Pan-cancer analyses of clinical prognosis, immune infiltration, and immunotherapy efficacy for TRPV family using multi-omics data.
Transient receptor potential cation channel subfamily V (TRPV) play an essential in cancer initiation, progression, and treatment. TRPV expression alteration are shown relate to multiple cancers prognosis and treatment of cancers but are less-studied in pan-cancer. In this study, we characterize the clinical prediction value of TRPV at pan-cancer level. Several databases were used to examine the transcript expression difference in tumor vs. normal tissue, copy-number variant (CNV) and single nucleotide polymorphisms (SNP) mutation of each TRPV members in pan-cancer, including The Cancer Genome Atlas (TCGA) and cBioPortal. We performed K-M survival curve and univariate Cox regression analyses to identify survival and prognosis value of TRPV. CellMiner were selected to explore drug sensitivity. We also analyzed association between tumor mutation burden (TMB), microsatellite instability (MSI), tumor immune microenvironment and TRPV family genes expression. Moreover, we investigated the relationship between TRPVs expression and effectiveness of immunotherapy in multiple cohorts, including one melanoma (GSE78220), one renal cell carcinoma (GSE67501), and three bladder cancer cohorts (GSE111636, IMvigor210, GSE176307 and our own sequencing dataset (TRUCE-01)), and further analyzed the changes of TRPVs expression before and after treatment (tislelizumab combined with nab-paclitaxel) of bladder cancer. Next, we made a special effort to investigate and study biological functions of TRPV in bladder cancer using gene set enrichment analysis (GSEA), and conducted immune infiltration analysis with TRPVs family genes expression, copy number or somatic mutations of bladder cancer by TIMER 2.0. Finally, real-time PCR and protein expression validation of TRPVs within 10 paired cancer and para-carcinoma tissue samples, were also performed in bladder cancer. Only TRPV2 expression was lower in most cancer types among TRPV family genes. All TRPVs were correlated with survival changes. Amplification was the significant gene alternation in all TRPVs. Next, analysis between TRPVs and clinical traits showed that TRPVs were related to pathologic stage, TNM stage and first course treatment outcome. Moreover, TRPV expression was highly correlated with MSI and TMB. Immunotherapy is a research hotspot at present, our result showed the significant association between TRPVs expression and immune infiltration indicated that TRPV expression alternation could be used to guide prognosis. In addition, we also discovered that the expression level of TRPV1/2/3/4/6 was positively or negatively correlated with objective responses to anti-PD-1/PD-L1 across multiple immunotherapy cohort. Further analysis of drug sensitivity showed the value to treatment. Based on the above analysis, we next focused on TRPV family in bladder cancer. The result demonstrated TRPV also played an important role in bladder cancer. Finally, qPCR assay verified our analysis in bladder cancer. Our study firstly revealed expression and genome alternation of TRPV in pan-cancer. TRPV could be used to predict prognosis or instructing treatment of human cancers, especially bladder cancer.


Modification of the risk of post-traumatic stress disorder (PTSD) by the 5-HTTLPR polymorphisms after Lorca's earthquakes (Murcia, Spain).
Information of the modulation effect of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) on post-traumatic stress disorder (PTSD) after earthquakes is scarce and contradictory. A cross-sectional face-to-face interview survey of a representative sample of the adults was carried out after the Lorca (Spain) earthquakes (May 11, 2011). Socio-demographic variables, DSM-IV diagnostic assessment and earthquake-related stressors were obtained from the Composite International Diagnostic Interview (CIDI). The triallelic and biallelic classification of the 5-HTTLPR polymorphism were genotyped from buccal swabs. Multivariate logistic regression models were used to predict PTSD, including interaction terms to explore gene-environment (G x E) interactions. The vast majority (83%, n = 341) of the Lorca survey respondents (n = 412, 71% response rate) were genotyped. Both classifications of the 5-HTTLPR genotype were in Hardy-Weinberg equilibrium. Prior lifetime PTSD was the only variable that remained a significant predictor after adjustments. There were no significant main effects of earthquake related stressors or 5-HTTLPR. However, G x E interactions of 5-HTTLPR with high emotional impact and prior lifetime anxiety disorders were statistically significant. These results provide new evidence of the modulation effect of the 5-HTTLPR polymorphisms on PTSD risk. This information might characterize people at higher risk of developing PTSD after an earthquake exposure.


Decontamination ofFusarium mycotoxins, nivalenol, deoxynivalenol, and zearalenone, in barley by the polishing process.
Korean dehusked and unhusked barley naturally contaminated withFusarium mycotoxins were polished using a Satake Grain Testing Mill. The pearled barley and bran fractions with different degrees of polishing were analyzed for nivalenol (NIV) and deoxynivalenol (DON) by gas chromatography with an electron capture detector, and for zearalenone (ZEN) by high-performance liquid chromatography with a fluorescence detector. NIV was detected in all the pearled barley fractions, but DON and ZEN were not detected in ≥27 % pearled barley fractions from dehusked barley and ≥36% pearled barley fractions from unhusked barley. However, for all degrees of polishing, NIV, DON, and ZEN were detected in bran fractions. The levels of NIV, DON, and ZEN in the bran fractions increased several fold over the original barley. Polishing was effective in removing DON and ZEN from the naturally contaminated barley, but not NIV.


Liver transplantation in children with cystic fibrosis: a long-term longitudinal review of a single center's experience.
Improved long-term survival in cystic fibrosis (CF) has led to an increased incidence of extrapulmonary complications of this disease. Of these, end-stage liver disease is a significant cause of morbidity and mortality with liver transplantation being the only effective therapy. Records of all CF pediatric liver transplant recipients were reviewed. Twelve children with CF were the recipients of 16 allografts. The 1- and 5-year survival was 91.6% and 75%, respectively. There were 5 deaths at a mean interval of 6.8 +/- 6.3 years. All of these deaths were related to pulmonary disease. Pulmonary function improved or remained stable in 8 of 9 patients tested. Despite an 83% incidence of positive sputum cultures, there was only one early mortality related to pulmonary sepsis in the setting of primary liver allograft nonfunction. Liver transplantation is acceptable treatment for children with CF and end-stage liver disease. Long-term survival is comparable to liver transplantation performed for other indications. Although posttransplant morbidity and mortality is related to lung disease, the authors speculate that as therapeutic improvements prolong the survival in CF, it is expected that longer survival after liver transplantation in this patient population may also be anticipated.


Lectin-gold cytochemistry of the Golgi apparatus in rabbit luteal cells, with special emphasis on the formation of a lysosomal-type membrane.
In rabbit luteal cells embedded in glycolmethacrylate and stained with PTA at low pH highly glycosylated membrane patches can be observed after vesiculation of the trans-Golgi network. As these membranes could be prelysosomal, their sialic acid content was investigated by post-embedding labeling with Limax flavus agglutinin (LFA)/fetuin-Au. Additional labeling of the Golgi apparatus was performed with Wheat germ agglutinin (WGA)/ovomucoid Au, Ricinus communis agglutininI (RCAI)/Au and Helix pomatia agglutinin (HPA)/Au. The sections were then counterstained with PTA at low pH, which allows a clear distinction between the elements of the trans-Golgi network (G2-G1) and the saccules of the stack (g). With WGA, LFA and RCAI the trans-Golgi network was observed to be clearly more reactive than the stack. After vesiculation most intense labeling was found over the highly glycosylated vacuolar membranes derived from the G2-element. The limiting membrane of lysosomes, the MvB's and the plasma membrane also reacted strongly. Colloidal gold particles were also found over the membranes of the vacuoles derived from G1. The Golgi stack showed a lower reactivity and label for all three lectins could be found over three to four saccules of the stack (g3-g4). The matrix of the lysosomes was slightly labeled. Labeling with HPA was absent from the trans saccules and was consistently found in the cis and cis-most (g4-g5) saccules of the stack. Some cytoplasmic vesicles near the cell border were also labeled. With our procedure the Golgi apparatus can easily be detected and it is apparent that in rabbit luteal cells the highest lectin reactivity is found in the trans-Golgi network.(ABSTRACT TRUNCATED AT 250 WORDS)


A phospholipid spin label used as a liposome-associated MRI contrast agent.
Given current clinical use of phospholipid bilayer structures (liposomes/vesicles) as nontoxic drug delivery vehicles, we have addressed the possibility of employing the phospholipids themselves as MRI contrast agents. To this end we have synthesized phosphatidylcholine with a nitroxide spin label replacing one methyl residue of the choline headgroup. This material was mixed with natural phosphatidylcholine in mole ratios from 1:50 to 1:1 and used to prepare sonicated unilamellar vesicles in saline. Expected structural features of these vesicles were verified by freeze-fracture electron microscopy. Proton T1 values of saline were readily decreased to less than 0.3 s by such preparations, yielding a net relaxivity of 0.6 M-1 s-1. The approach seems to be a realistic way of firmly associating a contrast agent of minimal toxicity with ordinary liposomes/vesicles in a manner that is not subject to leakage.


Revealing the Potential Impacts of Nutraceuticals Formulated with Freeze-Dried Jabuticaba Peel and Limosilactobacillus fermentum Strains Candidates for Probiotic Use on Human Intestinal Microbiota.
This study evaluated the impacts of novel nutraceuticals formulated with freeze-dried jabuticaba peel (FJP) and three potentially probiotic Limosilactobacillus fermentum strains on the abundance of bacterial groups forming the human intestinal microbiota, metabolite production, and antioxidant capacity during in vitro colonic fermentation. The nutraceuticals had high viable counts of L. fermentum after freeze-drying (≥ 9.57 ± 0.09 log CFU/g). The nutraceuticals increased the abundance of Lactobacillus ssp./Enterococcus spp. (2.46-3.94%), Bifidobacterium spp. (2.28-3.02%), and Ruminococcus albus/R. flavefaciens (0.63-4.03%), while decreasing the abundance of Bacteroides spp./Prevotella spp. (3.91-2.02%), Clostridium histolyticum (1.69-0.40%), and Eubacterium rectale/C. coccoides (3.32-1.08%), which were linked to positive prebiotic indices (> 1.75). The nutraceuticals reduced the pH and increased the sugar consumption, short-chain fatty acid production, phenolic acid content, and antioxidant capacity, besides altering the metabolic profile during colonic fermentation. The combination of FJP and probiotic L. fermentum is a promising strategy to produce nutraceuticals targeting intestinal microbiota.


Successful and unsuccessful university students: quantitative hemispheric EEG differences.
Quantitative measurements of EEG amplitudes were obtained on academically successful and unsuccessful university students during a 5 min, eyes closed, relaxed state. Integrations measured continuously the fully rectified amplitudes of brain waves cumulated over successive epochs of 5 s, regardless of the correlation of a wave to a particular frequency band. The poor academic students, as a group, displayed a significantly higher right/left variance ratio of the cumulated amplitudes at both the temporal and occipital sites than the academically successful group. Upon examining the histograms for these cumulated amplitudes, it was found that the unsuccessful students displayed a greater number of polymodal (non-Gaussian) distributions, particularly in the right hemisphere. These data, which resemble patterns often found in depression, suggest a relative disorganization of right hemispheric activity in the unsuccessful students, and within limits, seems related to the cognitive and/or emotional stability of these students.


Insulin degradation in human erythrocyte: effects of cations.
Insulin degradation by human erythrocyte fractions was studied using the TCA-precipitation method. Hemolysate exhibited an insulin degrading activity higher than membranes. Triton X-100 treatment of membranes led to the appraisal of Triton-soluble degrading activity and of a more efficient Triton-not-soluble degrading activity. Monovalent cations (Na+, K+, Li+) did not modify the insulin degradation by any of the erythrocyte fractions. Divalent cations, Ca++ and Zn++ selectively enhanced insulin degradation by the membranous fractions, and Cu++ and Zn++ strongly inhibited insulin degradation by all the erythrocyte fractions. The results supported the hypothesis of the existence of at least two different degrading systems in human erythrocytes: soluble (cytosolic) Ca++ and Mg++ insensitive system(s) and membrane associated Ca++ and Mg++ sensitive system(s).


Inhibition of osteoclast recruitment at a local site by 1-hydroxyethylidene-1,1-bisphosphonate (HEBP).
We hypothesized that bisphosphates, a class of antiosteolytic drugs that affect bone cells, may block localized bone modeling in the middle ear. Prior studies have shown that transmitted pressure in the middle ear leads to osteoclastic bone resorption. Catheters were surgically implanted into the middle ear cavity (bulla) of 31 Mongolian gerbils. The animals were then divided into two groups, one subset receiving a bisphosphonate, and the other receiving no drug. Positive air pressure was applied to one middle ear, and the other side served as a control. At the end of the experimental period, tissue specimens were obtained, and histomorphometric evaluation of the ventral bullae was performed. Significant differences in osteoclast surface, osteoclast number, and mean individual osteoclast profile area led us to conclude that administration of the bisphosphonate used at the dose studied inhibits localized recruitment and activation of osteoclasts.


[Morphometry of the adrenals].
The authors report on the method of determination of the weight indices of the adrenyl gland glomerular, testicular-reticular and medullar zones with a spheroid shape; it is substantiated by mathematical analysis of a plasticine model of the adrenal gland, whose characteristics approached the actual ones. The method was particularly accurate in determination of the weight of the fascicular-reticular and glomerular zones, and less--in determination of the weight of the medullary layer, the method's error being 0.6-0.9% in the first case, 2.7-3.5% in the second and 5.3-6.4 in the last.


In situ detection of frameshift mutations in mouse cells.
A reporter gene system that allows in situ detection of cells that have suffered a specific frameshift mutation was developed. To construct the reporter gene, the open reading frame of a human placental alkaline phosphatase (PLAP) gene was disrupted by insertion of either 5 or 7 G:C basepairs, which formed mutant alleles carrying 9 and 11 consecutive G residues, respectively. The mutant PLAP genes did not produce alkaline phosphatase activity in cultured mouse cells in transient transfection assays. Several cell lines that contained integrated copies of the mutant PLAP genes were made. Histochemical staining of fixed cells showed that these cell lines contained a small number of cells that expressed PLAP activity and bound antibodies directed against PLAP. Cells carrying the allele with 11 consecutive G residues (G11 allele) acquired PLAP activity at a rate between 2 x 10(-3) and 2 x 10(-4) events per cell per generation, depending on the cell line. Cells carrying the allele with 9 consecutive G residues (G09 allele) acquired PLAP activity at a rate between 2 x 10(-5) and 2 x 10(-6) events per cell per generation, depending on the cell line. Cultures of PLAP+ cells were derived from cell lines carrying PLAP mutant genes. All the cells in these cultures had PLAP activity and bound anti-PLAP antibody. PLAP mRNA levels were the same in cultures where all cells were PLAP+ and in cultures where less than 1% of the cells expressed PLAP activity. DNA sequence analysis of PLAP+ cells showed that the G11 allele reverted by losing one basepair, and the G09 allele reverted by gaining one basepair.


cDNA cloning and mRNA expression of L-3,4-dihydroxyphenylalanine decarboxylase gene homologue from the silkworm, Bombyx mori.
L-3,4-Dihydroxyphenylalanine decarboxylase (DDC) cDNA, from Bombyx mori that contains an open reading frame of 1437 bp encoding 478 amino acids, was cloned and characterized. Expression analyses of B. mori DDC mRNA by Northern and in situ hybridization indicated that expression of silkworm DDC expression is possibly controlled by neuropeptide hormones in tissue- and stage-specific manners.


B- and Plasma Cell Subsets in Autoimmune Diseases: Translational Perspectives.
B lymphocytes play a central role in immunity owing to their unique antibody-producing capacity that provides protection against certain infections and during vaccination. In autoimmune diseases, B cells can gain pathogenic relevance through autoantibody production, antigen presentation, and proinflammatory cytokine secretion. Recent data indicate that B and plasma cells can function as regulators through the production of immunoregulatory cytokines and/or employing checkpoint molecules. In this study, we review the key findings that define subsets of B and plasma cells with pathogenic and protective functions in autoimmunity. In addition to harsh B-cell depletion, we discuss the strategies that have the potential to reinstall the balance of pathogenic and protective B cells with the potential of more specific and personalized therapies.


Reducing the time and dose of morphine application used in Marshall and Grahame-Smith method for induction of morphine tolerance and dependence in mice.
To induce morphine dependence, different programs have been used and a wide range of behaviors evaluated. A quantitative method based on mice withdrawal jumping behavior has been suggested and later described by Marshall and Grahame-Smith. The purpose of this work was to evaluate different aspects of this method using variations in doses and duration of the protocol. All experiments were done in three parallel methods according to the Marshall protocol: (i) except the dose of morphine (n=20) where we divided all morphine doses by two in first 3 days, (ii) 2-day (M100%-2D, n=14) and (iii) 1-day morphine application (M100%-1D; n=13). The results showed that only 50% doses of morphine that are used according to Marshall method is sufficient to induce morphine dependence whereas they are not able to induce tolerance. On the other hand, M100%-2D protocol could induce morphine tolerance but not dependence whereas M100%-1D group could induce neither morphine tolerance nor dependence in mice. Therefore, these simple modifications in dose and period of morphine application in Marshall method resulted in distinct protocols for induction of morphine tolerance and dependence along with saving of drug and time.


The role of volunteer support in the community for adults with hearing loss and hearing aids.
To explore interactions between audiology patients and volunteers, to describe encounters and define the role of volunteers. Qualitative ethnographic and interview study of volunteer-patient interactions. Ten volunteer participants from two volunteer schemes in South West England were observed and interviewed. Three patient participants were interviewed. Analysis of observational data showed that volunteers provided support relating to local services and hearing aids, but did not engage in discussions about hearing loss. Interviews with volunteers identified gaps in audiology provision, including accessible services and clear information and highlighted a need for more support from audiology services to enable them to fulfil their role. Volunteer interactions with patients mimicked a clinician-patient encounter and volunteers employed strategies and behaviours used by professional audiologists. Audiology volunteers could provide an accessible bridge between health services and the community but their care is limited to focus on hearing aids. Volunteers enable patients to use hearing aids appropriately and are a core element of current care arrangements. However, volunteers express a need for adequate support from audiology services. Volunteers have the potential to increase service capacity and to bridge the gaps between community and audiology healthcare services.


Microvessels enhance vascularization and function of transplanted insulin-producing cells.
Transplantation of insulin-producing cells is an emerging treatment for type 1 diabetes. A recent report in Cell Stem Cell (Aghazadeh et al., 2021) outlines a new approach that accelerates the engraftment and improves the survival and function of such cell transplants by mixing adipose tissue-derived ready-made microvessels with human pancreatic progenitor cells or cadaveric islets prior to transplantation.


[Second-level hospitals in the health care model for the population without coverage].
Hospital health care may be a complement of ambulatory care and promotes the integration of a real National Health System. The measures adopted in the last years in Mexico to create a net of second level hospitals under a new model of health care are described; decentralization, the creation of high quality regional health care centers, administrative modernization, new financial formulas and community participation are some of the analyzed topics.


Longitudinal adherence to antiretroviral drugs for preventing mother-to-child transmission of HIV in Zambia.
Adherence to antiretroviral (ARV) drugs is essential for eliminating new pediatric infections of human immunodeficiency virus (HIV). Since the Zambian government revised the national guidelines based on option A (i.e., maternal zidovudine and infant ARV prophylaxis) of the World Health Organization's 2010 guidelines, no studies have assessed adherence to ARVs during pregnancy up to the postpartum period. This study aimed to examine adherence to ARVs and identify the associated risk factors. A prospective cohort study was conducted in the Chongwe district from June 2011 to January 2014. Self-reported adherence to ARVs was examined during pregnancy and at one week, six weeks, and 24 weeks postpartum among 321 HIV-positive women. The probability of remaining adherent to ARVs was estimated using the Kaplan-Meier method, and the risk factors for non-adherence were identified using the Cox proportional hazard regressions--treating loss to follow-up as non-adherence. The statuses of HIV in HIV-exposed infants were assessed in January 2014. During the study period, 326 infants were born to HIV-positive women, 262 (80.4%) underwent HIV testing, and 11 (3.4%) had their HIV infection detected at the time that they had the latest HIV testing as of January 2014. The ARV adherence rate was 82.5% during pregnancy, 84.2% at one week postpartum, 81.5% at six weeks postpartum, and 70.5% at 24 weeks postpartum. The probability of remaining adherent to ARVs was 0.61 at day 50, 0.35 at day 100, 0.18 at day 200, and 0.06 at day 300. Attending a referral health center (HC) was a risk factor for non-adherence compared with attending rural HCs that provided HIV care/treatment (adjusted hazard ratio [aHR] 0.71, 95% confidence interval [CI] 0.57-0.88) and those that did not provide HIV care/treatment (aHR 0.58, 95% CI 0.46-0.74). A new diagnosis of HIV infection compared to a known HIV-positive status before pregnancy was another risk factor for non-adherence (aHR 1.24, 95% CI 1.03-1.50). Maintaining adherence to ARVs through pregnancy to the postpartum period remains a crucial challenge in Zambia. To maximize the treatment benefits, adherence to ARVs and retention in care should be improved at all health facilities.


Increased expression of the TGF-b superfamily cytokine MIC-1/GDF15 protects ApoE(-/-) mice from the development of atherosclerosis.
MIC-1/GDF15 is a member of the TGF-b superfamily, which is thought to have pleiotropic roles in stress responses, inflammation, tissue injury and repair, energy homeostasis, and malignancy. MIC-1/GDF15 was recently identified as a new biomarker for the development of cardiovascular events and the outcome of atherosclerotic disease therapy. The aim of our study was to determine if MIC-1 also directly exerts pro- or antiatherogenic properties during the development of atherosclerosis. We investigated the effect of transgenic overexpression of MIC-1 in macrophages in the ApoE(-/-) mouse model of atherosclerosis. After 6 months of high-fat diet, MIC-1/GDF15 transgenic ApoE(-/-) mice had smaller atherosclerotic lesions; however, no differences in lesion composition, pro- or anti-inflammatory cytokine production, or serum levels of lipids or cytokines were detected. Our results suggest that MIC-1 has an overall protective effect on the disease process, but further studies will be required to define its mechanism of action.


Early presence of Bythotrephes cederströmii (Cladocera: Cercopagidae) in lake sediments in North America: evidence or artifact?
The spiny water flea (Bythotrephes cederströmii), a freshwater crustacean considered to be the world's best-studied invasive zooplankter, was first recorded in North America in the Laurentian Great Lakes during the 1980s. Its arrival is widely considered to be the result of ocean-going cargo ships that translocated contaminated ballast water from Eurasia to the Great Lakes during the 1970-1980s. The subsequent first discovery of the species in inland lakes is consistent with the hypothesis that propagules dispersed initially from established Great Lakes populations. Here we present evidence of exoskeletal remains, including mandibles, tail spines, and resting eggs, in 210Pb-dated lake sediment cores, which suggests that B. cederströmii was already resident in four inland North American lakes (two in Minnesota, USA; two in Ontario, Canada) by at least the early 1900s. Densities of exoskeletal remains were low and relatively steady from first appearance until about 1990, after which time they increased in all cores. The earliest evidence that we found was a mandible at 33-cm depth (pre-1650) in the sediments of Three Mile Lake, Ontario, Canada. These unexpected findings challenge the current paradigm of B. cederströmii invasion, renew uncertainty about the timing and sequence of its colonization of North American lakes, and potentially question our ability to detect invasive species with traditional sampling methods. We attempted to eliminate errors in the dated stratigraphies of the exoskeletal remains that might have been introduced either methodologically (e.g., core-wall smearing) or naturally (e.g., bioturbation). Nonetheless, given the very low numbers of subfossils encountered, questions remain about the possible artifactual nature of our observations and therefore we regard our results as 'preliminary findings' at this time.


Effects of Continuous Intake of Rosemary Extracts on Mental Health in Working Generation Healthy Japanese Men: Post-Hoc Testing of a Randomized Controlled Trial.
We previously performed a 4 week interventional trial that suggested that continuous intake of rosemary extract improves the mood states, fatigue, and cognitive function of working generation healthy adult Japanese men. However, the severity of depression in participants in our previous study was relatively mild. Therefore, in the present study, a post-hoc analysis of our previous study was conducted, limited to participants whose total mood disturbance (TMD) scores, which indicate greater mood disturbance, were above the median at baseline, to evaluate whether rosemary extract was effective for individuals with poor mental health. Following the intervention, the scores of TMD and "Confusion-Bewilderment" were significantly decreased (both p < 0.05), and scores of "Vigor-Activity" were significantly increased in the rosemary group (n = 8) compared with those in the control group (n = 13; p < 0.01). When comparing the scores from pre- and post-intervention, significant improvements in "Tension-Anxiety", "Vigor-Activity", "Fatigue on awakening", "Daytime sleepiness", and "Psychomotor speed" were observed in the rosemary group only (all p < 0.05). Based on these results, it was expected that rosemary extracts were effective for improving the mental energy and sleep quality of work-age men with poor mental health.


Impact of Anthropogenic Noise on Aquatic Animals: From Single Species to Community-Level Effects.
Anthropogenic noise underwater is on the rise and may affect aquatic animals of marine and freshwater ecosystems. Many recent studies concern some sort of impact assessment of a single species. Few studies addressed the noise impact on species interactions underwater, whereas there are some studies that address community-level impact but only on land in air. Key processes such as predator-prey or competitor interactions may be affected by the masking of auditory cues, noise-related disturbance, or attentional interference. Noise-associated changes in these interactions can cause shifts in species abundance and modify communities, leading to fundamental ecosystem changes. To gain further insight into the mechanism and generality of earlier findings, we investigated the impact on both a predator and a prey species in captivity, zebrafish (Danio rerio) preying on waterfleas (Daphnia magna).


Time-dependent changes of lumped and rate constants in the deoxyglucose method in experimental cerebral ischemia.
Time-dependent changes in the lumped and rate constants in a bilateral middle cerebral artery (MCA) occlusion in cats were evaluated. These variables were measured in 11 cats after a sham operation, in five after a 1-h occlusion, in two after a 2-h occlusion, in five after a 4-h occlusion, and in four after a 16-h occlusion. The time course of the cerebral tissue radioactivity [Ci* (t)] was monitored by external coincidence counting during a programmed infusion of [18F]2-fluorodeoxyglucose (FDG). Arterial plasma concentration [Cp* (t)] of tracer was kept constant during the first 45 min. Comparison of k2* and k3* in the sham-operated group, estimated by external coincidence counting, and by the ratio of extraction fractions of glucose and [18F]2-FDG, demonstrated no significant difference between these rate constants in these two groups of animals. The rate and lumped constants were also estimated from Ci* (t) and Cp* (t), as well as from the ratio of extraction fractions of glucose and [18F]2-FDG, respectively, in the MCA occlusion group. Significant decrease in k3* was observed after 1 h of occlusion (20% lower than in the sham operation, p less than 0.05); in k1* decrease occurred within 4 h of occlusion (21% lower than in the sham operation, p less than 0.05). However, decrease in k2* was observed only after 16 h of occlusion (26% lower than in the sham operation, p less than 0.05). Namely, decrease of rate constants occurred first in k3* then in k1* and k2*.(ABSTRACT TRUNCATED AT 250 WORDS)


Increased levels of vascular endothelial cell markers in thrombotic thrombocytopenic purpura.
We found that patients with thrombotic thrombocytopenic purpura (TTP) have significantly elevated plasma thrombin antithrombin III complex (TAT) and FDP-D-dimer levels, while the plasmin-alpha 2 plasmin inhibitor complex (PIC) level was only slightly increased. The tissue-type plasminogen activator (t-PA) level was increased, but it was well correlated with the plasminogen activator inhibitor-I (PAI-I) level. These findings suggest that hypercoagulable and hypofibrinolytic states coexist in these patients, in contrast to patients with disseminated intravascular coagulation, who exhibit coexisting hypercoagulable and hyperfibrinolytic states. Levels of vascular endothelial cell markers, such as PAI-I, thrombomodulin (TM), and t-PA, were increased at the onset of TTP, but the level of von Willebrand factor (vWF) antigen was not increased. The outcome in TTP patients was correlated with plasma t-PA and TM levels but not with TAT or PIC. These results suggest that vascular endothelial cell markers, such as TM and t-PA, are released from injured or stimulated endothelial cells, reflecting the degree of vascular endothelial damage, and that the main factor in the pathogenesis of TTP is vascular endothelial cell injury.


Development of an interprofessional rotation for pharmacy and medical students to perform telehealth outreach to vulnerable patients in the COVID-19 pandemic.
This report describes an interprofessional rotation for pharmacy and medical students focused on telehealth outreach to patients at high risk for delays in care due to the COVID-19 pandemic. The curriculum was designed around core competencies of interprofessional education. Student activities included participating in interprofessional huddles, collaborating on patient interviews, and practicing interprofessional communication. Three pharmacy students and two medical students completed the rotation. Evaluation was conducted via survey and exit interview. All students successfully increased their knowledge of their own and others' professional roles and demonstrated interprofessional communication and collaboration through telehealth.


Protective effects of glycyrrhizin in a gut hypoxia (ischemia)-reoxygenation (reperfusion) model.
This study investigated the effects of glycyrrhizin, a potent antioxidant, on tissue injury caused by ischemia/reperfusion (I/R) of the gut. I/R injury of the intestine was caused by clamping both the superior mesenteric artery and the celiac trunk for 45 min followed by release of the clamp allowing reperfusion for 1 or 6 h. Administration of glycyrrhizin, significantly reduced the (a) fall of mean arterial blood pressure, (b) mortality rate, (c) myeloperoxidase (MPO) activity, (d) production of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta)], (e) histological evidence of gut injury, (f) immunoreactivity of nitrotyrosine, (g) poly ADP-ribose (PAR) formation, (h) the expression of ICAM-1 and P-selectin, (i) activation of nuclear factor-kappaB (NF-kappaB) and (j) signal transducer and activator transcription-3 (STAT-3) induced by splanchnic artery occlusion-reperfusion shock. This study demonstrates that glycyrrhizin exerts multiple protective effects in splanchnic artery occlusion-reperfusion shock.


Excitatory effects of iontophoretically applied substance P on neurons in the nucleus tractus solitarius of the cat: lack of interaction with opiates and opioids.
The effects of iontophoretically applied substance P (SP), (D-Pro2, D-Trp7,9)-SP and (D-Pro4, D-Trp7,9,10)-SP were studied on neurons identified by their histological location in the nucleus tractus solitarius (NTS), their response to vagal or carotid sinus nerve stimulation and eventually their functional correlation with the central respiratory drive. Potent and consistent excitatory effects of SP were found supporting its role as a putative excitatory transmitter in the NTS. The effects of SP and L-glutamate (Glu) were differentiated by the relative insensitivity of SP-induced excitations to levorphanol and Met-enkephalin.


Field-applied biochar-based MgO and sepiolite composites possess CO2 capture potential and alter organic C mineralization and C-cycling bacterial structure in fertilized soils.
Agricultural soils contribute a significant amount of anthropogenic CO2 emission, a greenhouse gas of global environmental concern. Hence, discovering sustainable materials that can capture CO2 in cultivated soils is paramount. Since the effect of biochar on C mineralization/retention in fertilized soils is unclear, we produced biochar-based MgO and sepiolite-nanocomposites with CO2 capture potential. The field-scale impacts of the modified-biochars were evaluated on net C exchange rate (NCER) periodically for 3 months in fertilized plots. The effects of the modified-biochar on organic-C mineralization, the activities, and dynamics of C-cycling-related 16S rRNA which are unknown, were investigated. Results revealed an initial rapid and higher cumulative CO2 emission from the sole fertilizer treatment (F). Unlike the biochar treatment (BF), the successful incorporation of MgO/Mg(OH)2 nanoparticles into the matrix and surface of biochar, and the potential formation of MgCO3 with soil CO2, mitigated CO2 emission, especially in the MgO-modified biochar (MgOBF), compared to the sepiolite-biochar treatment (SBF). Compared to F and BF, the higher C retention as MgCO3 in the modified biochar treatments led to an increase in cellulase activity, stimulation of key C-cycling-related bacteria, and the expression of genes associated with starch, sucrose, amino sugar, nucleotide sugar, ascorbate, aldarate, cellulose, and chitin degradation, thus, increasing organic C mineralization. Among the modified-biochar treatments, higher C mineralization was recorded in SBF, resulting in increased cumulative CO2 emission, despite its initial capture for up to 42 days. However, MgOBF was effective in capturing soil-derived CO2, despite the increased C mineralization compared to biochar. The changes in soil moisture and temperature significantly regulated NCER. Also, the modified biochars positively influenced the distribution of C-cycling-related bacteria by improving soil pH and available nutrients. Among the modified biochars, the observed higher mitigation effect of MgOBF on NCER indicated that it could be preferably applied in agricultural soils.


[Treatment of an osteo-fascio-cutaneous defect of the femur with a serial connected flow-through free-flap].
Covering large osteo-fascio-cutaneous defects after debridement often calls for elaborate soft tissue reconstruction. Large tissue loss or structural damage that requires distinct repair is rarely coverable by a single conventional flap. Here, we report the case of serial flap coverage using sequentially connected fibular and latissimus dorsi free flaps.


Radiosynthesis and biological evaluation of fluorine-18 labeled N-acetylgalactosamine derivative [18F]FPGalNAc for PET imaging of asialoglycoprotein receptor-positive tumors.
The asialoglycoprotein receptor(ASGPR) is abundantly expressed on the surface of hepatocytes where it recognizes and endocytoses glycoproteins with galactosyl and N-acetylgalactosamine groups. ASGPR not only express on the surface of hepatocytes, but also express in several tumor cells (HepG2, A549 and HCT116). The purpose of this study was to develop a ASGPR-specific radiofluorinated ligand for positron emission tomography (PET) imaging in several tumor models. The radiosynthesis of [18F]FPGalNAc was initiated with fluorine-18 and 5-(p-toluenesulfonyl)-1-yne. The obtained 5-[18F]fluoro-1-pentyne intermediate was then reacted with 2-acetamido-2-deoxy-β-d-galactopyranosyl azide using "click chemistry" to produce the final product. The Kd of the product was determined in HepG2 cells at a range of concentrations of [18F]FPGalNAc. Cellular uptake and blocking experiments were also performed. In vivo biodistribution studies were performed in nude mice bearing HCT116 tumor and micro positron emission tomography/computed tomography (PET/CT) evaluations were then performed in tumor-bearing mice (HepG2, HCT116) models. The radiosynthesis of [18F]FPGalNAc required 50 min with 5-6% RCY (radiochemical yield). The Kd of [18F]FPGalNAc to ASGPR in HepG2 cells was 0.25 ± 0.02 mM. Uptake values of 0.29% were observed within 30 min of incubation with HepG2 cells, which could be blocked by 200 mM d(+)-galactose (< 0.13%). The data of biodistribution revealed that the uptake of [18F]FPGalNAc was higher in kidneys and liver, and lower in muscle, bone and brain. In vivo micro PET studies, both HCT116 and HepG2 tumors showed high uptake for [18F]FPGalNAc, the radio of tumor/muscle (T/M) was 3.7 and 3.91, respectively. In vitro assays and in vivo PET/CT imaging and biodistribution studies showed that [18F]FPGalNAc represents a promising tumor imaging agent that can provide insight into ASGPR related disease.


Can we ever stop imaging in surgically treated and radiotherapy-naive patients with non-functioning pituitary adenoma?
Non-functioning pituitary adenomas (NFAs) are slow-growing tumours with reported re-growth rates following surgical resection alone of up to 50% at 10 years. Currently, the desired length of follow-up surveillance imaging in un-irradiated patients is unclear. To clarify the timing of re-growth in patients with NFAs, treated solely by surgery without post-operative pituitary radiotherapy, and also to clarify whether continued imaging is necessary in these patients. A case note analysis of all patients who underwent surgery alone for NFA between January 1984 and December 2007 was undertaken. Patients were followed for a minimum of 1 year. Re-growth was diagnosed on the basis of radiological appearances with or without associated manifestations. One hundred and fifty-five patients (94 males, mean age at diagnosis 57.9 (range 18.3-88) years) were included. Twenty-nine were followed up for more than 10 years. The mean follow-up following surgery was 6.1 years (median 4.3 (range 1-25.8)). Re-growth was documented in 54 (34.8%) cases and 20.4% of these cases showed relapse/re-growth 10 or more years after the initial surgery. Kaplan-Meier analysis showed relapse rates of 23.1, 46.7 and 67.9% at 5, 10 and 15 years respectively. There was a significant increase in the re-growth rates if there was either pituitary tumour remnant observed on the first post-operative scan (P≤0.001) or a younger age at initial surgery (P=0.034). These results suggest that patients with NFAs need to be closely monitored following surgery, particularly those with post-operative tumour remnants. With 20% of relapse occurring after 10 years, follow-up surveillance needs to be continued beyond this time.


Head-to-Head Comparison of Aripiprazole and Risperidone in the Treatment of ADHD Symptoms in Children with Autistic Spectrum Disorder and ADHD: A Pilot, Open-Label, Randomized Controlled Study.
Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are frequently overlapping neurodevelopmental disorders. Individuals in whom the disorders are comorbid show more severe impairment because of deficits in the processing of social situations, adaptive functioning, and executive control than individuals with either disorder alone. This open-label pilot study aimed to evaluate and compare the efficacy and tolerability of risperidone and aripiprazole for treating ADHD symptoms in patients with both ASD and ADHD over the course of 24 weeks of treatment. Patients (n = 44) were randomly assigned to start treatment with risperidone (22 patients) or aripiprazole (22 patients). Children were evaluated before starting treatment (T0), and after 12 weeks (T1) and 24 weeks (T2) of treatment. At each visit, specific psychiatric clinical scales were administered to assess the efficacy of the two drugs. The mean age was 8.4 ± 2.9 years in the aripiprazole group and 7.8 ± 2.3 years in the risperidone group. A total of 37 children (29 boys and 8 girls) completed the study (18 in the aripiprazole group and 19 in the risperidone group). Aripiprazole and risperidone appeared to have similar benefits in terms of efficacy and tolerability, although there were slight differences between the two drugs. Both groups showed a significant improvement in ADHD symptoms after 24 weeks of treatment (ADHD Rating Scale, Conners Parent Rating Scale-Hyperactivity, and Clinical Global Improvement-Severity Scale). No significant difference between the two drugs on any parameters at 24 weeks were found. Prolactin levels were decreased in the aripiprazole group. Both drugs were well tolerated, with no serious adverse events detected. Our study confirms the efficacy of both aripiprazole and risperidone in ameliorating ADHD symptoms of children also presenting with ASD.


Potential environmental consequences of administration of ectoparasiticides to sheep.
Sheep ectoparasiticides, which include the synthetic pyrethroids, the organophosphates, the 'insect'-growth regulators, the formamidines and the spinocyns, enter into the environment primarily through disposal of dip or fleece scours, as well as with contaminated faeces and urine. Due to the large quantities of spent dip, risks associated with environmental contamination are high. Synthetic pyrethroids and organophosphates pose risks to dung, soil and aquatic fauna; concerns over potential ecotoxicity to vertebrates and invertebrates have resulted in the cessation of their use in many countries. There is very little information regarding the ecotoxicity of 'insect'-growth regulators, formamidines or spinocyns, with no studies focussing on sheep. Here, the impact of sheep ectoparasiticides is discussed in terms of their potential to enter into the environment, their toxicity and their impact on ecosystem functioning. Where there are no data for excretion or toxicity of the ectoparasiticides used in sheep production, examples to demonstrate potential impacts are taken from laboratory ecotoxicity tests and the cattle literature, as well on work with foliar insecticides. Future research priorities are suggested to allow assessment of the environmental consequences of sheep ectoparasiticide treatments, which are essential for future sustainable sheep production.


HIV-associated cerebral lymphocyte infiltration mimicking vestibular schwannoma.
The association of unilateral, rapidly progressive hearing loss, tinnitus and vestibular dysfunction in combination with a contrast-enhancing mass within the internal auditory canal on MRI is suggestive of a vestibular schwannoma (VS). We report the rare finding of a HIV-associated cerebral lymphocyte infiltration, most probably malignant lymphoma, which was presumed initially to be a VS. A 36-year-old male presented with progressive unilateral hearing loss accompanied by acute, ipsilateral tinnitus. Interpreted first as sudden sensorineural hearing loss, his symptoms were treated with rheologic therapy. Ipsilateral facial palsy appeared. MRI with gadolininium disclosed a contrast-enhancing mass within the internal auditory meatus of the left side. Within five weeks an extended leptomeningeal lymphocyte infiltration evolved and the diagnosis of an underlying HIV infection was made. Unilateral, rapidly progressive hearing loss and a fast growing cerebello-pontine mass is atypical for VS and highly suspicious of malignant disease. To our knowledge we report the first case of an HIV-associated cerebral lymphocyte infiltration, mimicking a VS. In such cases the diagnostic work-up should include a HIV test.


Prognostic systems for lymphomas.
The prognostication of lymphoma patients remains important to optimize treatments choices. Clinically based indices, such as the International Prognosis Index and the Follicular Lymphoma International Prognosis Index, developed respectively for aggressive and follicular lymphoma, are of great value in routine practice and clinical research, but they reflect only the biologic heterogeneity of these diseases. New techniques have made it possible to unravel the underlying biologic pathways associated with outcome. The current challenge, translating these molecular findings into clinical practice, requires the validation of those biomarkers in large cohorts of patients.


Enhanced apoptosis in prolonged cultures of senescent porcine pulmonary artery endothelial cells.
Senescent or aged endothelial cells in culture remain metabolically active after cessation of division, and are generally believed to eventually die. However, mechanisms underlying the terminal aging of cultured cells, i.e. from senescence to death, are poorly understood. Here, we report that culturing of replicative senescent endothelial cells for a prolonged period of time without passaging leads to enhanced programmed cell death or apoptosis. Senescent (passage 45) and young (passage 3) porcine pulmonary artery endothelial cells (PAEC) were cultured for 0-42 days post confluence. The cells attached to culture dishes and floating in medium were collected at 0, 7, 14, 21, 28, 35 and 42 days post confluence and were assessed for markers of apoptosis. Morphology studies showed that ratios between senescent and young cells attached to dishes declined to 45% after 42 days postconfluence. Apoptotic cells in prolonged cultures of senescent PAEC increased from 5 to 35% as determined by protein mass, DNA breakage, and caspase-3 activation. Steady state levels of Bcl-2, an anti-apoptotic protein, in senescent prolonged cultures decreased to less than 20% for all time points compared with young cells. Relative levels of Bad, a pro-apoptotic protein, in senescent cells were elevated from 60 to 130% during prolonged culturing. These results indicate that terminal cellular aging enhances apoptosis and the levels of Bcl-2/Bad may be associated with the apoptotic process in porcine lung endothelial cells.


Evaluation of Yellow Sea anchovy (Engraulis japonicus) fishery for management strategies using a data-limited management toolkit.
Most fisheries in developing countries are data-limited, which creates a huge challenge to the fishery management. Therefore full utilization of the available information is essential. Japanese anchovy (Engraulis japonicus) plays a key role in the marine ecosystem, but the anchovy population in the Yellow Sea of China has declined in the recent decades, which is also a data-limited fishery. In order to implement robust management strategies to recover the anchovy stock, based on the available information as well as the associated uncertainties, here we examine its management strategy evaluation using a computer software package data-limited management toolkit (DLMtool). Results indicated that fishing pressure on the Yellow Sea anchovy should be slightly reduced and the length at first capture should exceed the length at first maturity. These are high probably conductive to anchovy population recovery. We also selected some management procedures performed well in this study, such as minlenLopt1. Paying attention to quantitative population dynamics and perfecting data collection are important for future anchovy fisheries management against uncertainties in both model and data.


Automated Large Artery Occlusion Detection in Stroke: A Single-Center Validation Study of an Artificial Intelligence Algorithm.
Expediting notification of lesions in acute ischemic stroke (AIS) is critical. Limited availability of experts to assess such lesions and delays in large vessel occlusion (LVO) recognition can negatively affect outcomes. Artificial intelligence (AI) may aid LVO recognition and treatment. This study aims to evaluate the performance of an AI-based algorithm for LVO detection in AIS. Retrospective analysis of a database of AIS patients admitted in a single center between 2014 and 2019. Vascular neurologists graded computed tomography angiographies (CTAs) for presence and site of LVO. Studies were analyzed by the Viz-LVO Algorithm® version 1.4 - neural network programmed to detect occlusions from the internal carotid artery terminus (ICA-T) to the Sylvian fissure. Comparisons between human versus AI-based readings were done by test characteristic analysis and Cohen's kappa. Primary analysis included ICA-T and/or middle cerebral artery (MCA)-M1 LVOs versus non-LVOs/more distal occlusions. Secondary analysis included MCA-M2 occlusions. 610 CTAs were analyzed. The AI algorithm rejected 2.5% of the CTAs due to poor quality, which were excluded from the analysis. Viz-LVO identified ICA-T and MCA-M1 LVOs with a sensitivity of 87.6%, specificity of 88.5%, and accuracy of 87.9% (AUC 0.88, 95% CI: 0.85-0.92, p < 0.001). Cohen's kappa was 0.74. In the secondary analysis, the algorithm yielded a sensitivity of 80.3%, specificity of 88.5%, and accuracy of 82.7%. The mean run time of the algorithm was 2.78 ± 0.5 min. Automated AI reading allows for fast and accurate identification of LVO strokes with timely notification to emergency teams, enabling quick decision-making for reperfusion therapies or transfer to specialized centers if needed.


[The modality of endoconnective ossification on cartilaginous substrate: observations on the long bones in the embryo].
The authors conducted a histologic study on the modalities of ossification of the "diaphyseal osseous ferrule" in embryos between the sixth and eighth week of intrauterine life: the ossification of this "diaphyseal osseous ferrule" presents some peculiarities compared to that of other areas: it occurs with the modalities of periosteal ossification, exploiting, however, a cartilagenous substrate. In addition, the authors compared the ossification of the diaphyseal ferrule to that of the "perichondrial ferrule of the layer of ossification", examining histologic sections of embryos in the 25th week of intrauterine life.


A nutritional model of late embryonic vitamin A deficiency produces defects in organogenesis at a high penetrance and reveals new roles for the vitamin in skeletal development.
Vitamin A plays an essential role in vertebrate embryogenesis. In the present study, pregnant vitamin A-deficient (VAD) rats were maintained during early pregnancy on the short half-life vitamin A metabolite, all-trans retinoic acid (atRA), in an amount sufficient to support normal development to E10.5, with a higher level of atRA (250 microg atRA/g diet) provided from embryonic day (E) 8.5-10.5 to prevent mid-gestational resorption. When limiting amounts of atRA (1.5 or 12 microg/g diet) were provided after E10.5, a highly reproducible and penetrant state of late fetal vitamin A deficiency (late VAD) was induced in the organs of developing fetuses. In addition, late VAD fetuses displayed both anteriorization of cervical regions and novel posteriorization events at the thoracic and sacral levels of the skeleton, and showed sternal and pelvic malformations not previously observed in early VAD or genetic models. The expression of several Hox genes (Hoxd3 and Hoxb4) was altered in late VAD embryos, with a reduction in Hoxd3 noted as early as 1 day after instituting deficiency. All late VAD-induced malformations were prevented by the addition of retinol starting at E10.5, whereas provision of a high level of atRA throughout pregnancy improved but could not completely rescue the development of all organ systems. This work defines a nutritional model in which vitamin A deficiency can be induced during fetal development, and reveals new functions for the vitamin in the development of the axial and appendicular skeleton.


Enzymatic deacylations of esterified saccharides. II. De-esterifications of radiolabelled O-acylglucopyranosides by mice serum and liver esterases.
1. 14C-Labelled methyl 2,6-di-O-pivaloyl-alpha-D-glucopyranoside (1) was used as a novel substrate for esterases from mouse serum and liver. 2. Stepwise de-esterification of the diester substrate 1 was achieved, and data on time-course experiments are reported. 3. Kinetic studies were undertaken to compare deacylation rates for the enzymatic de-esterification of the diester substrate 1 using both, mice sera and liver microsomal fractions. 4. Serum and liver esterase activities were studied in mice treated with an immunostimulating agent, peptidoglycan monomer (PGM), and a comparison made with esterases from untreated mice.


Dynamics of intergestural timing: a perturbation study of lip-larynx coordination.
In this study, downward-directed mechanical perturbations were applied to the lower lip during both repetitive (/...paepaepae.../) and discrete (/pe'saepaepl/) utterances in order to examine the perturbation-induced changes of intergestural timing between syllables (i.e., between the bilabial and laryngeal gestures for successive /p/'s) and within phonemes (i.e., between the bilabial and laryngeal gestures within single /p/'s). Our findings led us to several conclusions. First, steady-state (phase-resetting) analyses of the repetitive utterances indicated both that "permanent" phase shifts existed for both the lips and the larynx after the system returned to its pre-perturbation rhythm and that smaller steady-state shifts occurred in the relative phasing of these gestures. These results support the hypothesis that central intergestural dynamics can be reset by peripheral articulatory events. Such resetting was strongest when the perturbation was delivered within a "sensitive phase" of the cycle, during which the downwardly directed lower-lip perturbation opposed the just-initiated, actively controlled bilabial closing gesture for /p/. Although changes in syllable duration were found for other perturbed phases, these changes were simply transient effects and did not indicate a resetting of the central "clock." Second, analyses of the transient portions of the perturbed cycles of the repetitive utterances indicated that the perturbation-induced steady-state phase shifts are almost totally attributable to changes occurring during the first two perturbed cycles. Finally, the transient changes in speech timing induced by perturbations in the discrete sequences appeared to share a common dynamical basis with the changes to the repetitive sequences. We conclude by speculating on the type of dynamical system that could generate these temporal patterns.


Neurophysiology of erection and ejaculation.
Penile erection and ejaculation are closely associated during sexual intercourse. Erection is a central psychoneuroendocrine and peripheral neuro-vasculo-tissular event, resulting in blood filling the sinusoidal spaces of the corpora cavernosa and corpus spongiosum. Ejaculation represents the climax of the sexual cycle and comprises emission (secretion of semen) and expulsion (propulsion of semen) phases. This article provides an overview of the proposed neurophysiology of erection and ejaculation. Review of the literature. Current data on the neurophysiology of erection and ejaculation. In terms of peripheral innervation, the pelvic plexus represents a junction for efferent nerves to the structures involved in erection and ejaculation. At the spinal level, the spinal cord contains three sets of neurons (thoracolumbar sympathetic, sacral parasympathetic, and somatic) innervating the sexual organs involved in erection and ejaculation. The presence of cerebral descending pathways to spinal erection and ejaculation centers indicates that the brain has an excitatory or inhibitory effect on these processes. Brain structures that modulate spinal command of erection and ejaculation are part of a larger network that is dedicated to regulating sexual responses. Neurophysiological and pharmacological research has elucidated that dopamine and serotonin have central roles in modulating erection and ejaculation. Interestingly, erection is not a prerequisite for ejaculation, and each of these sexual responses can exist without the other. Despite the association between erection and ejaculation during intercourse, these two processes can be considered distinct events from an anatomical, physiological, and pharmacological perspective.


How Should Implantable Cardioverter-Defibrillator Lead Failures be Managed and What is the Role of Lead Extraction?
Despite remarkable advances in design, implantable cardioverter-defibrillator (ICD) leads remain the component most susceptible to failure, which often leads to substantial adverse clinical outcomes. This article focuses on management strategies when ICD lead systems fail. Two cases involving management decisions for ICD lead failures are presented and discussed. One involves a common mode of presentation, inappropriate shocks. The second involves an alert in a patient with a complex system and multiple comorbidities. Although a systematic approach is outlined, management decisions must be balanced by a risk-and-benefit assessment of the individual patient.


Slowing down terahertz waves with tunable group velocities in a broad frequency range by surface magneto plasmons.
This paper proposes one broadly tunable terahertz (THz) slow-light system in a semiconductor-insulator-semiconductor structure. Subject to an external magnetic field, the structure supports in total two surface magneto plasmons (SMPs) bands above and below the surface plasma frequency, respectively. Both the SMPs bands can be tuned by the external magnetic field. Numerical studies show that leveraging on the two tunable bands, the frequency and the group velocity of the slowed-down THz wave can be widely tuned from 0.3 THz to 10 THz and from 1 c to 10(-6) c, respectively, when the external magnetic field increases up to 6 Tesla. The proposed method based on the two SMPs bands can be widely used for many other plasmonic devices.


A new water treatment technology for degradation of B[a]A by hydrodynamic cavitation and chlorine dioxide oxidation.
Managing environmental contamination with Benz[a]anthracene (B[a]A) is essential due to its carcinogenic, teratogenic and mutagenic effects on humans and the environment. At present, the mainly B[a]A degradation methods used are photodegradation, bioremediation and traditional advanced oxidation, although they all have disadvantages. In this study, B[a]A was degraded by hydrodynamic cavitation (HC), chlorine dioxide (ClO2), or an innovative combination of the two methods. According to high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analysed the degradation products and degradation pathway of B[a]A, with the kinetics of different degradation methods discussed. Under optimal conditions, HC combined with ClO2 oxidation can further degrade products to achieve ring cleavage. Compared with the two separate degradation process methods, the combined method exerts a synergistic effect on the degradation of B[a]A, with an enhancement factor of 1.48. Experimental results showed that the combination method can realize enhanced complete degradation of B[a]A, reduce ClO2 requirements, improve efficiency, reduce energy consumption and produce less harmful products with ring cleavage achieved.


A protein structure from nuclear magnetic resonance data. lac repressor headpiece.
A procedure is described to determine the three-dimensional structure of biomolecules from nuclear magnetic resonance data. This procedure combines model building with a restrained molecular dynamics algorithm, in which distance information from nuclear Overhauser effects is incorporated in the form of pseudo potentials. The method has been applied to the N-terminal DNA-binding domain or headpiece (amino acid residues 1 to 51) of the lac repressor from Escherichia coli, for which no crystal structure is available. The relative orientation of the three helices of the headpiece is similar to that of the three homologous helices found in the cI repressor of bacteriophage lambda.


In vivo imaging with antibodies and engineered fragments.
Antibodies have clearly demonstrated their utility as therapeutics, providing highly selective and effective drugs to treat diseases in oncology, hematology, cardiology, immunology and autoimmunity, and infectious diseases. More recently, a pressing need for equally specific and targeted imaging agents for assessing disease in vivo, in preclinical models and patients, has emerged. This review summarizes strategies for developing and optimizing antibodies as targeted probes for use in non-invasive imaging using radioactive, optical, magnetic resonance, and ultrasound approaches. Recent advances in engineered antibody fragments and scaffolds, conjugation and labeling methods, and multimodality probes are highlighted. Importantly, antibody-based imaging probes are seeing new applications in detection and quantitation of cell surface biomarkers, imaging specific responses to targeted therapies, and monitoring immune responses in oncology and other diseases. Antibody-based imaging will provide essential tools to facilitate the transition to truly precision medicine.


A randomized clinical trial of comprehensive education and care program compared to basic care for reducing anxiety and depression and improving quality of life and survival in patients with hepatocellular carcinoma who underwent surgery.
This study aimed to investigate the effect of comprehensive education and care (CEC) program on anxiety, depression, quality of life, and survival in patients with hepatocellular carcinoma (HCC) who underwent surgical resection.Totally 136 patients with HCC who underwent hepatectomy were randomly assigned to CEC group and control group as 1:1 ratio. CEC group received health education, psychological nursing, caring activity, and telephone condolence, whereas control group received basic health education and rehabilitation for 12 months. Anxiety and depression were assessed by Hospital Anxiety and Depression Scale (HADS); quality of life was evaluated using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30).HADS-Anxiety (HADS-A) score was decreased at 9 month (M9) and M12, and reduction in HADS-A score (M12-M0) was greater in CEC group compared with control group. At M12, percentage of anxiety patients was less, but anxiety severity was similar in CEC group compared with control group. HADS-Depression (HADS-D) score was decreased at M12, and reduction in HADS-D score (M12-M0) was greater in CEC group compared with control group. At M12, percentage of depression patients were less but depression severity was similar in CEC group compared with control group. In addition, QLQ-C30 global health status and functional score was increased at M12, and score improvement (M12-M0) was greater in CEC group compared with control group. In addition, overall survival was longer in CEC group compared with control group.CEC relieves anxiety and depression, improves quality of life, and prolongs survival in patients with HCC underwent surgical resection.


Opicapone: a short lived and very long acting novel catechol-O-methyltransferase inhibitor following multiple dose administration in healthy subjects.
The aim of this study was to assess the tolerability, pharmacokinetics and inhibitory effect on erythrocyte soluble catechol-O-methyltransferase (S-COMT) activity following repeated doses of opicapone. This randomized, placebo-controlled, double-blind study enrolled healthy male subjects who received either once daily placebo or opicapone 5, 10, 20 or 30 mg for 8 days. Opicapone was well tolerated. Its systemic exposure increased in an approximately dose-proportional manner with an apparent terminal half-life of 1.0 to 1.4 h. Sulphation was the main metabolic pathway. Opicapone metabolites recovered in urine accounted for less than 3% of the amount of opicapone administered suggesting that bile is likely the main route of excretion. Maximum S-COMT inhibition (Emax ) ranged from 69.9% to 98.0% following the last dose of opicapone. The opicapone-induced S-COMT inhibition showed a half-life in excess of 100 h, which was dose-independent and much longer than plasma drug exposure. Such a half-life translates into a putative underlying rate constant that is comparable with the estimated dissociation rate constant of the COMT-opicapone complex. Despite its short elimination half-life, opicapone markedly and sustainably inhibited erythrocyte S-COMT activity making it suitable for a once daily regimen.


Stress exertion on adjacent segments after ventral cervical fusion.
Special investigations of the adjacent segments are performed in patients with cervical fusion operations caused by different indications: Only a few of alteration was seen after operations caused by infectious disease, tumor or trauma. A different situation arises with degenerative lesions, where often progressive changes were seen in the adjacent segments. This phenomena may be dependent at first of the kind of lesion (degeneration) and only at second of the kind of operation.


Morphine induced increases in the incorporation of 3H-thymidine into brain striatal DNA.
3H-thymidine uptake into DNA fractions of rat brain regions was measured following in vivo administration of (methyl-3H)-thymidine and morphine. Acute morphine administration (10 mg/kg; 30 min prior to 3H-thymidine) increased incorporation of 3H-thymidine into DNA of rat striatum. This effect was antagonized by naloxone (1 mg/kg). Further, the observed change in incorporation of 3H-thymidine into DNA in striatum could not be accounted for by differences in the local availability of the label in morphinized rats. An autoradiographic study revealed that the 3H-thymidine was localized in nuclei in cells of the sub-ependymal layer lining the lateral ventricles, an area of glial cell proliferation in adult rats. No change in 3H-thymidine incorporation into DNA was observed in any area of the brain in morphine-addicted rats or in rats undergoing naloxone-precipitated withdrawal. The results indicate that opiates may induce permanent anatomical changes in the brain, including alterations of neuroglial interactions.


ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM.
Antigen-specific cell contacts in the immune system are strengthened by antigen-nonspecific interactions, mediated in part by lymphocyte-function associated (LFA) antigens. The LFA-1 antigen is widely expressed on cells of haematopoietic origin and is a major receptor of T cells, B cells and granulocytes. LFA-1 mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by natural killer cells and granulocytes. Recently, ICAM-1 (intercellular adhesion molecule-1) has been defined as a ligand for LFA-1. Monoclonal antibodies to ICAM-1 block T lymphocyte adhesion to fibroblasts and endothelial cells and disrupt the interaction between cytotoxic T cells and target cells. In addition, purified ICAM-1 reconstituted into artificial membranes binds LFA-1+ cells. ICAM-1 is found on leukocytes, fibroblasts, epithelial cells and endothelial cells and its expression is regulated by inflammatory cytokines. LFA-1 has been placed in the integrin family of cell surface receptors by virtue of the high sequence similarity between the LFA-1 and integrin beta chains. The adhesion ligands of the integrin family are glycoproteins bearing the Arg-Gly-Asp (RGD) sequence motif, for example, fibronectin, fibrinogen, vitronectin and von Willebrand factor. Here we show that a complementary DNA clone ICAM-1 contains no RGD motifs, but instead is homologous to the neural cell adhesion molecule NCAM.


Blood lead levels and risk factors for lead poisoning in children and caregivers in Chuuk State, Micronesia.
Lead poisoning is a preventable environmental disease. Children and developing fetuses are especially vulnerable; even low blood lead levels (BLLs) are linked with learning and behavioral problems. We assessed children's and their caregivers' BLLs and risk factors for lead exposure in Chuuk State, Federated States of Micronesia. Children aged 2-6 years were randomly selected within 20 randomly selected villages. Children and caregivers provided venous blood, and caregivers offered information about possible risk factors for lead exposure. Mean BLLs were 39 microg/l for children and 16 microg/l for caregivers. Children with BLLs of > or = 100 microg/l (elevated) were 22.9 (95% CI: 4.5-116.0) times more likely to have a caregiver with an elevated BLL, 6.2 (95% CI: 1.4-27.3) times more likely to live on an outer island, and 3.4 (95% CI: 1.7-6.9) times more likely to have a family member who made lead fishing weights than did other children even after controlling for age and sex. For children, 61% of elevated BLLs could be attributed to making fishing weights. Caregivers with elevated BLLs were 5.9 (95% CI: 1.5-23.7) times more likely to live in a household that melted batteries than other caregivers even after controlling for age and education. For caregivers, 37% of the elevated BLLs could be attributed to melting batteries. The association of elevated BLLs in children and their caregiver suggests a common environmental exposure. Melting batteries to make fishing sinkers is a preventable source of lead exposure for children and their caregivers in Chuuk. Published by Elsevier GmbH.


Tea catechin, (-)-epigallocatechin gallate, facilitates cholinergic ganglion transmission in the myenteric plexus of the guinea-pig small intestine.
Intracellular recordings were made from myenteric S neurons of the guinea-pig ileum. One of the major tea catechins, (-)-epigallocatechin gallate (EGCG at concentrations from 1 to 20 microM), was applied by superfusion to examine its effect on cholinergic ganglion transmission in the myenteric plexus. Fast excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation to ganglia and/or internodal fiber tracts were augmented in amplitude by EGCG in about 60% of tested neurons without changing the postsynaptic sensitivity to acetylcholine (ACh) applied by ionophoresis. Furthermore, the amplitude-ratio of paired fast EPSPs was increased by EGCG. These results indicated that the site at which EGCG augmented the fast EPSPs was presynaptic. It is concluded that EGCG can facilitate the cholinergic ganglion transmission possibly by increasing the amount of ACh released and, together with its previously described depolarizing action on myenteric neurons, may modulate the activity of the myenteric plexus of the guinea-pig ileum.


[Clinical experience with an antaminic drug in the treatment of post-traumatic and vasomotor headaches].
After some brief remarks on the pathogenesis of vasomotor cephalea, the properties of the antiaminic drug BC 105 (Sandomigran) are described and the results reported of using it in 171 patients suffering from cephalea of three types: vasomotor cephalea in 50 cases, vasomotor cephalea with associated neurosic component in 26 cases, and post-traumatic cephalea in 95 cases. In the first two types, the positive results obtained confirm the usefulness of BC 105 in basic treatment of vasomotor cephalea. In post-traumatic cephalea which is a notoriously difficult therapeutic problem, the results obtained, although only partially positive, are worthy of the fullest consideration.


Determine the impact of a structured pharmacist-led medication review - a controlled intervention study to optimise medication safety for residents in long-term care facilities.
Medication reviews contribute to protecting long-term care (LTC) residents from drug related problems (DRPs). However, few controlled studies have examined the impact on patient-relevant outcomes so far. We examined the impact of a one-time, pharmacist-led medication review on medication changes (primary endpoint) including discontinued medication, the number of chronic medications, hospital admissions, falls, and deaths (secondary endpoints). A prospective, controlled intervention study was performed in three LTC facilities. In the intervention group (IG), after performing a medication review, a pharmacist gave recommendations for resolving DRPs to physicians, nurses and community pharmacists. The control group (CG) received usual care without a medication review. (i) We assessed the number of medication changes and the secondary endpoints in both groups before (t0) and after (t1, t2) the intervention. (ii) Additionally, the medication review was evaluated in the IG with regard to identified DRPs, the healthcare professional's feedback on the forwarded pharmacist recommendations and whether DRPs were finally resolved. 107 (IG) and 104 (CG) residents were enrolled. (i) More medication changes were identified in the IG than in the CG at t1 (p = 0.001). However, no significant difference was identified at t2 (p = 0.680). Mainly, medication was discontinued in those medication changes. Chronic medications increased in the CG (p = 0.005) at t2 while hospital admissions, falls, and deaths showed no differences. (ii) Overall, 1252 DRPs (median: 10; minimum-maximum: 2-39) were identified. Recommendations for 82% of relevant DRPs were forwarded to healthcare professionals, of which 61% were accepted or clarified. 22% were not accepted, 12% required further review and 6% remained without feedback. 51% of forwarded DRPs were finally resolved. We found more medication changes in the IG compared to controls. Mostly, medication was discontinued. This suggests that our intervention was successful in discontinuing unnecessary medication. Other clinical outcomes such as falls, hospitalisations, and deaths were not improved due to the one-time intervention. The medication review further identified a high prevalence of DRPs in the IG, half of which were finally resolved. German Clinical Trials Register, DRKS00026120 ( www.drks.de , retrospectively registered 07/09/2021).


Three cases of organized hematoma of the maxillary sinus in patients who underwent preoperative arterial embolization.
Organized hematoma (OH) is benign tumor in the maxillary sinus. The standard treatment for OH is complete surgical resection, however massive bleeding can occur during the procedure, albeit rarely. Some reports have suggested preoperative embolization is useful for reducing the volume of intraoperative bleeding. We report 3 cases of OH in the maxillary performed preoperative embolization. We identified the feeding arteries by angiography or IVR-CT, and we embolized them using Gelatin sponge particles. The embolized artery was the maxillary artery or both the maxillary and the facial artery. There were no major complications as a result of embolization. The mean fluoroscopy time was 35.8 minutes, and the mean fluoroscopy dose was 329.3 mGy. Tumor resection was performed the next day after arterial embolization. The mean bleeding volume for surgery was 383.3 ml, and the mean operative time was 194 minutes. No recurrence was observed in any of the cases over a 4-year follow-up period. We considered that it is possible that preoperative artery embolization is useful for decreasing intraoperative bleeding volume. Although the methods and usefulness of embolization await future reports, it is a technique that should be considered preoperatively because of its potential to prevent massive bleeding.


Effects of follicular size of cytoplast donor on the efficiency of cloning in cattle.
In cattle, oocytes obtained from follicles smaller than 3 mm in diameter can undergo maturation in vitro, progressing to MII and undergoing fertilization, but are developmentally incompetent. Cytoplasts were prepared from in vitro matured oocytes aspirated from small (1-3 mm) or large (6-12 mm) follicles and fused to serum starved mural granulosa cells. Following activation, reconstructed embryos were cultured for 7 days and classified G1 to G4, before being processed for nuclei counting or transferred to synchronized recipients. Oocytes from small follicles had lower rates of polar body extrusion (59.6 vs. 69%; 731/1230 vs. 608/857) and fusion (71.4 vs. 78.8%; 360/497 vs. 364/465; P < 0.06). There were no differences in total rate of blastocysts development (60 vs. 59.8%; small vs. large), or any grade classification. A significant interaction was detected between follicle size and embryo grade with G3 embryos from small follicles having a greater cell number. Developmental competence of G1 and G2 embryos did not differ at day 27 (48 vs. 46%; 16/33 vs. 17/37; small vs. large). Although there were no differences in fetal size between the two groups, differences in allantois length (53 vs. 86 mm; small vs. large; P < 0.002) and allantois width (9.5 vs. 13 mm; small vs. large; P < 0.06) were seen. No differences in survival to term (2/13 in each group) were observed. These results indicate that cytoplasts from follicles of 1-3 and 6-12 mm in diameter are equally developmentally competent when used in a nuclear transfer procedure.


Functional connectivity between the habenula and default mode network and its association with the antidepressant effect of ketamine.
Recently, an animal model for depression has shown that ketamine, an N-methyl- d-aspartate receptor (NMDAR) antagonist, elicits a rapid-acting antidepressant effect by blocking NMDAR-dependent bursting in the lateral habenula (Hb). However, evidence from human studies remains scarce. This study explored the changes of resting-state functional connectivity (FC) of the Hb in responders and nonresponders who was diagnosed with unipolar or bipolar depression before and after ketamine treatment. The response was defined as a ≥50% reduction in the total MADRS score at Day 13 (24 h following the sixth infusion) in comparison with the baseline score. Correlation analyses were performed to identify an association between symptom improvement and the signals of the significantly different brain regions detected in the above imaging analysis. In the post-hoc region-of-interest analysis, an enhanced baseline FC between Hb and several hubs of the default mode network (including angulate cortex, precuneus, medial prefrontal cortex, and middle temporal cortex) was observed in responders (≥50% decrease in the Montgomery-Asberg Scale at 2 weeks) compared with nonresponders. These pilot findings may suggest a potential neural mechanism by which ketamine exerts its robust antidepressant efficacy via downregulation of aberrant habenular FC with parts of the default mode network.


Direct stent implantation without predilatation using the MultiLink stent.
The standard coronary stent implantation technique requires routine predilatation of the target lesion with a balloon catheter. In this study, we prospectively studied the feasibility and efficiency of elective coronary stent implantation without predilatation. In 94 patients who presented with various ischemic syndromes, direct implantation of 100 balloon expandable ACS MultiLink stents (7 over-the-wire, 93 rapid exchange) was attempted in 100 coronary lesions selected to have favorable characteristics. The stent crossed the lesion without predilatation in 97 cases (97%) and was successfully deployed in 93 (95.8%). In 4 patients, adjunctive high-pressure postdilatation was necessary to achieve optimal stent expansion. Reference vessel diameter was 3.12+/-0.77 mm and lesion length 8.8+/-2.7 mm. Minimal luminal diameter increased from 0.95+/-0.38 mm to 2.98+/-0.28 mm and diameter stenosis decreased from 71+/-11% to 8+/-11% after stenting. One occlusive dissection was treated by a second stent. There were no major in-hospital complications. At 1 month follow-up, 1 subacute thrombotic occlusion occurred. These results indicate that in a carefully selected coronary lesion subset, elective stent implantation without predilatation can be safely and effectively performed. The long-term results of this approach and possible advantages over the conventional implantation techniques remain unclear and need to be evaluated in further clinical studies.


High-throughput translational profiling with riboPLATE-seq.
Protein synthesis is dysregulated in many diseases, but we lack a systems-level picture of how signaling molecules and RNA binding proteins interact with the translational machinery, largely due to technological limitations. Here we present riboPLATE-seq, a scalable method for generating paired libraries of ribosome-associated and total mRNA. As an extension of the PLATE-seq protocol, riboPLATE-seq utilizes barcoded primers for pooled library preparation, but additionally leverages anti-rRNA ribosome immunoprecipitation on whole polysomes to measure ribosome association (RA). We compare RA to its analogue in ribosome profiling and RNA sequencing, translation efficiency, and demonstrate both the performance of riboPLATE-seq and its utility in detecting translational alterations induced by specific inhibitors of protein kinases.


NOVEL TECHNIQUE FOR INTRAOCULAR FOREIGN BODY REMOVAL: Magnetized Disposable Microforceps. A Systematic Approach and First Clinical Result.
To verify whether disposable microforceps can be magnetized to atraumatically attract and then grasp intraocular foreign bodies. An effective magnetization protocol was developed. The clinical relevance was tested, and a first practical application was performed. The magnetic flux density (MFD) of a bar magnet and an electromagnet was measured. Steel screws were used to determine the magnetization protocol. Disposable microforceps was magnetized, MFD generated at the tip was measured, and the weight that can be lifted was tested. Foreign body removal with such forceps was performed. The electromagnet MFD was much higher than the bar magnet. The most effective magnetization protocol was to pass the screw from the end along the shaft and back over the electromagnet. Magnetized microforceps had a 7.12 mT change in MFD at the tip. Steel balls up to 87 mg could be lifted in buffered saline solution. In clinical use, the intraocular foreign body could be attracted and grasped safely. Disposable microforceps can be easily and inexpensively magnetized. The achievable MFD is clinically relevant to attract typical intraocular foreign bodies. An electromagnet is best suited for this purpose. With such prepared forceps, foreign bodies can be attracted atraumatically and grasped securely.


The 0.3-kb fragment containing the R-U5-5'leader sequence of Friend murine leukemia virus influences the level of protein expression from spliced mRNA.
A neuropathogenic variant of Friend murine leukemia virus (Fr-MLV) clone A8 induces spongiform neurodegeneration when infected into neonatal rats. Studies with chimeras constructed from the A8 virus and the non-neuropathogenic Fr-MLV clone 57 identified a 0.3-kb KpnI-AatII fragment containing a R-U5-5'leader sequence as an important determinant for inducing spongiosis, in addition to the env gene of A8 as the primary determinant. This 0.3-kb fragment contains a 17-nucleotide difference between the A8 and 57 sequences. We previously showed that the 0.3-kb fragment influences expression levels of Env protein in both cultured cells and rat brain, but the corresponding molecular mechanisms are not well understood. Studies with expression vectors constructed from the full-length proviral genome of Fr-MLV that incorporated the luciferase (luc) gene instead of the env gene found that the vector containing the A8-0.3-kb fragment yielded a larger amount of spliced luc-mRNA and showed higher expression of luciferase when compared to the vector containing the 57-0.3-kb fragment. The amount of total transcripts from the vectors, the poly (A) tail length of their mRNAs, and the nuclear-cytoplasm distribution of luc-mRNA in transfected cells were also evaluated. The 0.3-kb fragment did not influence transcription efficiency, mRNA polyadenylation or nuclear export of luc-mRNA. Mutational analyses were carried out to determine the importance of nucleotides that differ between the A8 and 57 sequences within the 0.3-kb fragment. In particular, seven nucleotides upstream of the 5'splice site (5'ss) were found to be important in regulating the level of protein expression from spliced messages. Interestingly, these nucleotides reside within the stem-loop structure that has been speculated to limit the recognition of 5'ss. The 0.3-kb fragment containing the R-U5-5'leader sequence of Fr-MLV influences the level of protein expression from the spliced-mRNA by regulating the splicing efficiency rather than transcription, nuclear export of spliced-mRNA, or poly (A) addition to mRNA. Seven nucleotides in the 0.3-kb fragment, which reside within the stem-loop structure that has been speculated to limit recognition of the 5'ss, could pinpoint the function of this region.


Treatment of oral leukoplakia by topical application of 5-aminolevulinic acid.
A new therapy for the treatment of oral leukoplakia by 5-aminolevulinic acid (ALA) and photodynamic therapy (PDT) is presented. ALA, a precursor in the biosynthesis of haeme, induces the production of the endogenous photosensitizer protoporphyrin IX which can be used for PDT. Twelve patients, who had been suffering from leukoplakia of the oral mucosa for several years, were treated by ALA-mediated PDT. ALA was used as a topical photosensitizer and 20% ALA cream was applied to the leukoplakia lesion of the oral mucosa for two hours and then light activated at 630 nm, 100 mW/cm2 and 100 J/cm2. Five patients showed complete response to the treatment, four patients showed a partial response and in three patients treatment was unsuccessful. One patient with partial response was retreated, after which the lesion disappeared.


Survival Following Detection of Stage I Lung Cancer by Screening in the National Lung Screening Trial.
There is limited information about survival of stage I lung cancer diagnosed by screening. What was the survival rate of screen-detected stage I lung cancer in the National Lung Screening Trial (NLST), and was it affected by screening method, patient or tumor characteristics, or treatment method? The study cohort consisted of all NLST participants with screen-detected stage I lung cancer. Lung cancer-specific survival for stage I overall and for IA and IB substages were compared in the low-dose CT and chest radiography (CXR) screening randomization arms and with an analogous cohort from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute; the cumulative incidence competing risk method was used for analysis. Cox proportional hazards models were used to evaluate the association between lung cancer-specific survival and screening arm, patient factors, primary tumor size, and treatment. There were 324 screen-detected stage I lung cancers in the low-dose CT arm and 125 in the CXR arm. The 10-year survival in the low-dose CT arm was greater than in the CXR arm (73.4% vs 64.6%; P = .05), and both were greater than in the Surveillance, Epidemiology, and End Results cohort (55.6%; P < .001 vs low-dose CT arm, P = .04 vs CXR arm). Proportional hazards models revealed a greater likelihood of survival in the low-dose CT arm (hazard ratio [HR], 0.69; 95% CI, 0.5-0.98) and with primary tumor size below the median of 17 mm (HR, 0.61; 95% CI, 0.42-0.88). There was no survival difference between treatment with limited resection vs full resection (HR, 1.11; 95% CI, 0.6-1.9), whereas nonsurgical treatment was associated with a reduced likelihood of survival compared with full resection (HR, 3.1; 95% CI, 1.6-6.0). Long-term lung cancer-specific survival of stage I lung cancer was greater with low-dose CT imaging than with CXR screening or in the general population, for smaller primary tumor size, and with surgical treatment.


Imaging of peritoneal carcinomatosis with FDG PET-CT: diagnostic patterns, case examples and pitfalls.
Early diagnosis of peritoneal spread in malignant disease is essential to prevent unnecessary laparotomies and to select the patients in whom complete cytoreduction is feasible. Although anatomic imaging is the mainstay for evaluating peritoneal seeding, small neoplastic implants can be difficult to detect with CT and MR imaging. FDG PET-CT has the potential to improve detection of peritoneal metastases as lesion conspicuity is high at PET due to low background activity and fused PET-CT offers the combined benefits of anatomic and functional imaging. Correlation of uptake modalities with the pathogenesis of intraperitoneal spread of malignancies, provides a rational system of analysis and is essential to define disease. Distinct patterns appear to predict the presence of either nodular or diffuse peritoneal pathology. Main pitfalls are related to normal physiologic activity in bowel loops and blood vessels or focal retained activity in ureters and urinary bladder. PET-CT is most suitable in patients with high tumor markers and negative or uncertain conventional imaging data and in selecting patients for complete cytoreduction. FDG PET-CT adds to conventional imaging in the detection and staging of peritoneal carcinomatosis and is a useful diagnostic tool in monitoring response to therapy and in long term follow-up.


Heavy metals in human bones in different historical epochs.
The concentration of the metals lead, copper, zinc, cadmium and iron was determined in bone remains belonging to 30 individuals buried in the Region of Cartagena dating from different historical periods and in eight persons who had died in recent times. The metals content with respect to lead, cadmium and copper was determined either by anodic stripping voltammetry or by atomic absorption spectroscopy on the basis of the concentrations present in the bone remains. In all cases, zinc and iron were quantified by means of atomic absorption spectroscopy. The lead concentrations found in the bone remains in our city are greater than those reported in the literature for other locations. This led to the consideration of the sources of these metals in our area, both the contribution from atmospheric aerosols as well as that from the soil in the area. Correlation analysis leads us to consider the presence of the studied metals in the analysed bone samples to be the consequence of analogous inputs, namely the inhalation of atmospheric aerosols and diverse contributions in the diet. The lowest values found in the studied bone remains correspond to the Neolithic period, with similar contents to present-day samples with respect to lead, copper, cadmium and iron. As regards the evolution over time of the concentrations of the metals under study, a clear increase in these is observed between the Neolithic period and the grouping made up of the Bronze Age, Roman domination and the Byzantine period. The trend lines used to classify the samples into 7 periods show that the maximum values of lead correspond to the Roman and Byzantine periods. For copper, this peak is found in the Byzantine Period and for iron, in the Islamic Period. Zinc shows an increasing tendency over the periods under study and cadmium is the only metal whose trend lines shows a decreasing slope.


Cloning and expression of thermo-alkali-stable laccase of Bacillus licheniformis in Pichia pastoris and its characterization.
A thermo-alkali-stable laccase gene from Bacillus licheniformis was cloned and expressed in Pichia pastoris. The recombinant laccase was secreted into the culture medium with a maximum activity of 227.9 U/L. The purified laccase is a monomeric glycoprotein, and its molecular weight was estimated to be 65 kDa on SDS-PAGE after deglycosylation. Optimal enzyme activity was observed at pH 6.2 and 70°C with syringaldazine as substrate. The recombinant laccase was highly stable in the pH range 7-9 after 10 days at 30°C. The enzyme displayed remarkable thermostability at 50-70°C, with a half-life of inactivation at 70°C of 6.9 h. It also exhibited high tolerance to NaCl and organic solvents like the native spore laccase. The purified laccase could rapidly decolorize reactive blue 19, reactive black 5 and indigo carmine in the presence of acetosyringone. More than 93% of the tested dyes were decolorized in 4 h at pH 9.0.


The mechanism of growth-regulation of glioma cells by trapidil.
Trapidil is a PDGF antagonist that can inhibit the proliferation of the PDGF-producing glioma cells, U251MG. As the mechanism of growth-regulation by trapidil remains unclear, we studied its effect on the growth of U251MG cells. We performed a cell cycle analysis and examined the intracellular transduction pathway and oncogene expression in serum-stimulated glioma cells with or without trapidil. After the serum starvation for 3 days, glioma cell proliferation was stimulated by the addition of serum. Cell cycle analysis showed that cell cycle perturbations induced by trapidil included a decreased transition rate from G0-G1 to S phase, suggesting that some metabolic event is required for progress through the G0-G1 phase and that this event is sensitive to trapidil. Internal signal transduction mechanisms are central in the molecular control of cell growth. One such regulator is the protein kinase C(PKC) system and the c-fos gene is likely to be a direct target of intracellular signal transduction pathways. Therefore, we hypothesize that the intracellular PKC activity and c-fos expression of the trapidil-treated cells are suppressed. We posit that trapidil affects the intracellular signal transduction pathway PKC activity and c-fos expression in cells stimulated with serum containing growth factors.


Simultaneous naphthalene degradation and electricity production in a biowaste-powered microbial fuel cell.
Naphthalene is a very common and hazardous environmental pollutant, and its biodegradation has received serious attention. As demonstrated in this study, naphthalene-contaminated wastewater can be biodegraded using a microbial fuel cell (MFC). Furthermore, the potential of MFC for electricity generation appears to be a promising technology to meet energy demands other than those produced from fossil fuels. Nowadays, efforts are being made to improve the overall performance of MFC by integrating biowaste materials for anode fabrication. In this study, palm kernel shell waste was used to produce palm kernel shell-derived graphene oxide (PKS-GO) and palm kernel shell-derived reduced graphene oxide (PKS-rGO), which were then fabricated into anode electrodes to improve the system's electron mobilization and transport. The MFC configuration with the PKS-rGO anode demonstrated greater energy production potential, with a maximum power density of 35.11 mW/m2 and a current density of 101.76 mA/m2, compared to the PKS-GO anode, which achieved a maximum power density of 17.85 mW/m2 and a current density of 72.56 mA/m2. Furthermore, there is simultaneous naphthalene biodegradation with energy production, where the biodegradation efficiency of naphthalene with PKS-rGO and PKS-GO is 85.5%, and 79.7%, respectively. In addition, the specific capacitance determined from the cyclic voltammetry curve revealed a value for PKS-rGO of 2.23 × 10-4 F/g, which is also higher than the value for PKS-GO (1.57 × 10-4 F/g) on the last day of operation. Anodic microbial analysis shows that electrogens thrive in the MFC process. Finally, a comparison with previous literature and the future prospects of the study are also presented.