Academic Outcomes 2 Years After Working Memory Training for Children With Low Working Memory: A Randomized Clinical Trial.
Working memory training may help children with attention and learning difficulties, but robust evidence from population-level randomized controlled clinical trials is lacking. To test whether a computerized adaptive working memory intervention program improves long-term academic outcomes of children 6 to 7 years of age with low working memory compared with usual classroom teaching. Population-based randomized controlled clinical trial of first graders from 44 schools in Melbourne, Australia, who underwent a verbal and visuospatial working memory screening. Children were classified as having low working memory if their scores were below the 15th percentile on either the Backward Digit Recall or Mister X subtest from the Automated Working Memory Assessment, or if their scores were below the 25th percentile on both. These children were randomly assigned by an independent statistician to either an intervention or a control arm using a concealed computerized random number sequence. Researchers were blinded to group assignment at time of screening. We conducted our trial from March 1, 2012, to February 1, 2015; our final analysis was on October 30, 2015. We used intention-to-treat analyses. Cogmed working memory training, comprising 20 to 25 training sessions of 45 minutes' duration at school. Directly assessed (at 12 and 24 months) academic outcomes (reading, math, and spelling scores as primary outcomes) and working memory (also assessed at 6 months); parent-, teacher-, and child-reported behavioral and social-emotional functioning and quality of life; and intervention costs. Of 1723 children screened (mean [SD] age, 6.9 [0.4] years), 226 were randomized to each arm (452 total), with 90% retention at 1 year and 88% retention at 2 years; 90.3% of children in the intervention arm completed at least 20 sessions. Of the 4 short-term and working memory outcomes, 1 outcome (visuospatial short-term memory) benefited the children at 6 months (effect size, 0.43 [95% CI, 0.25-0.62]) and 12 months (effect size, 0.49 [95% CI, 0.28-0.70]), but not at 24 months. There were no benefits to any other outcomes; in fact, the math scores of the children in the intervention arm were worse at 2 years (mean difference, -3.0 [95% CI, -5.4 to -0.7]; P = .01). Intervention costs were A$1035 per child. Working memory screening of children 6 to 7 years of age is feasible, and an adaptive working memory training program may temporarily improve visuospatial short-term memory. Given the loss of classroom time, cost, and lack of lasting benefit, we cannot recommend population-based delivery of Cogmed within a screening paradigm. anzctr.org.au Identifier: ACTRN12610000486022.


Molecular characterization and function of a p38 MAPK gene from Litopenaeus vannamei.
p38 mitogen-activated protein kinases (MAPKs) are broadly expressed from yeasts to mammals, and are involved in the regulation of cells responsible to various extracellular stimuli. In this study, a p38 MAPK gene (designated as Lvp38) from Litopenaeus vannamei, was cloned and characterized. It contained the conserved structures of a Thr-Gly-Tyr (TGY) motif and a substrate-binding site, Ala-Thr-Arg-Trp (ATRW). The tissue distribution patterns showed that Lvp38 was widely expressed in all examined tissues, with the highest expression in hemocytes, nerves, and intestines. Quantitative real-time PCR revealed that Lvp38 was upregulated in gills and hemocytes after infection with the Gram-negative Vibrio alginolyticus and the Gram-positive Staphylococcus aureus. Reporter gene assays indicated that Lvp38 activated the expression of antimicrobial peptides (AMPs) of Drosophila and shrimp. Knockdown of Lvp38 by RNA interference (RNAi) resulted in a higher mortality of L. vannamei under V. alginolyticus and S. aureus infection, as well as a reduction in the expression of three shrimp AMP genes, namely, PEN4, crustin, and ALF2. Taken together, our data indicated that Lvp38 played a role in defending against bacterial infections.


[Not Available].
Multiple studies in osteoarthritis (OA), rheumatoid arthritis (RA), and several acute pain models indicate that the cyclooxygenase-2-specific inhibitors celecoxib and rofecoxib are equally effective as the conventional nonsteroidal antirheumatic drugs diclofenac, ibuprofen, and naproxen. Both drugs are approved for the treatment of OA and RA in a daily dosage of 2×100 mg, 1×200 mg, and 2×200 mg (celecoxib) or 1×12.5 mg and 1×25 mg (rofecoxib). In addition, rofecoxib has also been approved by the FDA for the treatment of postsurgical pain in a dosage of 50 mg. Normally celecoxib is used in a dosage of 1×200 mg for OA and 2×200 mg for RA, whereas both 12.5 and 25 mg rofecoxib are used for the treatment of OA and 25 mg for the treatment of RA. Coxibs might also be used for the treatment of seronegative spondarthritides, as is indicated by a successful study using celecoxib for the treatment of ankylosing spondylitis.


First report on the efficacy of l-alanine-based in situ-forming implants for the long-term parenteral delivery of drugs.
The recent advent of biotechnologies has led to the development of labile macromolecular therapeutic agents that require complex formulations for their efficient administration. This work reports a novel concept for the systemic, sustained delivery of such agents. The proposed approach is based on the spontaneous self-assembly of low-molecular weight amphiphilic amino acid derivatives in a hydrophobic pharmaceutical vehicle. The injectable, in situ-forming organogels were obtained by mixing N-stearoyl l-alanine (m)ethyl esters with a vegetable oil and a biocompatible hydrophilic solvent. The gels' in vivo-delivering properties were evaluated in rats with leuprolide, a luteinizing hormone-releasing hormone agonist used in prostate cancer, endometriosis and precocious puberty treatment. Following subcutaneous injection, the gels degraded and gradually released leuprolide for 14 to 25 days. Drug release was accompanied by sustained castration lasting up to 50 days, as assessed by testosterone levels. This study demonstrates that in situ-forming implants based on l-alanine derivatives represent a novel injectable platform for the controlled delivery of hydrophilic compounds, which is simpler than currently available implant and microsphere technologies.


Comparison of rehabilitation outcomes following vascular-related and traumatic spinal cord injury.
Previous studies have noted similar outcomes between vascular-related spinal cord injury (VR-SCI) and those with traumatic SCI (T-SCI), despite significant difference in their demographics and clinical presentation (age, level of injury (LOI), and degree of incompleteness). To review demographic and clinical presentation of VR-SCI and to compare outcomes with a matched group with T-SCI. Design Analysis of 10-year prospective data collection including 30 consecutive patients admitted to an SCI rehabilitation unit with VR-SCI and comparison with 573 patients with T-SCI. Outcomes were further analyzed comparing VR-SCI to T-SCI (n=30), matched for age, LOI, and ASIA (American Spinal Injury Association) Impairment Scale (AIS). A level 1 tertiary university trauma center. Functional independence measure (FIM) score changes from admission to discharge. Secondary outcome measures included admission and discharge FIM scores, FIM efficiency, rehabilitation length of stay (LOS), and discharge disposition. Overall, individuals with VR-SCI were more likely (P<0.0001) to be older (mean age 57.2 vs. 40.0 years) and have paraplegia (87 vs. 48%) than those with T-SCI. Common etiologies for VR-SCI were post-surgical complication (43%), arteriovenous malformation (17%), aortic dissection (13%), and systemic hypotension (13%). Common region of injury and AIS classification in VR-SCI was thoracic (73%) and AIS C (33%). Common SCI-related complications in VR-SCI included neurogenic bowel/bladder (93%), urinary tract infection (73%), pain (67%), pressure ulcers (47%), and spasticity (20%). Matched-group outcome comparisons did not reveal significant differences in FIM change, FIM efficiency, LOS, or disposition between VR-SCI and T-SCI. VR-SCI leads to significant disability and is associated with common secondary SCI complications as well as medical co-morbidities. This study notes differing demographic and injury characteristics between VR-SCI and T-SCI groups. However, when matched for these differences, rehabilitation functional outcomes were not significantly different between the two groups.


Transforming Growth Factor β1 Promotes Migration and Invasion of Human Hepatocellular Carcinoma Cells Via Up-Regulation of Connective Tissue Growth Factor.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a poor patient survival. Expression of TGF-β1 is up-regulated in HCC and is thought to play a crucial role in the occurrence and development of HCC. However, the mechanism of TGF-β1-mediated facilitation of malignant growth and invasion remains unclear, although some previous studies highlighted a potential involvement of the connective tissue growth factor (CTGF). Here we demonstrate that the in vitro migration of the HCC cell line SMMC-7721 is increased in the presence of recombinant TGF-β1, and that this effect is reversed by the specific inhibitor SB431542. Furthermore, TGF-β1 treatment up-regulated the expression of its own mRNA as well as the expression of CTGF mRNA. The TGF-β1-stimulated migration of SMMC-7721 cells was diminished by siRNA silencing of CTGF. These in vitro observations were validated in a murine xenograft model. In particular, silencing of CTFG diminished the TGF-β1-induced tumorigenesis in experimental animals. In conclusion, TGF-β1 plays a critical role in HCC migration and invasion, and this effect is dependent on CTGF.


The effect of glucuronidation on isoflavone induced estrogen receptor (ER)α and ERβ mediated coregulator interactions.
Non-prenylated isoflavone aglycones are known to have phyto-estrogenic properties and act as agonistic ligands on ERα and ERβ due to their structural resemblance to 17β-estradiol (E2). Genistein and daidzein are the two main dietary isoflavones; upon uptake they are extensively metabolized and exist nearly exclusively as their conjugated forms in biological fluids. Little is known about the effect of conjugation on the intrinsic estrogenic activities of these isoflavones. To characterize and compare the intrinsic estrogenic activities of genistein and daidzein, and their respective 7-O-glucuronide metabolites a cell-free assay system was employed that determines the ligand-induced changes in ERα- and ERβ-ligand binding domain (LBD) interactions with 154 different binding motifs derived from 66 different nuclear receptor coregulators. The glucuronides were 8 to 4400 times less potent than their respective aglycones to modulate ERα-LBD and ERβ-LBD-coregulator interactions. Glucuronidation changed the preferential activation of genistein from ERβ-LBD to ERα-LBD and further increased the slightly preferential activation of daidzein for ERα-LBD. The tested isoflavone compounds were less potent than E2 (around 5 to 1580 times for the aglycones) but modulated the LBD-coregulator interactions in a manner similar to E2. Our results show that genistein and daidzein remain agonistic ligands of ERα-LBD and ERβ-LBD in their conjugated form with a higher relative preference for ERα-LBD than the corresponding aglycones. This shift in receptor preference is of special interest as the preferential activation of ERβ is considered one of the possible modes of action underlying the supposed beneficial instead of adverse health effects of isoflavones.


Heterologous coexpression of Vitreoscilla hemoglobin and Bacillus megaterium glucanase in Streptomyces lydicus A02 enhanced its production of antifungal metabolites.
Streptomyces lydicus A02 is a novel producer of commercially important polyene macrocyclic antibiotic natamycin and a potential biocontrol agent to several plant fungal diseases, including wilt caused by Fusarium oxysporum f. spp. To improve the natamycin production and the antifungal activity of S. lydicus A02, we coexpressed gene vgb encoding Vitreoscilla hemoglobin (VHb) and bglC encoding Bacillus megaterium L103 glucanase, both under the control of the strong constitutive ermE* promoter, in S. lydicus A02. Our results showed that coexpressing VHb and glucanase improved cell growth, and the engineered strain produced 26.90% more biomass than the wild-type strain after 72h fermentation in YSG medium. In addition, coexpressing genes encoding VHb and glucanase led to increased natamycin production, higher endogenous chitinase activity and exogenous glucanase activity, as well as enhanced antifungal activity in the engineered S. lydicus AVG02 and AGV02, regardless of the position of the two genes on the plasmids. Compared with model strains, few reports have successfully coexpressed VHb and other foreign proteins in industrial strains. Our results illustrated an effective approach for improving antifungal activity in an industrial strain by the rational engineering of combined favorable factors.


Antigenic variation in trypanosomes.
In its mammalian host, Trypanosoma brucei is able to change the antigenic character of its glycoprotein surface coat and so evade the host's immune response. This phenotypic change seems to occur spontaneously in 1 in 10,000 individuals but is not due to genetic mutation: host antibody is not necessary for its induction but plays a selective part in bringing about the gross changes in parasite numbers and antigenic character observed in the bloodstream by destroying the main component of what is actually a heterogeneous population. The infecting trypanosome population injected into the mammalian host by the tsetse fly vector may also be heterogeneous. Such heterogeneity complicates plans to vaccinate cattle and people against the African trypanosomes based on the premise that the metacyclic trypanosomes of a clone bear the same surface antigen.


Effect of percutaneous transluminal coronary angioplasty on circulating endothelin levels.
Percutaneous transluminal coronary angioplasty (PTCA) is frequently associated with vasoconstriction involving large vessels as well as microcirculation, but the potential mechanisms remain poorly defined. In this study, we tested the hypothesis that endothelial disruption during PTCA is associated with an increase in circulating levels of endothelin, a potent endothelium-derived vasoconstrictor peptide. Circulating levels of endothelin and other potential vasoactive mediators such as atrial natriuretic factor, epinephrine and norepinephrine were measured immediately before and after PTCA in 23 patients with coronary artery disease. Although there was no change in the endothelin levels after angiography alone (43 +/- 5 vs 44 +/- 7 pg/ml, p = 0.5), there was a significant increase after PTCA (32 +/- 8 to 37 +/- 10 pg/ml, p < 0.005). The increase in endothelin was associated with a significant increase in atrial natriuretic factor (78 +/- 57 to 129 +/- 131 ng/ml, p = 0.01) and a decrease in epinephrine and norepinephrine levels (111 +/- 64 to 59 +/- 36 pg/ml, p = 0.005, and 1,131 +/- 500 to 811 +/- 311 pg/ml, p = 0.003, respectively). Circulating levels of endothelin did not correlate with the percent coronary stenosis before or after PTCA or the presence or absence of angiographically visible thrombus. These findings suggest that endothelial injury during PTCA may be associated with increased circulating levels of endothelin and its counter-regulatory hormone, atrial natriuretic factor, and also with a reciprocal decrease in epinephrine and norepinephrine levels. Thus, these humoral changes may modulate changes in coronary vascular tone after PTCA.


Radioguided occult lesion localization plus sentinel node biopsy (SNOLL) versus wire-guided localization plus sentinel node detection: a case control study of 129 unifocal pure invasive non-palpable breast cancers.
We compared histological patterns after lumpectomy for non-palpable breast cancers preoperatively localized by radioguided occult lesion localization plus sentinel node localization (SNOLL) versus wire-guided localization. To ensure a homogeneously treated cohort and rigorous comparisons, only patients with invasive cancer and measurable opacity by imaging were included. Exclusion criteria were one or more parameters that could interfere with localization and/or the surgical procedure. Forty-three SNOLL were compared with 86 WGL plus sentinel node (SN) localization. Cancer localization effectiveness was based on careful assessment of histological data from only the first resected glandular specimen, as any additional resection specimens were guided by intraoperative histological examination. Reexcisions to ensure free tissue margins were performed during the same procedure in 13.9% of SNOLL versus 31.3% of WGL; p = 0.02. Significantly more women in SNOLL (53.4%) also had free nearest margins of >9 mm after the first procedure compared with WGL (33.7%); p = 0.03. The median centricity ratio after the first procedure was better in SNOLL (2.8, range 1.3-14) than WGL (5, range 1-50); p = 0.008. The median number of SN detected by lymphoscintigraphy was the same in SNOLL and WGL (1, range 0-9, vs. 1, range 0-8). Intraoperative SN detection by blue dye and/or gamma probe was successful for 97.6% of SNOLL versus 93% of WGL. In this study, SNOLL was effective and safe, and this procedure significantly improved the rate of negative margins in the first specimen and the rate of reexcision for positive margins compared with WGL.


Characterization of ibrutinib as a non-covalent inhibitor of SRC-family kinases.
Ibrutinib is a BTK-targeted irreversible inhibitor. In this study, we demonstrate that ibrutinib potently inhibits SRC activity in a non-covalent manner via mass spectrometry and crystallography. The S345C mutation renders SRC to bind covalently with ibrutinib, and restores the potency of ibrutinib against the gatekeeper mutant. The co-crystal structure of ibrutinib/SRC shows Ser345 of SRC did not form covalent bond with ibrutinib, leading to a decrease of potency and loss of the ability to overcome the gatekeeper mutation of SRC. The X-ray crystallographic studies also provide structural insight into why ibrutinib behaves differently against gatekeeper mutants of different kinases.


Secretion of truncated recombinant rabies virus glycoprotein with preserved antigenic properties using a co-expression system in Hansenula polymorpha.
Rabies virus infection remains a serious public health threat in the developing world, where cost-concerns make wide-scale public health interventions impractical. The development of novel and inexpensive ELISA diagnostic antigens is critical in early detection and prevention of complications. The transmembrane glycoprotein (G) of rabies virus (RV) contains an external domain capable of inducing the synthesis of anti-rabies, virus-neutralizing antibodies, in infected or immunized hosts. In our study, the external G domain was synthesized and fused in-frame with a polyhistidine-tag coding sequence present in the expression plasmid. Soluble truncated recombinant G was secreted in Hansenula polymorpha (H. polymorpha) using H. polymorpha-derived calnexin (HpCNE1) overproduction and found to be correctly N-glycosylated. The truncated recombinant G was purified from cell culture supernatant by Ni-agarose affinity chromatography and when compared with the full-length glycoprotein, found to be similarly immunogenic in vaccinated rabbits. These results subsequently led us to explore the potential of truncated recombinant G as a diagnostic antigen in ELISA. Our results show that the truncated recombinant G can detect antibodies directed to both whole virion and native glycoprotein. More sophisticated applications of truncated recombinant G would profit from the correctly N-glycosylated and soluble monomer.


One predominant 5'-undecanucleotide in adenovirus 2 late messenger RNAs.
Oligonucleotides containing the 5' termini of adenovirus 2 mRNA are selectively retained on columns of dihydroxyboryl cellulose. When total late adenovirus 2 mRNA was treated with RNAase T1, a single 5' terminal oligonucleotide was isolated, although in several states of methylation. This oligonucleotide has the general structure m7G5'ppp5' AmCmU(C4,U3)G. Since at least twelve individual species of mRNA must be present late after infection, this finding was unexpected and its significance is discussed.


Thoracoscopic Surgical Ablation of Lone Atrial Fibrillation: Long-term Outcomes at 7 Years.
Antiarrhythmic drugs and transcatheter ablation in atrial fibrillation (AF) provide suboptimal rhythm control with a not negligible rate of failure in paroxysmal AF (PAF) and nonparoxysmal AF (n-PAF) at midterm and long-term follow-up. This study evaluated the safety profile and long-term efficacy of thoracoscopic ablation in patients with lone AF. A consecutive 153 patients with lone AF were prospectively enrolled and underwent thoracoscopic surgical ablation. Inclusion criteria were symptomatic AF refractory to pharmacologic therapy (Vaughan-Williams class I-III), age >18 years, and absence of left atrial thrombosis. Exclusion criteria were long-standing AF >5 years, left atrial diameter >55 mm, and contraindication to oral anticoagulation. The "box lesion set" (encircling of pulmonary veins) was always used. Exclusion of the left atrial appendage was performed only in selected cases. The primary study end point was freedom from AF. Secondary end points were overall survival and cumulative incidence function of cardiac event-related death, cerebrovascular accidents, and pacemaker implantation. There was no in-hospital mortality. Early postoperative complications were pacemaker implantation (4/153 [2.6%]), cerebrovascular accident (2/153 [1.3%]) with full recovery of both, and bleeding requiring surgical revision (2/153 [1.3%]). Overall freedom from AF at 7 years was 86% ± 4% (76.9% in n-PAF, 96.1% in PAF). Survival freedom from AF in patients without antiarrhythmic drugs in PAF and n-PAF groups was 79.1% and 52.2%, respectively. Thoracoscopic surgical ablation of lone AF by means of an isolated left atrial box lesion provided an excellent long-term rhythm outcome, even in long-standing persistent AF. The isolated left atrial ablation showed an excellent safety profile with low incidence of pacemaker implantation and postoperative complications.


Critically buried avalanche victims can develop severe hypothermia in less than 60 min.
A major challenge in the management of avalanche victims in cardiac arrest is differentiating hypothermic from non-hypothermic cardiac arrest, as management and prognosis differ. Duration of burial with a cutoff of 60 min is currently recommended by the resuscitation guidelines as a parameter to aid in this differentiation However, the fastest cooling rate under the snow reported so far is 9.4 °C per hour, suggesting that it would take 45 min to cool below 30 °C, which is the temperature threshold below which a hypothermic cardiac arrest can occur. We describe a case with a cooling rate of 14 °C per hour, assessed on site with an oesophageal temperature probe. This is by far the most rapid cooling rate after critical avalanche burial reported in the literature and further challenges the recommended 60 min threshold for triage decisions. The patient was transported under continuous mechanical CPR to an ECLS facility and rewarmed with VA-ECMO, although his HOPE score was 3% only. After three days he developed brain death and became an organ donor. With this case we would like to underline three important aspects: first, whenever possible, core body temperature should be used instead of burial duration to make triage decisions. Second, the HOPE score, which is not well validated for avalanche victims, had a good discriminatory ability in our case. Third, although extracorporeal rewarming was futile for the patient, he donated his organs. Thus, even if the probability of survival of a hypothermic avalanche patient is low based on the HOPE score, ECLS should not be withheld by default and the possibility of organ donation should be considered.


Effect of anodization on the surface characteristics and electrochemical behaviour of zirconium in artificial saliva.
The paper is focused on elaboration of ZrO2 films on pure zirconium via anodizing in phosphoric acid with and without fluoride at constant potentials of 30 V and 60 V. The structure and composition of the films were investigated using scanning electronic microscopy, Raman spectroscopy and X-ray photoelectron spectroscopy. The composition of the oxides formed at both potentials can be identified as monoclinic ZrO2. In addition to Zr and O, the layers formed in phosphoric acid contain phosphorus originating from the phosphoric acid. When the phosphoric acid solution contains NaF, fluorine is also incorporated into the oxide layer. The oxides formed at a higher voltage have greater roughness than those formed at 30 V. Anodized samples exhibit smaller current densities during anodic polarization compared to the as-received zirconium covered with native oxide.


Scrap tyre recycling process with molten zinc as direct heat transfer and solids separation fluid: A new reactor concept.
Every year about 1.5 billion tyres are discarded worldwide representing a large amount of solid waste, but also a largely untapped source of raw materials. The objective of the method was to prove the concept of a novel scrap tyre recycling process which uses molten zinc as the direct heat transfer fluid and, simultaneously, uses this media to separate the solids products (i.e. steel and rCB) in a sink-float separation at an operating temperature of 450-470 °C. This methodology involved: •construction of the laboratory scale batch reactor,•separation of floating rCB from the zinc,•recovery of the steel from the bottom of the reactor following pyrolysis.


Online analysis of protein inclusion bodies produced in E. coli by monitoring alterations in scattered and reflected light.
The online monitoring of recombinant protein aggregate inclusion bodies during microbial cultivation is an immense challenge. Measurement of scattered and reflected light offers a versatile and non-invasive measurement technique. Therefore, we investigated two methods to detect the formation of inclusion bodies and monitor their production: (1) online 180° scattered light measurement (λ = 625 nm) using a sensor platform during cultivation in shake flask and (2) online measurement of the light reflective interference using a porous Si-based optical biosensor (SiPA). It could be shown that 180° scattered light measurement allows monitoring of alterations in the optical properties of Escherichia coli BL21 cells, associated with the formation of inclusion bodies during cultivation. A reproducible linear correlation between the inclusion body concentration of the non-fluorescent protein human leukemia inhibitory factor (hLIF) carrying a thioredoxin tag and the shift ("Δamp") in scattered light signal intensity was observed. This was also observed for the glutathione-S-transferase-tagged green fluorescent protein (GFP-GST). Continuous online monitoring of reflective interference spectra reveals a significant increase in the bacterium refractive index during hLIF production in comparison to a non-induced reference that coincide with the formation of inclusion bodies. These online monitoring techniques could be applied for fast and cost-effective screening of different protein expression systems.


Isolation and expansion of human adenovirus-specific CD4+ and CD8+ T cells according to IFN-gamma secretion for adjuvant immunotherapy.
In patients with lymphopenia following allogeneic stem cell transplantation adenovirus (ADV) infection is associated with high morbidity and mortality despite aggressive antiviral drug therapy. Virus-specific T cells seem to be essential for virus elimination. The aim of this study was to isolate and expand donor-derived human ADV-specific T lymphocytes for adoptive transfer of sufficient cell numbers to restore protective immunity after allogeneic stem cell transplantation. A clinical-grade strategy to generate ADV-specific T cells using the interferon-gamma (IFN-gamma) secretion assay, followed by expansion to numbers sufficient for clinical application with interleukin-2 (IL-2) and feeder cell stimulation, is described. A mean number of 3.4 x 10(6) (+/-3 SD) ADV antigen-specific T lymphocytes were isolated from 0.1 to 2 x 10(9) mononuclear cells from peripheral blood (n=5) or leukapheresis products (n=6). Characterization of ADV-specific T cells after isolation revealed a mean purity of 85.1% (+/-12% SD) using antigen-specific intracellular cytokine staining. Isolated cells were expanded ex vivo for a median of 18 days (range 7-29 days; n=5) to greater than 10(8) total cells using IL-2 and autologous feeder cell stimulation. ADV-specific response to adenovirus antigen was confirmed in the generated T cell lines, using intracellular cytokine staining, IFN-gamma Elispot assay, and (3)H-thymidine uptake. Generated T-cell lines showed specific killing of ADV-infected B-LCL (n=4). Alloreactive proliferation of generated T-cell lines in mixed lymphocyte cultures was significantly reduced when compared to unmanipulated PBMCs. Generation of adenovirus-specific T cells in a simple and rapid clinical-grade protocol was established, using IFN-gamma secretion assay with short expansion times, leading to sufficient numbers of ADV-specific T cells that can be used for adoptive immunotherapy.


The effect of statin therapy in combination with ezetimibe on circulating C-reactive protein levels: a systematic review and meta-analysis of randomized controlled trials.
Previous studies have reported that statin or ezetimibe therapy has an anti-inflammatory effect. However, the results of individual studies on the effect of statin therapy in combination with ezetimibe on C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) levels have not been clear. Therefore, the present systematic review and meta-analysis were conducted on randomized clinical trials (RCTs) to evaluate the effect of statin therapy in combination with ezetimibe on CRP and hs-CRP levels. A literature search was carried out on the MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases up to February 2022 to find eligible studies. The pooled effect sizes were considered for weighted mean difference (WMD) and 95% confidence intervals (CI) for CRP and hs-CRP, and it was also determined as standardized weighted mean difference (SMD) for overall CRP. For all variables, a random-effects model was used. Of the 57 studies included in the systematic review, 53 were used for meta-analysis. Statin therapy in combination with ezetimibe significantly reduced the serum levels of hs-CRP (WMD - 0.2 mg/l; 95% CI - 0.4, - 0.1, P ˂ 0.001) and overall CRP (SMD - 0.16 mg/l; 95% CI - 0.2, - 0.07, P ˂ 0.001). Nevertheless, CRP levels were not significantly changed by combination therapy. A significant association was observed between the serum low-density lipoprotein cholesterol (LDL-C) changes and hs-CRP levels, which can justify the source of heterogeneity. The current study showed that statin therapy in combination with ezetimibe could be effective in reducing the levels of hs-CRP and overall CRP.


4-hydroxynonenal as a bioactive marker of pathophysiological processes.
The review is focused on the currently major aspect of 4-hydroxynonenal (HNE) research--studies that combine biological activities of the aldehyde together with the methods of its identification in cells and tissues. Because there were some excellent reviews on HNE published in recent years, starting in 1990 and 1991 with supreme reviews done by Hermann Esterbauer, who discovered the aldehyde, and colleagues from the Institute of Biochemistry in Graz, this article pays most of attention to the most recent articles, published in the last 15 months. Additionally, an overview on the relevance of HNE is given with respect to the research and publication trends in the period of 10 years (1993-2002) according to the data in the Current Contents and Medline data bases. It is obvious that HNE started in 1993 as a "toxic product of lipid peroxidation" and "second toxic messenger of free radicals", to become in 2002 a reliable marker of oxidative stress, a possible causative agent of several diseases (such as Alzheimer's disease), growth modulating factor and a signaling molecule. Novel analytical methods developed suitable pathways for HNE to become a clinically applicable marker of lipid peroxidation on one side and on the other a standardized parameter of food quality control. As it is also present physiologically in various cells and tissues, it is likely that HNE will soon become one of the most attractive factors for those who search for a small and reactive molecular link between genomics and proteomics.


Cytogenetic analysis of in vitro fertilization (IVF) failures.
Cytogenetic studies were carried out on 150 oocytes obtained in a human in vitro fertilization (IVF) program. Although all cells lacked signs of fertilization at light microscopy, 46 (30.7%) appeared to show cytological evidence of fertilization. At least one-third of these cells (with development arrested before first cleavage) had chromosomal aberrations. An aneuploidy rate of 35% was found in unfertilized oocytes. The results of this study explain some of the fertilization failures and of the failures of postfertilization development.


Assessing the preparedness and feasibility of an e-learning pilot project for university level health trainees in Ghana: a cross-sectional descriptive survey.
Ghana is challenged with shortage of critical human resources for health particularly nurses and midwives in rural hard-to-reach communities. This shortage potentially hinders efforts towards attaining universal access to basic healthcare. More importantly, poor quality of pre-service training for health trainees has the potential to worsen this predicament. There is therefore the need to leverage emerging digital innovations like e-learning to complement existing efforts. This study was conducted several months before the outbreak of COVID-19 to investigate the preparedness, acceptability and feasibility e-learning innovation for nursing and midwifery trainees. The study is a cross-sectional descriptive survey involving nursing and midwifery students (n = 233) in one of Ghana's public universities, located in the Volta region of Ghana. Simple random sampling technique was used to collect responses from eligible respondents using a structured questionnaire. Descriptive statistical analysis was done using STATA software (version 12.0). It was found that nearly 100% of respondents owned smartphones that were used mostly for learning purposes including sharing of academic information. Over 70% of respondents particularly used social media, social networking applications and internet searches for learning purposes. Health trainees were however constrained by low bandwidth and lack of seamless internet connectivity within their learning environments to maximize the full benefits of these e-learning opportunities. Respondents were predominantly prepared for an e-learning pilot project. These feability findings suggest e-learning is a huge potential that can be used to augment existing approaches for pre-service training of health trainees in Ghana, when implementation threats are sufficiently addressed. Compelling findings of this study are therefore timely to inform evidence-based policy decisions on innovative digitial solutions for pre-service training of health workforce even as the world adapts to the "new normal" situation induced by COVID-19.


Lethal case of myocardial ischemia following overdose of the synthetic cannabinoid ADB-FUBINACA.
The serious adverse effects of synthetic cannabinoids (SCB), the lack of human pharmacological data on SCBs, and the increasing number of SCBs with diverse structures are growing public health concerns. A fatal case of myocardial ischemia after ADB-FUBINACA overdose is reported. A 41-year-old male died after consuming a brown, powder-like drug. Autopsy revealed pallor in the left ventricle of the subendocardial two-third of the myocardium, and histological examination revealed early signs of myocardial ischemia: few wavy myocardial fibers, contraction band necrosis in the subendocardial region, and patchy subendocardial complement component 9 (C9) positivity. Toxicological analysis detected a high concentration of the indazole carboxamide derivative SCB ADB-FUBINACA (peripheral blood: 105 ng/mL) and a low concentration of the synthetic cathinone (SC) derivative stimulant N-ethylpentylone (NEP). The literature concerning ADB-FUBINCA overdoses is reviewed, and the possible mechanism of death and the cardiac effects of SCBs are discussed. Effects of SCBs are unpredictable, but they are potentially cardiotoxic, capable causing arrhythmias, cardiac hypertrophies, and myocardial ischemia. The cardiotoxicity of SCBs can be attributed to vasospasms, decreased myocardial contractility, and increased cardiac workload and oxygen demand. Based on the autopsy, histology, and toxicology, it could be reasonably suggested, that ADB-FUBINACA have been a significant contributor to the myocardial ischemia seen in histology. The mechanism of death was likely fatal arrhythmia induced by the patchy myocardial ischemia. Due to the low concentration of NEP, it's role in the fatal outcome is improbable.


Predictors of dental complications post-dental treatment in patients with sickle cell disease.
Our aim was to explore potential medical or dental indicators associated with dental complications and the utilization of emergency services in sickle cell disease (SCD), especially that clinical reports on adverse outcomes post-dental treatment are scarce. A retrospective analysis of dental treatments of 47 eligible adults with confirmed SCD between May 2016 and October 2019. Logistic regression analysis was used whether clinical outcomes, course of dental treatment, and regularity of dental care are associated with dental complications after dental procedures and/or resulted in emergency care or hospital admissions. We identified a new, statistically significant association (p-value = .01) between the number of prescription medications taken and complications (10%) after dental procedures. The most frequent dental procedures were tooth extractions (36%) and pain management (28%) during a non-scheduled dental encounter (68%). The majority of cases did not participate in regular recall exams and periodical oral hygiene maintenance. A higher number of prescription medications was associated with an increased risk of post-dental complications in SCD patients. A thorough medical history, including a list of prescribed medications, and collaboration with the patient medical team are important to assess the risk of complications post-dental procedures and the need for antibiotic prophylaxis according to the case complexity.


Axonal trajectories between mouse somatosensory thalamus and cortex.
An in vitro brain slice preparation has been used to label fibers connecting the somatosensory thalamus and cortex of the mouse. In 400-800-micron brain slices, the pathway between the ventrobasal complex and somatosensory cortex was labeled under direct vision with horseradish peroxidase crystals (HRP), HRP-Nonidet P-40 (NP40) detergent chips, or a solution of HRP/dimethylsulfoxide. Thalamocortical and corticofugal fibers are organized into a plexiform system of bundles that appears to be fairly constant from animal to animal. Bundles of fibers projecting from the ventrobasal complex course between regularly spaced groups of thalamic neurons. Thalamocortical axons do not invariably leave the thalamus via the fiber bundle closest to the perikarya. Thus, nearest-neighbor relationships are abolished before these axons have even left the thalamus. The axon bundles traverse the thalamic reticular nucleus lateral to the complex. The axons then rotate about one another, analogous to the coiling of strands in rope about a central axis. This accounts for the well known 180 degrees rotation in the mediolateral direction between thalamic and cortical maps. Laterally, fiber bundles converge and diverge within the internal capsule so that nearest-neighbor relationships are lost. Individual thalamocortical axons do not bifurcate proximal to the subcortical white matter. After single bundles of fibers reach a point just below the subcortical white matter, their individual fibers diverge widely. Within the subcortical white matter most afferent fibers make a small dorsally concave loop prior to taking one of two possible courses: some of the fibers ascend directly into the overlying cortex usually angled towards the dorsal surface of the brain; other fibers run in the subcortical white matter for variable distances prior to ascending into cortex. Within somatosensory cortex, smooth axons branch near their terminals in layers IV and VI. Axonal terminal and branching patterns of these axons within somatosensory cortex are similar to those found in in vivo preparations. Most axons are smooth, but other axons are beaded. Some beaded axons project to layer I. Corticofugal fibers are labeled. Fibers leaving somatosensory cortex have an angle of descent opposite to the angle of ascent for afferent fibers, and are often fasciculated in the cortex and subcortical white matter. Within the subcortical white matter efferent fibers often loop in a direction opposite to that of afferent fibers. Corticofugal fibers occasionally give off a collateral corticostriatal branch within the internal capsule.(ABSTRACT TRUNCATED AT 400 WORDS)


An exploration of professional and practice-based perspectives on reunification of children in out-of-home care in Ireland: The road less travelled?
The reunification of children in out-of-home care has gained increasing attention from both researchers and policy makers in many jurisdictions in recent years. In Ireland, however, reunification has received little attention and there is a dearth of data, research, policy and guidance in this area. This paper explores perspectives on, and experiences of, reunification in Ireland among respondents from a range of professional and practice backgrounds. The authors suggest that there are lessons to be learned from the Irish case for other jurisdictions with limited policy and research in the area of reunification. The research was carried out using a qualitative approach. Semi-structured interviews were carried out with 12 respondents from a range of professional and practice backgrounds and/or experience of reunification in Ireland. Findings suggest that there is a lack of clarity and a limited focus on the process of reunification for children in care in Ireland. This lack of focus on reunification and absence of national guidance appears to have resulted in some children 'drifting' through the care system with little exploration of the possibility to return home. Minimal emphasis on working with birth parents to support and enable them to resume caring for their children is reported. Findings suggest that future efforts in this area should focus on: 1) developing a comprehensive research agenda in relation to reunification; 2) ensuring reunification is clearly placed on the policy agenda in Ireland; and 3) establishing a framework for practice guidance and a specialised reunification service to promote working with birth parents.


Differential and unique patterns of synaptic miRNA expression in dorsolateral prefrontal cortex of depressed subjects.
Altered synaptic plasticity is often associated with major depressive disorder (MDD). Disease-associated changes in synaptic functions are tightly correlated with altered microRNA (miRNA) expression. Here, we examined the role of miRNAs and their functioning at the synapse in MDD by examining miRNA processing machinery at synapse and sequencing miRNAs and analyzing their functions in synaptic and total tissue fractions obtained from dorsolateral prefrontal cortex (dlPFC) of 15 MDD and 15 matched non-psychiatric control subjects. A total of 333 miRNAs were reliably detected in the total tissue fraction. Multiple testing following the Benjamini-Hochberg false discovery rate [FDR] showed that 18 miRNAs were significantly altered (1 downregulated 4 up and 13 downregulated; p < 0.05) in MDD subjects. Out of 351 miRNAs reliably expressed in the synaptic fraction, 24 were uniquely expressed at synapse. In addition, 8 miRNAs (miR-215-5p, miR-192-5p, miR-202-5p, miR-19b-3p, miR-423-5p, miR-219a-2-3p; miR-511-5p, miR-483-5p showed significant (FDR corrected; p < 0.05) differential regulation in the synaptic fraction from dlPFC of MDD subjects. In vitro transfection studies and gene ontology revealed involvement of these altered miRNAs in synaptic plasticity, nervous system development, and neurogenesis. A shift in expression ratios (synaptic vs. total fraction) of miR-19b-3p, miR-376c-3p, miR-455-3p, and miR-337-3p were also noted in the MDD group. Moreover, an inverse relationship between the expression of precursor (pre-miR-19b-1, pre-miR-199a-1 and pre-miR-199a-2) and mature (miR-19b-3p, miR-199a-3p) miRNAs was found. Although not significantly, several miRNA processing enzymes (DROSHA [95%], DICER [17%], TARBP2 [38%]) showed increased expression patterns in MDD subjects. Our findings provide new insights into the understanding of the regulation of miRNAs at the synapse and their possible roles in MDD pathogenesis.


Dataset of global extreme climatic indices due to an acceleration of ice sheet melting during the 21st century.
This article describes extreme indices maps (Data Cube, raster X Time) for different scenarios with a more important contribution to the sea level rise from Greenland and/or Antarctica during the 21st century under the Representative Concentration Pathway (RCP) 8.5 emission scenario. The indices are produced annually and globally with a resolution of 0.5° × 0.5° from 1951 to 2099. The data were generated by simulating daily maximum and minimum temperature and precipitation from the IPSL-CM5A-LR model from Coupled Model Intercomparison Project Phase 5 (CMIP5). These climatic data are unbiased and downscaled to the 0.5°x0.5 scale with the Cumulative Distribution Function transform (CDFt) and EWEMBI dataset compiled to support the bias correction of climate input data for ISIMIP. Finally, each extreme indice is computed on the unbiased data on each grid cell on all continents.


[Structural similarity and functional activity of molecular fragments of staphylococcal enterotoxin B and thymopoietin II].
Structural similarity between Staphylococcus enterotoxin B and a thymus hormone, thymopoietin, has been revealed concerning thymopentin, one of active centres of thymopoietin. Fragments of enterotoxin B homologous to thymopoietin and their analogues were synthesized their immunological activity studied. Acetyl derivative of the fragment 225-229 of enterotoxin B increased infectional resistance and stimulated delayed type of hypersensitivity reaction.


Combining synthetic carbohydrate vaccines with cancer cell glycoengineering for effective cancer immunotherapy.
Tumor-associated carbohydrate antigens (TACAs) are useful targets for the development of cancer vaccines or immunotherapies. However, a major obstacle in this application of TACAs is their poor immunogenicity. To overcome the problem, a new immunotherapeutic strategy combining synthetic vaccines made of artificial TACA derivatives and metabolic glycoengineering of cancer cells to express the artificial TACA derivatives was explored. Using a murine leukemia model FBL3 with GM3 antigen as the target, it was shown that artificial GM3 N-phenylacetyl derivative (GM3NPhAc) elicited robust antigen-specific T cell-dependent immunity and that N-phenylacetyl-D-mannosamine (ManNPhAc) as the biosynthetic precursor of GM3NPhAc selectively glycoengineered cancer cells to express GM3NPhAc both in vitro and in vivo. It was also demonstrated that GM3NPhAc-specific antisera and antibodies mediated strong cytotoxicity to ManNPhAc-treated FBL3 cell. Furthermore, vaccination with a conjugate vaccine made of GM3NPhAc followed by ManNPhAc treatment could significantly suppress tumor growth and prolong the survival of tumor-bearing mouse. These results have proved the feasibility of the new cancer immunotherapeutic strategy, as well as its efficacy to cure cancer, which is of general significance.


The effect of propolis extract on milk production and composition, serum biochemistry, and physiological parameters of heat-stressed dairy cows.
The aim of this study was to evaluate whether feeding propolis extract (PE) influences nutrient intake, milk production and composition, serum biochemistry, and physiological parameters of heat-stressed dairy cows. For this purpose, we used three primiparous Holstein cows with a lactation period of 94 ± 4 days and with 485 ± 13 kg body weight. The treatments were 0 mL/day, 32 mL/day, and 64 mL/day of PE randomly assigned in a 3x3 Latin square design, repeated over time. The experiment lasted a total of 102 days; each Latin square lasted 51 days divided into three 17-day periods (12 days for adaptation and five days for data collection). The PE supply did not influence (P > 0.05) the cows' intake of dry matter (18.96 kg/d), crude protein (2.83 kg/d), and neutral detergent-insoluble fiber (7.36 kg/d), but there was an increase in feeding time with the 64 ml/day PE supply (P < 0.05). Providing 64 ml/day of PE tended (P = 0.06) to increase milk production by 11.64% and improve gross feed efficiency of cows by 12.04%. The PE supply did not influence milk composition and blood parameters of cows (P > 0.05). Offering 32 mL/day of PE decreased (P < 0.05) the rectal temperature and respiratory rate of cows. We recommend a supply of 64 mL/day of PE for heat-stressed dairy cows.


The Effect of Successful Intubation on Patient Outcomes After Out-of-Hospital Cardiac Arrest in Taipei.
The effect of out-of-hospital intubation in patients with out-of-hospital cardiac arrest remains controversial. The Taipei City paramedics are the earliest authorized to perform out-of-hospital intubation among Asian areas. This study evaluates the association between successful intubation and out-of-hospital cardiac arrest survival in Taipei. We analyzed 6 years of Utstein-based registry data from nontrauma adult patients with out-of-hospital cardiac arrest who underwent out-of-hospital airway management including intubation, laryngeal mask airway, or bag-valve-mask ventilation. The primary analysis was intubation success on patient outcomes. The primary outcome was survival to discharge and the secondary outcomes included sustained return of spontaneous circulation and favorable neurologic survival. Sensitivity analysis was performed with intubation attempts rather than intubation success. Subgroup analysis of advanced life support-serviced districts was also performed. A total of 10,853 cases from 2008 to 2013 were analyzed. Among out-of-hospital cardiac arrest patients receiving airway management, successful intubation, laryngeal mask airway, and bag-valve-mask ventilation was reported in 1,541, 3,099, and 6,213 cases, respectively. Compared with bag-valve-mask device use, successful out-of-hospital intubation was associated with improved chances of sustained return of spontaneous circulation (adjusted odds ratio [aOR] 1.91; 95% confidence interval [CI] 1.66 to 2.19), survival to discharge (aOR 1.98; 95% CI 1.57 to 2.49), and favorable neurologic outcome (aOR 1.44; 95% CI 1.03 to 2.03). The results were comparable in sensitivity and subgroup analyses. In nontrauma adult out-of-hospital cardiac arrest in Taipei, successful out-of-hospital intubation was associated with improved odds of sustained return of spontaneous circulation, survival to discharge, and favorable neurologic outcome.


Quality changes, potential spoilage organisms, and shelf-life prediction of brackish river prawn (Macrobrachium macrobrachion) at different storage temperatures.
The brackish river prawn (Macrobrachium macrobrachion) is a species of commercial importance in West Africa. However, like other fishery products, it is prone to deterioration due mainly to microbial activities. The present study aimed at evaluating the spoilage characteristics of M. macrobrachion and predicting the growth of the main spoilage bacteria as well as the shelf-life of the product as a function of storage temperature. Freshly caught brackish river prawn samples from Lake Aheme were aerobically stored at 0, 7, 15, and 28 °C and, at pre-determined times during storage, they were taken for microbiological, chemical, and sensory analysis. At sensory rejection times, the spoilage potential of 185 isolates from specific groups of organisms enumerated was assessed in prawn of which the endogenous microbiota was heat inactivated. Isolates capable of producing strong off-odor were identified using 16S rRNA sequencing. Models predicting the maximum growth rate of Pseudomonas spp. and H2S-producing bacteria in the brackish river prawn as well as the shelf-life of the product were developed. These models were validated using an independent experiment during which prawn was stored at 0, 4, 10, and 25 °C. Results showed that Pseudomonas spp. at 0 °C, Pseudomonas spp. and H2S-producing bacteria at 7 °C, and H2S-producing bacteria at 15 °C and 28 °C were the dominant groups of microorganisms during storage. As expected, total volatile basic nitrogen, trimethylamine, and pH with initial values of 21.2 ± 3.0 mg-N/100 g, 4.1 ± 0.8 mg-N/100 g, and 7.46 ± 0.15 increased during storage reaching approximately 35 mg-N/100 g, 10 mg/ 100 g and 8, respectively at sensory rejection times which were 7 h at 28 °C, 1.2 d at 15 °C, 4.6 d at 7 °C, and 11.7 d at 0 °C. The main spoilage organisms were Citrobacter braakii at 28 °C, Citrobacter braakii, Pseudomonas kurunegalensis, and Shewanella bicestrii at 15 °C, Shewanella putrefaciens, Shewanella baltica, and Pseudomonas bubulae at 7 °C, and Pseudomonas versuta at 0 °C. The validation of the developed models showed an adequate agreement between the predicted and observed values. This study highlights the specific spoilage characteristics of the brackish river prawn and reveals that Gram-negative rod bacteria are the main spoilage organisms even at high storage temperatures, contrary to many earlier reports on the spoilage of tropical fishery products.


Outcomes of resective surgery in pediatric patients with drug-resistant epilepsy: A single-center study from the Eastern Mediterranean Region.
Epilepsy surgery is widely accepted as an effective therapeutic option for carefully selected patients with drug-resistant epilepsy (DRE). There is limited data on the outcome of epilepsy surgery, especially in pediatric patients from the Eastern Mediterranean region. Hence, we performed a retrospective study examining the outcomes of resective surgery in 53 pediatric patients with focal DRE. Patients with focal DRE who had undergone epilepsy surgery were included in the present study. All patients underwent a comprehensive presurgical evaluation. Postoperative seizure outcomes were classified using the Engel Epilepsy Surgery Outcome Scale. After surgery, 33 patients (62.2%) were Class I according to the Engel classification of surgical outcomes; eight patients (15.0%) were Class II, 11 (20.7%) were Class III, and one (1.8%) was Class IV. The relationships of presurgical, surgical, and postsurgical clinical variables to seizure outcomes were compared. Older age at seizure onset, older age at the time of surgery, the presence of focal to bilateral tonic-clonic seizures, seizure duration over 2 minutes, unsuccessful treatment with three or fewer antiseizure medications, lesions confined to one lobe (as demonstrated via magnetic resonance imaging [MRI]), surgical site in the temporal lobe, and histopathology including developmental tumors were significantly linked to an Engel Class I outcome. A univariate analysis of excellent surgical outcomes showed that lateralized semiology, localized interictal and ictal electroencephalogram (EEG) discharges, lateralized single-photon emission computed tomography and positron emission tomography findings, and temporal lobe resections were significantly related to excellent seizure outcomes. The results of our study are encouraging and similar to those found in other centers around the world. Epilepsy surgery remains an underutilized treatment for children with DRE and should be offered early.


Predictive factors on the efficacy and risk/intensity of tooth sensitivity of dental bleaching: A multi regression and logistic analysis.
The aim of this study was to identify predictor factors associated with the whitening outcome and risk and intensity of bleaching-induced tooth sensitivity from pooled data of 11 clinical trials of dental bleaching performed by the same research group. The individual patient data of several published and ongoing studies about dental bleaching was collected and retrospectively analyzed. At the patient-level, independent variables (bleaching techniques [at-home and in-office protocols], sex, age and baseline tooth color in shade guide unit [SGU]) as well as dependent variables (color change in shade guide units (ΔSGU), color change in the CIEL*a*b* system (ΔE), risk and intensity of TS in a visual analog scale) were collected. Multivariable linear regression and multivariable logistic regression models were carried out using backward elimination whenever the p-values were higher than 0.05. A significant relationship between baseline color and age on color change estimates was detected (p<0.001). Every increase of one SGU in the baseline color resulted in an increase of approximate 0.66 in the final ΔSGU and 2.48 for the ΔE. For every increase of one year in the participant's age we observed a decrease of the whitening degree of 0.07 for the final ΔSGU and 0.69 for the ΔE. The bleaching technique was shown to be a significant predictor of ΔSGU (p<0.001) but not of ΔE. In regard to TS, baseline color and bleaching technique are significant predictors (p<0.001). The risk of TS for at-home bleaching was 51% (95% CI 41.4-60.6) and for the in-office 62.9% (95% CI 56.9-67.3). Younger patients with darker teeth reach a higher degree of whitening. Patient with darker teeth and submitted to at-home bleaching presents lower risk and intensity of TS. The baseline color of the teeth and the patient's age is directly related to the effectiveness of dental bleaching and TS.


The effect of arginine and nitric oxide on resistance blood vessels of the perfused rat kidney.
1. The vasodilator effects of arginine, nitric oxide (NO), acetylcholine (ACh) and sodium nitroprusside (NP) in the noradrenaline-preconstricted ('high tone') perfused rat kidney have been examined. 2. L-Arginine (0.6-23 mumol) caused a biphasic change in renal perfusion pressure. D-Arginine (0.6-23 mumol) was without effect. The second vasodilator component was abolished and the first vasoconstrictor effect augmented following CHAPS-induced removal of the vascular endothelium suggesting that vasodilatation was endothelium-dependent. 3. L-Arginine salts produced transient and dose-related vasodilatation. L-Arginine methylester was the most potent with an ED50 of 2.2 +/- 0.4 mumol (n = 6). The rank order of potency of the salts tested was: methylester greater than hydroxamate greater than chloride. L-Homoarginine chloride was also vasodilator (ED50, 12.0 +/- 1.3 mumol, n = 5). D-Arginine chloride was without effect at doses up to 170 mumol. Responses to L-arginine chloride were endothelium-derived relaxing factor (EDRF)-dependent being abolished by CHAPS (4.7 mg ml-1, 30 s) and significantly inhibited (greater than 70%) by gossypol (3 microM) and nordihydroguaiaretic acid (NDGA, 10 microM). 4. Vasodilatation due to NO was unaffected by CHAPS and gossypol treatment but inhibited by NDGA. NO was approximately 3 times less potent than ACh but 3000 times more potent than L-arginine methylester. 5. Kidneys perfused for 1 h with Krebs solution containing L-arginine chloride (100 microM) or L-canavanine (50 microM) showed no change in sensitivity towards ACh or NP. Higher concentrations of L-arginine chloride (500 microM) or L-canavanine (150 microM) significantly reduced the response to both vasodilators 6. L-Arginine salts dilate resistance blood vessels of the perfused rat kidney by a mechanism which may involve the release of EDRF from vascular endothelial cells of the perfused rat kidney..


Selective insecticide-induced stimulation on fecundity and biochemical changes in Tryporyza incertulas (Lepidoptera: Pyralidae).
The use of selective insecticides in rice, Oryza sativa L., fields often causes resurgence of nontarget pest insects. This study was conducted to investigate the effect of two selective insecticides, buprofezin and imidacloprid, on Tryporyza incertulas (Walker), a nontarget pest. After larval feeding on rice plants treated with each insecticide, fecundity, ovary protein content, and titer of juvenile hormone III (JHIII) in the resulting female moths were determined with 'Xiushui 63' rice susceptible to T. incertulas and 'Zhendao 2' moderately resistant to T. incertulas. The fecundity of females developed from larvae that fed on the insecticide-treated Xiushui 63 plants was stimulated compared with that of moths from larvae that fed on rice plants that were not treated with either insecticide. There was no stimulating effect in females from larvae that fed on insecticide-treated Zhendao 2 plants. The weight of fourth instars (final instars) that fed on the insecticide-treated Xiushui 63 rice plants was significantly greater than that of control, increasing by 50.3 and 46.7% for 60 and 112.5 g (AI) ha(-1) buprofezin, and by 23.7 and 19.5% for 15 and 37.5 g (AI) ha(-1) imidacloprid treatments, respectively. Ovary protein content in adult females developed from larvae that fed on the rice treated with the high dose of buprofezin was significantly higher than that in control. For the high and low doses of imidacloprid during the second instar, and the low dose of imidacloprid during the fourth instar, JHIII titers in female adults were also significantly higher than that in control, increasing by 152.81, 90.52, and 114.19%, respectively.


Executive functioning and suicidal behavior among veterans with and without a history of traumatic brain injury.
To examine the relationship between executive dysfunction, as a multidimensional construct (ie, decision-making, impulsivity, aggression, concept formation), and suicide attempt (SA) history in a high-risk sample of veterans with moderate to severe traumatic brain injury (TBI). Observational, 2×2 factorial design. To estimate group differences, linear regression was used to model the primary and secondary outcomes of interest as a function of history of SA, TBI, and the interaction between the 2 variables. Additionally, to determine the pattern of performance over the course of the Iowa Gambling Test (IGT), scores were modeled across the 5 IGT blocks by using a varying-coefficient model. Veterans Health Administration. Veterans (N=133; no SA/no TBI, n=48; no SA/yes TBI, n=51; yes SA/no TBI, n=12; yes SA/yes TBI, n=22) completed the study measures. Not applicable. IGT, Immediate and Delayed Memory Test, State-Trait Anger Expression Inventory-2, Wisconsin Card Sorting Test. All groups demonstrated learning over the course of the IGT, except for veterans with a history of both SA and TBI. No group differences were identified on other measures of executive functioning. These findings highlight the potential, unique decision-making challenges faced by veterans with a history of TBI and SA. Specialized interventions focused on overall distress reduction and means restriction may be required to prevent future self-directed violence.


Studies on scavenger receptors under experimental hypercholesterolemia: modulation on selenium supplementation.
Scavenger receptors (SR) are the cell surface proteins that can bind and internalize modified lipoproteins. Because ox-LDL seems to play a key role in foam cell formation during atherogenesis, SR may be critical for pathogenesis of atherosclerosis. The present study was aimed to study the effect of selenium (Se) supplementation on SR, i.e., SRB1 and CD36 under experimental hypercholesterolemia. Male Sprague Dawley rats were divided into three groups and fed on the control diet, high cholesterol diet (HCD), and HCD + Se, respectively, for a period of 4 months. Selenium and reactive oxygen species (ROS) levels were estimated in serum and liver respectively. mRNA expression using RT-PCR and protein expression using ELISA were analyzed for SRB1 and CD36 receptors. Selenium levels decreased whereas ROS levels increased under experimental hypercholesterolemic state. Selenium supplementation (1 ppm), however, diminished the HCD-induced ROS levels. Furthermore, the protein expression of SRB1 was significantly reduced in HCD group in comparison to the control group. On the other hand, HCD-induced increase in CD36 mRNA and protein expression decreased significantly on Se supplementation. In conclusion, CD36 receptors seem to play a pro-atherogenic role under hypercholesterolemic state. Selenium supplementation, in addition, might prove to be a therapeutically valuable approach in near future to limit the adverse effect of hypercholesterolemia.


Exposure to PBDEs associated with farm animal meat consumption.
One of the ways to reduce the number of fires and the amount of damage caused by them is to use flame retardants (FRs). Polybrominated diphenyl ethers (PBDEs), like other FRs, have been used in a wide array of easily flammable products. As they are not chemically bonded with materials, PBDEs can be released from polymers into the environment. PBDEs can act as endocrine disruptors and affect neurological and thyroid activity. Although human intake of PBDEs is mainly through food, data about meat as a PBDE source and human exposure through diet are limited. The objective of the present study was to develop a comprehensive database of congener-specific PBDE concentrations in farm animal muscle and to characterize potential consumer exposure. For exposure assessment, two consumption scenarios were used for adults and children. The dietary exposure to PBDE congeners is based on the assumed portion size of 100 g of different meat species. Calculations for the participants were performed using food consumption data of the Statistical Yearbook (2015/2016). The intake of PBDEs was estimated as the median (P50) and the average for all kinds of tested meat. For health risk assessment, the margin of exposure (MOE) approach was used. MOE values were in range from 5 to 149 352 132. The obtained results indicate that concentrations of ten tested congeners (BDE-28,47,49,99,100,138,153,154,183,209) in different kinds of farm animal meat (cow, chicken, farm deer, horse, ostrich, pig, rabbit, sheep, turkey) are low and meat consumption does not pose a risk for human health.


Double Trouble in a Patient with Coronary Ectasia, Bradycardia with Angina: Epiphenomenal or Mechanistic Association.
Coronary artery ectasia is a rare angiographical finding, and it accounts for less than 5% of all coronary angiograms. We report a case of a 55-year-old male patient who presented with fatigue and exertional chest pain. Paraclinical tests revealed cardiac ischemia and sinus node dysfunction, as well as coronary artery ectasia without significant coronary stenosis. Factors involved in cardiac ischemia in this context comprise slow flow, poor collateral circulation, microcirculatory dysfunction, lack of adequate exertional coronary vasodilatation, and endothelial dysfunction. Moreover, poor collaterals with rudimentary sinus node artery may explain sinus node dysfunction. Discussion is made in light of the relevant medical literature.


Calcified Spinal Meningiomas.
To analyze outcomes of patients surgically treated for calcified spinal meningiomas and to determine factors associated with surgical morbidity. Between January 2000 and June 2013, a total of 54 patients underwent surgical resection of a spinal meningioma: 37 of these cases showed various degrees of calcification, confirmed by histopathologic analysis. The clinical evaluation was performed according to the American Spinal Injury Association Impairment Scale. At the last follow-up, neurologic status improved in 19 cases and remained unchanged in 20 cases; just 1 case worsened. According to the American Spinal Injury Association Impairment Scale, neurologic status was classified into 3 levels: poor (A + B), fair (C), and good (D + E). Neurologic status improvement (NSI) during postoperative time (considered as a transition from one lower level to the higher) was analyzed in relationship to the patient's age, length of clinical history, spine level, meningioma's position inside the spinal canal, and its degree of calcification. A statistically significant relationship between NSI and the degree of ossification of the meningioma was observed. in particular, a direct relationship with microcalcified meningiomas and an inverse relationship with ossified meningiomas. No relationship was observed between NSI and patient's age, length of clinical history, and the site of the lesion into the vertebral canal. The univariate analysis confirms that the degree of calcification affects the outcome, because extensive tumor calcification is associated with an increased surgical morbidity probably.


The relationship between transformation and somatic mutation in human and Chinese hamster cells.
The frequencies of transformations of primary human and Chinese hamster fibroblasts have been compared with the spontaneous and induced frequencies of mutation for resistance to thioguanine and ouabain, and for ability to use fructose, using the carcinogens benzo (alpha) pyrene and urethane. Whereas the rates and frequencies of mutation were similar in the two cell systems, transformations to morphologically altered cells was observed only in hamster cells. The frequency of this latter transformation event in hamster cells was abour 10(3) greater than the frequencies of mutation in these cells. The morphologically altered cells formed in the above transformation process cannot grow in agar (aga-) and do not produce tumors when injected into animals. The frequency of transition of these latter cells to aga+ cells which produce tumors in animals is similar to the mutation-like events.


Effect of copper and silver ions on sequence and DNA methylation changes in triticale regenerants gained via somatic embryogenesis.
Somatic embryogenesis is a plant regeneration method that can be exploited in tissue culture systems for a variety of tasks, such as genetic modification or the selection of somaclones with advantageous characteristics. Therefore, it is crucial to create efficient regeneration procedures and comprehend how medium components affect regeneration effectiveness or the degree of variation created in plant tissue cultures. The level of tissue culture-induced variation in triticale regenerants was examined in the current study in relation to the concentration of copper and silver ions in the induction media as well as the length of time immature zygotic embryo explants were incubated on these media. The high degree of variation (45%) revealed by the methylation-sensitive amplified fragment length polymorphism approach for estimating variation included 38% DNA sequence alterations, 6% DNA demethylation, and 1% de novo DNA methylation. Different levels of variance were found in relation to various DNA sequence settings. The CHG context had the most alterations, whereas CG experienced the fewest; sequence variation predominated in each sequence context. Lower copper ion concentrations showed the most variance. However, it could not be connected to the duration of in vitro culture or the effect of silver ions. Accordingly, we think that altering the concentration of copper ions in the induction medium may throw off the equilibrium of the metabolic processes in which copper is involved, resulting in tissue culture-induced variation.


The role of fine-needle aspiration biopsy and flow cytometry in the evaluation of persistent neck adenopathy.
The role of fine-needle aspiration biopsy (FNAB) and flow cytometry (FCM) in the evaluation of persistent neck adenopathy has not been completely defined. All patients who underwent FNAB of an abnormal lymph node from 1990 to 1997 were identified, and the results of FNAB and FCM were correlated with histology or clinical follow-up. FNAB was performed on 133 patients with an abnormal lymph node in the neck. FNAB was malignant in 82 (62%), atypical in 13 (10%), benign in 27 (20%), and nondiagnostic in 11 (8%) patients. FNAB was compared with histologic results in 114 (86%) or with the results of clinical follow-up (average 17 months) in 12 patients (9%). Seven patients (5%) were lost to follow-up. Lymphoma and metastatic carcinoma were diagnosed in 25 (19%) and 76 (57%) patients, respectively. Sensitivity of FNAB and FCM was 96% and 100%, respectively, and specificity was 58% and 100%, respectively. Patients with Hodgkin's lymphoma accounted for 80% of false negative FCM results. FCM was nondiagnostic in 3 of 34 patients (9%). Definitive subclassification of lymphoma was accomplished in only 3 of 17 (18%) patients in whom FCM was performed. FNAB is reliable in identifying metastatic disease, non-Hodgkin's lymphoma, and reactive lymphadenopathy in the neck. FNAB and FCM still have a limited role in definitive diagnosis of Hodgkin's lymphoma and classification of non-Hodgkin's lymphoma, underscoring the importance of excisional biopsy.


miR‑204 inhibits the osteogenic differentiation of mesenchymal stem cells by targeting bone morphogenetic protein 2.
Mesenchymal stem cells (MSCs) are used to investigate regeneration and differentiation. MicroRNA‑204 (miR‑204) in involved in the Runt‑related transcription factor 2/alkaline phosphatase/bone morphogenic protein 2 (Runx2/ALP/BMP2) signaling pathway that regulates bone marrow mesenchymal stem cell (BMSC) differentiation; however, the mechanisms underlying the effects of miR‑204 are yet to be determined. The aim of the present study was to investigate the effects of miR‑204 on BMSC differentiation. BMSCs were derived from rat bone marrow. The expression levels of Runx2, ALP and BMP2 were measured via reverse transcription‑quantitative polymerase chain reaction and western blot analyses following transfection of BMSCs with miR‑204 agomir or BMP2 expression vector. The ability of the miR‑204 gene to directly bind BMP2 mRNA was assessed using dual‑luciferase assays. Ossification was measured via alizarin red stain assays. It was observed that the expression levels of Runx2 and ALP increased over time, whereas those of miR‑204 decreased; additionally, miR‑204 agomir upregulation inhibited the expression of Runx2, ALP and BMP2 in BMSCs. It was revealed that miR‑204 directly interacted with BMP2 mRNA, and that transfection with miR‑204 agomir suppressed ossification in BMSCs by targeting the BMP2/Runx2/ALP signaling pathway.


In brief: BRCA1 and BRCA2.
The discovery of the first major breast cancer susceptibility gene, BRCA1, occurred almost 20 years ago. BRCA1, together with BRCA2 remain the most important discoveries in human cancer genetics. Identification of highly penetrant mutations in these two tumour suppressor genes has had broad implications for women at risk and their families, for health professionals caring for these persons and for basic researchers. The BRCA proteins have many critical functions, the most notable of which, from a clinical perspective, is repair of double-strand DNA breaks.


Comparative genomics and evolution of immunoglobulin-encoding loci in tetrapods.
The immunoglobulins (Igs or antibodies) as an integral part of the tetrapod adaptive immune response system have evolved toward producing highly diversified molecules that recognize a remarkably large number of different antigens. Antibodies and their respective encoding loci have been shaped by different and often contrasting evolutionary forces, some of which aim to conserve an established pattern or mechanism and others to generate alternative and diversified structural and functional configurations. The genomic organization, gene content, ratio between functional genes and pseudogenes, number and position of recombining genetic elements, and the different levels of divergence present at the germline of the Ig-encoding loci have been evolutionarily shaped and optimized in a lineage- and, in some cases, species-specific mode aiming to increase organismal fitness. Further, evolution favored the development of multiple mechanisms of primary and secondary antibody diversification, such as V(D)J recombination, class switch recombination, isotype exclusion, somatic hypermutation, and gene conversion. Diverse tetrapod species, based on their specific germline configurations, use these mechanisms in several different combinations to effectively generate a vast array of distinct antibody types and structures. This chapter summarizes our current knowledge on the Ig-encoding loci in tetrapods and discusses the different evolutionary mechanisms that shaped their diversification.


Bile acid feeding induces cholangiocyte proliferation and secretion: evidence for bile acid-regulated ductal secretion.
We have shown that taurocholate (TC) and taurolithocholate (TLC) interact in vitro with normal cholangiocytes, increasing DNA synthesis, secretin receptor (SR) gene expression, and adenosine 3',5'-cyclic monophosphate (cAMP) synthesis. To further extend these in vitro studies, we tested the hypothesis that bile acids (BAs) directly stimulate cholangiocyte proliferation and secretion in vivo. After feeding with TC or TLC (1% for 1-4 weeks), we assessed the following in vivo: (1) ductal proliferation by both morphometry and immunohistochemistry for proliferating cell nuclear antigen (PCNA) and measurement of [3H]thymidine incorporation; and (2) the effect of secretin on bile secretion and bicarbonate secretion in vivo. Genetic expression of H3-histone and SR and intracellular cAMP levels were measured in isolated cholangiocytes. After BA feeding, there was an increased number of PCNA-positive cholangiocytes and an increased number of ducts compared with control rats. [3H]Thymidine incorporation, absent in control cholangiocytes, was increased in cholangiocytes from BA-fed rats. In BA-fed rats, there was increased SR gene expression (approximately 2.5-fold) and secretin-induced cAMP levels (approximately 3.0-fold) in cholangiocytes, which was associated with de novo secretin-stimulated bile flow and bicarbonate secretion. These data indicate that elevated BA levels stimulate ductal secretion and cholangiocyte proliferation.


Telephone or face-to-face interviews?: a decision made on the basis of a pilot study.
De Vaus (1991) highlights five main considerations that may be key factors in decisions about whether to use telephone or face-to-face interviews for survey work: response rates, ability to produce representative samples, effects on interview schedule design, quality of responses and implementation problems. De Vaus' discussion of these five issues is outlined at the start of this article. The five issues are then applied to the experiences of researchers conducting a study on continence care. Description and discussion of pilot interviews, which explored both interview modes, are followed by a similar examination of the main study which employed telephone interviews. Ideas in this discussion are supported and challenged by reference to other publications on the subject of telephone and face-to-face interviews. The success of the decision to use telephone interviews in the main study is evaluated and recommendations are made.


Single-molecule detection and tracking of RNA transcripts in living cells using phosphorothioate-optimized 2'-O-methyl RNA molecular beacons.
Molecular Beacons (MBs) composed of 2'-O-methyl RNA (2Me) and phosphorothioate (PS) linkages throughout the backbone (2Me/PSFULL MBs) have enabled long-term imaging of RNA in living cells, but excess PS modification can induce nonspecific binding, causing false-positive signals. In this study, we evaluate the intracellular stability of MBs composed of 2Me with various PS modifications, and found that false-positive signals could be reduced to marginal levels when the MBs possess a fully PS-modified loop domain and a phosphodiester stem (2Me/PSLOOP MB). Additionally, 2Me/PSLOOP MBs exhibited uncompromised hybridization kinetics, prolonged functionality and >88% detection accuracy for single RNA transcripts, and could do so without interfering with gene expression or cell growth. Finally, 2Me/PSLOOP MBs could image the dynamics of single mRNA transcripts in the nucleus and the cytoplasm simultaneously, regardless of whether the MBs targeted the 5'- or the 3'-UTR. Together, these findings demonstrate the effectiveness of loop-domain PS modification in reducing nonspecific signals and the potential for sensitive and accurate imaging of individual RNAs at the single-molecule level. With the growing interest in the role of RNA localization and dynamics in health and disease, 2Me/PSLOOP MBs could enable new discoveries in RNA research.


Long-term follow up of experimental microvascular grafts using Doppler ultrasound.
Non-directional Doppler ultrasound was used to determine patency in prosthetic microvascular grafts in 30 rats over 24 weeks. Examinations were carried out every two weeks and exploration and arteriography were used at intervals during the study to confirm the Doppler findings. Two rats died and were excluded from the study. Twenty-six grafts were patent at the time of examination and these were correctly assessed by the Doppler technique. However, only one of two occluded grafts was correctly identified. Our results suggest that while this technique is sensitive, its specificity is low, and graft exploration may still be required to confirm patency. Doppler ultrasound may prove a useful non-invasive tool for long-term follow-up of experimental microvascular grafts if the false positive rate can be reduced by improved technique and further experience.


Lactic acidosis in thiamine deficiency.
Two chronically ill patients with limited nutritional intake during several weeks developed prolonged lactic acidosis. As no other causes of hyperlactaemia could be identified, thiamine deficiency was suspected. Supplementation of 600 mg thiamine resulted in a rapid normalisation of serum lactate levels (in patient 1 from 10.9-2.4 mmol/l; in patient 2 from 11.8-2.0 mmol/l) and acid base status (patient 1: pH from 7.11-7.30, bicarbonate from 8.6-21.2 mmol/l; patient 2: pH from 7.24-7.46, bicarbonate from 16-28 mmol/l; before and after treatment, respectively). Thiamine deficiency was confirmed by the degree of stimulation of erythrocyte transketolase activation by adding thiamine pyrophosphate, evaluated before and after thiamine replacement therapy. Stimulation decreased in patient 1 from 170% to 17% and in patient 2 from 20% to 0%, respectively. In addition to the metabolic derangement right ventricular heart failure was confirmed by echocardiography in both patients and again this was rapidly reversible by thiamine supplementation. We conclude that in malnourished patients unexplained prolonged lactic acidosis may result from thiamine deficiency, which is rapidly reversible by thiamine replacement therapy.


In situ immunodetection of activated caspase-3 in apoptotic neurons in the developing nervous system.
Activation of caspase-3 requires proteolytic processing of the inactive zymogen into p18 and p12 subunits. We generated a rabbit polyclonal antiserum, CM1, which recognizes the p18 subunit of cleaved caspase-3 but not the zymogen. CM1 demonstrated an apparent specificity for activated caspase-3 by specifically immunolabelling only apoptotic but not necrotic cortical neurons in vitro. In the embryonic mouse nervous system, CM1 immunoreactivity was detected in neurons undergoing programmed cell death and was markedly increased in Bcl-xL-deficient embryos and decreased in Bax-deficient embryos. CM1 immunoreactivity was absent in the nervous system of caspase-3-deficient mouse embryos and in neurons cultured from caspase-3-deficient mice. Along with neuronal somata, extensive neuritic staining was seen in apoptotic neurons. These studies indicate that caspase-3 is activated during apoptosis in the developing nervous system in vivo and that CM1 is a useful reagent for its in situ detection.


The rat striatum: a target nucleus for ascending axon collaterals of the entopedunculo-habenular pathway.
Direct projections from the entopeduncular nucleus (Ep) to the striatum were examined in the rat using retrograde tracing techniques. After injecting horseradish peroxidase (HRP) into the caudoputamen (CPU), labeled fibers could be traced medially to go through and/or terminate in both the globus pallidus (GP) and Ep ipsilateral to the injection. Interestingly, HRP-positive neuronal perikarya were observed in the Ep as well as in the GP after the CPU injections. These labeled Ep neurons were medium in size and restricted to the rostral 1/3 of the nucleus, in a distribution which overlapped the terminal fields from the CPU. A fluorescent tracer injection into the CPU resulted in retrograde labeling of Ep cells in the same fashion as after HRP injections. A second experiment was designed to determine whether the Ep cells projecting to the CPU have axon collaterals to any of the other known terminal fields of the Ep. Following True blue (TB) injections into the CPU and Diamidino yellow (DY) injections into the lateral habenular nucleus (lHb), all the TB-positive neurons in the rostral 1/3 of the Ep were unequivocally double-labeled with DY. On the other hand, the TB-labeled Ep neurons were never double labeled with DY injected into the centre median-parafascicular complex (CM-Pf) or ventroanterior-ventrolateral complex (VA-VL) of the thalamus or nucleus tegmenti pedunculopontinus pars compacta (TPC). The present study shows that single Ep neurons in the rostral 1/3 of the nucleus innervate both the striatum and lHb, and raises the possibility that these neurons may have a critical role in integrating motor and limbic functions in the basal ganglia.


Draft Whole-Genome Sequence of Serratia marcescens Strain RM66262, Isolated from a Patient with a Urinary Tract Infection.
Serratia marcescens strains are ubiquitous bacteria isolated from environmental niches and also constitute emergent nosocomial opportunistic pathogens. Here, we report on the draft genome sequence of S. marcescens strain RM66262, which was isolated from a patient with urinary tract infection in the Bacteriology Service of the Rosario National University, Rosario, Argentina.


Isoniazid-associated rhabdomyolysis.
We report the occurrence of rhabdomyolysis and hepatitis in a 17-year-old girl after the ingestion of up to 10.8 g of isoniazid. The initial isoniazid concentration in the blood was 1,230 mmol/L. There were no findings indicating the ingestion of other substances known to be associated with rhabdomyolysis. In addition to rhabdomyolysis (peak creatine phosphokinase 88,000 U/L), the patient had a significant elevation of her liver enzymes (peak aspartate aminotransferase 1,980 U/L). She recovered completely without evidence of liver or renal damage. Rhabdomyolysis and isoniazid-induced hepatitis are complications that should be considered when caring for patients with acute isoniazid ingestion.


Iranian nurses' perceptions of core competencies required for disaster risk management.
With an increase in the incidence and severity of disasters, disaster risk management receives an important priority in the health system. Nurses at all levels of healthcare play an important role in disaster risk management and they must have core preparation and competencies to respond to disasters. This study aimed to evaluate Iranian nurses' core competencies required for disaster risk management. This cross-sectional study was conducted on 277 nurses working in three hospitals affiliated to Kerman University of Medical Sciences in 2022. The demographic information questionnaire and the nurses' perceptions of disaster core competencies scale (NPDCC) were used to collect data, and SPSS21 was used to analyze data. Nurses' competencies in disaster risk management were favorable (3.67 ± 0.77), with the subscales of technical skills and special diagnostic skills receiving the highest (3.91 ± 0.65) and the lowest mean scores, respectively (3.46 ± 0.87). The results found a significant difference between the scores of nurses' competencies in disaster risk management in terms of education level, age, work experience, employment status, participation in training courses related to disaster risk management, work experience in incidents and disasters. The study results suggested nurses' high level of competency in disaster risk management, but indicated gaps in their core competencies. The study results recommend authorities provide various training courses related to disaster risk management for all nurses.


The Use of the Over the Scope Clip to Treat Upper Gastrointestinal Bleeding.
The over-the-scope clip is a novel endoscopic tool developed for tissue compression in the gastrointestinal tract. It has already revolutionized the management of acute perforations and leaks. In the past decade, it has also increasingly been used for treatment of severe and/or refractory gastrointestinal hemorrhage. Available studies report high rates of primary hemostasis and rebleeding. This article provides an overview on available literature, potential indications, and technical aspects of hemostasis with over-the-scope clip.


Axoplasmic transport block reduces ectopic impulse generation in injured peripheral nerves.
Afferent fibers ending in nerve end neuromas in rats generate a substantial ectopic discharge and are sensitive to light pressure and to circulating adrenaline. Treatment of the nerve with colchicine or vinblastine at the time of the nerve section resulted in a dose-dependent reduction in the extent of this discharge. Such treatment also reduced neuroma discharge that had already gotten underway.


Reasons for relativism: Feyerabend on the 'Rise of Rationalism' in ancient Greece.
This paper argues that essential features of Feyerabend's philosophy, namely his radicalization of critical rationalism and his turn to relativism, could be understood better in the light of his engagement with early Greek thought. In contrast to his earlier, Popperian views he came to see the Homeric worldview as a genuine alternative, which was not falsified by the Presocratics. Unlike socio-psychological and externalist accounts my reading of his published and unpublished material suggests that his alternative reconstruction of the ancient beginnings of the Western scientific tradition motivate and justify his moderate Protagorean relativism.


Capsulotomy technique in the presence of an anterior chamber lens.
A modified Sato technique has proved to be a highly successful and atraumatic method of posterior capsulotomy in the presence of an anterior chamber lens. The lens remains undisturbed and iris-ciliary body, vitreous-retinal traction is avoided.


Transparent floatable magnetic alginate sphere used as photocatalysts carrier for improving photocatalytic efficiency and recycling convenience.
Practical application of powder photocatalysts is far from satisfying due to their low photon utilization, inconvenient recovery and potential environmental risk. In this study, an easily recoverable, environmentally friendly and highly transparent floatable magnetic photocatalyst carrier was prepared based on biopolymer alginate and Fe3O4 particles. Further, three different types of photocatalysts were chosen as model semiconductor photocatalysts and loaded on the shell of the carriers. The freeze process facilitated the formation of internal cavities that enhanced floating ability and transparency of the spheres. Meanwhile, the excellent floating performance offered massive reaction sites for pollutants reacting with photocatalysts, O2 and photons on the air/water interface. Photodegradation results showed all three floatable hybrid photocatalysts exhibited enhanced photocatalytic efficiencies compared to the virgin photocatalysts. In short, the carrier can integrate excellent floating ability, environmental friendliness and full recycling with good stability, and it can greatly improve the photocatalytic efficiency of various powder semiconductor photocatalysts.


Colchicine effect on B-50/GAP43 phosphoprotein localization in rat dorsal root ganglion explants.
In rat embryonic dorsal root ganglion explants stimulated by nerve growth factor, the neuron-specific phosphoprotein B-50 (GAP43) is primarily localized in the distal portion of outgrowing neurites. Addition of colchicine leads to a decrease in total amount of B-50 and a marked redistribution in the neurons. The data underscore the role of axonal transport in the concentration of B-50 in growth cones of growing neurites.


Development and evaluation of Moringa extract incorporated Chitosan/Guar gum/Poly (vinyl alcohol) active films for food packaging applications.
The present study contributes the synthesis of active films with the incorporation of moringa extract (ME) into chitosan (CS)/guar gum (GG)/poly(vinyl alcohol) (PVA) matrix (CGPM) by simple solvent casting technique. The effect of ME on the mechanical, thermal, structural and morphological properties of CGPM active films were investigated. ME has shown a marked influence on the optical, thermal properties and swelling behaviour of CGPM active films. The improvement in the tensile strength of CGPM-1 active film (53.7 MPa) was observed compared to control CS/GG/PVA (CGP) film. DSC study revealed that glass transition temperature (Tg) and melting temperature (Tm) decreased with the addition of ME in the CGP matrix, which confirmed the miscibility among the components of active films. There was an improvement in the thermal stability of the CGPM active films. The FTIR study confirmed the molecular interaction between ME and CS/GG/PVA matrix. The XRD analysis showed a decrease in crystallinity with an increase in the ratio of CS for CGPM active films. The CGPM active films were an excellent barrier to UV- light and have exhibited a decrease in moisture adsorption and water solubility compared to CGP control film. The inclusion of ME in the CGP matrix leads to the formation of a dense compact surface, which in turn enhanced hydrophobicity of active films. The CGPM active films showed minimum WVP, OP values and overall migration values were within the limits of 10 mg/dm2. It was also observed that CGPM active films effectively inhibited the growth of E. coli and S. aureus bacteria. These findings suggest CGPM active films are biodegradable, biocompatible, non-toxic and hence can find application as food packaging materials.


Arctic Ocean: hydrothermal activity on Gakkel Ridge.
In the hydrothermal circulation at mid-ocean ridges, sea water penetrates the fractured crust, becomes heated by its proximity to the hot magma, and returns to the sea floor as hot fluids enriched in various chemical elements. In contradiction to earlier results that predict diminishing hydrothermal activity with decreasing spreading rate, a survey of the ultra-slowly spreading Gakkel Ridge (Arctic Ocean) by Edmonds et al. and Michael et al. suggests that, instead of being rare, the hydrothermal activity is abundant--exceeding by at least a factor of two to three what would be expected by extrapolation from observation on faster spreading ridges. Here we use helium-3 (3He), a hydrothermal tracer, to show that this abundance of venting sites does not translate, as would be expected, into an anomalous hydrothermal 3He output from the ridge. Because of the wide implications of the submarine hydrothermal processes for mantle heat and mass fluxes to the ocean, these conflicting results call for clarification of the link between hydrothermal activity and crustal production at mid-ocean ridges.


Barium aspiration - Accident or complication?
Aspiration of barium sulfate is possible during radiographic contrast procedures and is potentially life-threatening in severe cases. In patients with dysphagia or suspected tracheoesophageal fistula, barium compounds may be used, considering lateral projection fluoroscopy of the pharyngeal phase of swallowing, but iso-osmotic agents should also be considered.


The change of the neuron-glia differentiation rate in human neural precursor cells (HPCs) and Ad-BDNF-/-GDNF-infected HPCs following the administration of a neurotoxin.
Neurotrophic factors promote the survival of various neurons, including peripheral autonomic and sensory neurons, as well as central motor and dopamine neurons, and it is expected that they could function as therapeutic agents for neurodegenerative disease. We examined the changes in the neuron-glia differentiation rate in normal human neural precursor cells (HPCs), Ad-BDNF- and Ad-GDNF-infected HPCs following their treatment with 6-OHDA. We isolated the precursor cells from the human fetal midbrain. To investigate the expression of differentiated cell markers within neurons and glia after 6-OHDA-induced toxicity in HPCs, immunocytochemistry was performed. Our results showed that the treatment with 6-OHDA (100, 200, 300, 400 and 500 microM) for 24 h decreased the viability of the HPCs in vitro. Among the growth factors tested, BDNF and GDNF protected the HPCs against 6-OHDA-induced toxicity. Approximately, 5.8+/-2.2% and 0.5+/-0.1% of the HPCs treated with 6-OHDA were positive for the neuron marker, MAP2, and the oligodendrocyte marker, GalC, respectively, while 13.8+/-3.2% and 1.1+/-0.36% of the Ad-BDNF- or Ad-GDNF-infected HPCs treated with 6-OHDA stained positive for MAP2 and GalC, respectively. These results suggest that cocktail therapy using human precursor cells (HPCs) and certain neurotrophic factors (BDNF, GDNF) provide direct protection against 6-OHDA-induced toxicity and has an effect on the differentiation rate.