout (Salmo gairdneri) beta 1----4galactosyltransferase has been characterized and its properties compared to the mammalian enzyme. 2. Transfer of galactose to lactotriaosylceramide (Lc3) was optimal in the presence of 0.12% Triton CF-54 and Mn2+, in a pH range of 6.5-7.5. 3. Apparent Km values for donor UDPgalactose and acceptor Lc3 were determined to be 40 and 38 microM, respectively. 4. Glycolipid substrate specificity was found with only Lc3 being an efficient acceptor. Transfer of galactose to glycosylceramide, efficient with mammalian enzyme, was 42-fold slower. 5. In contrast to mammalian enzyme, rainbow trout beta 1----4galactosyltransferase was found to be independent from regulation by alpha-lactalbumin by the inability of alpha-lactalbumin-Sepharose to bind the enzyme and by failure of alpha-lactalbumin to inhibit the enzyme activity.


Habituation and recovery of a slow negative wave of the event-related brain potential.
This study is concerned with the question of whether the late, slow negative wave 2 (SNW2) component of the event-related brain potential is a component of the orienting response (OR). As habituation of the SNW2 would be an argument for such a link with the OR, it was investigated using a variant of the classical repetition/change paradigm. Results supported major claims to be made for a component of the OR: the amplitude of the vertex SNW2 exhibited roughly the typical exponential decline with repeated stimulations (six numeric verbal stimuli presented seriatim in an ascending order) and responded incrementally to a change, at least in a narrow time slot, i.e. it exhibited partial recovery to an out-of-sequence stimulus. These findings were accompanied by similar effects on an exemplary OR component, the skin conductance response, and on such possible components of the OR as heart rate deceleration and the vertex P3 of the event-related brain potential. In so far as OR components should behave in comparable fashion in response to orienting stimuli, it is thus reasonable to suppose that the SNW2 relates to the OR.


Acute effect of interval step exercise versus continuous walk exercise on cardiovascular parameters in hypertensive postmenopausal women: A clinical, controlled, and randomized study.
Aiming the prevention and treatment of hypertension, regular physical exercise has become important to reduce blood pressure. The present experiment compared the effect of interval step exercise with continuous walking exercise on cardiovascular parameters of post-menopausal hypertensive women. The volunteers were submitted to three experimental sessions: control (CO), interval exercise (IE) and continuous exercise (CE), in randomized order. The sessions lasted 120 min and during this period, resting blood pressure was evaluated after 10min of siting rest before exercise, and 30, 40 and 60min of siting rest position after exercise. Heart rate variability (HRV) were estimated at rest before exercise and 30min after exercise. Blood pressure reactivity (BPR) to the Stroop Color-Word test was measured at rest before exercise and 60min after exercise. Twelve women finished the study (59 ± 4 years and BMI of 29.78 ± 4.10 kg/m2). The One way ANOVA showed that systolic blood pressure (SBP) area under the curve over time were lower (p = 0.014) in both exercise sessions comparing with control session. The Generalized estimation equations (GEE) showed that SDNN and RMSSD indices of HRV decreases (p < 0.001) in both exercises session as well, comparing with CO. Maximal SBP during Stroop test were lower after both IE and CE exercises session comparing with CO session. We conclude that interval step exercise can reduce blood pressure responses and improve HRV acutely after its performance and these responses are similar to continuous walking exercise.


Properties and efficient scrap-and-build repairing of mechanically sheared 3' DNA ends.
Repairing of DNA termini is a crucial step in a variety of DNA handling techniques. In this study, we investigated mechanically-sheared DNA 3'-ends (MSD3Es) to establish an efficient repair method. As opposed to the canonical view of DNA terminus generated by sonication, we showed that approximately 47% and 20% of MSD3Es carried a phosphate group and a hydroxyl group, respectively. The others had unidentified abnormal terminal structures. Notably, a fraction of the abnormal 3' termini (about 20% of the total) was not repaired after the removal of 3' phosphates and T4 DNA polymerase (T4DP) treatment. To overcome this limitation, we devised a reaction, in which the 3'- > 5' exonuclease activity of exonuclease III (3'- > 5' exonuclease, insensitive to the 3' phosphate group) was counterbalanced by the 5'- > 3' polymerase activity of T4DP. This combined reaction, termed "SB-repairing" (for scrap-and-build repairing), will serve as a useful tool for the efficient repair of MSD3Es.


High heterogeneity on the accepted vaccines for COVID-19 certificates in European countries.
We aimed to elucidate which vaccines were accepted by European countries as valid proof of vaccination against COVID-19 for international travelers. On 27-September-2021 a cross-sectional study was conducted on VisaGuide.World, that reports on valid vaccines for international travelers. Other databases, lay press and regulatory agencies were also checked. The main outcome measure was which of the vaccines included on the WHO emergency use listing (EUL) [ChAdOx1 (Vaxzevria, Covishield),BNT162b2,mRNA-1273,Ad26.CoV2.S,BBIBP-CorV,CoronaVac] and Sputnik V, were accepted in each country. The influence of the vaccines approved for COVID-19 vaccination programs on the vaccines recognized as proof of vaccination was assessed. There was a remarkable heterogeneity on the vaccines accepted as proof of vaccination among 46 countries. Russia accepted only one. Cyprus, Greece and Slovenia accepted all vaccines considered. Eleven countries accepted the seven WHO EUL vaccines: eight EU countries, plus Iceland, Norway and Switzerland. Seven EU countries accepted only the four EMA-authorized vaccines. Considering Covishield as equivalent to Vaxzevria, 69% of countries recognized only vaccinated travelers who received any of the vaccines approved for vaccination programs in the country of arrival as valid. Vaccines accepted as proof of vaccination should be harmonized. Accepting any of the WHO EUL vaccines would be a scientifically sound objective.


Photostability studies of phycobiliprotein fluorescent labels.
Photostability studies of four fluorescent phycobiliproteins were conducted to identify stable chromophores for biological labeling applications. Phycobiliprotein photodestruction was linear with the applied laser power and depended on the total number of photons absorbed per molecule. Photodestruction quantum yields phi of 1.1 X 10(-5) for R-phycoerythrin, 6.6 X 10(-6) for B-phycoerythrin, 4.5 X 10(-6) for allophycocyanin, and 2.5 X 10(-6) for C-phycocyanin were measured. C-Phycocyanin is a factor of 10.8 more photostable than fluorescein. The photostability of R-phycoerythrin was improved by a factor of 1.7 by adding n-propyl gallate. The addition of superoxide dismutase, catalase, sodium dithionite, ascorbate, dithiothreitol, EDTA, or deoxygenation with argon bubbling had no effect on the photostability of R-phycoerythrin.


Comparison of DNA scission and cytotoxicity produced by Adriamycin and 5-iminodaunorubicin in human colon carcinoma cells.
The quinone-modified anthracycline, 5-iminodaunorubicin, which does not spontaneously generate free radicals, was compared to Adriamycin on the basis of DNA-protein crosslink-associated single-strand breakage, cell lethality, and the pharmacokinetics of drug uptake and efflux in human colon carcinoma cells in culture. At equivalent cytocidal concentrations, 5-iminodaunorubicin produced more single-strand breakage of DNA than Adriamycin after a 2-hr treatment interval, but the DNA scission produced by 5-iminodaunorubicin rapidly disappeared after drug removal. The kinetics of DNA breakage correlated with the rapid rates of uptake and efflux of 5-iminodaunorubicin in comparison to Adriamycin. These data emphasize the importance of the cellular pharmacokinetics of anthracyclines in relation to their cytocidal and DNA damaging properties. Moreover, the induction of equivalent single-strand breakage of DNA by similar intracellular concentrations of both drugs suggests that the free radical properties of Adriamycin are not involved in DNA scission.


Pneumatic retinopexy. A collaborative report of the first 100 cases.
The preliminary experience of one surgeon, using pneumatic retinopexy for 20 consecutive cases of rhegmatogenous retinal detachment, was previously reported. The collaborative experience of six surgeons using pneumatic retinopexy for 100 cases is now reported. This series includes cases with pseudophakia, aphakia, macular detachment, macular breaks, vitreous hemorrhage, trauma, and old detachments. Initially, 91% were reattached, but seven recurrences yielded a 6-month follow-up cure rate of 84% with pneumatic retinopexy. With subsequent scleral buckling, 98% were reattached. Postoperative complications included proliferative vitreoretinopathy (3%), macular pucker (3%), and new/missed retinal breaks (7%). A review of the literature disclosed postoperative new/missed retinal breaks in nine series: 21, 3, 8, 4, 9, 7, 5, 4, and 13%. There were no cases of glaucoma, cataract, subretinal gas, endophthalmitis, or extension of the detachment into a previously attached macula. Pneumatic retinopexy offers the advantages of reduced tissue trauma, fewer complications, no hospitalization, and less expense. The major disadvantage is the need for postoperative positioning.


Effects of excess thymidylate on thymidylate low-requiring strains of Saccharomyces cerevisiae: high mutagenicity and absence of DNA strand breaks.
dTMP exposure concentrations of 0.1 mM or higher are genotoxic in exponentially growing cells of thymidylate low-requiring mutants of Saccharomyces cerevisiae. Mutagenicity of excess dTMP is highest in an exposure concentration 10-fold of that needed for external supplementation of endogenously blocked thymidylate synthesis. Still higher dTMP concentrations are primarily cytotoxic. The canavanine forward-mutation system shows excess dTMP to be as potent a mutagen as irradiation by ultraviolet light. Mutagenicity of excess dTMP, however, differs from that of direct DNA-attacking mutagens in that it is highest in the absence of significant toxicity. Alkaline sucrose gradient centrifugation shows that excess dTMP does not induce significant numbers of DNA single- or double-strand breaks, while conditions of thymidylate deprivation lead to DNA-strand breaks and thymineless death.


Percutaneous peritoneovenous shunt positioning: technique and preliminary results.
Nine peritoneovenous shunts were positioned by percutaneous technique in seven patients with advanced malignancy causing severe refractory ascites, and in two patients with hepatic cirrhosis (one with hepatocarcinoma). In all patients the shunts were percutaneously placed through the subclavian vein in the angiographic suite under digital fluoroscopic guide. No complications directly related to the procedure occurred. The shunt was successfully positioned in all patients in 60 min average time. No patient showed symptoms related to pulmonary overload or to disseminated intravascular coagulation. All patients had a significant improvement of the objective symptoms related to ascites such as respiratory symptoms, dyspepsia, and functional impairment to evacuation describing an improvement of their quality of life. Maximum shunt patency was 273 days. Percutaneous placement of peritoneovenous shunt is a safe, fast, and inexpensive procedure, extremely useful in resolution of refractory ascites, reducing symptoms, and allowing effective palliation, with a great improvement in quality of life.


Recognition and release of uridine and hCNT3: From multivariate interactions to molecular design.
As a vital target for the development of novel anti-cancer drugs, human concentrative nucleoside transporter 3 (hCNT3) has been widely concerned. Nevertheless, the lack of a comprehensive understanding of molecular interactions and motion mechanism has greatly hindered the development of novel inhibitors against hCNT3. In this paper, molecular recognition of hCNT3 with uridine was investigated with molecular docking, conventional molecular dynamics (CMD) simulations and adaptive steered molecular dynamics (ASMD) simulations; and then, the uridine derivatives with possibly highly inhibitory activity were designed. The result of CMD showed that more water-mediated H-bonds and lower binding free energy both explained higher recognition ability and transported efficiency of hCNT3. While during the ASMD simulation, nucleoside transport process involved the significant side-chain flip of residues F321 and Q142, a typical substrate-induced conformational change. By considering electronegativity, atomic radius, functional group and key H-bonds factors, 25 novel uridine derivatives were constructed. Subsequently, the receptor-ligand binding free energy was predicted by solvated interaction energy (SIE) method to determine the inhibitor c8 with the best potential performance. This work not only revealed molecular recognition and release mechanism of uridine with hCNT3, but also designed a series of uridine derivatives to obtain lead compounds with potential high activity.


Forecast for Pollen Allergy: A Review from Field Observation to Modeling and Services in Korea.
Pollen, a major causal agent of respiratory allergy, is mainly affected by weather conditions. In Korea, pollen and weather data are collected by the national observation network. Forecast models and operational services are developed and provided based on the national pollen data base. Using the pollen risk forecast information will help patients with respiratory allergy to improve their lives. Changes in temperature and CO2 concentration by climate change affect the growth of plants and their capacity of producing more allergenic pollens, which should be considered in making the future strategy on treating allergy patients.


Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1.
Biased signaling of G protein-coupled receptors describes an ability of different ligands that preferentially activate an alternative downstream signaling pathway. In this work, we identified and characterized different N-terminal truncations of endogenous chemokine CCL15 as balanced or biased agonists targeting CCR1, and presented three cryogenic-electron microscopy structures of the CCR1-Gi complex in the ligand-free form or bound to different CCL15 truncations with a resolution of 2.6-2.9 Å, illustrating the structural basis of natural biased signaling that initiates an inflammation response. Complemented with pharmacological and computational studies, these structures revealed it was the conformational change of Tyr291 (Y2917.43) in CCR1 that triggered its polar network rearrangement in the orthosteric binding pocket and allosterically regulated the activation of β-arrestin signaling. Our structure of CCL15-bound CCR1 also exhibited a critical site for ligand binding distinct from many other chemokine-receptor complexes, providing new insights into the mode of chemokine recognition.


[Study of the diffusion of water absorbed on proteins by the ESR methods using a new magnetic field impulse gradient program].
Modification of the program of impulse gradient removing anomalous suppression of the echo at small time intervals between gradient impulses is presented. The results are given of measuring the diffusion of water adsorbed on bovine serum albumin. An efficient diffusion coefficient for 20 degrees C is evaluated as 2.4.10(-6) cm2 sec at the activation energy in the temperature range 5 divided by 40 degrees C for 0.42 g H2O/g of protein and 20 divided by 50 degrees C for 0.22 g H2O/g of protein equal to 6.5 kcal/mol.


Chemotherapeutic agents with an imidazole moiety. II. Synthesis and biological activities of new 1,4-diarylimidazoles.
The synthesis, antifungal and pharmacological activities of new 1,4-diarylimidazoles are reported. Antimicrobial data in comparison with antifungal antibiotic pyrrolnitrin pointed out that the 1,4-diaryl-2-mercaptoimidazole derivatives were inactive and all 1,4-diarylimidazoles exhibited a weak antifungal activity. Some compounds showed a selective activity against strains of Candida sp. Instead pharmacological data did not evidence any significant antiinflammatory activity. The tested compounds were prepared by reacting appropriate phenacylanilines with potassium thiocyanate in acidic medium to afford 1,4-diaryl-2-mercapto imidazoles which were then transformed into title compounds by treatment with nitric acid.


Chemical of current interest--benzene.
Benzene is one of the world's major commodity chemicals. It is derived from petroleum and coal and is used both as a solvent and as a starting material in chemical syntheses. The numerous industrial uses of benzene over the last century need not be recounted here, but the most recent addition to the list of uses of benzene is as a component in a mixture of aromatic compounds added to gasoline for the purpose of replacing lead compounds as anti-knock ingredients. The best known and longest recognized toxic effect of benzene is the depression of bone marrow function seen in occupationally exposed individuals. These people have been found to display anemia, leucopenia, and/or thrombocytopenia. When pancytopenia, i.e., the simultaneous depression of all three cell types, occurs and is accompanied by bone marrow necrosis, the syndrome is called aplastic anemia. In addition to observing this decrease in humans and relating it to benzene exposure, it has been possible to establish animal models which mimic the human disease. The result has been considerable scientific investigation into the mechanism of benzene toxicity. Although the association between benzene exposure and aplastic anemia has been recognized and accepted throughout most of this century, it is only recently that leukemia, particularly of the acute myelogenous type, has been related to benzene. The acceptance of benzene as an etiological agent in aplastic anemia in large measure derives from our ability to reproduce the disease in most animals treated with sufficiently high doses of benzene over the necessary time period. Unfortunately, despite extensive efforts in several laboratories, it has not been possible to establish a reproducible, reliable model for the study of benzene-induced leukemia. The recent demonstration that several animals exposed to benzene either by inhalation or in the drinking water during studies by Drs. B. Goldstein and C. Maltoni suggests that such a model may be forthcoming. Nevertheless, at this time it is not clear whether bone marrow damage of the type that leads to aplastic anemia is required for the development of leukemia. Most studies of benzene toxicity have involved dosing animals with benzene either by inhalation or by injection, using high doses to ensure a toxic response. Very few studies have concentrated on the oral route of administration and none have concentrated on administering benzene by mouth at the low doses occasionally detected in drinking water.(ABSTRACT TRUNCATED AT 400 WORDS)


A dual-specific anti-IGF-1/IGF-2 human monoclonal antibody alone and in combination with temsirolimus for therapy of neuroblastoma.
The insulin-like growth factors (IGFs), IGF-1 and IGF-2, have been implicated in the growth, survival and metastasis of a broad range of malignancies including pediatric tumors. They bind to the IGF receptor type 1 (IGF-1R) and the insulin receptor (IR) which are overexpressed in many types of solid malignancies. Activation of the IR by IGF-2 results in increased survival of tumor cells. We have previously identified a novel human monoclonal antibody, m708.5, which binds with high (pM) affinity to both human IGF-1 and IGF-2, and potently inhibits phosphorylation of the IGF-1R and the IR in tumor cells. m708.5 exhibited strong antitumor activity as a single agent against most cell lines derived from neuroblastoma, Ewing family of tumor, rhabdomyosarcoma and osteosarcoma. When tested in neuroblastoma cell lines, it showed strong synergy with temsirolimus and synergy with chemotherapeutic agents in vitro. In xenograft models, the combination of m708.5 and temsirolimus significantly inhibited neuroblastoma growth and prolonged mouse survival. Taken together, these results support the clinical development of m708.5 for pediatric solid tumors with potential for synergy with chemotherapy and mTOR inhibitors.


Evaluation of Unmet Restorative Treatment Needs among Pediatric Patients of King Faisal University Dental Clinics, Saudi Arabia.
To evaluate unmet restorative treatment needs (URTN) among the children visiting Dental Clinics Complex (DCC), King Faisal University in Al Ahsa region of Eastern Province, Kingdom of Saudi Arabia (KSA). A cross-sectional study was conducted among 332 children, 3-13 years old. All the children were grouped based on dentition and gender. Details of patient history, clinical examination, radiographs, and the proposed treatment plan was accessed from Titanium patient management software to assess URTN. Only 37 children (11.14%) reported to be caries free while the remaining 295 children (88.16%) had one or more carious teeth which needed treatment. Unmet restorative treatment needs were higher for restorable teeth and stainless steel (SS) crown in deciduous dentition group while mixed dentition group showed higher URTN for unrestorable teeth, missing tooth due to caries, filled tooth with caries, remaining root and space maintenance. Based on gender, URTN like restorable teeth and filled tooth with caries were more among girls while missing tooth due to caries and SS crown were more among boys. Majority of the children had untreated carious teeth. Children in the mixed dentition group showed higher URTN. More emphasis on addressing URTN is needed. Improving dental healthcare services to meet the oral healthcare needs, eventually promotes overall quality of life of an individual. Alfayz SY, Alabdulsalam M, Alabdulathim A, et al. Evaluation of Unmet Restorative Treatment Needs among Pediatric Patients of King Faisal University Dental Clinics, Saudi Arabia. Int J Clin Pediatr Dent 2022;15(3):366-370.


Early parenteral lipids and growth velocity in extremely-low-birth-weight infants.
Whether early parenteral lipids improve postnatal growth of preterm neonates remains unclear. We aimed to assess the effects of parenteral lipids on growth velocity in extremely-low-birth-weight infants. This retrospective cohort study included 121 extremely-low-birth-weight infants. The associations between parenteral lipids (cumulative intakes during the first week and delays in their introduction) and growth velocities (weight, head circumference and length) up to 28 days of life and to 36 weeks of corrected age were analysed using uni- and multivariate linear regression. Univariate analyses showed a significant positive association between the cumulative intakes of parenteral lipids during the first week and i) weight gain up to day 28; ii) weight gain up to 36 weeks of corrected age; iii) head circumference growth up to day 28. There was a negative correlation between the delay in parenteral lipid introduction and weight gain up to day 28. In multivariate analyses, the association between the cumulative intakes of parenteral lipids and weight gain up to 28 days was independent of gestational age at birth, birth weight, sex, smallness for gestational age, and enteral intakes (regression coefficient: 0.19; 95% CI: 0.01-0.38) and, up to 36 weeks, independent of gestational age, birth weight, sex, smallness for gestational age and parenteral glucose and amino acids (0.16; 95% CI: 0.04-0.27). Parenteral lipids during the first week were positively associated with weight gain in extremely-low-birth-weight infants and could improve early nutritional support of preterm neonates.


The presence of herpes simplex virus DNA in hamster embryo cells transformed by a temperature sensitive mutant, TS-4.
Hamster embryo cells transformed with a temperature sensitive mutant of HSV-2, ts-4T, were examined for the presence of viral genomes. DNA-DNA reassociation kinetics showed that only a small portion (11 +/- 4%) of HSV-2 was present in the transformed cells.


Jak1 Integrates Cytokine Sensing to Regulate Hematopoietic Stem Cell Function and Stress Hematopoiesis.
JAK1 is a critical effector of pro-inflammatory cytokine signaling and plays important roles in immune function, while abnormal JAK1 activity has been linked to immunological and neoplastic diseases. Specific functions of JAK1 in the context of hematopoiesis, and specifically within hematopoietic stem cells (HSCs), have not clearly been delineated. Here, we show that conditional Jak1 loss in HSCs reduces their self-renewal and markedly alters lymphoid/myeloid differentiation in vivo. Jak1-deficient HSCs exhibit decreased competitiveness in vivo and are unable to rescue hematopoiesis in the setting of myelosuppression. They exhibit increased quiescence, an inability to enter the cell cycle in response to hematopoietic stress, and a marked reduction in cytokine sensing, including in response to type I interferons and IL-3. Moreover, Jak1 loss is not fully rescued by expression of a constitutively active Jak2 allele. Together, these data highlight an essential role for Jak1 in HSC homeostasis and stress responses.


The characterization of androstenone transport in boar plasma.
The transport of steroids by plasma proteins influences the amount of steroid available for uptake by the target tissue. In the boar, androstenone is transported to the adipose tissue where it accumulates to cause an off-odour or off-flavour in pork, known as boar taint. The mechanism of the transport of androstenone in the boar remains unclear, and the plasma protein responsible for binding androstenone has yet to be identified. Therefore, the purpose of the present study was to characterize the binding of androstenone to plasma proteins in the boar. The binding specificity of androstenone to plasma proteins was first investigated using a HPLC gel filtration method. [3H]-androstenone was incubated with plasma in the presence or absence of unlabeled competitors and the displacement of androstenone from plasma proteins was measured. In the presence of excess unlabeled competitors, [3H]-androstenone was only partially displaced from plasma proteins, indicating it binds to a low affinity high capacity plasma protein. Binding kinetics studies were also conducted to characterize the binding of androstenone and dehydroepiandrosterone (DHEA) to plasma proteins. The Bmax of androstenone and DHEA was approximately the same (89.1% and 92.3%, respectively). However, the binding affinity (K) of androstenone was 6.5 fold greater than DHEA (0.39 nmol/ml and 0.06 nmol/ml, respectively). Affinity chromatography was used to remove albumin from the plasma proteins. Following incubations with androstenone and DHEA, the binding observed in the albumin free protein fraction was reduced 2.6 and 2.1 fold, respectively relative to the binding in the albumin protein fractions. These results provide direct evidence that androstenone is transported non-specifically by albumin in the plasma of the boar.


Mutations on RBD of SARS-CoV-2 Omicron variant result in stronger binding to human ACE2 receptor.
The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to more than 270 million infections and 5.3 million of deaths worldwide. Several major variants of SARS-CoV-2 have emerged and posed challenges in controlling the pandemic. The recently occurred Omicron variant raised serious concerns about reducing the efficacy of vaccines and neutralization antibodies due to its vast mutations. We have modelled the complex structure of the human ACE2 protein and the receptor binding domain (RBD) of Omicron Spike protein (S-protein), and conducted atomistic molecular dynamics simulations to study the binding interactions. The analysis shows that the Omicron RBD binds more strongly to the human ACE2 protein than the original strain. The mutations at the ACE2-RBD interface enhance the tight binding by increasing hydrogen bonding interaction and enlarging buried solvent accessible surface area.


Serpent/dGATAb regulates Laminin B1 and Laminin B2 expression during Drosophila embryogenesis.
Transcriptional regulation of Laminin expression during embryogenesis is a key step required for proper ECM assembly. We show, that in Drosophila the Laminin B1 and Laminin B2 genes share expression patterns in mesodermal cells as well as in endodermal and ectodermal gut primordia, yolk and amnioserosa. In the absence of the GATA transcription factor Serpent, the spatial extend of Laminin reporter gene expression was strongly limited, indicating that Laminin expression in many tissues depends on Serpent activity. We demonstrate a direct binding of Serpent to the intronic enhancers of Laminin B1 and Laminin B2. In addition, ectopically expressed Serpent activated enhancer elements of Laminin B1 and Laminin B2. Our results reveal Serpent as an important regulator of Laminin expression across tissues.


Effects of bisphenol A on antioxidation and nitrogen assimilation of maize seedlings roots.
Bisphenol A (BPA) is becoming a potential environmental toxicity factor. However, BPA's effect and function mechanism on maize roots remain unknown. Here, we investigated characters of root growth of maize seedlings exposed to BPA for 8 d and without BPA for 3 d, and a series of indicators on reactive oxygen homeostasis and nitrogen assimilation were measured. High-dose BPA(15 and 50 mg·L-1) suppressed the root growth and caused increased contents of O2ˑ-, H2O2 and MDA in maize seedling roots. The disturbed ROS homeostasis resulted from the change of antioxidant enzymes, including the increase of APX, GPX, and CAT, and decrease of SOD and POD, and a decrease of antioxidant substance GSH. Meanwhile, High-dose BPA caused a decrease in the soluble protein content, nitrate reductase (NR), glutamate dehydrogenase (GDH), and glutamine oxoglutarate aminotransferase (GOGAT) under the BPA processing phase and recovery period. The low-dose BPA(1.5 and 5 mg·L-1)significantly promoted root growth of maize seedlings and maintained the ROS homeostasis through antioxidant enzyme APX and GPX eliminating redundant ROS. Our results showed that BPA could cause a dual effect on the root growth of maize seedlings, that is, promotion of low-dose and inhibition of high-dose, through ROS homeostasis and nitrogen assimilation in Zea mays.


Adsorption of fluoranthene in surfactant solution on activated carbon: equilibrium, thermodynamic, kinetic studies.
Adsorption of fluoranthene (FLA) in surfactant solution on activated carbon (AC) was investigated. Isotherm, thermodynamic, and kinetic attributes of FLA adsorption in the presence of the surfactant on AC were studied. Effects of AC dosage, initial concentration of TX100, initial concentration of FLA, and addition of fulvic acid on adsorption were studied. The experimental data of both TX100 and FLA fitted the Langmuir isotherm model and the pseudo-second-order kinetic model well. Positive enthalpy showed that adsorption of FLA on AC was endothermic. The efficiency of selective FLA removal generally increased with increasing initial surfactant concentration and decreasing fulvic acid concentration. The surface chemistry of AC may determine the removal of polycyclic aromatic hydrocarbons. The adsorption process may be controlled by the hydrophobic interaction between AC and the adsorbate. The microwave irradiation of AC may be a feasible method to reduce the cost of AC through its regeneration.


Pivotal Trials in Multiple Sclerosis: Similarities Prove Not to Be Useful.
We present a commentary on the inclusion criteria and outcome measures of the major randomized trials on multiple sclerosis. A qualitative comparison of the characteristics of the enrolled patients is done. The objective is to stimulate a discussion about the need to improve research strategies. The discovery of new drugs studied without personalized criteria does not allow for useful advances in knowledge.


Clinical and histological significance of the testicular remnant found on inguinal exploration after diagnostic laparoscopy in the absence of a patent processus vaginalis.
We reviewed the histological findings of cord structures excised at inguinal exploration after diagnostic laparoscopy in patients with a nonpalpable testis with the vas deferens and spermatic vessels exiting the internal inguinal ring in the absence of a patent processus vaginalis. A retrospective review of 809 laparoscopic explorations for nonpalpable testes between 1981 and 2003 was conducted. The histological findings of the excised remnants of those patients with a closed processus vaginalis were reviewed. A total of 110 patients underwent excision of a testicular remnant at inguinal exploration in association with a closed processus vaginalis. Of the specimens 31 (28%) were on the right side and 79 (72%) were on the left side. The incidence of viable germ cell elements was 8 of 110 (7%). The presence of hemosiderin, calcification and fibrosis was identified in all 8 remnants with viable germ cell elements. The incidence of viable germ cell elements in the excised remnant when the vas deferens and spermatic vessels are identified exiting a closed internal ring in patients with a nonpalpable testis is 7%. To our knowledge no prior study has evaluated the incidence of viable germ cell elements in remnants associated with a closed internal inguinal ring. Based on these findings, we advocate inguinal exploration and excision of testicular remnants in these patients.


Afferent projections to the self-stimulation regions of the dorsal pons, including the locus coeruleus, in the rat as demonstrated by the horseradish peroxidase technique.
Afferent projections to the dorsal pons of the rat have been studied using the horseradish peroxidase (HRP) technique. HRP injections were made in each of the following regions: the vicinity of the locus coeruleus (LC); the periventricular gray, medial to the LC; the medial parabrachial region, lateral to the LC; the ventral cerebellum, dorsal to the LC; and the pontine reticular formation, ventral to the LC. Because intracranial self-stimulation (ICSS) has been obtained in these regions, the afferents have been discussed in terms of their possible contributions to the behavior. Previous ICSS studies of the dorsal pons have focussed on the LC as playing a central role. Presently identified inputs to the LC include: the dorsal raphe nucleus: the ventrolateral periaqueductal gray: the pontine reticular formation: the areas that contain the pontine and medullary noradrenergic and adrenergic cell groups: the lateral hypothalamic area: the contralateral LC: the deep cerebellar nuclei: the ventrolateral and parafascicular thalamic nuclei: and the parabrachial regions of the pons and midbrain.


Tardive dystonia. Prevalence, risk factors, and comparison with tardive dyskinesia in a population of 200 acute psychiatric inpatients.
In a population of 200 consecutive inpatients with a history of at least 3 months' total cumulative neuroleptic exposure, the prevalence of tardive dystonia (TDt) was 4%, higher than previously reported. The prevalence of tardive dyskinesia (TDk) was 22%. Patients with TDt did not differ in demographic or clinical variables from nondyskinetic patients. In comparison with patients with TDk, patients with TDt were significantly younger, had a more severe movement disorder, and had received neuroleptics for the first time fewer years before. Patients with TDk were significantly older than patients without tardive disorders, both when they were examined and when they had started their first neuroleptic treatment. Furthermore, they had started their first neuroleptic treatment more years before. These results support the distinction between TDt and TDk, and suggest that the previously reported prevalence of TDt might have been underestimated.


Radiation Oncology in the Developing Economies of Central and Eastern Europe.
Eastern Europe is represented by 22 countries of significant variability in population density and degree of economic development. They have been affected by past geopolitical isolation due to their association with the "Soviet Block." Currently, all Eastern European countries except Slovenia are low- or middle-income level and 10 of them are part of European Union. Health care systems in Central and Eastern Europe have been influenced by the legacy of centralized soviet-era governance; however, most countries, particularly in European Union zone, have gone through health care reforms directed toward modernizing infrastructure and staffing. The level of health financing available through health insurance has increased in the region, although still lags behind the Western European levels. After adjusting for differing population age structures, overall incidence rates in both sexes are lower in Eastern and Central Europe compared with the Northern and Western European countries; however, mortality remains higher. There is an ongoing shortage of oncology services in Eastern Europe, including radiotherapy equipment and personnel. Eastern European radiotherapy field is highly diverse with large differences among countries regarding staffing structure, training, accreditation, and defined roles and responsibilities. The rapid diffusion of technological innovations has been identified as one of the most important factors driving the escalating health care expenses, and the need for better cost-effective solutions applicable to the local health care systems and levels of economic development.


Sinus node potential during cold cardioplegia.
Epicardial potentials of the sinus node, the right atrium, and the right ventricle were recorded in dogs during cold potassium-induced cardioplegia. We found that the sinus node fibers were more resistant to the cardioplegia than were the other myocardial fibers. When the cardioplegia rendered the atrial muscle inexcitable, the high frequency atrial potential was delayed and then abolished in the sinus node electrogram, and a smooth tracing similar to the action potential of the sinus node cell appeared. These findings should be pertinent for the cardiac surgeon attempting to avoid surgically-induced sinoatrial arrhythmias.


A simple procedure for obtaining large quantities of tubulin subunits from newborn mouse brain.
A simple, efficient two-step procedure of DEAE--Sephadex A--50 column chromatography followed by hydroxyapatite column chromatography for purification of alpha- and beta-tubulin subunits from newborn mouse brain is described. Stored frozen mouse brains can be used as a convenient starting material. Differential elution of alpha and beta subunits from hydroxyapatite was achieved using a linear gradient of 0.2--0.3 M phosphate buffer containing 2 M urea, 0.1% sodium dodecyl sulphate and 1 mM dithiothreitol. 20 mg of alpha-tubulin (purity: greater than 85%) and 16 mg of beta-tubulin (purity greater than 95%) completely separated from each other can be obtained in one experiment.


Experiment research of cisplatin implants inhibiting transplantation tumor growth and regulating the expression of KLK7 and E-cad of tumor-bearing mice with gastric cancer.
To study the influence of cisplatin implants on transplantation tumor growth and the expression of tissue kallikrein-7 (KLK7) and E-cadherin (E-cad) in tumor-bearing mice with gastric cancer. BALB/c nude mice were collected as experimental animal and were randomly divided into model control group (Group A), tail intravenous injection of cisplatin group (Group B), intratumor injection of cisplatin group (Group C) and cisplatin implants treatment group (Group D). After the drugs intervening, the weight and volume of transplantation tumors were measured on Day 20, Day 30 and Day 40 and serum and KLK7 and E-cad contents in transplanted tumor tissue were examined. On Day 20, Day 30 and Day 40 after treatment, the weight and volume of transplantation tumors of tumor-bearing mice in four groups were different (Group A > Group B > Group C > Group D). The contents of KLK-7 and E-cad in tumor tissue and serum of tumor-bearing mice in four groups were different (Group A > Group B > Group C > Group D in KLK-7) and (Group A < Group B < Group C < Group D in E-cad). The weight and volume, and KLK7 and E-cad contents of transplantation tumors in four groups were significant difference (P < 0.05). Cisplatin implants can inhibit the growth of transplanted tumor tissue and down-regulated KLK7 expression and up-regulated E-cad expression of tumor-bearing mice with gastric cancer.


A reverse transcriptase-polymerase chain reaction assay for detection of viable Escherichia coli O157:H7: investigation of specific target genes.
To determine suitable target genes for detection of the pathogen Escherichia coli O157:H7 by reverse transcriptase-polymerase chain reaction (RT-PCR). Potential genes used as indicators for viability included rfbE, fliC, stx1, stx2, mobA, eaeA, hly and 16S rRNA. Under normal growth conditions, rfbE, stx1, hly and 16S rRNA amplicons were detected in association with all growth phases. The products of 16S rRNA, mobA, rfbE and stx1 were readily visualized in RNA isolated from viable but non-culturable cells. The 16S rRNA gene was not amplified following heat treatment of cells at 121 degrees C for 15 min and mRNA targets were not amplified after treatment at 60 degrees C for 20 min. In this instance, genes that are not amplified are good targets for determining viability. The results of RT-PCR amplification indicate that, under the conditions examined, the rfbE gene is the most appropriate target for detection of viable E. coli O157:H7. Prior to detection or identification from an environmental or food sample E. coli O157:H7 may be exposed to many harsh conditions that influence nucleic acid (RNA and DNA) stability. This study gives an insight into the effects of temperature and nutrient deprivation on identification of viable cells using RT-PCR. It also suggests that, if RT-PCR is to be used for detection of live cells in a sample without enrichment, 10(7) cfu of the target organism are required.


Zinc binding of Tim10: evidence for existence of an unstructured binding intermediate for a zinc finger protein.
Zinc-finger proteins are among the most abundant proteins in eukaryotic genomes. Tim10 and all the small Tim proteins of the mitochondrial intermembrane space contain a consensus twin CX(3)C zinc-finger motif. Zn(2+) can bind to the reduced Tim10, but not disulphide bonded (oxidized) protein. However, the zinc-binding reaction of Tim10 and of zinc-finger proteins, in general, is ill-defined. In this study, the thermodynamic and kinetic properties of zinc-binding to reduced Tim10 were investigated using circular dichroism (CD), fluorescence spectrometry, and stopped-flow fluorescence techniques. At equilibrium, coupled with the use of protein fluorescence and metal chelators, the zinc-binding affinity was determined for Tim10 to be about 8 x 10(-10)M. Then, far UV CD was used to investigate the secondary structure change upon zinc-binding of the same set of protein samples at various free Zn(2+) concentrations. Comparison between the results of CD and fluorescence studies showed that the zinc-binding reaction is not a simple one-step process. It involves formation of a binding intermediate that is structurally as unfolded as the apoTim10; subsequently, a degree of folding is induced at increased zinc concentrations in the final complex. Next, the stopped-flow fluorescence technique was used to investigate the kinetic process of the binding reaction. Data analysis shows that the reaction has a single kinetic phase at a low free Zn(2+) concentration ( approximately 1 nM), and a double kinetic phase at a high free Zn(2+) concentration. The kinetic result is consistent with that of the studies at equilibrium. Therefore, a two-step reaction model mechanism is proposed, in which zinc-binding is regulated by the initial selective-binding of Zn(2+) to Cys followed by folding. Implication of the two-step zinc-binding mechanism for Zn(2+) trafficking in the cell is discussed.


AstragalosideII inhibits autophagic flux and enhance chemosensitivity of cisplatin in human cancer cells.
Inhibition of autophagy has been daily served as a promising anti-cancer treatment strategies. AstragalosideII (ASII), a main compound isolated from traditional Chinese medicine Radix Astragali, has been demonstrated to inhibit autophagy and reverse multidrug resistance in human hepatic cancer cells Bel-7402/5-FU. In this study, we inspected the function and mechanisms of ASII and cisplatin on autophagy in human cancer cells, and assessed the effect of ASII on cisplatin-induced apoptosis. We found ASII increased LC3II protein level, p62 protein level and GFP-LC3 puncta accumulation in human cancer cells. Furthermore, we found that ASII downregulated the expression of lysosomal cathepsinB/L (CTSB/L) in EBSS medium and affected the lysosomal acidification. Finally, we demonstrated that cisplatin induced protective autophagy which was involved of PI3K/Akt/mTOR pathway. Moreover, ASII in conjunction with cisplatin significant reduced cell viability, arrested in S phase and increased apoptosis. In conclusion, these findings suggested that ASII served as autophagy inhibitor which restored chemosensitivity of anticancer agent cisplatin and enhanced tumor cell death.


A rare case of penile metastases from small cell prostate cancer.
We present a case of an 83-year-old-male with painless penile nodules several months after he was diagnosed with pure prostatic small cell carcinoma. Penile doppler ultrasound and magnetic resonance imaging demonstrated solid nodules in both corpora cavernosa. Fine-needle aspiration of the nodules with immunohistochemical examination confirmed prostatic small cell carcinoma origin of metastases. Small cell carcinoma of the prostate is a rare disorder accounting for less than 1% of all prostate cancers, the penis being an uncommon site for metastasis. An extremely low number of cases of penile metastases from prostatic small cell carcinoma has been reported to date in the literature.


Ear nose and throat diseases in the Bedouin of the South Sinai Desert: a cross-sectional survey and discussion of healthcare needs.
In the summer of 2000, a team of medical and affiliated workers visited the South Sinai Desert to assess the medical problems and needs of the Bedouin population. This paper reports on the ENT diseases of this population, and discusses their healthcare needs.


Identification and quantification of major maillard cross-links in human serum albumin and lens protein. Evidence for glucosepane as the dominant compound.
Glycation reactions leading to protein modifications (advanced glycation end products) contribute to various pathologies associated with the general aging process and long term complications of diabetes. However, only few relevant compounds have so far been detected in vivo. We now report on the first unequivocal identification of the lysine-arginine cross-links glucosepane 5, DOGDIC 6, MODIC 7, and GODIC 8 in human material. For their accurate quantification by coupled liquid chromatography-electrospray ionization mass spectrometry, (13)C-labeled reference compounds were synthesized independently. Compounds 5-8 are formed via the alpha-dicarbonyl compounds N(6)-(2,3-dihydroxy-5,6-dioxohexyl)-l-lysinate (1a,b), 3-deoxyglucosone (), methylglyoxal (), and glyoxal (), respectively. The protein-bound dideoxyosone 1a,b seems to be of prime significance for cross-linking because it presumably is not detoxified by mammalian enzymes as readily as 2-4. Hence, the follow-up product glucosepane 5 was found to be the dominant compound. Up to 42.3 pmol of 5/mg of protein was identified in human serum albumin of diabetics; the level of 5 correlates markedly with the glycated hemoglobin HbA(1c). In the water-insoluble fraction of lens proteins from normoglycemics, concentration of 5 ranges between 132.3 and 241.7 pmol/mg. The advanced glycoxidation end product GODIC 8 is elevated significantly in brunescent lenses, indicating enhanced oxidative stress in this material. Compounds 5-8 thus appear predestined as markers for pathophysiological processes.


Platelets, platelet-derived growth factor and arteriosclerosis.
Platelets participate in the pathogenesis of arteriosclerosis and in the progression of atherosclerosis by adhering to the damaged arteries and subsequently forming mural thrombi which are either swept away and embolize or are endothelialized and thus become part of the vessel wall. Rheologic considerations predict and blood perfusion experiments using flow chambers with exposed vessel wall components demonstrate that platelet participation increases with the wall shear rate and is thus particularly important in stenosed arteries (acute thrombosis) and the microvasculature (hemostasis). In addition to their involvement in thrombosis, activated platelets release growth factors, most notably a platelet-derived growth factor (PDGF) which may be the principal mediator of smooth muscle cell migration from the media into the intima and of smooth muscle cell proliferation in the intima as well as of vasoconstriction. The recent discovery that PDGF can be produced by additional cells involved in the pathogenesis of arteriosclerosis (endothelial cells, monocytes/macrophages, smooth muscle cells themselves) and that they may play a role in tumorigenesis has tremendously increased the interest in this growth factor and in potential antagonists.


Angiography before and after radiotherapy for a thalamic tumor.
A patient with a thalamic tumor received radiotherapy. A right cerebral angiogram seven days after the irradiation was finished revealed increased vascularity, early filled deep cerebral veins and signs of increased mass. A subsequent angiogram showed gradual regression of these features. There is no literature on angiographic progression with early venous filling following radiotherapy.


Polymorphism of apolipoprotein E. I. Methodological aspects and diagnosis of hyperlipoproteinemia type III without ultracentrifugation.
Two methods for phenotyping apolipoprotein E are compared. One is based on preparation of VLDL by conventional ultracentrifugation, whereas the other uses heparin/Mg precipitation of VLDG. In principle, the same results were obtained by both methods. However, the group limits for the three different phenotypes Apo E-N, Apo E-ND and Apo E-D were slightly different by the two methods. Phenotype Apo E-D - the phenotype characterizing type III dyslipoproteinemia - is clearly definable by both methods. Hence the precipitation-I.E.F. method for Apo E phenotyping provides a simple tool for genetic and population genetic studies and also for the routine diagnosis of hyperlipoproteinemia type III, based on the only specific marker known for this disease.


Hippocampal damage mediated by corticosteroids--a neuropsychiatric research challenge.
There is an increasing evidence that corticosteroids damage the hippocampus in rodents and in primates. Hippocampal atrophy induced by corticosteroids may play an important role in the pathogenesis of a range of neuropsychiatric disorders. Hippocampus is necessary for short-term memory consolidation and HPA axis regulation. Signs of hippocampal damage (HPA dysregulation in combination with memory impairment) are found in affective disorders, Alzheimer's disease and in posttraumatic stress disorder. MRI volumetry reveals reduced hippocampal volume in these diseases. Evidence supporting the "glucocorticoid hypothesis" of psychiatric disorders is reviewed in the first part of the paper. Unresolved questions concerning temporary aspects of neurodegeneration, causality, reversibility, type of damage, factors increasing hippocampal vulnerability, and both pharmacological (CRH antagonists, antiglucocorticoid drugs, GABA-ergic, serotonergic, glutamatergic agents) and non-pharmacological (psychotherapy) treatment approaches are discussed in the second part.


Cone synapses of a flat diffuse cone bipolar cell in the primate retina.
A Golgi-stained flat diffuse cone bipolar cell from a vervet monkey's retina (Cercopithecus aethiops), contacting six cones, was serially sectioned for electron microscopy (EM) to determine the types of synapses it made with the cone pedicles. All the synapses were basal (flat) contacts. Their distribution and ultrastructural type were similar at each pedicle. Approximately half the synapses were definable as triad-associated and the rest were elsewhere on the cone pedicle base. Their ultrastructure is the same regardless of those positions. About 25 synapses were made with each cone. Thus this type (DB2 of Boycott & Wässle, 1991) of flat diffuse cone bipolar cell is in contact with six cones through about 150 synapses. At the eccentricity studied each cone pedicle probably makes 90-100 basal synapses with between three and four DB2 bipolar cells. This is between two and three times the number that are made with all the types of invaginating bipolar cells. A brief review of cone photoreceptor synapses with bipolar cells shows that, for those so far examined in the primate retina, the dichotomy into two types of bipolar cell invaginating (ribbon-related), with axons ending in the b-layer of the inner plexiform layer (IPL) (hence presumptive On-bipolars) and flat (basal synapses), with axons ending in the a-layer of the inner plexiform layer (hence presumptive Off-bipolars) is the rule. But other vertebrate retinae, including that of the cat, also have bipolar cells which vary from this pattern.


Course and prognosis of childhood schizophrenia.
Follow-up data on 57 schizophrenic patients, including 25 boys and 32 girls between the ages of 7 and 13, is reported. Average length of follow-up was 15 years. Symptoms found in children under 10 and in prepubertal cases are described. Cases with acute, relapsing episodes occurred more often than chronic cases, but before age 11 acute cases were less frequent. Twenty percent of the patients recovered completely, 30% reached a relatively good social adjustment, and 50% had moderate or poor remission. Family incidence of psychiatric disorders had no influence on prognosis, nor did unfavorable family environment. Premorbid personality development was, however, found to be of prognostic value. Prodromal episodes occurred in 55% of the cases, and 65% of the patients were preoccupied by death. Additional follow-up findings are presented, and problems of diagnosis are discussed.


Antimicrobial activities of clarithromycin, gatifloxacin and sitafloxacin, in combination with various antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex.
We studied the activities of clarithromycin and fluoroquinolones (gatifloxacin, sitafloxacin, levofloxacin) in combination with other antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex (MAC). Clarithromycin potentiated the activities of rifampicin and rifalazil against both extracellular and intramacrophage MAC. In contrast, all the test quinolones exhibited antagonistic effects against extracellular MAC when combined with either clarithromycin or rifamycins. Such an antagonism was not observed for the activity of these combinations against intramacrophage MAC. Combined effects were observed with combinations of these fluoroquinolones with either ethambutol or streptomycin. Similar profiles were seen for the activities of two-drug combinations of clarithromycin or fluoroquinolones with other drugs against intramacrophage MAC isolated from pulmonary and disseminated MAC infections.


The role of the protein tyrosine phosphatase SHP2 in ossification.
SHP2, encoded by the PTPN11 gene, participates in multiple cell functions including cell proliferation, movement, and differentiation. PTPN11 loss-of-function and gain-of-function mutations are both associated with diseases, such as Noonan syndrome, whose manifestations include bone defects, suggesting a crucial role for SHP2 in the skeleton. However, the exact mechanisms by which SHP2 regulates bone development remain unclear. This review focuses on the current understanding of the regulation of SHP2 and highlights the vital roles of SHP2 in skeletal development, especially its roles in ossification. Overall, a better understanding of the functions of SHP2 in ossification will provide a new avenue to treat-related skeletal diseases.


Bacterial polysaccharide capsule synthesis, export and evolution of structural diversity.
Elaboration of a capsule composed of one of a range of acidic polysaccharides is a common feature of many bacteria, particularly those capable of causing serious infections in humans. Biochemical and genetical analyses of capsule biogenesis in Escherichia coli are beginning to reveal new aspects of polysaccharide biosynthesis. Genes have been identified which are thought to encode products responsible for the translocation of these high molecular-weight polysaccharides across the cytoplasmic and outer membranes, and the organization of exported polysaccharide into a capsule. Their further analysis should provide new insights into membrane biology, particularly since the genes in question are absent from the often used laboratory strains of E. coli. Genetic analysis of capsule diversity is beginning to suggest possible mechanisms for the generation of the structural diversity of polysaccharides.


Educational value of spinal injection therapy videos in Korean YouTube for back pain patients.
YouTube, the largest online video platform, has become increasingly popular as a source of health information to patients. The aim of the study was to assess whether Korean patients were well informed about spinal injection from YouTube. Search for the keyword "cheog-chu ju-sa" in Korean language was done, and the quality of the 51 videos with the highest number of views was evaluated independently by two pain management doctors. The averages of global quality scores evaluated by the two doctors were 3.0 and 3.5 and modified DISCERN (mDISCERN) scores were 2.8 and 3.0, respectively. The Kappa statistic between the two doctors' scores was 0.285 and 0.417. The percentage of low-quality videos with a global quality score of 2 or less is 18-36%, which indicated that these videos might provide inaccurate or misleading medical information to the patient. Pain clinic doctors should be wary of medically misleading information available on online platforms, such as YouTube, and strive to create and distribute professional quality educational materials.


Au-F127 strawberry-like nanospheres as an electrochemical interface for sensitive detection of carcinoembryonic antigen in real sample.
Nanomaterial-based signal-amplification strategies hold a great promise in realizing sensitive biological detection. A simple label-free electrochemical immunosensor for sensitive detection of carcinoembryonic antigen (CEA) was developed by immobilizing anti-CEA antibodies onto the Au-F127 strawberry-like nanospheres modified glassy carbon electrode (Au-F127/GCE). The Au-F127 strawberry-like nanospheres offered a large surface and multifunctional substrate for the effective immobilization of anti-CEA and the existence of Au could accelerate electron transfer and make the electrochemical signal amplified. The Au-F127 nanocomposites and anti-CEA were characterized by transmission electron microscopy (TEM), polycrystalline electron diffraction ring pattern, ultra-violet visible (UV-vis) spectra and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectra. Electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) were employed to verify the stepwise assembly of the immunosensor and evaluated the analytical performance of the fabricated immunosensor, respectively. The immunosensor showed a wide liner response range between 0.01 and 80 ng mL(-1) with a low detection limit of 0.24 pg mL(-1) at a signal-to-noise (S/N) ratio of 3. Additionally, the proposed method was successfully applied to determine CEA in human serum samples with satisfactory results.


Prevalence of adolescent risk behaviors at 11 and 15 years of age: data from the 2004 Pelotas birth cohort.
The objective of this study was to investigate the prevalence of the following risk behaviors: experimentation with cigarettes, electronic cigarettes, alcohol, substances, delinquent behavior, and sex at age 15, stratified by sex and socioeconomic position. We also investigated the prevalence of cigarette and alcohol experimentation at age 11 and the persistence and cumulative incidence of these behaviors between 11 and 15 years of age. In this cohort study, we included 3,491 11-year-olds and 1,949 15-year-olds from the 2004 Pelotas Birth Cohort. All outcomes were identified via confidential questionnaires and were analyzed as binary variables. At age 11, there was a higher prevalence of cigarette experimentation among boys. At age 15, there was a higher prevalence of experimentation with alcohol, cigarettes, and substances among girls; experimentation with cigarettes and sex were more prevalent among those in a low socioeconomic position. We found a high cumulative incidence of alcohol experimentation, as well as persistent alcohol experimentation, in both boys and girls. Further research should clarify causal paths of the high prevalence of risk behaviors during adolescence and its increase among girls.


Manovolumetric characteristics and functional results in three different pelvic pouch designs.
Different pouch designs and techniques for the perineal approach have been on trial in an attempt to improve results after restorative proctocolectomy. The 1-year results of two currently advocated procedures, the J-pouch and the S-pouch, were compared with the results obtained in patients with a pelvic pouch fashioned according to the folding technique used for the Kock continent ileostomy, all pouches having been constructed from equal 30 cm lengths of ileum. The maximal volume of the S- and Kock pouches at one year was 420 ml (250-570) (median and (range] and 410 ml (244-490) respectively, while it was significantly less, 305 ml (200-445) in the J-pouch (p less than 0.05). The compliance of the J-pouches was also significantly lower at all distension pressures. The median day-time defaecation frequency was four and was equal in the three groups. Although there was a tendency towards a more favourable overall functional result with less soiling, and less need for night evacuations among patients with a Kock-folded pouch compared to the other pouch types these differences failed to reach statistical significance. The favourable properties of the Kock pouch, well-known also from the conteinent ileostomy and urostomy, suggest that its design should be considered an interesting alternative even for restorative proctocolectomy. These encouraging results have yet to be confirmed in a comparative randomized trial.


Automatic Visual Acuity Estimation by Means of Computational Vascularity Biomarkers Using Oct Angiographies.
Optical Coherence Tomography Angiography (OCTA) constitutes a new non-invasive ophthalmic image modality that allows the precise visualization of the micro-retinal vascularity that is commonly used to analyze the foveal region. Given that there are many systemic and eye diseases that affect the eye fundus and its vascularity, the analysis of that region is crucial to diagnose and estimate the vision loss. The Visual Acuity (VA) is typically measured manually, implying an exhaustive and time-consuming procedure. In this work, we propose a method that exploits the information of the OCTA images to automatically estimate the VA with an accurate error of 0.1713.


False ST elevation in a modified 12-lead surface electrocardiogram.
Precise recording of the standard 12-lead electrocardiogram (ECG) is technically time consuming. Placing limb leads on the torso has the major advantages of ease of use, increased speed of application, and decreased artifact. This modified ECG frequently substitutes for the standard 12-lead ECG in intensive care units to detect ischemia, although its implementation should be limited to interpreting arrhythmias. We describe a patient who was misdiagnosed with acute inferior myocardial infarction in a modified 12-lead ECG. To the best of our knowledge, this is the first case report regarding detection of false ST elevations in this setting. Always, a standard 12-lead ECG is recommended to evaluate any ST-T changes.


Naproxen ophthalmic solution to manage inflammation after phacoemulsification.
To explore the efficacy and safety of 2 concentrations (0.1% and 0.2%) of sodium naproxen ophthalmic solution in controlling ocular inflammation in patients having phacoemulsification and intraocular lens implantation. Service d'Ophtalmologie La Pitie' and Centre Ophtalmologique, Paris, and Clinique Sourdille, Nantes, France; Department of Ophthalmology, University of Lausanne, Switzerland. One hundred one patients were randomly treated with naproxen 0.1%, naproxen 0.2%, or diclofenac 0.1% 3 times a day for 30 days starting the day before surgery. Postsurgical ocular inflammation was measured after 1, 10, and 30 days using the Kowa FC-1000 laser flare-cell meter and a conventional slitlamp biomicroscope. Safety parameters were evaluated at the same visits. Naproxen 0.2% ophthalmic solution and diclofenac 0.01% were comparable in controlling postsurgical inflammation. The naproxen was well tolerated. No serious adverse events occurred during the study. These preliminary results suggest that naproxen ophthalmic solution may be effectively and safely used to control inflammation after uneventful phacoemulsification. Because of the limited number of patients, larger studies are needed to confirm these results.


Burkitt cell acute lymphoblastic leukemia with partial expression of T-cell markers and subclonal chromosome abnormalities in a man with acquired immunodeficiency syndrome.
A 45-year-old white male, bisexual, with a 2-year history of acquired immunodeficiency syndrome (AIDS) prodrome, developed a Burkitt cell-like acute lymphoblastic leukemia (ALL). Marker studies of marrow blasts show an unusual and possibly unique pattern, in that an unequivocal monoclonal B cell leukemia, having K-IgM with HLA-DR and B cell subset antigen (BA-1) expression, was superimposed with a mature suppressor T cell marker profile (pan-T, mature T, and suppressor/cytotoxic T antigens). The leukemic blasts were totally negative for terminal deoxynucleotidyl transferase (TdT), human T cell leukemia-lymphoma virus (HTLV) p19 antigen, and other immunoglobulin isotypes. Chromosome analysis of marrow cells disclosed that 70% of the cells had 47,XY, + 12,t(8;14)(q24;q32) chromosome complement, and 30% of the cells had a 47,XY, + 12,dup1q + (q22-31),t(8;14)(q24;q32). The consistent finding of the specific chromosome rearrangement (8/14 translocation) in all abnormal cells suggests that the cells were derived from a common precursor. With regard to the partial T cell marker expression, the significance of these markers in B cell leukemia is unclear, as is their relation to the additional chromosome abnormalities that apparently developed in the process of clonal evolution.


In utero exposure to diethylstilbestrol and blood DNA methylation in adult women: Results from a meta-analysis of two cohort studies.
Prenatal exposure to diethylstilbestrol (DES) is associated with several adverse health outcomes. Animal studies have shown associations between prenatal DES exposure and DNA methylation. The aim of this study was to explore blood DNA methylation in women exposed and unexposed to DES in utero. Sixty women (40 exposed and 20 unexposed) in the National Cancer Institute's Combined DES Cohort Study and 199 women (99 exposed and 100 unexposed women) in the Sister Study Cohort were included in this analysis. Within each study, robust linear regression models were used to assess associations between DES exposure and blood DNA methylation. Study-specific associations were combined using fixed-effect meta-analysis with inverse variance weights. Our analysis focused on CpG sites located within nine candidate genes identified in animal models. We further explored whether in utero DES exposure was associated with age acceleration. Blood DNA methylation levels at 10 CpG sites in six of the nine candidate genes were statistically significantly associated with prenatal DES exposure (P < 0.05) in this meta-analysis. Genes included EGF, EMB, EGFR, WNT11, FOS, and TGFB1, which are related to cell proliferation and differentiation. The most statistically significant CpG site was cg19830739 in gene EGF, and it was associated with lower methylation levels in women prenatally exposed to DES compared with those not exposed (P < 0.0001; false discovery rate<0.05). The association between prenatal DES exposure in utero and age acceleration was not statistically significant (P = 0.07 for meta-analyzed results). There are few opportunities to investigate the effects of prenatal DES exposure. These findings suggest that in utero DES exposure may be associated with differential blood DNA methylation levels, which could mediate the increased risk of several adverse health outcomes observed in exposed women. Our findings need further evaluation using larger data sets.


Posterior leaflet extension with an autologous pericardial patch in rheumatic mitral insufficiency.
We describe our technique of posterior leaflet extension with an autologous pericardial patch in patients suffering from rheumatic mitral regurgitation. Several simple rules have allowed us to achieve satisfying long-term results.


Obstetric anal sphincter injury by maternal origin and length of residence: a nationwide cohort study.
To estimate the association between maternal origin and obstetric anal sphincter injury (OASI), and assess if associations differed by length of residence. Population-based cohort study. The Medical Birth Registry of Norway. Primiparous women with vaginal livebirth of a singleton cephalic fetus between 2008 and 2017 (n = 188 658). Multivariable logistic regression models estimated adjusted odds ratios (aORs) for OASI with 95% CI by maternal region of origin and birthplace. We stratified models on length of residence and paternal birthplace. OASI. Overall, 6373 cases of OASI were identified (3.4% of total cohort). Women from South Asia were most likely to experience OASI (6.2%; aOR 2.24, 95% CI 1.87-2.69), followed by those from Southeast Asia, East Asia & the Pacific (5.7%; 1.59, 1.37-1.83) and Sub-Saharan Africa (5.2%; 1.85, 1.55-2.20), compared with women originating from Norway. Among women born in the same region, those with short length of residence in Norway (0-4 years), showed the highest odds of OASI. Migrant women across most regions of origin had the lowest risk of OASI if they had a Norwegian partner. Primiparous women from Asian regions and Sub-Saharan Africa had up to two-fold risk of OASI, compared with women originating from Norway. Migrants with short residence and those with a foreign-born partner had higher risk of OASI, implying that some of the risk differential is due to sociocultural factors. Some migrants, especially new arrivals, may benefit from special attention during labour to reduce morbidity and achieve equitable outcomes. Anal sphincter injury during birth is more common among Asian and Sub-Saharan migrants and particularly among recent arrivals.


[Long-term results of sentinel node biopsy diagnostics in penile carcinoma : Dynamic sentinel node biopsy in cases with nonpalpable lymph nodes in the groin].
Dynamic sentinel node biopsy (DSNB) has been recommended in the EAU guidelines for several years as a minimally invasive method for lymph node staging in patients with penile carcinoma and nonpalpable lymph nodes. However, due to the high methodological demands and the primarily unreliable results, this method is rarely used in Germany. The aim of this study was to establish the reliability and morbidity of this method. The frequency of lymph node recurrent disease and complications were prospectively recorded in patients with initially nonpalpable inguinal lymph nodes and histologically negative sentinel lymph nodes. Quality criteria were the false negative rate (percentage of lymph node recurrence in negative procedures) and the morbidity rate. Inguinal regions with palpable lymph nodes and/or evidence of metastases were not considered. The study included 37 patients with histologically negative sentinel lymph nodes in 63 groins with nonpalpable inguinal lymph nodes. There were 21 T1(a/b) stages, 10 T2, and 6 T3 stages. Tumor differentiation was good in 4, moderate in 26, and poor in 7 patients. During a median follow-up of 52 months (range 1-131 months), we observed a bilateral lymph node recurrence in 1 patient and a conservatively managed prolonged lymphorrhea in another patient. Per inguinal region the false-negative rate was 3.2 % and the morbidity rate was 1.6 %; seen per patient the rates were both 2.7 %. DSNB is a reliable method of lymph node staging in patients with penile carcinoma and nonpalpable inguinal lymph nodes. The high degree of reliability in combination with the low morbidity justifies the higher methodical complexity of this method.


Engineering Pseudomonas putida KT2440 to convert 2,3-butanediol to mevalonate.
Biological production of 2,3-butanediol (2,3-BDO), a C4 platform chemical, has been studied recently, but the high cost of separation and purification before chemical conversion is substantial. To overcome this obstacle, we have conducted a study to convert 2,3-BDO to mevalonate, a terpenoid intermediate, using recombinant Pseudomonas putida and this biological process won't need the separation and purification process of 2,3-BDO. The production of mevalonate when 2,3-BDO was used as a substrate was 6.61 and 8.44 times higher than when glucose and glycerol were used as substrates under the same conditions, respectively. Lower aeration contributed to higher yields of mevalonate in otherwise identical conditions. The maximum mevalonate production on the shaking flask scale was about 2.21 g/L, in this study (product yield was 0.295, 27% of theoretical yield (1.10)). This study was the first successful attempt for mevalonate production by P. putida using 2,3-BDO as the sole carbon source and presented a new metabolic engineering tool and biological process for mevalonate synthesis.