Nineteenth century mortality at the Royal Hospital for Sick Children, Glasgow.
Since Glasgow's Royal Hospital for Sick Children opened in 1882, significant advances have been made in child health. Our aim was to investigate the hospital mortality that occurred in the last decade of the 19th century at Royal Hospital for Sick Children. Hospital mortality records for the decades, 1890-1899, were collected from the Archives of the Royal Hospital for Sick Children. Data were extracted from the hospital inpatient records and the pathology records. In the decade 1890-1899, there were 731 hospital deaths. The main cause of death at that time in the 19th Century was infection, particularly of the respiratory tract. The age at which death occurred was analysed and the recorded cause were analysed as was the distance patients travelled to the hospital. The ratio of boys to girls and length of inpatient stay was similar to that seen in the hospital currently. This study records the mortality in a children's hospital in a large developing industrial city in the 19th century as experienced in a children's hospital.


Saturation Mutagenesis of the Antithrombin Reactive Center Loop P14 Residue Supports a Three-step Mechanism of Heparin Allosteric Activation Involving Intermediate and Fully Activated States.
Past studies have suggested that a key feature of the mechanism of heparin allosteric activation of the anticoagulant serpin, antithrombin, is the release of the reactive center loop P14 residue from a native state stabilizing interaction with the hydrophobic core. However, more recent studies have indicated that this structural change plays a secondary role in the activation mechanism. To clarify this role, we expressed and characterized 15 antithrombin P14 variants. The variants exhibited basal reactivities with factors Xa and IXa, heparin affinities and thermal stabilities that were dramatically altered from wild type, consistent with the P14 mutations perturbing native state stability and shifting an allosteric equilibrium between native and activated states. Rapid kinetic studies confirmed that limiting rate constants for heparin allosteric activation of the mutants were altered in conjunction with the observed shifts of the allosteric equilibrium. However, correlations of the P14 mutations' effects on parameters reflecting the allosteric activation state of the serpin were inconsistent with a two-state model of allosteric activation and suggested multiple activated states. Together, these findings support a minimal three-state model of allosteric activation in which the P14 mutations perturb equilibria involving distinct native, intermediate, and fully activated states wherein the P14 residue retains an interaction with the hydrophobic core in the intermediate state but is released from the core in the fully activated state, and the bulk of allosteric activation has occurred in the intermediate.


Screening of cord blood low-density-lipoprotein cholesterol in the diagnosis of familial hypercholesterolaemia: a study of 2000 infants.
A prospective follow-up study of infants selected by cord blood total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) levels from 2000 consecutive live births was undertaken to reassess the role of cord blood screening in the diagnosis of familial hypercholesterolaemia (FH). Mean values for serum cholesterol were (mmol/l +/- S.D.): TC, 1.83 +/- 0.56; LDL-C, 0.90 +/- 0.49; HDL-C, 0.70 +/- 0.33; TG, 0.38 +/- 0.16. Seventy-three of 117 infants who had had a cord TC and/or LDL-C greater than 95th percentile, and 373 control group children (cord TC and/or LDL-C less than 95th percentile) were followed up at age 3--12 months. Six of the 117 were hypercholesterolaemic (HC), and one child had an HC parent: positive detection rate greater than or equal to 0.05%; false positive rate greater than or equal to 3.7%. Four control-group children were HC and had an HC parent; false negative rate greater than or equal to 1.1%. With the possible exception of detecting FH in a child with a known affected parent, cord blood screening appears to be unreliable for the diagnosis of FH.


Local 5HT3 receptors mediate fluoxetine but not desipramine-induced increase of extracellular dopamine in the prefrontal cortex.
Fluoxetine and desipramine, two antidepressants that block selectively the serotonin and the noradrenaline carrier, increase extracellular dopamine concentrations in the prefrontal cortex of freely-moving rats. This effect is calcium dependent and is prevented, in the case of fluoxetine but not desipramine, by systemic pretreatment with low doses or by low concentrations in the dialyzing Ringer of the potent 5-HT3 antagonist ICS 205930. Fluoxetine, but not desipramine, increases extracellular serotonin concentrations in the prefrontal cortex. The results indicate that selective serotonin reuptake blockers increase extracellular dopamine in the prefrontal cortex by stimulating local 5-HT3 receptors.


Increased risk of severe infections in cancer patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a meta-analysis.
Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) have been widely used in a variety of solid malignancies. Concerns have arisen regarding the risk of severe infections (≥grade 3) with use of these drugs, but the contribution of VEGFR-TKIs to infections is still unknown. The databases of PubMed and abstracts presented at oncology conferences' proceedings were searched for relevant studies from January 2000 to December 2014. Summary incidences, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were calculated by using either random-effects or fixed-effects models according to the heterogeneity of included studies. A total of 16,488 patients from 27 randomized controlled trials were included. The risk of developing severe (Peto OR 1.69, 95% CI: 1.45-1.96, P<0.001) and fatal infections (Peto OR 1.78, 95% CI: 1.13-2.81, P=0.013) was significantly increased in patients treated with VEGFR-TKIs when compared to controls. Exploratory subgroup analysis showed no effect of tumor types, phase of trials, or agent used on the Peto OR of severe infections. When stratified according to specific infectious events, the risks of high-grade febrile neutropenia, pneumonia, fever, and sepsis were increased compared with controls, with Peto ORs of 1.57 (95% CI: 1.30-1.88, P<0.001), 1.79 (95% CI: 1.29-2.49, P<0.001), 5.35 (95% CI: 1.47-19.51, P=0.011), and 3.68 (95% CI: 1.51-8.99, P=0.004), respectively. Additionally, VEGFR-TKIs significantly increased the risk of fatal sepsis (OR 3.66, 95% CI: 1.47-9.13, P=0.005) but not fatal pneumonia (OR 1.34, 95% CI: 0.80-2.25, P=0.26). The use of VEGFR-TKIs significantly increases the risk of developing severe and fatal infectious events in cancer patients. A close monitoring for any signs of infections is recommended for patients treated with VEGFR-TKIs.


Association of spermidine plasma levels with brain aging in a population-based study.
Supplementation with spermidine may support healthy aging, but elevated spermidine tissue levels were shown to be an indicator of Alzheimer's disease (AD). Data from 659 participants (age range: 21-81 years) of the population-based Study of Health in Pomerania TREND were included. We investigated the association between spermidine plasma levels and markers of brain aging (hippocampal volume, AD score, global cortical thickness [CT], and white matter hyperintensities [WMH]). Higher spermidine levels were significantly associated with lower hippocampal volume (ß = -0.076; 95% confidence interval [CI]: -0.13 to -0.02; q = 0.026), higher AD score (ß = 0.118; 95% CI: 0.05 to 0.19; q = 0.006), lower global CT (ß = -0.104; 95% CI: -0.17 to -0.04; q = 0.014), but not WMH volume. Sensitivity analysis revealed no substantial changes after excluding participants with cancer, depression, or hemolysis. Elevated spermidine plasma levels are associated with advanced brain aging and might serve as potential early biomarker for AD and vascular brain pathology.


Optical properties of CAD-CAM monolithic systems compared: three multi-layered zirconia and one lithium disilicate system.
this in vitro investigation aims to evaluate and compare optical properties of three types of esthetic CAD-CAM monolithic multi-layered zirconia materials with a control (conventional lithium disilicate, IPS e. max CAD). Four monolithic CAD-CAM ceramic materials were investigated: Ceramill Zolid® FX Multilayer (ZF), IPS e. max® ZirCAD MT Multi (ZM), Katana® STML (KS) and one lithium disilicate glass-ceramics as a control (IPS e. max® CAD LT; LC). A total of 72 (15 × 15 × 1 mm) samples were CAD CAM fabricated and sintered based on sample-size power calculations, and each material comprised 18 samples. The translucency and opalescence parameters with the contrast ratio were evaluated with a dental spectrophotometer over the backgrounds of black and white. The data were analyzed by ANOVA, then Bonferroni post hoc comparison test was made between groups. The statistical significance was set at p < 0.05. Zirconia materials revealed lower optical properties than the lithium disilicate control LC (P < 0.05). TP values ranged from 14.174 to 20.439. No differences were detected between the zirconia products in terms of TP and CR (P = 1.000). OP values ranged from 5.068 to 10.097. The lowest OP values were found statistically significant for ZF followed by KS and ZM (P = 1.000). LC had the highest TP and OP values, as well as the lowest CR (p < 0.05). The optical properties of monolithic zirconia systems tested here are still lower than those of lithium disilicate glass-ceramics. The only difference observed between the monolithic CAD CAM zirconia materials, was for the low opalescence parameter for the ZF. Multi-layered monolithic zirconia systems have better esthetics by shade layers resembling natural tooth color gradients. CAD-CAM technology allowed for in-office milling and shaping of restorations using these systems. This study reports on their optical properties affecting human vision/perception of natural tooth shade to conclude about their use in the esthetic zones.


Epidemiology of carbapenem-resistant and carbapenemase-producing Enterobacterales in the Netherlands 2017-2019.
The Netherlands is currently considered a low endemic country for carbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE), experiencing only sporadic hospital outbreaks. This study aims to describe susceptibility to carbapenems and the epidemiology of carbapenemase production in Enterobacterales in the Netherlands in 2017-2019. Three complementary nationwide surveillance systems are in place to monitor carbapenem susceptibility in the Netherlands. Routine antimicrobial susceptibility test results from medical microbiology laboratories were used to study phenotypic susceptibility of Escherichia coli and Klebsiella pneumoniae. Pathogen surveillance (of all Enterobacterales species) and mandatory notifications were used to describe the characteristics of CPE positive isolates and affected persons. The prevalence of isolates with gradient strip test-confirmed elevated meropenem (> 0.25 mg/L) or imipenem (> 1 mg/L) minimum inhibitory concentration (MIC) in the Netherlands was very low in 2017-2019, with percentages of 0.06% in E. coli and 0.49% in K. pneumoniae, and carbapenem resistances of 0.02% and 0.18%, respectively. A total of 895 unique species/carbapenemase-encoding allele combinations of CPE from 764 persons were submitted between 2017 and 2019, with the annual number of submissions increasing slightly each year. Epidemiological data was available for 660 persons. Screening because of presumed colonisation risk was the reason for sampling in 70.0% (462/660) of persons. Hospitalization abroad was the most common risk factor, being identified in 45.9% of persons. Carbapenem resistance of E. coli and K. pneumoniae remains low in the Netherlands. The annual number of CPE isolates slightly increased during the period 2017-2019. Recent hospitalization abroad is the main risk factor for acquisition of CPE.


Synthesis and antibacterial and cytotoxic activities of new N-3 substituted thiazolidine-2,4-dione derivatives bearing the pyrazole moiety.
Two new series of N-3 substituted thiazolidine-2,4-dione derivatives bearing the pyrazole moiety (5a-j and 7a-j) were synthesized and assessed in vitro for their efficacy as antibacterial agents against gram-positive and gram-negative bacterial strains. Among the tested compounds, 7b, 7c, 7i, and 7j were found to be active against gram-positive bacteria (Staphylococcus aureus and Streptococcus pyogenes) with minimum inhibitory concentration (MIC) values in the range of 6.25-25 µg/mL, and some compounds were also tested against methicillin-resistant S. aureus (MRSA). Compounds 7c and 7j inhibited the growth of MRSA at MIC values of 6.25 and 12.5 µg/mL, respectively. The influence of the lipophilicity (C log P) on the biological profile (MIC) of the prepared products was also discussed. From the standpoint of structure-activity relationship studies, it was observed that the lipophilic profiles of the compounds were crucial for their antibacterial activities. Further, the results of the MTT cytotoxicity studies on a human cervical cancer cell line (HeLa) and a mouse embryonic fibroblast cell line (NIH 3T3) suggested that compounds 7b, 7c, 7i, and 7j were endowed with low levels of cytotoxicity.


8-isoprostanes and resistin as markers of vascular damage in non-hypersomnolent obstructive sleep apnoea patients.
Oxidative stress and inflammation are assumed as the main pathological triggers for vascular damage in hypersomnolent obstructive sleep apnoea (OSA) patients, whereas their exact role in less symptomatic population is currently unknown. To determine whether oxidative stress (urinary 8-isoprostane concentration) and inflammation (plasma resistin levels) are associated with vascular damage in non-hypersomnolent (Epworth Sleep Score <11) OSA patients. A total of 325 consecutive patients have undergone standard polysomnography, and 256 of them were diagnosed with OSA. Excessive daytime sleepiness was assessed by the Epworth Sleepiness Scale (ESS). Only 86 patients with ESS <11 participated in the study. The control group was presented by 45 subjects without OSA. Endothelial function was assessed by ultrasonographic measurement of flow-mediated dilatation (FMD). Intima-media thickness (IMT) and ankle-brachial index (ABI) were determined by ultrasonography. Urinary 8-isoprostanes (Cayman Chemical, USA) were measured, applying mass spectrometry. Resistin (RayBio_ Human ResistinCat#:ELH-Resistin-001) plasma levels were detected by ELISA. In patients with OSA, flow-mediated dilatation was significantly lower than in control subjects (4·62% ±1·9) and (7·1% ±2·8), respectively (P: 0·013). The prevalence of plaques in a.carotis communis was higher in OSA (16% versus 4%). The same is observed regarding a.tibialis posterior (81% vs. 29%). The average IMT and ABI in OSA and in the control group were, respectively, (IMT - 800 µm versus. 666 µm); (ABI -1·06 versus 1·20). Urinary isoprostanes were higher in OSA patients (0·091 versus 0·078) and correlated negatively to FMD (r: -0·825, P: 0·00), IMT (r: -0·324, P: 0·003) and ABI (r: -0·226, P: 0·043). No association between resistin and the degree of vascular injury was found. In comparison with the control group, increased prevalence of endothelial dysfunction and vascular damage was established in OSA patients without excessive daytime sleepiness. Urinary 8-isoprostanes (oxidative stress markers) are closely associated with FMD (endothelial dysfunction), IMT and ABI (vascular damage). Resistin plasma levels correlated neither to FMD, nor to IMT or ABI.


Targeting regulated cell death (RCD) with small-molecule compounds in cancer therapy: A revisited review of apoptosis, autophagy-dependent cell death and necroptosis.
Evasion of regulated cell death (RCD), mainly referring to apoptosis, autophagy-dependent cell death, necroptosis, and other subroutines, is one of the well-established hallmarks of cancer cells. Accumulating evidence has revealed several small-molecule compounds that target different subroutines of RCD in cancer therapy. In this review, we summarize key pathways of apoptosis, autophagy-dependent cell death and necroptosis in cancer, and describe small-molecule compounds that target these pathways and have potential as therapeutics. These inspiring findings light the way towards the discovery of more 'magic bullets' that could work individually or cooperatively to target precisely the three RCD subroutines and so improve cancer treatment.


Experience alters hippocampal and cortical network communication via a KIBRA-dependent mechanism.
Synaptic plasticity is hypothesized to underlie "replay" of salient experience during hippocampal sharp-wave/ripple (SWR)-based ensemble activity and to facilitate systems-level memory consolidation coordinated by SWRs and cortical sleep spindles. It remains unclear how molecular changes at synapses contribute to experience-induced modification of network function. The synaptic protein KIBRA regulates plasticity and memory. To determine the impact of KIBRA-regulated plasticity on circuit dynamics, we recorded in vivo neural activity from wild-type (WT) mice and littermates lacking KIBRA and examined circuit function before, during, and after novel experience. In WT mice, experience altered population activity and oscillatory dynamics in a manner consistent with incorporation of new information content in replay and enhanced hippocampal-cortical communication. While baseline SWR features were normal in KIBRA conditional knockout (cKO) mice, experience-dependent alterations in SWRs were absent. Furthermore, intra-hippocampal and hippocampal-cortical communication during SWRs was disrupted following KIBRA deletion. These results indicate molecular mechanisms that underlie network-level adaptations to experience.


Glutamate-induced free radical formation in rat brain synaptosomes is not dependent on intrasynaptosomal mitochondria membrane potential.
Glutamate induces reactive oxygen species formation (ROS) in neurons. Free radicals can potentially be synthesized by NADPH oxidase or mitochondria. The primary source of ROS origin has yet to be identified. In addition, pro-oxidant action of glutamate receptors on neuronal presynaptic terminals is still not characterized. We investigated the influence of glutamate and agonists of its ionotropic receptors on ROS formation detected by fluorescent dye DCFDA in rat brain synaptosomes. Glutamate in concentration 10 and 100μM led to an increase of probe fluorescence pointing to free radical accumulation. This effect was mimicked by 100μM of NMDA or 100μM of kainate. Glutamate-induced ROS formation was sensitive to NMDA inhibitors MK-801 (10μM), NO synthase (NOS) inhibitor l-NAME (100μM) and NADPH oxidase inhibitors DPI (30μM) and not affected by mitochondrial uncoupler CCCP (10μM) and mitochondrial toxins rotenone (10μM)+oligomycin (5μg/ml). We also showed that 100μM of glutamate leads to a decrease of intrasynaptosomal mitochondrial potential monitored by fluorescent dye Rhodamine-123. Hence, the depolarization of intrasynaptosomal mitochondria is not a primary cause of glutamate-induced ROS formation in neuronal presynaptic terminals. Activation of NMDA receptors might be responsible for a certain part of glutamate pro-oxidant action. Most likely, sources of glutamate-induced ROS formation in neuronal presynaptic terminals are NADPH oxidase and NOS activation.


Correction: Dietary polyphenols as a safe and novel intervention for modulating pain associated with intervertebral disc degeneration in an in-vivo rat model.
[This corrects the article DOI: 10.1371/journal.pone.0223435.].


A genetic correlation scan identifies blood proteins associated with bone mineral density.
Osteoporosis is a common metabolic bone disease that is characterized by low bone mass. However, limited efforts have been made to explore the functional relevance of the blood proteome to bone mineral density across different life stages. Using genome-wide association study summary data of the blood proteome and two independent studies of bone mineral density, we conducted a genetic correlation scan of bone mineral density and the blood proteome. Linkage disequilibrium score regression analysis was conducted to assess genetic correlations between each of the 3283 plasma proteins and bone mineral density. Linkage disequilibrium score regression identified 18 plasma proteins showing genetic correlation signals with bone mineral density in the TB-BMD cohort, such as MYOM2 (coefficient = 0.3755, P value = 0.0328) among subjects aged 0 ~ 15, POSTN (coefficient = - 0.5694, P value = 0.0192) among subjects aged 30 ~ 45 and PARK7 (coefficient = - 0.3613, P value = 0.0052) among subjects aged over 60. Our results identified multiple plasma proteins associated with bone mineral density and provided novel clues for revealing the functional relevance of plasma proteins to bone mineral density.


Hyaluronic acid thiol modified injectable hydrogel: Synthesis, characterization, drug release, cellular drug uptake and anticancer activity.
Dimethyl sulfoxide (DMSO) is an excellent solvent for various types of anticancer drugs. Here, beyond that, it can participate in a disulfide bond crosslink between sulfhydryl (-SH) modified hyaluronic acid (HA-SH) molecules to form the hydrogel. Thus, during the above crosslink process, the dissolved drug in DMSO could be effectively loaded inside the hydrogels' porous structures as an injectable peritumoral implant. The loaded drugs can be sustained released through hydrogel swelling and degradation around the tumor tissue to suppress tumor growth. In this paper, the above hydrogel was used as a peritumoral drug-loaded implant for chemotherapeutics, photosensitizer, and photothermal reagent, respectively, for chemotherapy, photodynamic therapy, and photothermal therapy in cancer treatment. Therefore, this DMSO involved HA-SS-HA (HA, hyaluronic acid; -SS-, disulfide bond) hydrogel fabrication method is simple and widely applicable for drug-loaded peritumoral implant preparation.


PCR detection of cytokines in normal human and pagetic osteoblast-like cells.
We investigated the expression of cytokine transcripts in osteoblast-like cells derived from explants of pagetic and normal bone. A reverse transcription-linked PCR was used that allowed the simultaneous analysis of a range of cytokines. Normal osteoblast-like cells were found to contain the transcripts for IL-1 beta, IL-6, and TGF-beta 1. For the first time we detected in bone cells the two other mammalian isoforms of TGF-beta, beta 2, and beta 3. Furthermore, we have also identified mRNA for IL-3 and the novel chemotactic factor, IL-8. Using this sensitive technique it was not possible to detect mRNA for IL-1 alpha, IL-2, IL-4, IL-5, IL-7, TNF-alpha, or interferon-gamma. The human osteosarcoma cell line Saos-2 also showed a similar pattern of expression of these cytokines to primary osteoblast-like cells, with the exception that TNF-alpha was also identified. Cells isolated from pagetic bone showed essentially the same profile of cytokine expression as normal bone except that TNF-alpha was also detected in two of four samples. The cytokine profile of successive populations of cells harvested from one explant culture at 9, 22, and 57 days showed a consistent pattern of cytokine expression, demonstrating the phenotypic stability of the osteoblast-like cells in long-term cultures.


Can red deer antlers be used as an indicator of environmental and edible tissues' trace element contamination?
Venison is an attractive product for consumers concerned with healthy lifestyle; however, it can contain high levels of toxic elements, and therefore, it is a possible source of hazardous contaminants in human diet. Antlers are suitable bioindicators of environmental metal contamination, and herein, we assessed the ability of trace element levels in antlers to indicate levels in edible soft tissues. We determined the concentrations of lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), copper (Cu), zinc (Zn), and iron (Fe) in the liver, kidney, muscle, and antlers of 14 free-ranging red deer (Cervus elaphus) from northeastern Poland using atomic absorption spectrometry. We found the highest concentrations of Pb (0.321 ± 0.165 mg/kg), As (0.045 ± 0.074 mg/kg), Zn (105.31 ± 16.33 mg/kg), and Fe (220.92 ± 117.18 mg/kg) in antlers; of Cd (4.974 ± 1.90 mg/kg) and Hg (0.048 ± 0.102 mg/kg) in kidney; and of Cu (7.29 ± 7.02 mg/kg) in the liver. A positive relationship between concentrations in antlers and muscle was found only for Cu (p = 0.001), and it therefore appears that red deer antlers cannot be used as an index for element concentrations in soft tissues. While our results confirm that the Mazury region is little polluted, consumption of red deer offal from this area should be limited according to extant legal limits set for livestock consumption.


Comparative Study of Anterior Eye Segment Measurements with Spectral Swept-Source and Time-Domain Optical Coherence Tomography in Eyes with Corneal Dystrophies.
To compare anterior eye segment measurements and morphology obtained with two optical coherence tomography systems (TD OCT, SS OCT) in eyes with corneal dystrophies (CDs). Fifty healthy volunteers (50 eyes) and 54 patients (96 eyes) diagnosed with CD (epithelial basement membrane dystrophy, EBMD = 12 eyes; Thiel-Behnke CD = 6 eyes; lattice CD TGFBI type = 15 eyes; granular CD type 1 = 7 eyes, granular CD type 2 = 2 eyes; macular CD = 23 eyes; and Fuchs endothelial CD = 31 eyes) were recruited for the study. Automated and manual central corneal thickness (aCCT, mCCT), anterior chamber depth (ACD), and nasal and temporal trabecular iris angle (nTIA, tTIA) were measured and compared with Bland-Altman plots. Good agreement between the TD and SS OCT measurements was demonstrated for mCCT and aCCT in normal individuals and for mCCT in the CDs group. The ACD, nTIA, and tTIA measurements differed significantly in both groups. TBCD, LCD, and FECD caused increased CCT. MCD caused significant corneal thinning. FECD affected all analyzed parameters. Better agreement between SS OCT and TD OCT measurements was demonstrated in normal individuals compared to the CDs group. OCT provides comprehensive corneal deposits analysis and demonstrates the association of CD with CCT, ACD, and TIA measurements.


[Tobacco consumption among high school students. Preliminary results from a survey in Tampico, Tamaulipas, Mexico].
Tobacco consumption constitutes a public health problem among adolescents. National addiction surveys in Mexico have documented a growing trend in this habit over the years. Describe the prevalence of tobacco consumption among a sample of high school students sample in Tampico, Tamaulipas and identify socio-demographic variables. Students enrolled in the 2006-2007 school year attending 31 schools located in this county were surveyed. The sample was probabilistic, stratified and random. Students were the sampling units. We used a standardized questionnaire. 5,060 students were surveyed, 50.99% were female, mean age was 13.5 +/- 1 range 11-17. 66.7% started tobacco consumption between the ages of 13- 14, 28.5% (CI 27.2-29.8) had smoked once in their lives, 17% (CI 15.9-18.5) in the last twelve months and 9% (CI 18.2-9.8) in the last thirty days. A small percentage (7.2%) believed smoking was not dangerous and 1.6% of smokers meet the criteria for nicotine dependence. We recommend to increase prevention programs targeted at high-risk groups such as adolescents.


Plasma thrombopoietin in patients with cavernous transformation of the portal vein.
Thrombopoietin (TPO), the primary regulator of thrombopoiesis, is produced mainly in the liver. Previous studies investigating blood TPO in chronic liver diseases revealed conflicting results. It has been suggested that hepatic TPO production is regulated by the portal blood supply to the liver. However, the role of TPO in the pathobiological basis of idiopathic portal vein thrombosis (PVT) and cavernous transformation of the portal vein (CTPV) has not been elucidated. The objective of this study is to assess plasma TPO concentrations in patients with CTPV. Eleven patients (4 men and 7 women, aged 38+/-12 years) with CTPV were studied. Sixteen healthy adults served as the control group (8 men and 8 women, aged 34+/-12 years). Median plasma TPO concentration was 326 pg/mL (range, 15-1402 pg/mL) in the patients with CTPV and 62.65 pg/mL (range, 38.5-102 pg/mL) in the control group (P = .003). In this study, we found significantly higher TPO concentrations in the plasma of patients with CTPV. The higher concentrations could be a result of the altered portal hemodynamics due to thrombosis. Moreover, TPO release by activated platelets might lead to the subsequent propagation of thrombosis in PVT.


Quality assessment tools: ACOG Voluntary Review of Quality of Care Program, Peer Review Reporting System.
The Voluntary Review of Quality of Care Program is the American College of Obstetricians and Gynecologists' program of peer review. It is dedicated to quality improvement, patient safety, and peer review, which is conducted by a national professional specialty organization. Since the program's inception, 236 hospitals providing obstetric and gynecologic services in this country have been reviewed. This article presents the results of these reviews. Common problems are identified and possible corrective action is recommended. This program represents a useful model of national peer review activity that can impact patient care.


The role of molecular mechanism of Ten-Eleven Translocation2 (TET2) family proteins in pathogenesis of cardiovascular diseases (CVDs).
Cardiovascular disease (CVD) is one of the most common diseases worldwide. The underlying pathogenesis of the disease has not yet been determined, but many factors have been identified. Tet methylcytosine dioxygenase 2 (TET2) is one of the epigenetic factors involved in regulating many genes. Therefore, based on the studies shown, this factor plays an important role in preventing the occurrence of CVD. TET2 has been shown to increase angiogenesis by expressing Robo4. It also increases the activity of Matrix metalloproteinases (MMPs) and stimulates the secretion of Vascular endothelial growth factor angiogenesis. On the other hand, it has been shown that TET2 regulates the expression of several genes and the development of the heart during the embryonic period due to its oxygenating role. TET2 has been shown to regulates the expression of the genes such as Ying Yang1 (YY1), Sox9b, Inhbaa and many other genes that ultimately lead to the differentiation of cardiomyocytes. On the other hand, it has been shown that some Long non coding RNA and MicroRNAs reduce TET2 expression and CVD. Finally, it is concluded that inducing TET2 expression can be a good therapeutic strategy to prevent or improve CVD.


Melatonin exerts neuroprotective effects by inhibiting neuronal pyroptosis and autophagy in STZ-induced diabetic mice.
Diabetes mellitus (DM) patients are at a higher risk of developing brain injury characterized by neuronal death. Melatonin, a hormone produced by the pineal gland, exerts neuroprotective effects against brain damage. However, the effect of melatonin on diabetes-induced brain injury has not been elucidated. This study was to evaluate the role of melatonin against neuronal death in DM and to elucidate the underlying mechanisms. Herein, we found that melatonin administration significantly alleviated the neuronal death in both streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-treated neuronal cells. Melatonin inhibited neuronal pyroptosis and excessive autophagy, as evidenced by decreased levels of NLRP3, cleaved caspase-1, GSDMD-N, IL-1β, LC3, Beclin1, and ATG12 both in vivo and in vitro. MicroRNA-214-3p (miR-214-3p) was decreased in DM mice and HG-treated cells, and such a downregulation was corrected by melatonin, which was accompanied by repression of caspase-1 and ATG12. Furthermore, downregulation of miR-214-3p abrogated the anti-pyroptotic and anti-autophagic actions of melatonin in vitro. Our results indicate that melatonin exhibits a neuroprotective effect by inhibiting neuronal pyroptosis and excessive autophagy through modulating the miR-214-3p/caspase-1 and miR-214-3p/ATG12 axes, respectively, and it might be a potential agent for the treatment of brain damage in the setting of DM.


Corticotropin-releasing hormone (CRH) alters mitochondrial morphology and function by activating the NF-kB-DRP1 axis in hippocampal neurons.
Neuronal stress-adaptation combines multiple molecular responses. We have previously reported that thorax trauma induces a transient loss of hippocampal excitatory synapses mediated by the local release of the stress-related hormone corticotropin-releasing hormone (CRH). Since a physiological synaptic activity relies also on mitochondrial functionality, we investigated the direct involvement of mitochondria in the (mal)-adaptive changes induced by the activation of neuronal CRH receptors 1 (CRHR1). We observed, in vivo and in vitro, a significant shift of mitochondrial dynamics towards fission, which correlated with increased swollen mitochondria and aberrant cristae. These morphological changes, which are associated with increased NF-kB activity and nitric oxide concentrations, correlated with a pronounced reduction of mitochondrial activity. However, ATP availability was unaltered, suggesting that neurons maintain a physiological energy metabolism to preserve them from apoptosis under CRH exposure. Our findings demonstrate that stress-induced CRHR1 activation leads to strong, but reversible, modifications of mitochondrial dynamics and morphology. These alterations are accompanied by bioenergetic defects and the reduction of neuronal activity, which are linked to increased intracellular oxidative stress, and to the activation of the NF-kB/c-Abl/DRP1 axis.


Systemic lupus erythematosus due to Epstein-Barr virus or Epstein-Barr virus infection provocating acute exacerbation of systemic lupus erythematosus?
Systemic lupus erythematosus (SLE) is a rheumatologic disease characterized by an inflammatory destruction of the target organ systems of the body in an unknown way by autoantibodies formed against self-antigens. Infectious agents like Epstein-Barr virus (EBV), cytomegalovirus and parvovirus B19 may have a role in the occurrence or the exacerbation of the SLE. In this report, the clinical follow-up of a 14-year-old girl diagnosed with SLE following an EBV infection with bicytopenia, lymphadenomegaly and hepatomegaly is discussed. This case could support the role of viral infections in the etiology of SLE.


Exploring a causal model in observational cohort data: The role of parents and peers in shaping substance use trajectories.
To explore the process of applying counterfactual thinking in examining causal determinants of substance use trajectories in observational cohort data. Specifically, we examine the extent to which quality of the parent-adolescent relationship and affiliations with deviant peers are causally related to trajectories of alcohol, tobacco, and cannabis use across adolescence and into young adulthood. Data were drawn from the Australian Temperament Project, a population-based cohort study that has followed a sample of young Australians from infancy to adulthood since 1983. Parent-adolescent relationship quality and deviant peer affiliations were assessed at age 13-14 years. Latent curve models were fitted for past month alcohol, tobacco, and cannabis use (n = 1590) from age 15-16 to 27-28 years (5 waves). Confounding factors were selected in line with the counterfactual framework. Following confounder adjustment, higher quality parent-adolescent relationships were associated with lower baseline cannabis use, but not alcohol or tobacco use trajectories. In contrast, affiliations with deviant peers were associated with higher baseline binge drinking, tobacco, and cannabis use, and an earlier peak in the cannabis use trajectory. Despite careful application of the counterfactual framework, interpretation of associations as causal is not without limitations. Nevertheless, findings suggested causal effects of both parent-adolescent relationships and deviant peer affiliations on the trajectory of substance use. Causal effects were more pervasive (i.e., more substance types) and protracted for deviant peer affiliations. The exploration of causal relationships in observational cohort data is encouraged, when relevant limitations are transparently acknowledged.


Template active chromatin structures: degradation by deoxyribonuclease I.
Chicken embryos were pulse-labelled in vivo with [3H]uridine (10 min), the chromatin isolated and treated with DNAse I. The residual chromatin was separated from the degradation products by centrifugation. The nascent pulse-labelled RNA is completely recovered in the residual chromatin even after prolonged incubation with DNAase I, whereas the DNA is completely degraded to 80 base polynucleotide fragments and smaller fragments.


The effects of aspirin on the development of the mouse third molar. A potential screening system for weak teratogens.
Aspirin is teratogenic at high doses in rodents. A dose related effect is shown at much lower levels in an animal testing system which permits subthreshold effects on development to be measured. This system, which depends on changes in tooth size in the mouse, has advantages in assessing weak or cumulative teratogens.


Sequential release of TNFalpha and phospholipase A(2) in a rat model of LPS-induced pleurisy.
The levels of extracellular phospholipase A(2) (sPLA(2)) and TNFalpha, and cell accumulation were measured in the pleural washings obtained at different times following the induction of Escherichia coli lipopolysaccharide (LPS, 100 mug/cavity) pleurisy in rats. TNFalpha peaked at 2 hours (3036 +/- 160.3 units/ml) and decreased thereafter. Conversely, levels of sPLA(2) peaked at 48 hours (1.97 +/- 0.64 ng/ml) and were increased further (14.02 +/- 4.16 ng/ml) by pretreatment with anti-TNFalpha antibody. Cell accumulation was not affected by antibody pretreatment. These data indicate that the sPLA(2) enzyme is involved in LPS-induced pleurisy. The enzyme seems not to be stimulated by TNFalpha which may be involved in the downregulation of sPLA(2) in this model of inflammation.


Biofeedback therapy after perineal rectosigmoidectomy or J pouch procedure.
The aim of this study was to determine the outcome and to identify possible predictors of success for biofeedback therapy after perineal rectosigmoidectomy (PRS) or coloanal or ileoanal J pouch. A retrospective chart review of all patients with electromyography-based biofeedback therapy due to fecal incontinence after PRS or a J pouch procedure was undertaken. Follow-up was obtained by telephone survey. Fourteen patients (4 men and 10 women) were included in this study. In the 9 patients after PRS, the frequency of daily bowel movements was 3.6+/-2.8 preoperatively, 4.1+/-3.2 prebiofeedback, and 2.2+/-1.3 postbiofeedback (P<.05). The frequency of daily incontinent episodes was reduced from 2.4+/-2.2 preoperatively and 2.0+/-1.9 prebiofeedback to 0.26+/-0.3 postbiofeedback (P<.05). The incontinence scores decreased from 17+/-3.1 preoperatively to 16+/-2.1 prebiofeedback and to 8.2+/-5 postbiofeedback (P<.001). At a follow-up of 15.8+/-7.1 months, 5 patients after the J pouch had decreased daily bowel frequency from 6.6+/-4.2 prebiofeedback to 3.3+/-2 postbiofeedback and 3.1+/-2 at follow-up (P<.05). The frequency of daily incontinent episodes was reduced from 1.9+/-1.3 prebiofeedback to 0.9+/-0.7 postbiofeedback to 0.7+/-0.8 at follow-up (P<.05). The incontinence scores decreased from 13.4+/-2.7 prebiofeedback to 8.8+/-5.1 postbiofeedback to 6.8+/-5.5 at follow-up (P<0.05). In both groups, the postbiofeedback incontinence score correlated with the prebiofeedback incontinence score. Furthermore, there was no correlation between outcome and age, interval between surgery and biofeedback therapy, frequency of biofeedback sessions, or manometry results in either group. Biofeedback therapy is an effective option for patients with fecal incontinence after perineal rectosigmoidectomy or colonic or ileal J pouch.


Parents' Education Level and Children's BMI Explain Caries Distribution Among Kindergarten Students: A Cross-Sectional Study.
Dental caries is a common but preventable, multifactorial disease in children. Among several others, it is influenced by child- and parent-related factors. To describe knowledge, attitude and practices about oral health among parents of kindergarten children and assess factors influencing caries distribution among the children. Parents of 290 kindergarten children in AlMadinah, Saudi Arabia, answered questions concerning their oral health knowledge, attitudes and practices. The children underwent an oral clinical examination. Data were collected between February and April 2018. Comparison between groups was done using the Kruskal-Wallis test. All parents agreed on the importance of fluoride to strengthen teeth, while 91.7% thought that sweets have a negative impact on teeth. Almost all children ate sweets and candies (99%), while most of them used toothbrushes and fluoride to clean their teeth (98%). Only 66% of parents took their children to the dentist. The 2-step cluster analysis revealed that clusters of children with high body mass index (BMI) and those whose parents had only primary education had the highest caries prevalence compared to clusters of children with lower BMI and parents with higher education (P < 0.05). Within the study limits, parents demonstrated good oral health knowledge, attitudes and practices. Kindergarten children had high caries, especially those with high BMI and whose parents had low educational levels.


Precocious puberty.
The past decade has seen tremendous advances in both the diagnosis and treatment options for children with precocious puberty. Although the precise cause of CPP is still not known, long-acting GnRH analogues provide a safe and effective form of therapy. Treatment slows the progression of secondary sexual characteristics and rates of linear growth and bone maturation. Although the final verdict on how beneficial GnRH analogue therapy is in preserving the final adult height in children with precocious puberty is still not in, achieved heights are generally greater than pretreatment predicted heights. However, treatment may not be appropriate for all children with GDPP. Some children progress through puberty slowly and may not have significant compromise in final height. Furthermore, some children who come from tall families who may be subject to the same deterioration from target height as children who come from short families may not require therapy because their expected final heights may still fall within an acceptable range even if they are shorter than their siblings. Therapy offers the greatest advantage for those children in whom the onset of puberty is at a very early age, those who demonstrate rapidly accelerating bone age, or those with lower genetic height potential. In the past 3 years, the molecular mechanisms by which precocious puberty develops in children with MAS and FMPP have been elucidated. The molecular defects characterized explain the clinical manifestations. Future challenges will include the development of an effective, targeted form of therapy for gonadotropin-independent forms of precocious puberty.


Impacts of the Dependent Care Expansion on the Allocation of Mental Health Care.
We examine the impact of insurance expansion under the Affordable Care Act's Dependent Care Expansion (DCE) on allocation of mental health care across illness severity, types of care and racial/ethnic groups. Evidence suggests that the increase in mental health care utilization resulting from the DCE was restricted to individuals with clinically significant mental health conditions. There is no evidence suggesting that the increase occurred disproportionately in medication-only treatment or that it increased racial/ethnic disparities. The DCE appears to have been successful in increasing utilization of mental health care among a high need group without lowering quality or increasing disparities.


Interactions between chilean matorral shrubs and phytophagous insects.
Lithraea caustica (Mol.) H. et Arn. and Colliguaya odorifera Mol. are two sclerophyllous shrubs of the scrub vegetation in Central Chile. These two species commonly grow in close association on equator-facing slopes. Leaves of L. caustica are severely predated upon by phytophagous insects while those of C. odorifera are rarely attacked. Leaf growth dynamics, leaf loss, and leaf predation by insects were correlated through the year with leaf phenolic compounds. Leaf structural properties (cuticle thickness, density, sclerenchymatic fibers, leaf thickness) were similar between the two species, while leaf phenol content differed significantly. The higher phenol content in C. odorifera may influence leaf palatability, and thus account for the observed lower leaf area loss in that species due to insect damage.


Combining prostate health index and multiparametric magnetic resonance imaging may better predict extraprostatic extension after radical prostatectomy.
In patients undergoing radical prostatectomy (RP) for prostate cancer (PCa), preoperative prediction of extraprostatic extension (EPE) can facilitate patient selection for nerve-sparing procedures. Since both multiparametric magnetic resonance imaging (mpMRI) and prostate health index (PHI) have shown promise for the diagnosis and prognostication of PCa, we investigated whether a combination of mpMRI and PHI evaluations can improve the prediction of EPE after RP. Patients diagnosed with PCa and treated with RP were prospectively enrolled between February 2017 and July 2019. Preoperative blood samples were analyzed for PHI (defined as [p2PSA/fPSA] × √tPSA), and mpMRI examinations were performed and interpreted by a single experienced uroradiologist retrospectively. The area under the receiver operating characteristic curve (ROC) was used to determine the performance of mpMRI, PHI, and their combination in predicting EPE after RP. A total of 163 patients were included for analysis. The pathological T stage was T3a or more in 59.5%. Overall staging accuracy of mpMRI for EPE was 72.4% (sensitivity and specificity: 73.2% and 71.2%, respectively). The area under the ROC of the combination of mpMRI and PHI in predicting EPE (0.785) was higher than those of mpMRI alone (0.717; p = 0.0007) and PHI alone (0.722; p = 0.0236). mpMRI showed false-negative non-EPE results in 26 patients (16%), and a PHI threshold of >40 could avoid undiagnosed EPE before RP in 21 of these 26 patients. The combination of PHI and mpMRI may better predict the EPE preoperatively, facilitating preoperative counseling and tailoring the need for nerve-sparing RP.


Two alloalleles of Xenopus laevis hairy2 gene--evolution of duplicated gene function from a developmental perspective.
Gene duplication is a fundamental source of a new gene in the process of evolution. A duplicated gene is able to accept many kinds of mutations that could lead to loss of function or novel phenotypic diversity. Alternatively, the duplicated genes complementarily lose part of their functions to play original roles as a set of genes, a process called subfunctionalization. Pseudotetraploid frog Xenopus laevis has four sets of genes, and it is generally thought that the alloalleles in X. laevis have mutually indistinguishable functions. In this paper, we report differences and similarities between Xhairy2a and Xhairy2b in the neural crest, floor plate, and prechordal plate. Knockdown studies showed that Xhairy2a seems not to function in the neural crest, although both of them are required in the floor plate and the prechordal plate. Temporal expression pattern analysis revealed that Xhairy2a is a maternal factor having lower zygotic expression than Xhairy2b, while Xhairy2b is not loaded in the egg but has high zygotic expression. Spatial expression pattern analysis demonstrated that future floor plate expression is shared by both alloalleles, but Xhairy2b expression in the neural crest is much higher than Xhairy2a expression, consistent with the results of individual knockdown experiments. Therefore, our data suggest that subfunctionalization occurs in Xhairy2.


ECL cell histamine mobilization and parietal cell stimulation in the rat stomach studied by microdialysis and electron microscopy.
Gastrin stimulates acid secretion by mobilizing histamine from enterochromaffin-like (ECL) cells that occur predominantly at the base of the gastric glands. The parietal cells occur higher up in the glands nearer to the gastric lumen. The present study was performed to assess whether histamine is transported from the ECL cell via the microcirculation (endocrine route) or local diffusion (paracrine route). Totally isolated, vascularly perfused, rat stomachs were examined both in basal and gastrin-stimulated state. Histamine concentrations, determined by radioimmunoassay in venous effluent and microdialysate from an indwelling probe in the submucosa, were monitored over a period of 240 min. Gastrin-17 was infused through an arterial catheter for 120 min. The parietal cells were examined by electron microscopy, and the percentage of actively secreting parietal cells (displaying secretory canaliculi) in four regions along the glands (basal to surface, zones I-IV) was determined. Gastrin stimulated acid secretion and histamine release as well as parietal cell activation. Upon gastrin stimulation, histamine concentration in the microdialysate was 2.5-fold higher than in the venous effluent (P = 0.008). The parietal cells in the upper part of the gland (zone III) were found to be activated the most. As the histamine concentrations were higher in the tissue (microdialysate) than in blood, histamine seems to reach the parietal cells via the paracrine route. The fraction of active parietal cells seems to depend more on the age of the parietal cells than on the distance from the ECL cell.


[Validation of the French version of the expanded Brief Psychiatric Rating Scale with anchor BPRS-E(A)].
The Brief Psychiatric Rating Scale was initially developed as a rapid method to assess symptom change in psychiatric inpatients of various diagnoses. The original version was expanded to an 18-item version and thereafter to a 24-item version to increase sensitivity to a broader range of psychotic and affective symptoms. The latest version of the expanded 24- item BPRS provides probe questions and detailed anchor points for the ratings for each item. Studies have shown the expanded and anchored 24-item BPRS to be a sensitive and effective measure of psychiatric symptoms with good interrater reliability that can be maintained over time. To our knowledge, there are eight published papers including factor analyses of the BPRS-E(A). While many similarities are evident between these studies, inconsistencies are apparent that may have been due to sample size, characteristics and / or methodological differences in the factor analysis computation. Among these studies, six provided a four-factor solution. There was no French version of this scale available. After its translation into French and back translation, we investigated the validity of the French BPRS-E(A) version. We carried out a component analysis on the data of 111 participants of various diagnoses, mostly hospitalised for a first psychotic episode, yielding to a three-factor solution (positive symptoms--disorganisation; depression-anxiety and negative symptoms). A good internal consistency and interrater reliability were found. These results confirm the psychometric value of the BPRS-E(A) in its French version. We compared those findings to earlier reports; similarities and differences are discussed.


A nurse-developed prechemotherapy education checklist.
Many patients diagnosed with cancer receive chemotherapy. Oncology nurses are responsible for educating patients prior to the chemotherapy experience. Studies have examined what topics should be covered for such patients and how education should be delivered, but little literature exists regarding how to help nurses organize the data and perform education. This article examines how a community oncology practice developed a checklist to assist oncology nurses in organizing and delivering chemotherapy education to patients. Principles of adult education are reviewed briefly. The principles can aid nurses in understanding how adult patients learn and how sessions can be most effective.


Development of a dispersive liquid-liquid microextraction method for organophosphorus flame retardants and plastizicers determination in water samples.
A fast, inexpensive and efficient sample preparation method for the determination of 10 organophosphorus compounds in water samples is presented. Analytes were extracted using the dispersive liquid-liquid microextraction (DLLME) technique and determined by gas chromatography with nitrogen-phosphorus detection (GC-NPD). The influence of several variables (e.g. type and volume of dispersant and extraction solvents, ionic strength, shaking time and mode, etc.) on the performance of the sample preparation step was carefully evaluated. Under final working conditions, 1 mL of acetone containing a 2% of 1,1,1-trichloroethane (20 microL) was added to 10 mL of water with 20% of sodium chloride. The ternary mixture was centrifuged at 3500 rpm to allow phase separation. After removing the aqueous supernatant, an aliquot of the settled extract was injected in the GC-NPD system. Under the above conditions, the method provided enrichment factors between 190 and 830 times (depending on the considered compound), relative standard deviations below 10%, except for tris(2-ethylhexyl) phosphate (TEHP), and quantification limits between 0.01 and 0.08 ng/mL. Matrix effects were assessed using different water samples, and accuracy was evaluated by comparison with solid-phase microextraction.


Chemical composition and pharmacological potential of aromatic water from Salix caprea inflorescence.
To evaluate the chemical composition and pharmacological potential of hydro distillate from Salix caprea inflorescence. Fresh flowers were subjected to conventional hydrodistillation. Antioxidant activity was assessed as free radical scavenging capacity (RSC) towards 2, 2-diphenyl-1-picrylhydrazil (DPPH) radicals. Anti inflammatory activity was examined by human red blood cell (HRBC) membrane stabilization method. Qualitative and Quantitative analysis of hexane extract of aromatic water was performed by gas chromatography (GC) and gas chromatography-mass spectrometric (GC-MS). A total of 19 constituents representing (99.2%) of the aromatic water were identified; Hexahydrofarnesylacetone (38.3%), 2-butyl-octanol (24.0%), 2.hexyl-1-octanol (8.6%) were the main components. Results suggest that the hydro distillate possess significant antioxidant and anti-inflammtory properties. The aromatic water's composition and its pharmacological evaluations has been reported in our results for this unique and endemic species.


[Epilepsy surgery in France].
We report here the results of the first survey on epilepsy surgery activity in France. Data from a questionnaire sent to 17 centers practicing epilepsy surgery were analyzed. All centers responded; however, all items were not completely documented. Over 50 years, more than 5000 patients have been operated on for drug-resistant epilepsy and more than 3000 patients underwent some invasive monitoring, most often SEEG. Currently, nearly 400 patients (including more than 100 children) are operated on yearly for epilepsy in France. Over a study period varying among centers (from two to 20 years; mean, 9.5 years), results from more than 2000 patients including one-third children were analyzed. Important differences between adults and children, respectively, were observed in terms of location (temporal: 72% versus 4.3%; frontal: 12% versus 28%; central: 2% versus 11%), etiology (hippocampal sclerosis: 41% versus 2%; tumors 20% versus 61%); and procedures (cortectomy: 50% versus 23%; lesionectomy: 8% versus 59%), although overall results were identical (seizure-free rates following temporal lobe surgery: 80.6% versus 79%; following extratemporal surgery: 65.9% versus 65%). In adults, the best results were observed following temporomesial (TM) resection associated with hippocampal sclerosis or other lesions (class I: 83% and 79%, respectively), temporal neocortical (TNC) lesional (82%), while resections for cryptogenic temporal resections were followed by 69% (TM) and 63% (TNC) class I outcome. Extratemporal lesional resections were associated with 71% class I outcome and cryptogenic 43%. In children, the best results were obtained in tumor-associated epilepsy regardless of location (class I: 80%). A surgical complication occurred in 8% after resective surgery - with only 2.5% permanent morbidity - and 4.3% after invasive monitoring (mostly hemorrhagic). Overall results obtained by epilepsy surgery centers were in the higher range of those reported in the literature, along with a low rate of major surgical complications. Growing interest for epilepsy surgery is clearly demonstrated in this survey and supports further development to better satisfy the population's needs, particularly children. Activity should be further evaluated, while existing epilepsy surgery centers as well as healthcare networks should be expanded.


Detection of human neutrophil elastase by aptamer affinity capillary electrophoresis coupled with laser-induced fluorescence using specified site fluorescently labeled aptamer.
As a multifunctional serine protease, human neutrophil elastase (HNE) plays critical roles in a variety of physiopathological processes, such as acute lung injury, emphysema, atherosclerosis, and arthritis. The quantification of HNE is important in many applications. In this paper, we report an aptamer affinity capillary electrophoresis coupled with laser-induced fluorescence (CE-LIF) assay for detection of HNE using a tetramethylrhodamine (TMR)-labeled DNA aptamer probe. The affinity complex of HNE and DNA aptamer probe was well separated from the unbound aptamer probe in CE separation based on the difference of electrophoretic mobility. Broad complex peaks appeared due to possible multiple binding. The 45-mer aptamer having TMR labeling on the 40th T base was used as affinity probe, as larger complex peaks were obtained. We investigated the effects of various metal cations (Na+, K+, and Mg2+) in sample buffer on the binding of HNE and the aptamer in CE-LIF analysis. The presence of Na+, K+, or Mg2+ in sample buffer caused a decrease of complex peaks, and Mg2+ showed a larger effect. Under optimized conditions, this aptamer CE-LIF assay enabled the detection of HNE at 0.5 nM. This assay showed good specificity and allowed for detection of HNE spiked in diluted human serum sample. Graphical abstract The complex of HNE and DNA aptamer probe was isolated from the unbound aptamer probe in CE separation due to difference of electrophoretic mobility, allowing a CE-LIF assay for HNE.


Impact of Center Procedural Volume on Mortality and Readmission Rates Following Pericardiectomy in the United States.
Our study aimed to explore the national trends in the rates of perioperative complications, in-hospital mortality, and readmissions after pericardiectomy and the impact of center volume on these outcomes. Using the Nationwide Readmission Database, we identified patients who underwent isolated pericardiectomy from 2010 to 2019. In-hospital mortality and readmission rates were assessed using orthogonal polynomial contrasts, with the linear and nonlinear trends evaluated as needed. Multivariable logistic regression models were constructed to identify the independent predictors of mortality and readmission. All analyses accounted for the Nationwide Readmission Database sampling design and were performed using SAS version 9.4 (SAS Institute Inc. Cary, NC.) with p <0.05 used to indicate statistical significance. A total of 26,169 hospitalizations for pericardiectomy were identified during the study period. The median age was 59 years and 44% were female. In-hospital mortality was 5.2%, and the median length of stay was 7 days. Advanced age, higher co-morbidity index, and lower annual facility pericardiectomy volume were independent predictors of in-hospital mortality. The 30- and 90-day readmission rates after pericardiectomy were 18% and 28%, respectively. Previous cardiac surgery, diagnosis of constrictive pericarditis, and greater co-morbidity score were independent predictors of readmission. In conclusion, isolated pericardiectomy rates have remained mostly constant, with relatively small changes in in-hospital mortality and 30- and 90-day readmission rates over the last decade. Advanced age, lower facility pericardiectomy volume, and higher Elixhauser co-morbidity index are independent predictors of surgical mortality.


Tests for the presence of two linked disease susceptibility genes.
For diseases with complex genetic etiology, more than one susceptibility gene may exist in a single chromosomal region. Under explicit assumptions about the number of disease genes in a region, generalized estimating equations (GEE) can be used to estimate the putative disease gene location(s) and expected identical-by-descent allele sharing in affected sib pairs at these gene(s). Extending the work of Liang et al. developed a method for simultaneous localization of two susceptibility genes in one region using marker identical-by-descent (IBD) sharing in affected sib pairs. Here we propose methods to evaluate the evidence for two versus one disease loci in a region in a quasi-likelihood/GEE framework. We describe tests based on approximate quasi-likelihood ratio and generalized score test statistics. Because of difficulties in determining the asymptotic null distributions of these statistics and the small sample sizes that can be available in genetic studies, we recommend that significance be evaluated empirically. Application of the described methods to data from a genome scan for type 1 diabetes yielded some evidence for two linked disease genes on chromosome 6, approximately 20 cM apart (p value for an approximate quasi-likelihood ratio test=0.049). In simulation studies, we found that both tests performed quite well for a range of scenarios. Power to detect the presence of two linked disease genes increased with the number of affected sib pairs, greater IBD sharing at the two loci, and larger distance between the two loci.


Famciclovir leads to failure of hematopoiesis, but may have the benefit of relieving myeloid expansion in MDS-like zebrafish.
Famciclovir (FCV) is an antiviral drug that is often utilized after bone marrow transplantation to prevent viral infection. Yet, its role in hematopoiesis is poorly understood. Here, by utilizing a zebrafish model, we found that FCV exposure led to hematopoietic failure by impairing the proliferation of hematopoietic stem and progenitor cell (HSPC) and inducing HSPC apoptosis. On the other hand, FCV treatment could effectively relieve myeloid malignancies in the c-mybhyper MDS-like fish model, and played a role not only in the embryonic stage but also in adult zebrafish. This study reveals that FCV functions as a double-edged sword, with hematotoxicity at a high level, but that appropriate FCV treatment may be beneficial for the treatment of MDS.


Educational level and HIV disease progression before and after the introduction of HAART: a cohort study in 989 HIV seroconverters in Spain.
To analyse the effect of educational level on the progression from HIV seroconversion to highly active antiretroviral therapy (HAART) requirement, HAART initiation, AIDS and death from any cause at different periods of the HIV epidemic in Spain. Open, prospective, multicentre cohort of HIV seroconverters set up in 1983. The risk of progression was calculated by the multiple decrements method. Effect of educational level was estimated by Fine and Gray model, adjusting for sex, HIV transmission category, age and method to estimate seroconversion. Calendar period was introduced as a variable that could change over time (<1997; 1997-2003; >2003). Up to 2009, 989 HIV seroconverters with information on educational level were identified. Some 52% and 48% had a low and a high educational level respectively. Persons with higher education had 32% lower risk of death (HR: 0.68; 95% CI 0.45 to 1.03). Regarding progression to AIDS, educational level had no effect in the pre-HAART era (HR: 1.47; 95% CI 0.91 to 2.38), but did show an effect in the period 1997-2003 (HR: 0.58; 95% CI 0.34 to 0.99), which was accentuated after 2004 (HR: 0.26; 95% CI 0.10 to 0.68). No difference was found in time to HAART requirement or initiation. Results suggest that, despite similar access to HAART, persons with low educational level are at increased risk of HIV disease progression, highlighting the impact of social inequities on health. The availability of more effective treatments over time will strengthen the protective effect of higher education on the development of AIDS.


Effect of amino acids and antibodies against nerve growth factor receptors on the development of organotypic culture of lymphoid tissue.
We studied the effects of 20 L-amino acids on organotypic culture of splenic lymphoid tissue from 3-month-old rats were studied in the presence of apoptosis-inducing monoclonal antibodies against low-affinity receptors for nerve growth factor NGFRp75. The influence of amino acids stimulating cell proliferation in explants (lysine, asparagine, and glutamic acid) did not depend on NGFRp75. Hydrophobic amino acids inhibiting the growth zone in isolated application and abolished the inhibition of explant development in the presence of antibodies against NGFRp75. These amino acids can mediate the proapoptotic effect on lymphoid tissue via low-affinity receptors for nerve growth factor.


The proliferation of adrenal medullary cells in newborn and adult mice. A light and electron microscopic autoradiographic study.
The proliferative activity of newborn and adult mouse adrenal medullary cells was determined with light and electron microscopic autoradiography. The H3 thymidine labelling index of 2 weeks old mice adrenal medullary cells was about 9.4% and declined to less than 1% in adult mice. In electron microscopic autoradiography labelled norepinephrine as well as epinephrine cells could be seen. Only in 1 and 2 weeks old mice some morphologically undifferentiated cells were visible. In formaldehyde induced fluorescence combined with light microscopic autoradiography the fluorescence intensities of labelled and unlabelled medullary cells were measured. On average the fluorescence intensity of labelled cells was lower than that of unlabelled cells. The differences could be explained by a higher number of autoradiographic silver grains laying on the cytoplasm of labelled cells. These results give evidence that fully differentiated adrenal medullary cells are capable of division.


[Trial study on DENG Tie-tao's coronary heart disease capsules in improving patients' quality of life].
To assess the efficacy of the Coronary Heart Disease (CHD) Capsules worked out by Prof. Deng --in improving quality of life of CHD patients of qi deficiency with phlegm and blood stasis syndrome. According to the WHO's diagnosis criteria of CHD, a total of 93 stable angina patients were divided into 3 groups using the single blinded method. The groups were evenly distributed into CHD Capsule treated group (CHDC), isosorbide dinitrate control group (ID), and Compound Prescription Danshen Droplet Pills control group (CPDDP). Two courses of treatment lasting for 6 months were given. During the courses of treatment, the following parameters were observed: clinical symptoms of angina pectoris, ECG change, treadmill exercise test, 36 items in short form of health survey (SF-36) and Seattle Angina Questionnaire (SAQ) scale. After 6 months of treatment, all the three groups showed good curative effect in angina pectoris, ECG and treadmill exercise test, differences between them had no statistical significance. The CHDC group showed a better result in nitro-glycerine stopping or alleviation rate and in improving symptoms than the other groups (P < 0.05). The general health, vitality, role-emotional, mental health and reported health transition in the CHDC group were significantly better than those in the control groups (P < 0.05). The scores in physiological functioning role, physiological function and pain alleviation were not different among the three groups. Prof. DENG Tie-tao's CHDC is effective in treating CHD with qi deficiency, phlegm and blood stasis and also in improving the quality of life. CHDC is more suitable to be used in long-term treatment than isosorbide dinitrate. The SF-36 and SAQ can be used to appraise the curative effect of traditional Chinese medicine agents for CHD angina pectoris.


Persistent disparities in cholesterol screening among immigrants to the United States.
This study compared differences in cholesterol screening among immigrant populations and US born race/ethnic groups and whether improving access to health care reduced differences in screening. Self-reported cholesterol screening for adults was calculated from multivariate logistic regression analysis of the 1988-2008 National Health and Nutrition Examination Surveys (N = 17,118). Immigrant populations were classified by place of birth and length of residency. After adjusting for individual characteristics and access to health care, the multivariate adjusted probability of cholesterol screening is significantly lower for persons originating from Mexico (70.9%) compared to persons born in the US (80.1%) or compared to US born Hispanic persons (77.8%). Adjustment for access to care did significantly reduce the difference in screening rates between immigrants and natives because the rate for natives remained the same, but the rate for immigrants improved. For example, the difference in screening between US born persons and persons born in Mexico was reduced by nearly 10% after adjustment for access to care. There are persistent disparities in cholesterol screening for immigrants, particularly recent immigrants from Mexico, but improved access to health care may be a viable policy intervention to reduce disparities.


Spontaneous regression of a presumed orbital apex cavernous venous malformation.
A 42-year-old non-menopausal, non-pregnant woman presented with an incidentally noted right orbital apex lesion producing mild compressive optic neuropathy. Imaging revealed an apical, intraconal, inhomogenously enhancing mass consistent with a cavernous venous malformation displacing the optic nerve. The patient was monitored over a 15-year period with serial orbital imaging and clinical examinations and ultimately demonstrated significant regression in the size of the lesion, accompanied by the complete resolution of optic neuropathy. She was non-menopausal when the regression was noted and remained non-pregnant throughout the follow-up period.


Effect of liming and seasonal variation on lead concentration of tea plant (Camellia sinensis (L.) O. Kuntze).
Tea is a widely consumed beverage. However, recent studies revealed that there were an increasing number of cases of tea products exceeding the former maximum permissible concentration (MPC) in China for Pb (2 mg kg(-1)). Tea Pb contamination is an issue affecting trade and consumer confidence. Root uptake of Pb could contribute significantly to Pb accumulation in tea leaves due to the strong acidity of many tea garden soils. We conducted pot and field experiments to evaluate the effect of liming on Pb uptake by tea plants on two highly acidic soils (pH3.6). Additions of CaCO(3) significantly increased soil pH by up to 1 unit and decreased soil extractable Pb by up to 32%. Liming resulted in a decrease in the proportion of Pb in the exchangeable and carbonate-bound fractions, with a concurrent increase in the fractions bound to Fe/Mn oxides and residues. Liming significantly decreased Pb concentrations of fine roots, stems and new shoots of tea plants in the pot experiment. In the field experiments, the effect of liming was not significant during the first year following CaCO(3) application, but became significant during the second and third years and Pb concentration in the new shoots was decreased by approximately 20-50%, indicating that liming of acidic tea garden soils is an effective way to reduce Pb contamination of tea. The study also reveals a distinct seasonal variation, with Pb concentration in the new shoots following the order of spring>autumn>summer.


Surgical and long-term antifungal therapy for fungal prosthetic valve endocarditis.
Fungal prosthetic valve endocarditis is an uncommon but serious disease. We have developed a strategy of treatment that includes perioperative amphotericin B, radical debridement of infected tissue, reconstruction using biologic tissue when possible, and prolonged oral suppressive antifungal therapy. We retrospectively reviewed the charts of 12 patients reoperated on for fungal prosthetic valve endocarditis involving the aortic valve (10 patients: six porcine valves, two mechanical valves, two homografts) and the mitral valve (2 patients, both porcine valves). Prosthetic valve endocarditis developed in 7 within 12 months after the first valve procedure. The organisms included Candida species (9 patients), Scopulariopsis brevicaulis (1), Saccharomyces cervisiae (1), and histoplasmosis (1). At operation, all patients had prosthetic vegetations, 8 had abscesses, and 4 had sinus tracts. Seven received aortic homografts, 4 received porcine valves (two mitral), and 1 received a mechanical prosthesis. Two patients died in the hospital after prolonged illnesses (83% hospital survival). Four patients had recurrence an average of 25 months later and 3 underwent further surgical intervention. One patient had recurrence and died 17 months postoperatively. One other late death occurred 96 months after operation, and there was no evidence of recurrence. Eight patients (67%) are alive and well 51.5 +/- 61.0 months (range, 1 to 189 months) after the first redo procedure for fungal prosthetic valve endocarditis. We conclude that preoperative treatment with amphotericin B, radical resection of all infected tissue, cardiac reconstruction using biologic tissue when possible, and life-long oral antifungal therapy is effective for fungal prosthetic valve endocarditis.


Anti-sense peptide recognition of sense peptides: direct quantitative characterization with the ribonuclease S-peptide system using analytical high-performance affinity chromatography.
The ability of peptides coded by the anti-sense strand of DNA to interact specifically with peptides coded by the sense strand has been evaluated. The sense peptide examined, ribonuclease S-peptide, was immobilized on a coated silica affinity chromatographic matrix. Anti-sense peptides were synthesized on the basis of the anti-sense DNA sequence for the S-peptide region in native pancreatic ribonuclease A. The interaction of synthetic anti-sense peptides with sense peptide was quantitated from the degree of retardation during chromatographic elution on the sense peptide affinity matrix in buffers with and without soluble competing sense peptide. Sense/anti-sense peptide interactions were found to occur with significant affinities with each of two anti-sense 20-residue peptides of opposite amino-to-carboxyl orientations and to weaken progressively with decreasing length of anti-sense peptide. The substantial chromatographic retardation of anti-sense peptides was specific, since it decreased as expected with increasing concentration of the soluble competing S-peptide, could not be mimicked by the elution of several control peptides (including S-peptide itself) on the S-peptide matrix, and did not occur with a blank chromatographic matrix (no S-peptide attached). The stoichiometry of anti-sense peptide binding to immobilized sense peptide was found to be far greater than 1:1, and at least 4-5:1, for the two 20-mer anti-sense peptides. In sum, the analytical affinity chromatographic experiments have established quantitatively that anti-sense peptide binding to sense peptides occurs in the ribonuclease S-peptide case and have identified some structural elements that govern these interactions.(ABSTRACT TRUNCATED AT 250 WORDS)


Prophylactic therapy for rejection after cardiac transplantation. A comparison of rabbit antithymocyte globulin and OKT3.
The value of prophylactic monoclonal or polyclonal antibody therapy early after cardiac transplantation is controversial. Between Jan. 1, 1987, and July 1, 1988, 32 consecutive patients underwent cardiac transplantation (cyclosporine, azathioprine, and prednisone maintenance therapy) with either early prophylactic rabbit antithymocyte globulin (n = 17) or monoclonal OKT3 (Ortho Diagnostic Systems, Inc., Raritan, N.J.) (10 days) (n = 15). Follow-up was through Sept. 1, 1988, for morbid events and through Jan. 1, 1989, for survival. All patients (100%) survived the study period (follow-up of 6 to 24 months). The efficacy of rabbit antithymocyte globulin and OKT3 prophylaxis was similar regarding median time (days) to first rejection (16 versus 21 days, p = 0.5), number of rejection episodes during first 2 months (1.5 versus 1.3 days, p = 0.8), and freedom from rejection at 2 months (18% versus 27%, p = 0.8). Early infections were slightly less common in the rabbit antithymocyte globulin group than the OKT3 group (median time to first infection: 318 versus 250 days, p = 0.5; freedom from rejection at 2 months: 82% versus 64%, p = 0.21), although differences were likely due to chance. Cytomegalovirus syndrome was common, with one case of cytomegalovirus pneumonia. T-cell markers during OKT3 treatment did not predict subsequent rejection (within 2 weeks after OKT3) as assessed by mean T3-lymphocyte count during OKT3 use (p = 0.3) or T3-lymphocyte count during the last 3 days of OKT3 use (p = 0.4). Inferences: (1) Prophylactic rabbit antithymocyte globulin or OKT3 with triple-drug immunosuppression yields excellent intermediate survival after heart transplantation. (2) These protocols for rabbit antithymocyte globulin and OKT3 provide similar protection against early rejection with a relatively low risk of early infection. (3) T-cell markers do not predict early rejection after OKT3.


Isotropic half-millimeter angiography of coronary artery bypass grafts with 16-slice computed tomography.
Computed tomography (CT) with four detector rows and magnetic resonance imaging (MRI) are still of limited value for the assessment of coronary artery bypass grafts (CABG). We investigated the abilities of 16-slice CT in these patients. A retrospective analysis of all noninvasive coronary angiographies with multislice computed tomography (MSCT; Aquilion, Toshiba) on patients with CABG referred to our institution between October 2002 and April 2003 was conducted. MSCT angiography was performed using a standard protocol (0.5-seconds rotation time, 16 x 0.5 mm detector collimation, 120 kV, 250 to 300 mA, and 0.25 pitch). None of the patients received beta-blockers to reduce the heart rate. Seventy-five CABGs (20 arterial grafts and 55 venous grafts) in 27 patients were evaluated for patency and adequate diagnostic quality by two radiologists in consensus. All arterial and venous grafts were depicted with adequate diagnostic quality and were eligible for evaluation. Fifteen occlusions and five significant stenoses (at least 50%) could be identified. All of the proximal and 99% of the distal anastomoses were eligible. One distal anastomosis of an arterial graft was not assessable due to surgical clip artifacts. The length of the acquisition window was 174 +/- 46 ms (range 71 to 234 ms). The majority of the patients (70%) had a heart rate above 65 beats/min. However, due to the improved temporal and spatial resolution none of the examinations had an insufficient image quality. MSCT angiography with 16 detector rows and an isotropic high resolution reliably depicts CABG with adequate diagnostic quality.


5-Fluorouracil-Impregnated PLGA Coated Gold Nanoparticles for Augmented Delivery to Lung Cancer: In Vitro Investigations.
The study aimed to investigate the augmented cytotoxic effects of polymer-coated (polylactic- co-glycolic acid-PLGA) gold nanoparticles (GNPs) carrying 5-fluorouracil (5-FU) in the management of lung cancer. In this study, several formulations were prepared using a double emulsion (water-oil-water) method and evaluated for drug release behavior, compatibility, cell line toxicity (A549), and apoptosis assessment. Characterization results showed spherical polydispersed particles with size 29.11-178.21 nm, polydispersity index (PDI) 0.191-292, and zeta potential (ZP) 11.19-29.21 (-mV), respectively. Compared to others, the optimized polymer-coated 5-FU loaded gold nanoparticles (PFGNPs) illustrated a maximum drug loading (93.09±10.75%). The percent cumulative drug release of polymer-coated 5-FU loaded nanoparticles (PFNPs), 5-FU loaded gold nanoparticles (FGNPs), (PFGNPs) and 5-FU solution were 47.87±1.5, 41.09±1.8, 56.31±1.05, and 98.8±4.2%, respectively, over 10 h. following zero-order release kinetics (except 5-FU solution). From the MTT results, the cytotoxic effect of PFGNPs on the A549 cells was 82.89% compared to the 5-FU solution (74.91 %). EGFR and KRAS gene expression analysis under the influence of PFNPs, FGNPs, PFGNPs, and 5-FU was studied and observed maximum potency for PFNPs. PLGA coated biogenic gold nanoparticles have a combined effect to achieve high drug loading, sustained delivery, improved efficacy, and enhanced permeation. Conclusively, the approach may be promising to control lung cancer with reduced toxicity and improved efficacy.


Anesthetic Management of Living-Donor Renal Transplantation in a Patient With Epstein Syndrome Using Rotational Thromboelastometry: A Case Report.
Epstein syndrome is a myosin heavy chain 9 (MYH9)-related disorder characterized by hearing loss and macrothrombocytopenia with renal failure, which usually requires platelet transfusion during surgery. We report the case of a 22-year-old man who underwent living-donor renal transplantation without platelet transfusion using rotational thromboelastometry (ROTEM) monitoring. His intraoperative laboratory coagulation findings were a platelet count of 28-31 × 10/L based on microscopy and fibrinogen of 256 mg/dL. However, his extrinsic pathway evaluations by ROTEM were normal. The estimated blood loss during the operation was 150 mL, and the patient showed no bleeding complications without platelet transfusion.


Molecular interaction analysis of β-1, 3 glucan binding protein with Bacillus licheniformis and evaluation of its immunostimulant property in Oreochromis mossambicus.
Analyzing the health benefits of any two immunostimulants (synbiotics) in combined form and information on their interactions gain more visibility in the usage of synbiotics in aquafarms. With this intention, the current work explores the immunostimulant effect and structural interaction of synbiotic (β-1, 3 glucan binding protein from marine crab, Portunus pelagicus (Ppβ-GBP) and Bacillus licheniformis) on Oreochromis mossambicus. The experimental diet was prepared with Ppβ-GBP and B. licheniformis, and nourished to the fingerlings of O. mossambicus for 30 days. After the experimental trial, a higher growth rate and immune reactions (lysozyme, protease, myeloperoxidase and alkaline phosphatase activity) were noticed in the fish nourished with synbiotic (B. licheniformis and Ppβ-GBP) enriched diet. Moreover, the synbiotic enriched diet elevated the antioxidant responses like glutathione peroxidase (GSH-Px) and catalase (CAT) activity in the experimental diet-nurtured fish. At the end of the feed trial, synbiotic diet nourished fish shows an increased survival rate during Aeromonas hydrophila infection, reflecting the disease resistance potential of experimental fish. Also, the interaction between Ppβ-GBP and Bacillus licheniformis was analyzed through computational approaches. The results evidenced that, Ppβ-GBP interacts with the B. licheniformis through sugar-based ligand, β-glucan through a hydrogen bond with a good docking score. Thus, the synbiotic diet would be an effective immunostimulant to strengthen the fish immune system for better productivity.


Infarction of the omentum after cesarean section. A case report.
Omental infarction occurred in a woman immediately after cesarean section. This entity is difficult to diagnose, as illustrated by the course and management of this case.


The effectiveness of ornamental building materials (tiles) for retrospective thermoluminescence dosimetry.
Like many other decorative building materials, tiles are one of the most precious ornamental ingredients for making a lucrative building image. It not only offers beauty and luxury but also added value by protecting/monitoring ionizing radiation. In this study, the utmost regular use of seven varieties of tile samples has been considered for retrospective thermoluminescence dosimetry. To observe the potentials of tiles for retrospective dosimetry, the major thermoluminescence properties (such as dose-response, energy dependence, self-sensitivity, relative sensitivity, glow curves, repeatability, fading, and also effective atomic number) has been investigated following the annealing - irradiation - readout cycles. Making an allowance for the various TL parameters, White Horse (Mirror Polish) tiles demonstrate suitability to be used as emergency TL dosimeter in 0.5-100 Gy dose array. Comparing the values of Zeff of these numerous tiles' samples (11.6-12.7) with TLD-200 (Zeff = 16.3), it is to be noted that tiles can be used as a suitable material for environmental radiation dosimetry. The thermoluminescent characteristics of tiles in the dose limit from 0.5 Gy to 100 Gy are reported here for the first time.


A novel deletion of the L-ferritin iron-responsive element responsible for severe hereditary hyperferritinaemia-cataract syndrome.
In the last few years, mutations that cause disease through increased efficiency of mRNA translation have been discovered. Hereditary hyperferritinaemia-cataract syndrome (HHCS) arises from various point mutations or deletions within the iron-responsive element (IRE) in the 5'-UTR of the L-ferritin mRNA. Each unique mutation confers a characteristic degree of hyperferritinaemia and severity of cataract in affected individuals. We report a novel six-nucleotide deletion identified in an Italian family presenting with elevated serum ferritin and early onset bilateral cataract. This deletion involves a sequence with a TCT repetition and may have occurred through a mechanism of slippage mispairing. Because of the above repetition, the observed mutation can be interpreted as deletion 22-27, 23-28, 24-29 or 25-30. Structural modelling predicted an IRE stem modification that is expected to markedly reduce the binding to iron-regulatory proteins. A double-gradient denaturing gradient gel electrophoresis (DG-DGGE) method easily detected the above deletion.


Plant growth promoting rhizobacteria isolated from halophytes and drought-tolerant plants: genomic characterisation and exploration of phyto-beneficial traits.
Plant growth promoting rhizobacteria (PGPR) are able to provide cross-protection against multiple stress factors and facilitate growth of their plant symbionts in many ways. The aim of this study was to isolate and characterize rhizobacterial strains under natural conditions, associated with naturally occurring representatives of wild plant species and a local tomato cultivar, growing in differently stressed Mediterranean ecosystems. A total of 85 morphologically different rhizospheric strains were isolated; twenty-five exhibited multiple in vitro PGP-associated traits, including phosphate solubilization, indole-3-acetic acid production, and 1-aminocyclopropane-1-carboxylate deaminase activity. Whole genome analysis was applied to eight selected strains for their PGP potential and assigned seven strains to Gammaproteobacteria, and one to Bacteroidetes. The genomes harboured numerous genes involved in plant growth promotion and stress regulation. They also support the notion that the presence of gene clusters with potential PGP functions is affirmative but not necessary for a strain to promote plant growth under abiotic stress conditions. The selected strains were further tested for their ability to stimulate growth under stress. This initial screening led to the identification of some strains as potential PGPR for increasing crop production in a sustainable manner.


Internuclear ophthalmoplegia following arch aortography. Occurrence in association with an occult vertebral artery aneurysm.
The onset of internuclear ophthalmoplegia immediately following arch aortography in a previously healthy 49-year-old female is presented. This is the second description of internuclear ophthalmoplegia developing after cerebral angiography and represents the first report of its occurrence in association with an occult traumatic vertebral artery aneurysm.


Evaluating factors of greater patient satisfaction with outpatient cardiology telehealth visits during the COVID-19 pandemic.
The impact of telehealth on cardiovascular care during the COVID-19 pandemic on patient satisfaction and factors associated with satisfaction are not well characterized. We conducted a nonrandomized, prospective cross-sectional survey study for outpatient telehealth cardiovascular visits over a 169-day period utilizing a validated telehealth usability questionnaire. For each variable, patients were divided into 2 groups-1 with scores above the median, labeled "greater satisfaction," and the other with scores below the median, labeled "less satisfaction." A total of 13,913 outpatient telehealth encounters were successfully completed during the study period. A total of 7327 unique patients were identified and received a survey invitation; 5993 (81.8%) patients opened the invitation, and 1034 (14.1%) patients consented and completed the survey. Overall mean and median scores were 3.15 (standard deviation 0.74) and 3.37 (interquartile range 2.73-3.68) (maximum score 4.00). Greater satisfaction was noted among younger patients (mean age 63.3 ± 14.0 years, P = .005), female gender (46.3%, P = .007), non-White ethnicity (24.2% P = .006), self-identified early adopters and innovators of new technology (49.8%, P < .001), 1-way travel time greater than 1 hour (22.3%, P < .001), 1-way travel distance greater than 10 miles (49.0%, P < .001), patients needing child care arrangement (16.4%, P < .001), and history of orthotopic heart transplant (OHT) (5.1%, P = .04). Patients reported overall satisfaction with telehealth during the COVID-19 pandemic. Factors associated with patient convenience, along with female gender, younger age, and non-White ethnicity, correlated with greater satisfaction. Cardiovascular comorbidities did not correlate with greater satisfaction except for OHT. Further research into the impact of telehealth on patient satisfaction, safety, and clinical outcomes is needed.


Compensation of gradient-induced magnetic field perturbations.
Pulsed magnetic field gradients are essential for MR imaging and localized spectroscopy applications. However, besides the desired linear field gradients, pulsed currents in a strong external magnetic field also generate unwanted effects like eddy currents, gradient coil vibrations and acoustic noise. While the temporal magnetic field perturbations associated with eddy currents lead to spectral line shape distortions and signal loss, the vibration-related modulations lead to anti-symmetrical sidebands of any large signal (i.e. water), thereby obliterating the signals from low-concentration metabolites. Here the measurement, characterization and compensation of vibration-related magnetic field perturbations is presented. Following a quantitative evaluation of the various temporal components of the main magnetic field, a digital B0 magnetic field waveform is generated which reduces all temporal variations of the main magnetic field to within the spectral noise level.


Colonic surveillance by CT colonography using axial images only.
Patients at increased risk of colon cancer require strict colon surveillance. Our objective was to establish the efficacy of 2D axial CT colonography as a surveillance test when performed in routine clinical practice. Eighty-two patients at increased risk of colon cancer underwent CT colonography followed by conventional colonoscopy on the same morning. CT colonography studies were performed on a four-ring multidetector CT scanner (100 mAs, 120 kVp, 4 x 2.5 collimation) and were interpreted by two radiologists using 2D axial images only. Results were correlated with findings at colonoscopy. Note was made of subsequent histology reports from polypectomy specimens. A total of 52 polyps were detected at colonoscopy. Using 2D axial images alone, with no recourse to 2D multiplanar or 3D views, the sensitivity of CT colonography was 100, 33 and 19% for polyps larger than 9, 6-9 and smaller than 6 mm, respectively. Per-patient specificities were 98.8, 96 and 81.5%, respectively. Twenty-nine percent of polyps smaller than 1 cm were adenomatous and there were no histological features of severe dysplasia. CT colonography is a useful colon surveillance tool for patients at increased risk of colon cancer. It has a high specificity for identifying patients who should proceed to colonoscopy and polypectomy, while allowing further colon examination to be deferred in patients with normal studies. Using 2D axial images only, CT colonography can be performed as part of the daily CT workload, with a very low rate of referral for unnecessary colonoscopy.


Is Wilson's disease a dementing condition?
A case presentation in this journal by Rosselli, Lorenzana, Lasselli and Vergara (1981) has raised the issue of intellectual deterioration in Wilson's Disease. Relevant findings in the recent literature are discussed.


Effects of surgical induction of endometriosis on response properties of preoptic area neurons in rats.
Subfertility and severe pelvic pains are symptoms associated with endometriosis (ENDO), a common condition among women that is characterized by the growth of the uterine endometrium on the surface of organs within the pelvic region and abdominal cavity. The contribution of the CNS to symptoms associated with ENDO is not known. In the present study, the preoptic area (POA) of the hypothalamus was investigated, as this region of the forebrain is known to play an important role in the neuroendocrine control of the reproductive cycle, mating behavior, and antinociception. Female rats were either induced for ENDO by autotransplantation of uterine tissue (n=20) or uterine fat for surgical sham controls (n=11). Terminal extracellular electrophysiological recordings (urethane anesthesia) were conducted in the POA six weeks post-ENDO induction when the rats were in either the proestrus or metestrus stages of their estrous cycle. Significant differences were found between the ENDO versus SHAM groups of animals for the proportion of inhibitory responses as well as the percentage of neurons responding to stimulation of the abdominal branches of the vagus, which innervates portions of the female reproductive tract, including the ovaries. The endometriotic cysts were found to be significantly larger in proestrus rats (stage when hormones are elevated). These data demonstrate that the responses of POA neurons are influenced by the presence of endometriotic cysts in the abdominal cavity. Since the POA is known to be part of the neural circuitries that mediate nociception and fertility, any deviation from its normal activity under ENDO conditions could contribute to the constellation of symptoms that ensue.


Experimental murine models of brainstem gliomas.
As an intractable central nervous system (CNS) tumor, brainstem glioma (BG) is one of the leading causes of pediatric death by brain tumors. Owing to the risk of surgical resection and the little improvement in survival time after radiotherapy and chemotherapy, there is an urgent need to find reliable model systems to better understand the regional pathogenesis of the brainstem and improve treatment strategies. In this review, we outline the evolution of BG murine models, and discuss both their advantages and limitations in drug discovery.