Effects of tolterodine, trospium chloride, and oxybutynin on the central nervous system.
Antimuscarinic compounds are increasingly used to treat the symptoms of overactive bladder; however, their use is often restricted by peripheral adverse effects (AEs). On the other hand, data regarding their influence on the central nervous system (CNS) are limited. This randomized, single-blind, parallel-group quantitative-topographical EEG (qEEG) study of clinical phase I investigates the potential CNS adverse effects of the three antimuscarinic drugs--tolterodine, oxybutynin, and trospium chloride--in comparison to placebo. Overall, 4 x 16 (total 64) young, healthy male volunteers were included in the study. The subjects were given either placebo or the clinically recommended daily doses of the drugs dispensed in three doses on a single day (tolterodine 2 mg bid and once placebo, total 4 mg/d; oxybutynin 5 mg tid, total 15 mg/d; and trospium chloride 15 mg tid, total 45 mg/d). The qEEG was recorded prior to and up to 4 hours after each intake of the trial medication (a total of 10 qEEG sessions) under three different conditions: at rest with eyes open, eyes closed, and under mental demand. The drug tolerability was subjectively evaluated by the volunteer and the investigator. In comparison to placebo (10% confidence interval), tolterodine and trospium chloride did not induce changes of the qEEG power in five of the six frequency bands (i.e., delta, alpha 1, alpha 2, beta 1, and beta 2). Isolated power decreases were only observed in the theta frequency band. In contrast, oxybutynin caused significant power reductions in four frequency bands (theta, alpha 1, alpha 2, and beta 1; p < 0.01). The subjectively evaluated drug tolerability was comparable between all treatment groups, although differences in the AE occurrence existed, with the AE frequency being higher in the oxybutynin group. The results of this study support the findings that oxybutynin as a tertiary amine crosses the blood-brain barrier, causing significant qEEG activity changes and more pronounced central adverse effects. Although tolterodine is also a tertiary amine, it shows limited effects on qEEG activity (i.e., slight theta power reductions), comparable to the effects of trospium chloride, a quarternary amine, which barely crosses the blood-brain barrier. The minimal qEEG changes observed with tolterodine and trospium chloride reflect most probably a rebound message from the peripheral target organs. Prescription of oxybutynin thus implicates a higher risk of CNS side effects.


Unusual substrate specificity in GH family 12: structure-function analysis of glucanases Bgh12A and Xgh12B from Aspergillus cervinus, and Egh12 from Thielavia terrestris.
In this study, we compared the properties and structures of three fungal GH12 enzymes: the strict endoglucanase Bgh12A and the xyloglucanase Xgh12B from Aspergillus cervinus, and the endoglucanase Egh12 from Thielavia terrestris combining activity on linear β-glucan and branched xyloglucan. Egh12 from T. terrestris was produced in Pichia pastoris, purified, and characterized as a thermostable enzyme with maximal activity at 70 ºC and a half-life time of 138 min at 65 °C. We for the first time demonstrated that the GH12 endoglucanases Egh12 and Bgh12A, but not the strict xyloglucanase Xgh12B, hydrolyzed (1,3)-β-linkages in (1,3;1,4)-β-D-glucooligosaccharides and had transglycosylase activity on (1,3)-β-D-glucooligosaccharides. Phylogenetic analysis indicated that Egh12 from T. terrestris and Bgh12A from A. cervinus are more related than Bgh12A and Xgh12B isolated from one strain. The X-ray structure of Bgh12A was determined with 2.17 Å resolution and compared with 3D-homology models of Egh12 and Xgh12B. The enzymes have a β-jelly roll structure with a catalytic cleft running across the protein. Comparative analysis and a docking study demonstrated the importance of endoglucanase-specific loop 1 partly covering the catalytic cleft for correct placement of the linear substrates. Variability in substrate specificity between the GH12 endoglucanases is determined by non-conservative residues in structural loops framing the catalytic cleft. A residue responsible for the thermostability of Egh12 was predicted. The key structural elements and residues described in this study may serve as potential targets for modification aimed at the improvement of enzymatic properties. KEY POINTS: • Thermostable endoglucanase Egh12 from T. terrestris was produced in P. pastoris, purified, and characterized • The X-ray structure of GH12 endoglucanase Bgh12A from A. cervinus was resolved • GH12 endoglucanases, but not GH12 xyloglucanases, hydrolyze (1,3)-β-linkages in (1,3;1,4)-β-D-glucooligosaccharides.


Microsurgical reconstruction of hepatic artery in living donor liver transplantation: experiences and lessons.
Hepatic artery (HA) reconstruction is one of the key steps for living donor liver transplantation (LDLT). The incidence of HA thrombosis has been reduced by the introduction of microsurgical techniques under a high resolution microscope or loupe. We report our experience in 101 cases of HA reconstruction in LDLTs using the graft-artery-unclamp and posterior-wall-first technique. The reconstructions were completed by either a plastic surgeon or a transplant surgeon. The rate of HA thrombosis was 2% (2/101). The risk factors for failed procedures appeared to be reduced by participation of the transplant surgeon compared with the plastic surgeon. For a graft with duplicate arteries, we considered no branches should be discarded even with a positive clamping test. HA reconstruction without clamping the graft artery is a feasible and simplified technique, which can be mastered by transplant surgeons with considerable microsurgical training.


Ovarian intrabursal administration of insulin-like growth factor-binding protein inhibits follicle rupture in gonadotropin-treated immature female rats.
The effects of an insulin-like growth factor-binding protein (IGF-BP) on rat follicular function were examined by using the technique of ovarian intrabursal (IB) injection. Immature female rats were injected with 15 IU of eCG followed immediately with IB injections of 4 micrograms IGF-BP3 (right ovary) and vehicle (left ovary). Forty-eight hours later, the same animals were either killed (eCG-treated group) or injected with 1 microgram of hCG as an ovulatory stimulus. These animals were killed 24 h later (eCG/hCG-treated group). Intrabursal administration of IGF-BP3 inhibited ovulations in the eCG/hCG-treated rats by 55% when compared with the contralateral vehicle-treated ovary (p = 0.01). Examination of the ovaries exposed to IGF-BP3 revealed the presence of unruptured follicles containing a matured oocyte and a disintegrated basement membrane, in addition to normal follicles and corpora lutea. In contrast, IB injection of IGF-BP3 had no effect on ovarian weights or circulating estradiol concentrations in the eCG-treated animals, and the ovaries appeared to be morphologically normal. Ligand blotting experiments using [125I]-labeled insulin-like growth factor I revealed that granulosa cells obtained from both untreated and eCG-treated rats synthesized and secreted two IGF-BPs of Mr 35,000 and 30,000. Equine chorionic gonadotropin treatment reduced the amount of the 30,000 Mr form of IGF-BP. These data suggest that locally produced ovarian IGF-BPs may modulate follicle functions in vivo.


Somatoform pain disorder.
Chronic pain is common; it is found in up to 15% of randomly selected population samples, and psychosocial factors including those provoked by physical trauma associated with industrial and motor vehicular accidents are very common in etiology. The diagnosis of post-traumatic stress disorder may be appropriate in many of these cases. The objectives of this paper are to review the psychological and social factors which contribute to the etiology of chronic pain syndromes. It reviews also the relationship of pain to Depressive, Anxiety and Substance Abuse Disorders and the principles of management of Pain Disorder. Supportive psychotherapy, pharmacotherapy (in particular tricyclic antidepressant medication) and behavioral rehabilitation programs may all be helpful in producing symptomatic improvement. An interdisciplinary pain clinic, particularly one which involves non-medical health professionals such as psychologists, social workers, occupational therapists and physiotherapists are very helpful in the management of complex cases.


The Use of Bilberry Leaves (Vaccinium myrtillus L.) as an Efficient Adsorbent for Cationic Dye Removal from Aqueous Solutions.
In this study, a new lignocellulosic bioadsorbent, bilberry (Vaccinium myrtillus L.) leaves powder, was used to remove the methylene blue dye from aqueous solutions. The characterization of the adsorbent was performed by FTIR, SEM and color analysis. The influence of pH, contact time, adsorbent dose, initial dye concentration, temperature and ionic strength on the adsorption process were followed. Equilibrium, kinetic, and thermodynamic studies were conducted in order to understand the adsorption process mechanism. Process optimization was performed using the Taguchi method. Sips isotherm and general order kinetic model characterize the adsorption process. The maximum adsorption capacity, 200.4 (mg g-1), was better compared with other similar bioadsorbents. Thermodynamic parameters indicated that the adsorption process is spontaneous, favorable and endothermic and also that physisorption is involved in the process. The factor with the highest influence on the dye removal process was pH, followed by contact time, temperature, adsorbent dose, ionic strength and initial dye concentration. The obtained results revealed that the bioadsorbent material based on bilberry (Vaccinium myrtillus L.) leaves is highly efficient for cationic dyes removal from aqueous solutions.


Usefulness of defined daily dose and days of therapy in pediatrics and obstetrics-gynecology: a comparative analysis of antifungal drugs (2000-2001, 2005-2006, and 2010-2011).
The objective was to describe antifungal drug use by using the number of defined daily doses (DDD)/1000 patient-days per antifungal, the number of days of therapy (DOT)/1000 patient-days per antifungal, and the mean dose in mg/kg/day per antifungal during a 10-year period. Retrospective, cross-sectional, descriptive study, in a mother-child university hospital center, with 400 pediatric beds and 100 obstetrics-gynecology beds. All inpatients who received 1 of the 7 authorized antifungals on the institution's local formulary in 2000-2001, 2005-2006, or 2010-2011 were included. Prescriptions for emergency department and outpatient clinics were excluded. The data were extracted from the patients' computerized medication profiles linked to patient admission, discharge, and transfer data. The DDD, DOT, and the mean dose in mg/kg/day were calculated for each antifungal and overall. There was a 2.97-fold increase in the overall number of DDD/1000 patient-days, from 14.8 in 2000-2001 to 37.5 in 2005-2006 and 43.9 in 2010-2011. There was a 2.97-fold increase in the overall number of DOT/1000 patient-days, from 22.8 in 2000-2001 to 50.3 in 2005-2006 and 67.8 in 2010-2011. It can be difficult to compare the use of antifungal drugs among institutions, owing to numerous factors, but it gives an idea about the consumption outside the studied center. Moreover, these ratios help to evaluate the use of antifungals within a same institution. These data could be correlated among others, with resistance patterns, in order to improve our daily practice concerning antifungal prescription.


Reduce confusion--share your objective.
Individual Performance Review relates performance to objectives. Hugh Flanagan argues that an individual manager's objectives must be related to those of other managers and of the whole organisation, and that harmonisation will not be achieved without special effort.


Degradation of sulfonamides in aqueous solution by membrane anodic fenton treatment.
Two agricultural antibiotics used heavily in agriculture, sulfamethazine and sulfadiazine, were degraded in an aqueous system by anodic Fenton treatment (AFT), an advanced oxidation technique that has been shown to be effective in degrading various pesticides but has not been applied to antibiotics. The effects of the H(2)O(2)/Fe(2+) ratio, Fe(2+) delivery rate, and initial contaminant concentration on the degradation of sulfamethazine by AFT were determined. The optimal H(2)O(2)/Fe(2+) ratio was determined to be 10:1, and the optimal Fe(2+) delivery rate was found to be between 38.9 and 54.4 microM min(-1). Under these conditions, sulfamethazine was completely degraded within 10 min at a range of concentrations (18-250 microM) commonly found in manure lagoons, contaminated rivers, and groundwater. Using the same optimal conditions, the effect of pH on the degradation of sulfadiazine by AFT was analyzed, and 100 microM sulfadiazine was degraded within 6-8 min of treatment at a range of pH values (3.1-7.1) that could potentially be found in aquatic environments. Degradation products and pathways were proposed for both compounds, and it was inferred that AFT degradation products of sulfadiazine and sulfamethazine are unlikely to retain the bacteriostatic properties of their parent compounds. An aquatic toxicity test employing Lemna gibba confirmed that AFT removes the bacteriostatic properties of sulfamethazine and sulfadiazine during degradation.


Low-Level Laser Application in the Early Myocardial Infarction Stage Has No Beneficial Role in Heart Failure.
Low-level laser therapy (LLLT) has been targeted as a promising approach that can mitigate post-infarction cardiac remodeling. There is some interesting evidence showing that the beneficial role of the LLLT could persist long-term even after the end of the application, but it remains to be systematically evaluated. Therefore, the present study aimed to test the hypothesis that LLLT beneficial effects in the early post-infarction cardiac remodeling could remain in overt heart failure even with the disruption of irradiations. Female Wistar rats were subjected to the coronary occlusion to induce myocardial infarction or Sham operation. A single LLLT application was carried out after 60 s and 3 days post-coronary occlusion, respectively. Echocardiography was performed 3 days and at the end of the experiment (5 weeks) to evaluate cardiac function. After the last echocardiographic examination, LV hemodynamic evaluation was performed at baseline and on sudden afterload increases. Compared with the Sham group, infarcted rats showed increased systolic and diastolic internal diameter as well as a depressed shortening fraction of LV. The only benefit of the LLLT was a higher shortening fraction after 3 days of infarction. However, treated-LLLT rats show a lower shortening fraction in the 5th week of study when compared with Sham and non-irradiated rats. A worsening of cardiac function was confirmed in the hemodynamic analysis as evidenced by the higher LV end-diastolic pressure and lower +dP/dt and -dP/dt with five weeks of study. Cardiac functional reserve was also impaired by infarction as evidenced by an attenuated response of stroke work index and cardiac output to a sudden afterload stress, without LLLT repercussions. No significant differences were found in the myocardial expression of Akt1/VEGF pathway. Collectively, these findings illustrate that LLLT improves LV systolic function in the early post-infarction cardiac remodeling. However, this beneficial effect may be dependent on the maintenance of phototherapy. Long-term studies with LLLT application are needed to establish whether these effects ultimately translate into improved cardiac remodeling.


Prediction of Response to Irinotecan and Drug Toxicity Based on Pharmacogenomics Test: A Prospective Case Study in Advanced Colorectal Cancer
Background: FOLFIRI regimen, which is composed of 5-FU, Leucovorin, and Irinotecan, is used in the first-line chemotherapy of metastatic colorectal cancer. Irinotecan life threatening toxicity is partly related to cytotoxic drug metabolite which is primarily inactivated by the UGT1A1 enzyme. The primary aim of the present research was to find the correlation between UGT1A1-genotype and clinical toxicity of irinotecan. Methods: In a prospective study from March 2011 to December 2013, all patients with metastatic colorectal cancer who had been referred to Medical Oncology Department of Iran Cancer Institute were genotyped for UGT1A1*28 before the first cycle of chemotherapy. All of the patients signed informed consent and trial approved by Ethics Committee of the Tehran University of Medical Sciences. Reduction of the standard dose of Irinotecan (180 mg/m2 body surface area) was measured based on NCI toxicity criteria after the first cycle of chemotherapy. Patients with previous treatment with Oxaliplatin and fluorouracil (5-FU) in the adjuvant setting and adequate liver, kidney, and heart function were included in the trial. Both synchronous and metachronous metastatic disease were noticeable. Results: A total of 50 patients with median age of 52 years were included. Most (70%) of the patients had more than one site of metastases in peritoneum, liver, and/or lung. Thirty-one patients had UGT1A1*1 normal genotype, 13 were in heterozygote and 6 were in homozygote state ofUGT1A1*28/*28. A clinically relevant increase in early toxicity was found in patients carrying the UGT1A1*28/*28 genotype with odds Ratio (OR) of 2.6 (95%CI 2.5-27.28). Similarly, there was a trend of lower overall survival in homozygote group with an HR (Hazardous Ratio) of 2.76 (95%CI .88-.61). No statistically significant relationship was found between UGT1A1genotypes and response to therapy. Conclusions: UGT1A1 28*/28* is strongly associated with drug's life-threatening toxicity even in a moderate dose of Irinotecan. On the other hand, UGT1A1 genotype data was not helpful to differentiate response to treatment.


CRH test prior to discontinuation of long-term low-dose glucocorticoid therapy.
Often long-term low-dosage glucocorticoid therapy cannot be terminated. This is due to the fact that even low doses which are within the physiological replacement range can cause a detectable, though clinically insignificant suppression of the adrenal gland function, resulting in "corticosteroid withdrawal syndrome". Another reason is the fact that it is necessary to be able to suppress undesirable inflammatory reactions caused by the underlying disease. ACTH testing of the adrenal capacity is widespread, but repeated testing may lead to undesirable side effects, such as allergic reactions. This study investigates the usefulness of testing the function of the pituitary-adrenal axis in predicting withdrawal problems. In 21 patients with chronic inflammatory disease who were treated with glucocorticoid doses of 5 to 10 mg prednisolone equivalent daily for a period of 2 to 131 months, stimulation with 100 microg hCRH (human corticotrophin-releasing hormone) was performed prior to the gradual withdrawal of medication. Blood samples were taken at baseline and after 45 minutes to measure ACTH and cortisol levels. Four weeks after steroid withdrawal the patients were reevaluated for signs of a relapse of the underlying disease in order to establish the necessity of reintroducing steroid therapy. This reevalution comprised clinical criteria, laboratory tests and the patients' own assessment of his/her well-being. In sixteen patients who later successfully withdrew from glucocorticoid therapy, a significant increase in cortisal levels was noticed after stimulation with CRH (p < 0.05). In five patients, with whom steroid withdrawal was not successful, baseline levels of cortisol were significantly lower than in the others (p < 0.05) and no sufficient increase was achieved after stimulation with CRH. These results show that successful withdrawal of a long-term low-dosage glucocorticoid therapy depends on the integrity of the pituitary-adrenal axis. Therefore CRH testing for evaluation of the pituitary-adrenal axis can be helpful in identifying patients in whom glucocorticoid withdrawal would be troublesome.


Validation of the German Version of the New Freezing of Gait Questionnaire for People with Parkinson's Disease.
Freezing of gait (FOG) in Parkinson's disease (PD) is a highly disabling symptom which impacts quality of life. The New FOG Questionnaire (NFOG-Q) is the most commonly used tool worldwide to characterize FOG severity in PD. This study aims to provide a German translation of the NFOG-Q and to assess its validity in people with PD. The questionnaire was translated using forward-backward translation. Validity was tested in 57 PD patients with FOG via Cronbach's alpha for internal consistency and Spearman correlations with several clinical measures to quantify disease severity, mobility, fall risk, and cognitive state for convergent and divergent validity. The German version of the NFOG-Q shows good internal consistency (Cα = 0.84). Furthermore, the NFOG-Q score was significantly correlated with the MDS-UPDRS III, H&Y stage, Timed Up and Go test, and the subjective fear of falling (FES-I). The lack of correlation with cognition (MoCA) points towards good divergent validity. This study provides a German version of the NFOG-Q which proved to be valid for the assessment of FOG severity in individuals with PD.


A dominant positive and negative selectable gene for use in mammalian cells.
We have constructed three different fusion genes containing the herpes simplex virus thymidine kinase (HSV tk) and the bacterial neomycin phosphotransferase (neo) genes. All three fusion genes utilize the HSV tk promoter but differ at the junction of their components. We have determined if the fusion genes are bifunctional by introducing them into mammalian cells and testing for function of the individual components. One of the fusion genes, TNFUS 69, produced a bicistronic message and a fusion protein that has TK and NEO protein functions. This and other fusion genes of a similar nature could serve as dominant positive and negative selectable markers in mammalian cells.


[Analysis of expression profiles of some tumor growth-related genes after silencing of pleiotrophin in human small cell lung cancer H446 cells].
To investigate the changes in expression profiles of angiomotin (Amot), schlafen5 (Slfn5), metalloproteinase-9 (MMP-9) and vascular endothelial cell growth factor (VEGF), which are genes associated with angiogenesis, tumor growth and invasion, after gene silencing of pleiotrophin (PTN) in human small cell lung cancer H446 cells. PTN expression in H446 cells was determined by RT-PCR and Western blot. After constructing a lentiviral vector interfering PTN expression, it was packaged into virus in 293T cells. Then the virus was used to infect human small cell lung cancer H446 cells. The expressions of Amot, Slfn5, MMP-9 and VEGF were detected by RT-PCR in normal non-interference group, negative control group, PTN-interference group and group combining PTN interference and chemotherapy. The results of RT-PCR and Western blot test showed that PTN expression in H446 cells was high. The interference efficiency of constructed ShRNA sequences (GCAGCTGTGGATACTGCTGAA) targeting PTN was as high as 72.1% and 59.2% at the mRNA and protein levels, respectively, in H446 cells. Compared with the negative control group, the expressions of Slfn5 and MMP-9 in H446 cells were increased by 165.1% and 47.3%, while the ones of Amot and VEGF were down-regulated by 33.1% and 26.6%, respectively, after gene silencing of PTN. The changes of gene expression profile became more evident when chemotherapy was superimposed on PTN interference. Gene silencing of PTN using siRNA lentiviral expressing vector can influence the expression of proliferation and metastasis-related genes in human small cell lung cancer H446 cells.


Application of modified subtotal resection of adenomyosis combined with LNG-IUS and GnRH-a sequential therapy in severe adenomyosis: A case series.
Adenomyosis focus resection has always been the main surgical method for patients with uterine preservation, but its curative effect and surgical method are still controversial. We improved this method on the basis of the "double-flap method" and combined it with the levonorgestrel intrauterine delivery system (LNG-IUS) and gonadotropin-releasing hormone agonist (GnRH-a) sequential treatment to determine the clinical effect and feasibility of this scheme in the treatment of severe adenomyosis. This is a retrospective review. A total of 64 patients with severe adenomyosis were treated in the Department of Gynecology of Changzhou Second People's Hospital, which is affiliated to Nanjing Medical University, from December 2017 to September 2021. The transabdominal approach and laparoscopic approach were adopted for the purposes of treatment in this study. Hence, the patients were subdivided into the transabdominal approach subgroup and the laparoscopic approach subgroup. The hemoglobin, visual analog score (VAS) score, menstruation score, and other indices of each patient before and after treatment were observed, recorded, and analyzed. All 64 patients underwent the operation successfully. After the completion of sequential treatment, the CA125 decreased significantly 1 month after the operation, the average uterine volume significantly reduced, the hemoglobin value increased to a certain extent 3 months after the operation, and the menstrual score and dysmenorrhea during the first menstruation were significantly lower than they were before the operation. After the treatment, the therapeutic results of the transabdominal approach subgroup and endoscopic approach subgroup were compared on the basis of the observed indices, and no significant difference was observed (P > 0.05). Only one patient had a downward movement of the LNG-IUS, and the vaginal ultrasound showed that the upper end of the LNG-IUS was approximately 1.5 cm from the bottom of the uterine cavity. The average follow-up period was 24.02 ± 11.77 months, and no lesion progression was found in any patients. For patients suffering from severe adenomyosis who have no pregnancy plans and require uterine preservation, transabdominal or laparoscopic subtotal resection of the focus of adenomyosis, combined with the LNG-IUS + GnRH-a sequential treatment, may be a safe and effective alternative when conservative treatments such as drugs fail.


[Yersinia pestis as a dangerous biological weapon].
Plague is an infectious disease caused by the Yersinia pestis microorganism, which is transmitted to the human host from a natural reservoir (different rodent species) by a flea bite. Plague is still encountered in humans in the areas of its enzootic prevalence in local rodent populations. Infection by flea bite results in a bubonic or septicemic plague, possibly complicated by secondary pneumonia. The person with pneumonic symptoms may be a source of a droplet-borne inhalatory infection for other people who consequently develop primary pneumonic plague. Despite a clinical form, plague is a severe infection characterized by a short incubation period, rapid onset and quick progress with mortality exceeding 50% if not treated properly. The pneumonic plague is associated with a particularly rapid progress and the mortality rate of almost 100% if not treated properly. As Yersinia pestis can be easily obtained and cultured and is highly pathogenic for humans, it poses a serious threat of being used for bioterrorism purposes. Artificially created aerosol containing plague bacilli can cause numerous and almost simultaneous cases of primary pulmonic plague in an exposed population. Persons exposed would most likely develop severe pneumonia with rapidly progressing respiratory and circulatory failure. The use of the Yersinia pestis strains resistant to antibiotics typically applied cannot be excluded.


An in silico study on the effect of the radionuclide half-life on PET/CT imaging with PSMA-targeting radioligands.
The aim of this work was to systematically investigate the influence of the radionuclide half-life and affinity of prostate-specific membrane antigen (PSMA)-targeting ligands on the activity concentration for PET/CT imaging. A whole-body physiologically-based pharmacokinetic (PBPK) model with individually estimated parameters of 13 patients with metastatic castration-resistant prostate cancer (mCRPC) was used to simulate the pharmacokinetics of PSMA-targeting radioligands. The simulations were performed with 68Ga (T1/2 = 1.13 h), 18F (T1/2 = 1.83 h), 64Cu (T1/2 = 12.7 h) and for different affinities (dissociation constants KD of 1-0.01 nM) and a commonly used ligand amount of 3 nmol. The activity concentrations were calculated at 1, 2, 3, 4, 8, 12, and 16 h after injection. The highest tumor uptake was achieved 1 h p. i. for 68Ga-PSMA. For 18F-PSMA, the highest tumor uptake was at 1 h p. i. and 2 h p.i for dissociation constants KD = 1 nM and KD = 0.1-0.01 nM, respectively. For 64Cu-PSMA, the highest tumor uptake was at 4 h p. i. for dissociation constant KD = 1 nM and at 4 h p. i. (9 patients) and 8 h p. i. (4 patients) for higher affinities. Compared to 68Ga-PSMA (1 h p. i.), the activity concentrations in the tumor for 18F-PSMA (2 h p. i.) increased maximum 1.3-fold with minor differences for all affinities. For 64Cu-PSMA (4 h p. i.), the improvements were in the range of 2.8 to 3.2-fold for all affinities. The simulations indicate that the highest tumor-to-background ratio can be achieved after 4 hours in PET/CT using high-affinity 64Cu-PSMA.


Prediction of the next major outbreak of COVID-19 in Mainland China and a vaccination strategy for it.
After the widespread prevalence of COVID-19 at the end of 2022 in Mainland China, a major concern is when will the second major outbreak occur and with what prevalence and fatality rates will it be associated with, as peoples' immunity from natural infection subsides. To address this, we established an age-structured model considering vaccine and infection-derived immunity, fitted an immunity-waning curve, and calibrated the model using the epidemic and vaccination data from Hong Kong in 2022. The model and the situation of the first major epidemic in Mainland China were then used to predict the prevalence rate, fatality rate and peak time of the second wave. In addition, the controlling effects of different vaccination strategies on the second major outbreak are discussed. Finally, a characterization indicator for the level of population immunity was provided. We conclude that if the prevalence of the first major epidemic was 80%, the prevalence rate of the second major outbreak would be about 37.64%, and the peak time would have been July 2 2023. Strengthening vaccination can effectively delay the peak of the second wave of the epidemic and reduce the prevalence.


Why can deep convolutional neural networks improve protein fold recognition? A visual explanation by interpretation.
As an essential task in protein structure and function prediction, protein fold recognition has attracted increasing attention. The majority of the existing machine learning-based protein fold recognition approaches strongly rely on handcrafted features, which depict the characteristics of different protein folds; however, effective feature extraction methods still represent the bottleneck for further performance improvement of protein fold recognition. As a powerful feature extractor, deep convolutional neural network (DCNN) can automatically extract discriminative features for fold recognition without human intervention, which has demonstrated an impressive performance on protein fold recognition. Despite the encouraging progress, DCNN often acts as a black box, and as such, it is challenging for users to understand what really happens in DCNN and why it works well for protein fold recognition. In this study, we explore the intrinsic mechanism of DCNN and explain why it works for protein fold recognition using a visual explanation technique. More specifically, we first trained a VGGNet-based DCNN model, termed VGGNet-FE, which can extract fold-specific features from the predicted protein residue-residue contact map for protein fold recognition. Subsequently, based on the trained VGGNet-FE, we implemented a new contact-assisted predictor, termed VGGfold, for protein fold recognition; we then visualized what features were extracted by each of the convolutional layers in VGGNet-FE using a deconvolution technique. Furthermore, we visualized the high-level semantic information, termed fold-discriminative region, of a predicted contact map from the localization map obtained from the last convolutional layer of VGGNet-FE. It is visually confirmed that VGGNet-FE could effectively extract distinct fold-discriminative regions for different types of protein folds, thereby accounting for the improved performance of VGGfold for protein fold recognition. In summary, this study is of great significance for both understanding the working principle of DCNNs in protein fold recognition and exploring the relationship between the predicted protein contact map and protein tertiary structure. This proposed visualization method is flexible and applicable to address other DCNN-based bioinformatics and computational biology questions. The online web server of VGGfold is freely available at http://csbio.njust.edu.cn/bioinf/vggfold/.


Percutaneous balloon pericardiotomy for malignant pericardial tamponade.
Recurrent pericardial effusion or tamponade can complicate malignant disease. The medical approach with pharmacologic agents has a high recurrence rate. Balloon pericardiotomy (BP) may provide a less invasive alternative to surgery. We performed BP in ten high-risk patients with malignant pericardial tamponade (MPT). BP was performed with aseptic technique under fluoroscopic and echocardiographic guidance. We used a percutaneous subxiphoid approach. A 20- to 25-mm-wide and 4-cm-long balloon was introduced over a stiff guide wire, positioned across the parietal pericardium, and manually inflated until the waisting disappeared. Echocardiographic study and chest radiograph were taken before, immediately after the procedure, and during follow-up. The procedure was successful and well tolerated in all patients. There were no immediate or late complications. No patients developed recurrence of pericardial effusion at up to 10 months' follow-up. In conclusion, BP can be performed in patients with MPT with high rate of procedural success. It may become the preferred treatment to avoid a more invasive procedure in these critically ill patients.


An investigation into community psychiatric nurses' use of humour during client interactions.
Community psychiatric nurses' (CPNs') accounts of interactions with clients often reflect benefits of using humour appropriately. This is despite the use of humour as a specific therapeutic form of communication generally being ignored during CPNs' professional development. With the growth in community care, mental health nurses are required to function more autonomously within the client's home environment, thus the contextual nature of the nurse's use of humour may have to be adjusted accordingly. How nurses makes this adjustment of their use of humour appears to be left to their own experiences. Yet inappropriate use of humour may be costly to the nurse-client relationship. The research described in this paper used a descriptive qualitative methodology to explore the perceptions of seven CPNs working in Scotland in relation to their use of humour during client interactions. As this study did not specifically access clients, ethical permission was not required from the local research and ethics committee. This did not excuse the author from recognizing ethical considerations of the subjects in relation to sharing information about being volunteers, their rights of withdrawal and the risks and benefits of the study. Confidentiality and anonymity were also maintained by the use of pseudonyms. Data collected through critical incident analysis and interviews were subjected to content analysis. Findings confirm the paradoxical nature of humour. Humour, when used appropriately, assisted the development of trust and changing the client's restrictive perceptions. Damaging effects were reported, however, if the humour was misinterpreted or perceived by the client as demeaning their experience. Although the CPNs had not received any formal education about the use of humour, recommendations centred on raising student nurses' and CPNs' awareness about their own use of humour.


Dynamic contrast enhanced magnetic resonance imaging subtraction in evaluating osteosarcoma response to chemotherapy.
To evaluate the results of a new technique of dynamic contrast enhanced Magnetic Resonance (MR) imaging subtraction in the assessment of osteosarcoma response to chemotherapy. 24 patients with high grade osteosarcoma, treated with preoperative neo-adjuvant chemotherapy, underwent MR at high field strength (1.5 T). Both unenhanced conventional SE T1- and T2-weighted sequences in the coronal and axial plane and dynamic Gd-DTPA-enhanced SE T1-weighted sequences in the coronal plane were performed. Image postprocessing included subtraction of unenhanced image from enhanced images (arbitrary called "angiographic subtraction") and subtraction of each enhanced image from the last-enhanced image (arbitrary called "pathologic area" subtraction). The early enhancing areas detected in the angiographic subtraction and the pathologic areas detected in the pathologic area subtraction were correlated with histopathological findings on histological macrosections obtained from the resected specimen. The sensitivity, specificity, accuracy, positive and negative predictive value of both the subtraction techniques were calculated. The early enhancing areas of angiographic subtraction were related not only to viable tumor but also to the host reactions such as flogosis and granulation tissue. The pathologic areas detected at the pathologic area subtraction correlated in most cases with viable tumor, while in 3 cases they did not correspond to viable tumor tissue and in 1 case a small area of residual viable tumor was missed. In assessing response to chemotherapy, pathologic areas subtraction had an accuracy of 95% (specificity: 100%, sensitivity: 93%, PPV: 100%, NPV: 88%), whereas angiographic subtraction had an accuracy of 79% (specificity: 37%, sensitivity: 100%, PPV: 76%, NPV: 100%). Pathologic area subtraction may be a useful technique for assessing the response of osteosarcoma to chemotherapy and for detecting residual viable tumor tissue.


Variation in the efficacy of hormone replacement therapy in the prevention of hip fracture. Swedish Hip Fracture Study Group.
Use of postmenopausal hormone replacement therapy (HRT) has been associated with a reduced risk of osteoporotic fractures. However, it is uncertain whether this risk reduction is modified by other risk factors for hip fracture. In a population-based case-control study in Sweden, we investigated the association between HRT and hip fracture risk within categories of age, body measures and lifestyle factors in postmenopausal women, 50-81 years of age. Mailed questionnaires and telephone interviews were used to collect data. Of those eligible, 1328 incident cases with hip fracture (82.5%) and 3312 randomly selected controls (81.6%) answered the questionnaire. Ever use of HRT in women less than 75 years old was associated with an odds ratio (OR) of 0.66 (95% confidence interval: 95% CI 0.50-0.87) for hip fracture compared with OR 0.40 (95% CI 0.21-0.77) in women 75 years or older. We found a significant interaction between HRT and both weight and physical activity (p < 0.05). The protective effect of HRT was particularly pronounced in lean women: compared with never HRT users, ever users weighing under 60 kg had an OR of 0.44 (95% CI 0.30-0.66) whereas women weighing more than 70 kg had an OR of 0.91 (95% CI 0.53-1.56). Women with low recent leisure physical activity (less than 1 h/week) similarly benefited more from HRT for hip fracture prevention than women with a higher degree of recreational physical activity. The observed interactions with weight and physical activity suggest that HRT has the best protective effect against hip fracture among high-risk women.


Morphological characteristics of intrinsic foot muscles among flat foot and normal foot using ultrasonography.
The purpose of this study was to compare the morphology of the intrinsic foot muscle between typical foot and flat foot with the use ultrasound. Thirty-seven healthy participants were recruited in this study. Foot types were classified using the Foot posture index 6-item version. A total of 43 flat feet and 31 typical feet were examined. Using B-mode ultrasound imaging, the morphology of the abductor hallucis, oblique head of adductor hallucis, abductor digiti minimi, and flexor digitorum brevis muscles were measured. Morphology of all muscles measured was normalized by body height. The independent Student's t-test was used to examine the differences in the thickness and the cross-sectional area (CSA) of the intrinsic foot muscle among the two groups. The thickness of abductor hallucis was significantly larger in flat foot group. The thickness and CSA of abductor digiti minimi and the thickness of oblique head of adductor hallucis were significantly smaller in flat foot group. Our results showed hypertrophied adductor hallucis, atrophied abductor digiti minimi, and atrophied oblique head of the adductor hallucis in individuals with flat feet, suggesting a possible tendency to hypertrophy in muscles that are located in a medial position and a possible tendency to atrophy in muscles that are located in a lateral position in flat feet.


Differentiation Induction of Human Stem Cells for Corneal Epithelial Regeneration.
Deficiency of corneal epithelium causes vision impairment or blindness in severe cases. Transplantation of corneal epithelial cells is an effective treatment but the availability of the tissue source for those cells is inadequate. Stem cells can be induced to differentiate to corneal epithelial cells and used in the treatment. Multipotent stem cells (mesenchymal stem cells) and pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) are promising cells to address the problem. Various protocols have been developed to induce differentiation of the stem cells into corneal epithelial cells. The feasibility and efficacy of both human stem cells and animal stem cells have been investigated for corneal epithelium regeneration. However, some physiological aspects of animal stem cells are different from those of human stem cells, the protocols suited for animal stem cells might not be suitable for human stem cells. Therefore, in this review, only the investigations of corneal epithelial differentiation of human stem cells are taken into account. The available protocols for inducing the differentiation of human stem cells into corneal epithelial cells are gathered and compared. Also, the pathways involving in the differentiation are provided to elucidate the relevant mechanisms.


Anguilla anguilla L. biochemical and genotoxic responses to benzo[a]pyrene.
Eels (Anguilla anguilla L.) were exposed for 2, 4, 6, 8, 16, 24, 48, 72, 144, and 216 h to 0 (control), 0.3, 0.9, and 2.7 microM benzo[a]pyrene (BaP). The biotransformation induced by BaP was measured as liver ethoxyresorufin O-deethylase (EROD) activity and cytochrome P450 content, and compared with the genotoxic effects, such as erythrocytic nuclear abnormalities (ENA), and blood and liver DNA strand breaks. The liver exhibited a highly significant EROD activity increase from 2 up to 216 h exposure to 0.9 and 2.7 microM BaP, whereas 0.3 microM BaP exposure induced a significant liver EROD increase from 2 up to 144 h. Liver cytochrome P-450 content was significantly increased at 8 h to 2.7 microM BaP exposure. Liver DNA integrity was decreased at 16 h, from 8 up to 144 h and 8 up to 72 h exposure to 0.3, 0.9, and 2.7 microM BaP, respectively. A significant decrease in blood DNA integrity was observed at 48, 72, 144 h, from 8 up to 72, and from 6 up to 72 h exposure to 0.3, 0.9, and 2.7 microM BaP, respectively. The A. anguilla L. genotoxic response to BaP, measured as ENA induction, was significantly increased at 144 h exposure to 0.3 microM BaP. The intermediate BaP concentration tested (0.9 microM) induced a significant three fold ENA increase at 48 and 72 h exposure compared to their controls. The highest BaP concentration (2.7 microM) induced a significant increase in ENA frequency at 72, 144 and 216 h exposure.


Bioaugmentation Technology for Treatment of Toxic and Refractory Organic Waste Water Based on Artificial Intelligence.
With the development of modern chemical synthesis technology, toxic and harmful compounds increase sharply. In order to improve the removal efficiency of refractory organic matter in waste water, the method of adding powdered activated carbon (PAC) to the system for adsorption was adopted. Through the analysis of organic matter removal rule before and after waste water treatment, it can be found that PAC is easy to adsorb hydrophobic organic matter, while activated sludge is easy to remove hydrophilic and weakly hydrophobic neutral organic matter. Powdered activated carbon-activated sludge SBR system (PAC-AS) system is obviously superior to AS and PAC system in removing organic matter of hydrophilic and hydrophobic components, that is, biodegradation and PAC adsorption are additive. Compared with the control system, the Chemical Oxygen Demand (COD) removal rate of refractory substances increased by 8.36%, and PAC had a good adsorption effect on small molecular weight organic compounds, but with the increase of molecular weight of organic compounds, the adsorption effect of PAC gradually weakened, and it had no adsorption effect on macromolecular organic compounds. Based on the research of fuzzy control theory, an Agent control system for ozone oxidation process of industrial waste water based on Mobile Agent Server (MAS) theory was established, which was realized by fuzzy control method. The simulation results showed strong stability and verified the feasibility and adaptability of the distributed intelligent waste water treatment system based on MAS theory in the actual control process.


Vascular dementia prevention: a risk factor analysis.
Brain injury from ischemic or hemorrhagic cerebrovascular disease (CVD) produces decline in cognitive functions and vascular dementia (VaD). Likewise, CVD may cause VaD from hypoperfusion of susceptible brain areas. CVD may also worsen degenerative dementias such as Alzheimer's disease. Significant advances have been made in the identification and control of risk factors for stroke and cardiovascular disease. The main risk factors for VaD include age, hypertension and absence of antihypertensive medication, diabetes, cigarette smoking, history of cardiovascular disease (coronary heart disease, congestive heart failure, peripheral vascular disease), atrial fibrillation, left ventricular hypertrophy, hyperhomocysteinemia, orthostatic hypotension, cardiac arrhythmias, hyperfibrinogenemia, and sleep apnea. Recently identified risk factors include chronic infection and elevation of C-reactive protein, particularly in patients with diabetes. Evidence from controlled clinical trials strongly suggests that control of vascular risk factors, in particular hypertension, could prevent the development of dementia.


Liposomes derived from Mycobacterium smegmatis promote immune activation of mice bone marrow-derived dendritic cells.
Tuberculosis (TB) is the leading cause of mortality due to infectious diseases. The development of new generation vaccines against TB is of paramount importance for the control of the disease. In previous studies, liposomes obtained from lipids of Mycobacterium smegmatis (LMs) demonstrated their immunogenicity and protective capacity against Mycobacterium tuberculosis in mice. To characterize the immunomodulatory capacity of this experimental vaccine candidate, in the current study, the stimulatory capacity of LMs was determined on bone marrow-derived dendritic cells (BMDCs) from mice. LMs were obtained and incubated with mature BMDCs. The internalization of LMs by BMDCs was studied by confocal microscopy, and the LMs immune-stimulatory capacity was determined by the expression of surface molecules (CD86 and MHCII) and the cytokine production (interleukin [IL]-12, interferon-Υ, tumor necrosis factor-α, and IL-10) 24 h after exposure to LMs. The interaction of LMs with BMDCs and its internalization was demonstrated as well as the immune activation of BMDCs, characterized by the increased expression of CD86 and the production of IL-12. The LMs internalization and immune activation of BMDCs were blocked in the presence of cytochalasin, filipin III and chlorpromazine, which demonstrated that internalization of LMs by BMDCs is a key process for the LMs induced immune activation of BMDCs. The results obtained support the further evaluation of LMs as a mycobacterial vaccine, adjuvant, and in immunotherapy.


Differential regulation of plasminogen activator and inhibitor gene transcription by the tumor suppressor p53.
The ability of p53 to activate or repress transcription suggests that its biological function as tumor suppressor is in part accomplished by regulating a number of genes including such required for inhibition of cell growth. We here give evidence that p53 also may regulate genes responsible for the proteolytic degradation of the extracellular matrix, which is considered a crucial feature for local invasion and metastasis of neoplastic cells. An important and highly regulated cascade of such proteolytic events involves the plasminogen activator system. We show that wild-type p53 represses transcription from the enhancer and promoter of the human urokinase-type (u-PA) and the tissue-type plasminogen activator (t-PA) gene through a non-DNA binding mechanism. Oncogenic mutants lost the repressing activity. In contrast, wild-type but not mutant p53 specifically binds to and activates the promoter of the plasminogen activator inhibitor type-1 (PAI-1) gene. Interestingly, one of the p53 mutants (273his) inhibited PAI-1 promoter activity. Our results suggest that altered function of oncogenic forms of p53 may lead to altered expression of the plasminogen activators and their inhibitor(s) and thus to altered activation of the plasminogen/plasmin system during tumor progression.


Cigarette Smoking and Alcohol Use among Adolescents and Young Adults with Asthma.
Asthma is one of the most common, serious chronic diseases in pediatric and young adult populations. Health-risk behaviors, including cigarette smoking and alcohol use, may exacerbate chronic diseases and complicate their management. The aim of this study was to longitudinally analyze rates of cigarette smoking and alcohol use in adolescents and young adults who have asthma and those who do not have asthma. A secondary analysis of data from the National Longitudinal Study of Adolescent Health was undertaken. Individuals with asthma were found to exhibit increasing rates of cigarette smoking and alcohol use as they aged. When an adolescent with a chronic health issue begins health-risk-taking behaviors, behavior change interventions must be planned. Pediatric nurses, practitioners, and clinicians are uniquely positioned to assess for health-risk behaviors in youth with asthma and to intervene with plans of care that are tailored for the needs of this vulnerable population.


Correlation between Preoperative Ultrasonographic Findings and Clinical, Intraoperative, Cytopathological, and Histopathological Diagnosis of Acute Abdomen Syndrome in 50 Dogs and Cats.
Acute abdomen syndrome is an emergency in small animal practice that requires rapid diagnosis to determine the appropriate treatment. No studies have correlated the preoperative abdominal ultrasonography (US) findings with the clinical, surgical, cytopathologic, and histopathologic findings. This retrospective study was designed to evaluate abdominal US in the diagnosis of acute abdomen syndrome using surgery as a "criterion standard". The most frequently misinterpreted lesions with US were also identified. The study included 50 dogs and cats with physical examination, an US diagnosis, US guided fine-needle aspiration cytology, intraoperative findings, and histopathology. Intraoperatively, 49 primary and 43 secondary lesions were identified. The sensitivity, specificity, and positive and negative predictive values for US were calculated. There was a good agreement between the US diagnosis and intraoperative findings of 86.9% (80/92), for both primary and secondary lesions (p < 0.0001). Cytology and histopathology examinations corroborated the US in 86.4% (n = 64/74) of primary and 66.2% of secondary (n = 49/79) lesions. Using US as the "criterion standard", the sensitivity of abdominal palpation for identification of ascites and masses was 32.4% and 43.7%, respectively, while the specificity was 93.7% and 94.4%, respectively. Abdominal US is a useful preoperative modality for diagnosing acute abdominal diseases in dogs and cats. Care should be taken with interpretation of gastrointestinal perforation, omental tumors, and common bile duct rupture, as these lesions are frequently misinterpreted with US.


SARS-CoV-2 antibody prevalence, titres and neutralising activity in an antenatal cohort, United Kingdom, 14 April to 15 June 2020.
SARS-CoV-2 IgG screening of 1,000 antenatal serum samples in the Oxford area, United Kingdom, between 14 April and 15 June 2020, yielded a 5.3% seroprevalence, mirroring contemporaneous regional data. Among the 53 positive samples, 39 showed in vitro neutralisation activity, correlating with IgG titre (Pearson's correlation p<0.0001). While SARS-CoV-2 seroprevalence in pregnancy cohorts could potentially inform population surveillance, clinical correlates of infection and immunity in pregnancy, and antenatal epidemiology evolution over time need further study.


Differential thermoluminescence (DTL) -a new instrument for measurement of thermoluminescence with suppression of blackbody radiation.
A new instrumental technique for the determination of thermoluminescent glow curves, especially useful for investigation at high temperatures, is described. Two samples, identical in all respects except that one is preheated, are simultaneously heated. The light outputs from the samples are individually modulated at two different frequencies, fed to a single photomultiplier tube the output of which is amplified by two lock-in amplifiers. The selectively amplified signals are further fed to a differential amplifier which cancels out the undesirable blackbody radiation to give a signal due only to the luminophor. This technique conveniently extends the temperature range of thermoluminescence and further allows high-temperature investigation of emissions in the red region of the spectrum.


An animal model of peripheral nerve regeneration after the application of a collagen-polyvinyl alcohol scaffold and mesenchymal stem cells.
Extensive nerve injuries often leading to nerve gaps can benefit, besides the gold standard represented by autologous nerve grafts, by the inciting field of tissue engineering. To enhance the role of biomaterials in nerve regeneration, the nerve conduits are associated with Schwann or Schwann-like cells. In this study, we evaluated rat sciatic nerve regeneration, by using a biodegradable nerve guide composed of Collagen (COL) and Polyvinyl Alcohol (PVA), associated with mesenchymal stem cells (MSC). After the exposure of the rat sciatic nerve, a nerve gap was created by excising 1 cm of the nerve. Three experimental groups were used for nerve gap bridging: autografts, nerve conduits filled with medium culture and nerve conduits filled with MSC. The methods of sensory and motor assessment consisted of the functional evaluation of sciatic nerve recovery - toe-spread, pinprick tests and gastrocnemius muscle index (GMI). The histological and immunocytochemical analysis of the probes that were harvested from the repair site was performed at 12 weeks. Successful nerve regeneration was noted in all three groups at the end of the 12th week. The functional and immunocytochemical results suggested that COL-PVA tubes supported with mesenchymal stem cells could be considered similar to autologous nerve grafts in peripheral nerve regeneration, without the drawbacks of the last ones. The functional results were better for the autografts and the ultrastructural data were better for the nerve conduits, but there were not noticed any statistical differences.


[Antihypertensive drug trials also reveal renoprotective effects].
The author analyzes the applicability of the renin-angiotensin system blocking drugs in patients with chronic kidney disease emphasizing their renoprotective (blood pressure and albuminuria lowering) and cardiovascular risk decreasing effects. As opposed to a previously-published statement, the author believes that their application is fundamental, particularly in combination with calcium-antagonist drugs. Relying on many references the author suggests that combined treatment with different renin-angiotensin system blocking drugs cannot be entirely ruled out, although it is not yet recommended.


Performance Characterization and Validation of Saliva as an Alternative Specimen Source for Detecting Hereditary Breast Cancer Mutations by Next Generation Sequencing.
Identification of pathogenic germline mutations by next generation sequencing is a widely accepted tool for predicting the risk of hereditary cancer development. Blood is the most common source of DNA for such tests. However, blood as a sample type has many drawbacks, including the invasive collection method, poor sample stability, and a relatively high cost of collection. Therefore, in the current study we have assessed the suitability of saliva as an alternative source of genomic DNA for the identification of germline mutations in the BRCA1/2 genes by next generation sequencing (NGS). Our results show that all of the samples yielded DNA concentrations sufficient for library preparation. The concentrations of the final libraries, which were generated by PCR using target specific primers, fall into the expected range with no notable difference between libraries generated from DNA derived from saliva or blood. Quality parameters indicate that sequencing performance is comparable across sample source. An average of (98 ± 0.02)% variant calling concordance was obtained between the two specimen sources. Our data recommends saliva as a potential alternative for detecting germline mutation by next generation sequencing.


[Influence of Opiate Abuse on Expression of Toll-like Receptor 9 in Peripheral Blood Mononuclear Cells of HIV-1-Infected Individuals].
The aim of this study was to investigate the influence of opiate abuse on the expression of Toll-like receptor 9 (TLR9) in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected patients and to elucidate possible mechanisms involved in the enhancement of HIV-1 replication by opiate abuse. A total of 200 participants were enrolled in the study by random selection from methadone treatment centers and voluntary HIV counseling and testing centers in the cities of Nanning, Liuzhou, and Qinzhou. These participants included 50 HIV-positive opiate abusers (Opiates HIV(+) group), 50 HIV-negative opiate abusers (Opiates HIV(-) group), 50 HIV-positive subjects who were not opiate abusers (Non-opiates HIV (+) group), and 50 HIV-negative subjects who were not opiate abusers (Control group). PBMCs were isolated from the peripheral blood samples from the subjects and the expression levels of TLR9 mRNA and protein were determined by q-PCR and western blot respectively. There was no significant difference among the four groups in age, gender, nationality, domicile, marital status, educational background or duration of drug abuse (P > 0.05). The median viral loads of the Opiates HIV(+) were significantly higher than those of the Non-Opiates HIV(+) groups (4.450 x 10(3) and 3.977 x 10(3) copies/mL respectively, P < 0.05). The relative expression levels of TLR9 mRNA in the Opiates HIV(+), Non-Opiates HIV(+), Opiates HIV(-) and Control groups were (2.13 +/- 1.59) x 10(-3), (3.66 +/- 2.22) x 10(-3), (1.96 +/- 1.42) x 10(-3) and (7.66 +/- 4.87) x 10(-3), respectively. The expression of TLR9 mRNA was significantly lower in both HIV-1-infected and -uninfected groups of opiate abusers compared with groups of non-abusers (P < 0.05). There was no significant difference in TLR9 mRNA expression levels between the Opiates HIV(+) group and the Opiates HIV(-) group (P > 0.05). However, in the non-opiate groups, the expression levels of TLR9 mRNA in the HIV(+) group were significantly lower than that of the control group (P< 0.05). Western blot results confirmed that the expression of TLR9 protein was lower in the Opiates HIV(+), Non-Opiates HIV(+), and Opiates HIV(-) groups compared to the control group. These results suggest that opiate abuse can decrease the expression of TLR9 in PBMCs, which may result in the enhancement of HIV-1 infection and replication due to a decline in immune response mediated by the TLR9 pathway.


[The risk of vibrations to the hand-arm system and cumulative trauma disorders in shoe manufacturing: a clinical case report].
The article reports the case of a woman working in a shoe factory who had been using vibrating tools for 5 years. Because of paresthesia in her left hand, in 1989 she underwent various diagnostic trials that revealed an initial carpal tunnel syndrome of the left wrist and a homolateral epicondylitis. Measurement of the vibrations transmitted to the hand from the vibrating tool confirmed the probability of a high risk of exposure for the hand-arm system. Such adverse effects have been described by British authors as "cumulative trauma disorders" and were confirmed in this study. The importance of further studies aimed at estimating the type and degree of exposure to vibrations in shoe manufacturing workers is stressed.


Group G streptococcal bacteraemia in a community teaching hospital.
The group G streptococci are beta-haemolytic streptococci which are characterised by the presence of the Lancefield group G antigen, and have been implicated in a variety of infections. Underlying malignancy has been reported in up to 67% of patients with group G streptococcal bacteraemia in some series. The clinical records of 11 patients with positive blood cultures for group G streptococci over the period from January 1993 to December 1997 were evaluated. Group G streptococci were recovered from only 0.025% (19 out of 77,323 total cultures) of blood cultures during this period. The source of bacteraemia was determined to originate from skin in seven patients (64%). Bacteraemia in the other four patients was probably due to endometritis, septic arthritis, osteomyelitis, and a central venous catheter. All of the patients had an underlying chronic disease or other predisposing factor such as a joint prosthesis or venous catheter. Only one patient in this series had an underlying malignancy, a metastatic pelvic sarcoma. One patient died of multiple organ failure after several days in the hospital. All surviving patients were successfully treated with antibiotics, typically a beta-lactam agent. This study suggests that in the community-hospital setting, skin infection is the most common source of group G streptococcal bacteraemia, typically in patients with underlying chronic disease; however, malignancy appears to be an uncommon predisposing factor.


Effect of activated lymphocytes on the regulation of hematopoiesis: enhancement and suppression of in vitro BFU-E growth by T cells stimulated by autologous non-T cells.
Autologous mixed lymphocyte culture (AMLR) is an immunologic response with memory and specificity and plays a role in immune regulation. Effects of T cells activated by AMLR were studied in the regulation of in vitro erythropoiesis. AMLR-activated T cells were cocultured with autologous non-T, nonphagocytic peripheral blood mononuclear cells for assaying erythroid progenitor cells (BFU-E). T cells activated for 3 days in AMLR showed significant enhancement of in vitro colony growth by BFU-E. In contrast, activated T cells from day 7 AMLR caused significant suppression of BFU-E growth. Both enhancing and suppressing activities of AMLR-activated T cells were mediated by an la-positive and radiosensitive population within the OKT4+ subset. These observations suggest that AMLR-activated T cells may play a role in the immune-mediated regulation of in vitro erythropoiesis. It is also suggested that heterogeneous T-cell subsets may exert regulatory functions in the regulation of in vitro hematopoiesis.


Effects on endotoxin pathogenicity in pigs with acute septicemia of Haemophilus parasuis infection.
Changes of endotoxin in plasma, and the response of the coagulation system and blood cells in septicemia of Haemophilus parasuis infection were examined by inoculation with H. parasuis in specific pathogen-free (SPF) pigs. Eight pigs were inoculated intratracheally with 10(5), 10(6) and 10(7) colony formation units (CFU) of the strain Nagasaki (serovar 5). All pigs died 28 to 42 hr after inoculation. Haematologically, severe leukopenia occurred 24 hr post inoculation (hpi) until death. Glucose concentration decreased from 24 hpi to death. In the coagulation system, decrease of platelet counts, prolongation of prothrombin time, activated partial thromboplastin time, and increase of fibrinogen-fibrin degradation products were observed in all inoculated pigs. Endotoxin was detected in the plasma of all the inoculated pigs from 16 hpi to death, and its concentration rose dramatically just before death. H. parasuis was re-isolated from the blood of all inoculated pigs from 16 hpi to death, and also from almost all organs and body fluids of the pigs. The pigs had microthrombi in the kidney, liver and lungs, and many also had pneumonia, meningitis and serositis. H. parasuis antigen was detected in the lesions by the immunoperoxidase technique. The results indicated that disseminated intravascular coagulation (DIC) and endotoxin shock involved aggravation of clinical signs and death on the pigs induced to septicemia of H. parasuis.


Self-consistent mode-coupling approach to the nonlocal Kardar-Parisi-Zhang equation.
The dynamic scaling of the nonlocal Kardar-Parisi-Zhang equation in the strong-coupling regime is investigated by a self-consistent mode-coupling approximation. The values of the dynamic exponent depending on nonlocal parameter rho are calculated numerically for the substrate dimension d=1, d=2, and d=3, respectively.


Differential effects of primary human immunodeficiency virus type 1 nef sequences on downregulation of CD4 and MHC class I.
We analyzed two primary nef sequences, KS2 (subtype B) and K306 (subtype D), each directly isolated from patients. Cell lines constitutively expressing respective Nef proteins were constructed using a retroviral vector. There were significant differences in the ability to downregulate surface CD4 and MHC class I proteins between different nef sequences. When the nef sequence from NL432 was used as a reference, KS2 Nef demonstrated the highest ability to downregulate MHC class I, whereas it appeared to lack the ability to downregulate CD4. On the contrary, Nef from K306 decreased the level of surface CD4 to a greater extent, but was less effective on downregulation of MHC class I. These results showed that the levels of downregulation of CD4 and MHC class I could significantly vary among HIV strains and that two well-known functions of Nef, downregulation of CD4 and MHC class I, would be separated.


Overexpression of Dlx5 in chicken calvarial cells accelerates osteoblastic differentiation.
Our laboratory and others have shown that a homeodomain protein binding site plays an important role in transcription of the Collal gene in osteoblasts. This suggests that homeodomain proteins have an important role in osteoblast differentiation. We have investigated the role of Dlx5 in osteoblastic differentiation. In situ hybridization studies indicated that Dlx5 is expressed in chick calvarial osteoblasts (cCOB) in vivo. Northern blot analysis indicated that Dlx5 expression in cultured cCOBs is induced concurrently with osteoblastic markers. To study the effect of overexpression of Dlx5 on osteoblast differentiation, we infected primary osteoblast cultures from 15-day-old embryonal chicken calvaria with replication competent retroviral vectors [RCASBP(A)] expressing Dlx5 or control replication competent avian splice acceptor brianhightiter polymerase subtype A [RCASBP(A)]. Expression of Collal, osteopontin, alkaline phosphatase, and osteocalcin messenger RNA (mRNA) occurred sooner and at higher levels in cultures infected with RCASBP(A)DLX5 than in RCASBP(A)-infected cultures. Mineralization of Dlx5-expressing cultures was evident by days 12-14, and RCAS-infected control osteoblasts did not begin to mineralize until day 17. Dlx5 also stimulated osteoblastic differentiation of calvarial cells that do not normally undergo osteoblastic differentiation in vitro. Our results suggest that Dlx5 plays an important role in inducing calvarial osteoblast differentiation.


Relapse pattern of Plasmodium vivax in Kheda district, Gujarat.
A study on relapse pattern of P. vivax in Kheda district of Gujarat revealed that the relapse rate in P. vivax within 8 months of primary attack was around 40% in untreated cases. It was 2.6% within one year in patients treated with 5-day course of primaquine. Relapses occurred more frequently from April to October and 82% relapses occurred within one year of the primary attack. Relapses occurred up to 4 years after primary attack but they were less frequent in 3rd and 4th year.


Autosomal recessive primary microcephaly: an analysis of locus heterogeneity and phenotypic variation.
Locus heterogeneity is well established in autosomal recessive primary microcephaly (MCPH) and to date five loci have been mapped. However, the relative contributions of these loci have not been assessed and genotype-phenotype correlations have not been investigated. A study population of 56 consanguineous families resident in or originating from northern Pakistan was ascertained and assessed by the authors. A panel of microsatellite markers spanning each of the MCPH loci was designed, against which the families were genotyped. The head circumference of the 131 affected subjects ranged from 4 to 14 SD below the mean, but there was little intrafamilial variation among affecteds (+/- 1 SD). MCPH5 was the most prevalent, with 24/56 families consistent with linkage; 2/56 families were compatible with linkage to MCPH1, 10/56 to MCPH2, 2/56 to MCPH3, none to MCPH4, and 18/56 did not segregate with any of the loci. MCPH5 is the most common locus in this population. On clinical grounds alone, the phenotype of families linked to each MCPH locus could not be distinguished. We have also shown that further MCPH loci await discovery with a number of families as yet unlinked.


[Comparison of 4 plasmapheresis procedures].
In recent years the collection of plasma has been increasingly carried out by apparative plasmapheresis. In the University Hospitals of Göttingen and Würzburg the plasmapheresis machines PCS from Haemonetics, Autopheresis-C from Baxter, as well as Plasmapur-Monitor from Organon-Teknika, were compared with each other and with the conventional centrifugation of blood bags; experiences in routine use were complemented by specific studies. Altogether, the apparative methods distinguished themselves through a high quality of retransfused blood and collected plasma. Furthermore, practicability, donor compatibility and donor safety resulted in good acceptance by both donors and staff.


A pre/post analysis of the impact of the COVID-19 pandemic on the psychosocial work environment and recovery among healthcare workers in a large university hospital in Sweden.
The impact of the COVID-19 pandemic on workload, mental health, and well-being of healthcare workers, and particularly those on the front-line, has received considerable attention. We surveyed hospital employees about their working environment during the pandemic and identified departments which were negatively affected in comparison to the pre-pandemic situation, as well as factors contributing to this. Setting and participants We surveyed all hospital employees at Sahlgrenska University Hospital, Sweden in September 2020 and compared results across departments and to the results of a large employee survey from October 2019. The overall impact of the pandemic on perceived working conditions and possibility for recovery differed among departments. During the pandemic, healthcare workers working with COVID-19 patients reported poorer working environments than other employees. Factors significantly related to perception of work environment and recovery during the pandemic included worries of being infected, departmental transfer, and having insufficient access to personal protective equipment. Men reported better working conditions than women in all, but one item and higher age was related to better perceived working environment. Our results indicate that the pandemic differentially affects hospital departments and underscores the multifactorial nature of this topic. Contributing factors to poor perceived working environment could be addressed at times of high workload, such as during the pandemic, including providing appropriate support to managers, ensuring possibility for recovery during working hours, and acknowledging worries about infection. Young healthcare workers and staff who are relocated due to the pandemic warrant special attention.


Psoas abscess from ureteric stone perforation.
This case illustrates a rare complication of an impacted ureteric stone which eroded through the wall of the ureter leading to formation of a psoas abscess. Ureteric stent placement and percutaneous drainage of the abscess were insufficient to resolve the problem. Renal scan revealed poor function and the left kidney was removed. It showed evidence of acute supporative pyelonephritis with nephrolithiasis.


Oxidation state dependence of the geometry, electronic structure, and magnetic coupling in mixed oxo- and carboxylato-bridged manganese dimers.
Approximate density functional theory has been used to investigate changes in the geometry and electronic structure of the mixed oxo- and carboxylato-bridged dimers [Mn(2)(mu-O)(2)(O(2)CH)(NH(3))(6)](n+)and [Mn(2)(mu-O)(O(2)CH)(2)(NH(3))(6)](n+)in the Mn(IV)Mn(IV), Mn(III)Mn(IV), and Mn(III)Mn(III) oxidation states. The magnetic coupling in the dimer is profoundly affected by changes in both the bridging ligands and Mn oxidation state. In particular, change in the bridging structure has a dramatic effect on the nature of the Jahn-Teller distortion observed for the Mn(III) centers in the III/III and III/IV dimers. The principal magnetic interactions in [Mn(2)(mu-O)(2)(O(2)CH)(NH(3))(6)](n+)() involve the J(xz/xz)and J(yz/yz) pathways but due to the tilt of the Mn(2)O(2) core, they are less efficient than in the planar di-mu-oxo structure and, consequently, the calculated exchange coupling constants are generally smaller. In both the III/III and III/IV dimers, the Mn(III) centers are high-spin, and the Jahn-Teller effect gives rise to axially elongated Mn(III) geometries with the distortion axis along the Mn-O(c) bonds. In the III/IV dimer, the tilt of the Mn(2)O(2) core enhances the crossed exchange J(x)()()2(-)(y)()()2(/)(z)()()2 pathway relative to the planar di-mu-oxo counterpart, leading to significant delocalization of the odd electron. Since this delocalization pathway partially converts the Mn(IV) ion into low-spin Mn(III), the magnetic exchange in the ground state can be considered to arise from two interacting spin ladders, one is the result of coupling between Mn(IV) (S = 3/2) and high-spin Mn(III) (S = 2), the other is the result of coupling between Mn(IV) (S = 3/2) and low-spin Mn(III) (S = 1). In [Mn(2)(mu-O)(O(2)CH)(2)(NH(3))(6)](n+)(), both the III/III dimer and the lowest energy structure for the III/IV dimer involve high-spin Mn(III), but the Jahn-Teller axis is now orientated along the Mn-oxo bond, giving rise to axially compressed Mn(III) geometries with long Mn-O(c) equatorial bonds. In the IV/IV dimer, the ferromagnetic crossed exchange J(yz)()(/)(z)()()2 pathway partially cancels J(yz/yz) and, as a consequence, the antiferromagnetic J(xz/xz) pathway dominates the magnetic coupling. In the III/III dimer, the J(yz/yz) pathway is minimized due to the smaller Mn-O-Mn angle, and since the ferromagnetic J(yz)()(/)(z)()()2 pathway largely negates J(xz/xz), relatively weak overall antiferromagnetic coupling results. In the III/IV dimer, the structures involving high-spin and low-spin Mn(III) are almost degenerate. In the high-spin case, the odd electron is localized on the Mn(III) center, and the resulting antiferromagnetic coupling is similar to that found for the IV/IV dimer. In the alternative low-spin structure, the odd electron is significantly delocalized due to the crossed J(yz)()(/)(z)()()2 pathway, and cancellation between ferromagnetic and antiferromagnetic pathways leads to overall weak magnetic coupling. The delocalization partially converts the Mn(IV) ion into high-spin Mn(III), and consequently, the spin ladders arising from coupling of Mn(IV) (S = 3/2) with high-spin (S = 2) and low-spin (S = 1) Mn(III) are configurationally mixed. Thus, in principle, the ground-state magnetic coupling in the mixed-valence dimer will involve contributions from three spin-ladders, two associated with the delocalized low-spin structure and the third arising from the localized high-spin structure.


Glycemic index and phenolics of partially-baked frozen bread with sourdough.
Different lactic acid bacteria starters were used to prepare sourdough to make partially-baked frozen wholemeal wheat bread. The sourdough was prepared with a pure culture of Lactobacillus plantarum or with commercial starters containing Lactobacillus brevis combined with Saccharomyces cerevisiae var. chevalieri (LV4), Lactobacillus fermentum (PL1), or Lactobacillus fermentum with phytase (PL3). We determined the acetic and lactic acid concentrations in sourdough, bread chemical composition, total phenolics content and glycemic index (GI) in vivo. Depending on the starter, the lactic to acetic acid ratio in the sourdough was significantly different. The GI of control bread without sourdough (70) was significantly higher than that of bread containing sourdough prepared with LV4 starter (50), PL1 starter (56) or PL3 starter (56), but not from bread with L. plantarum sourdough (60). The addition of 10% sourdough with a lower molar ratio of lactic to acetic acid ( ≤ 4) and higher total phenolics content is preferable for generating bread with medium and low GI.


Adenylyl cyclase activity in human decidua and myometrium during pregnancy and labour.
Adenylyl cyclase activity was studied in human decidua and myometrium in early pregnancy and at term before and after the onset of labour. Decidual basal, prostaglandin-, catecholamine- and forskolin-stimulated adenylyl cyclase activities at term before the onset of labour were significantly lower than those in early pregnancy. After the onset of labour at term, decidual basal, prostaglandin-, catecholamine-, NaF- and forskolin-stimulated adenylyl cyclase activities significantly increased compared with those at term before the onset of labour. Myometrial prostaglandin- and catecholamine-stimulated activities did not alter during pregnancy, except for basal and forskolin-stimulated activity. Myometrial basal, prostaglandin-, catecholamine-, NaF- and forskolin-stimulated activities at term showed no change after the onset of labour. At term, before the onset of labour, myometrial basal, prostaglandin, catecholamine-, NaF- and forskolin-stimulated activities were the same as those in the decidua. However, after the onset of labour at term, decidual basal and the stimulated activities were significantly higher than those in the myometrium. These results suggest that decidual prostaglandin- and catecholamine-stimulated adenylyl cyclase may play an important role in the initiation or maintenance of human labour or in both processes.


Effects of Probiotic Supplementation on Exercise with Predominance of Aerobic Metabolism in Trained Population: A Systematic Review, Meta-Analysis and Meta-Regression.
The scientific literature about probiotic intake and its effect on sports performance is growing. Therefore, the main aim of this systematic review, meta-analysis and meta-regression was to review all information about the effects of probiotic supplementation on performance tests with predominance of aerobic metabolism in trained populations (athletes and/or Division I players and/or trained population: ≥8 h/week and/or ≥5 workouts/week). A structured search was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA®) statement and PICOS guidelines in PubMed/MEDLINE, Web of Science (WOS), and Scopus international databases from inception to 1 November 2021. Studies involving probiotic supplementation in trained population and execution of performance test with aerobic metabolism predominance (test lasted more than 5 min) were considered for inclusion. Fifteen articles were included in the final systematic review (in total, 388 participants were included). After 3 studies were removed due to a lack of data for the meta-analysis and meta-regression, 12 studies with 232 participants were involved. With the objective of assessing the risk of bias of included studies, Cochrane Collaboration Guidelines and the Physiotherapy Evidence Database (PEDro) scale were performed. For all included studies the following data was extracted: authors, year of publication, study design, the size of the sample, probiotic administration (dose and time), and characteristics of participants. The random effects model and pooled standardized mean differences (SMDs) were used according to Hedges' g for the meta-analysis. In order to determine if dose and duration covariates could predict probiotic effects, a meta-regression was also conducted. Results showed a small positive and significant effect on the performance test with aerobic metabolic predominance (SMD = 0.29; CI = 0.08−0.50; p < 0.05). Moreover, the subgroup analysis displayed significant greater benefits when the dose was ≥30 × 109 colony forming units (CFU) (SMD, 0.47; CI, 0.05 to 0.89; p < 0.05), when supplementation duration was ≤4 weeks (SMD, 0.44; CI, 0.05 to 0.84; p < 0.05), when single strain probiotics were used (SMD, 0.33; CI, 0.06 to 0.60; p < 0.05), when participants were males (SMD, 0.30; CI, 0.04 to 0.56; p < 0.05), and when the test was performed to exhaustion (SMD, 0.45; CI, 0.05 to 0.48; p < 0.05). However, with references to the findings of the meta-regression, selected covariates did not predict probiotic effects in highly trained population. In summary, the current systematic review and meta-analysis supported the potential effects of probiotics supplementation to improve performance in a test in which aerobic metabolism is predominant in trained population. However, more research is needed to fully understand the mechanisms of action of this supplement.


Next-generation sequencing applications for wheat crop improvement.
Bread wheat (Triticum aestivum; Poaceae) is a crop plant of great importance. It provides nearly 20% of the world's daily food supply measured by calorie intake, similar to that provided by rice. The yield of wheat has doubled over the last 40 years due to a combination of advanced agronomic practice and improved germplasm through selective breeding. More recently, yield growth has been less dramatic, and a significant improvement in wheat production will be required if demand from the growing human population is to be met. Next-generation sequencing (NGS) technologies are revolutionizing biology and can be applied to address critical issues in plant biology. Technologies can produce draft sequences of genomes with a significant reduction to the cost and timeframe of traditional technologies. In addition, NGS technologies can be used to assess gene structure and expression, and importantly, to identify heritable genome variation underlying important agronomic traits. This review provides an overview of the wheat genome and NGS technologies, details some of the problems in applying NGS technology to wheat, and describes how NGS technologies are starting to impact wheat crop improvement.


Granulocytic sarcoma of the spine.
Granulocytic sarcomas (chloromas) are tumors consisting of primitive myeloid cells. They are rare manifestations of acute and chronic leukemias and can occasionally precede the development of systemic disease by weeks to years. Spinal complications of chloromas, such as cord compression secondary to epidural tumor or cauda equina syndrome, have been described but are uncommon. We present eight new cases of spinal chloroma. Three patients displayed significant motor deficit in the form of paraparesis or paraplegia. All patients complained of lower back pain, with other complaints including generalized pain, abdominal pain, numbness and pain in the lower extremities and perianal region, and poor appetite. The average age of the patients was 37 years. Treatment strategies included surgery, chemotherapy, and radiotherapy. Three patients underwent surgical decompression. Six patients received chemotherapy, and six patients received radiotherapy at doses of 2000 to 3000 cGy in up to 30 fractions. Patient survival ranged from 18 days to 9.5 years after diagnosis. A review of the previously reported cases of granulocytic sarcoma in addition to our new cases reveals that the most effective treatment is multimodality therapy coupled with early diagnosis. Increased awareness of this entity will facilitate early diagnosis and minimize potentially preventable neurological morbidity.


Targeting cluster of differentiation 47 improves the efficacy of anti-cytotoxic T-lymphocyte associated protein 4 treatment via antigen presentation enhancement in pancreatic ductal adenocarcinoma.
Treatment with cluster of differentiation 47 (CD47) monoclonal antibody has exhibited promising antitumor effects in various preclinical cancer models. However, its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In the present study, the CD47 expression level was measured in PDAC patient samples. The effects of CD47 on antigen presentation and anti-tumor immunity were evaluated using phagocytotic assays and animal models. The results indicated that CD47 was overexpressed in the tumor tissue of PDAC patients compared with that in normal adjacent tissues. In the human samples, antigen-presenting cells (macrophages and dendritic cells) in tumors with high CD47 expression demonstrated low CD80 and CD86 expression levels. In an in vitro co-culture tumor cell system, CD47 overexpression was observed to inhibit the function of phagocytic cells. Furthermore, in a PDAC mouse model, CD47 overexpression was indicated to reduce antigen-presenting cell tumor infiltration and T-cell priming in tumor-draining lymph nodes. Anti-CD47 treatment appeared to enhance the efficacy of the approved immune checkpoint blockade agent anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA4) in suppressing PDAC development in a mouse model. Therefore, it was concluded that CD47 overexpression suppressed antigen presentation and T-cell priming in PDAC. Anti-CD47 treatment may enhance the efficacy of anti-CTLA4 therapy and may therefore be a potential strategy for the treatment of PDAC patients in the future.


Treatment of Helicobacter pylori infection 2011.
This article reviews the literature published pertaining to Helicobacter pylori eradication over the last year. The general perception among clinicians and academics engaged in research on H. pylori has been that eradication rates for first-line therapies are falling, although some data published this year have cast doubt on this. The studies published this year have therefore focussed on developing alternative strategies for the first-line eradication of H. pylori. In this regard, clear evidence now exists that both levofloxacin and bismuth are viable options for first-line therapy. The sequential and "concomitant" regimes have also been studied in new settings and may have a role in future algorithms also. In addition, data have emerged that the probiotic Saccharomyces boulardii may be a useful adjunct to antibiotic therapy. Other studies promote individualized therapies based on host polymorphisms, age, and other such demographic factors.


Platelet, Plasma, Urinary Tryptophan-Serotonin-Kynurenine Axis Markers in Hyperacute Brain Ischemia Patients: A Prospective Study.
Background and Purpose: Ischemic stroke is one of the most common causes of morbidity and mortality and has numerous clinical mimics. Previous studies have suggested a potential role of the tryptophan-serotonin (5-HT)-kynurenine (TSK) axis in ischemic stroke. Studies assessing this axis in the hyperacute phase of ischemic stroke (<4.5 h) are lacking. This prospective study thus evaluates the TSK axis in transient ischemic attack (TIA) and hyperacute ischemic stroke (AIS) patients. Methods: This study included 28 patients (24 AIS and 4 TIA) and 29 controls. The blood and urine samples of patient were collected within 4.5 h of symptoms onset (day 0, D0), then at 24 h and 3 months. Control blood and urine samples were collected once (D0). The TSK axis markers measured were platelet serotonin transporter (SERT) and 5-HT2A receptor (5-HT2AR) densities and platelet, plasma, and urinary 5-HT, plasma and urinary 5-hydroxyindole acetic acid (5-HIAA), and plasma kynurenine and tryptophan (TRP) levels. Results: At D0, patients exhibited a lower (p = 10-5) platelet SERT density, higher (p < 10-6) platelet 5-HT2AR density, higher (p = 10-5) plasma kynurenine/tryptophan (K/T) ratio, and higher urinary 5-HT (p = 0.011) and 5-HIAA (p = 0.003) levels than controls. Conclusions: We observed, for the first time, a hyperacute dysregulation of the serotonergic axis, and hyperacute and long-lasting activation of the tryptophan-kynurenine pathway in brain ischemia.


[Behaviours related to infectious disease and family factors in primary and middle school students].
To explore the behaviors related to infectious disease and family factors in primary and middle school students, and to provide evidence for improving behaviors related to infectious disease. A total of 8465 students were randomly surveyed by a standard questionnaire of behaviors related to infectious disease. Chi-square test was used to analyze the influential factors for behaviors related to infectious disease, and non conditional logistic regression analysis was used to analyze the multiple factors. The total formation rate of behaviors related to infectious disease was 66.4%. The rates for primary and middle school students were 69.4% and 62.8% respectively, with significant difference (P<0.05). There were significant differences in the following behaviors, such as washing hands before eating food, rarely buying snacks on outside stalls, informing teachers when showing infectious disease symptoms (all P<0.05), the degree for such behaviors in primary school students was higher than that in middle school students. There were also significant differences in the following behaviors, such as washing hands after using the toilet, blocking with a handkerchief, wiping while coughing and sneezing (all P<0.05), the degree for such behaviors in middle school students was higher than that in primary school students. Non conditional logistic regression analysis showed that the behaviors related to infectious disease in primary and middle school students were associated with parents' education degree, mother's occupation and living status with parents. Behaviors related to infectious disease in primary and middle school students need to be improved, and the formation of these behaviors may be related to many family factors.


Stabilization of Lithium Metal Interfaces by Constructing Composite Artificial Solid Electrolyte Interface with Mesoporous TiO2 and Perfluoropolymers.
The next generation of high-energy-density storage devices is expected to be rechargeable lithium metal batteries. However, unstable metal-electrolyte interfaces, dendrite growth, and volume expansion will compromise lithium metal batteries (LMB) safety and life. A simple drop-casting method is used to create a double-layer functional interface composed of inorganic mesoporous TiO2 and F-rich organics PFDMA. For high-quality lithium deposition, TiO2 can provide uniform mechanical pressure, abundant mesoporous channels, and increased ionic conductivity, while PFDMA provides enough F to form LiF in the first cycle and improves Li-electrolyte compatibility. Experiments and simulations are combined to investigate the optimized mechanism of the LiF-rich solid electrolyte interface (SEI). The high binding energy of organic matter and Li demonstrates that Li+ preferentially binds with the F atom in organic matter. As a result, the tightly bound double-layer structure can inhibit lithium dendrite growth and slow electrolyte decomposition. Consequently, the symmetric Li||Li cell has a high stability performance of over 800 h. The assembled LiFePO4 ||Li cell can sustain 300 cycles at a 1 C rate and has a reversible capacity of 136.7 mAh g-1 .


Assessing implicit motives in U.S. college students: effects of picture type and position, gender and ethnicity, and cross-cultural comparisons.
We assessed implicit needs for power, achievement, and affiliation in 323 U.S. college students using a Picture Story Exercise (PSE; McClelland, Koestner, & Weinberger, 1989) consisting of 6 picture cues and Winter's (1994) content coding system. Picture cues differed markedly in the amount of motive imagery they elicited and picture motive profiles closely resembled those reported by Schultheiss and Brunstein (2001) for a German student sample. Picture position influenced the expression of power and affiliation motivation, with affiliation motivation being most strongly expressed at the beginning and power motivation being most strongly expressed in the middle of the PSE. Women had higher affiliation motive scores than men. Asian Americans had higher affiliation motive scores than Whites, and African Americans had higher levels of achievement motivation than Asian Americans or Whites. PSE motive measures showed little or no overlap with questionnaire measures of impulsivity and anxiety (Behavioral Inhibition System-Behavioral Activation System scales; Carver & White, 1994) or specific motivational orientations (Personality Research Form; Jackson, 1984). Comparisons with Schultheiss and Brunstein's (2001) German sample indicate that U.S. students have higher achievement motivation and lower power motivation and activity inhibition scores than German students.


Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth.
The inhibitory activity associated with myelin is a major obstacle for successful axon regeneration in the adult mammalian central nervous system (CNS). In addition to myelin-associated glycoprotein (MAG) and Nogo-A, available evidence suggests the existence of additional inhibitors in CNS myelin. We show here that a glycosylphosphatidylinositol (GPI)-anchored CNS myelin protein, oligodendrocyte-myelin glycoprotein (OMgp), is a potent inhibitor of neurite outgrowth in cultured neurons. Like Nogo-A, OMgp contributes significantly to the inhibitory activity associated with CNS myelin. To further elucidate the mechanisms that mediate this inhibitory activity of OMgp, we screened an expression library and identified the Nogo receptor (NgR) as a high-affinity OMgp-binding protein. Cleavage of NgR and other GPI-linked proteins from the cell surface renders axons of dorsal root ganglia insensitive to OMgp. Introduction of exogenous NgR confers OMgp responsiveness to otherwise insensitive neurons. Thus, OMgp is an important inhibitor of neurite outgrowth that acts through NgR and its associated receptor complex. Interfering with the OMgp/NgR pathway may allow lesioned axons to regenerate after injury in vivo.


[Occult breast cancer causing axillary metastasis].
Authors review 43 cases of occult breast cancer selected from 6396 patients operated on for breast cancer in the National Institute of Oncology, Budapest over a 20-year period (1972-1991). In 20 patients mastectomy and axillary block dissection, in 9 upper-outer quadrant resection of the breast with axillary block dissection, in 12 only axillary block dissection, and in 2 axillary biopsy were carried out. The primary tumor was localized only in 11 patients during the first operation either by macroscopic or by microscopic examination. In 12 patients' breast the primary tumor became detectable only later. Out of the 20 mastectomy specimens, 2 primary tumors could not be identified even with the most thoroughful examination. Out of the breast conservation group in 4 patients, the primary tumor remained occult until recently, and in the axillary block dissection group (12 patients) the site of the primary cancer could be identified only in 2 patients. The authors deal with diagnostic difficulties and the dilemmas of the surgical indications and treatment.