One-stage pulmonary nodule detection using 3-D DCNN with feature fusion and attention mechanism in CT image.
Lung cancer is the most common cause of cancer-related death in the world. Low-dose computed tomography (LDCT) is a widely used modality in lung cancer detection. The nodule is an abnormal tissue and may evolve into lung cancer. Hence, it is crucial to detect nodules in the early detection stage. However, reviewing the LDCT scans to observe suspicious nodules is a time-consuming task. Recently, designing a computer-aided detection (CADe) system with convolutional neural network (CNN) architecture has been proven that it is helpful for radiologists. Hence, in this study, a 3-D YOLO-based CADe system, 3-D OSAF-YOLOv3, is proposed for nodule detection in LDCT images. The proposed CADe system consists of data preprocessing, nodule detection, and non-maximum suppression algorithm (NMS). At first, the data preprocessing including the background elimination, the spacing normalization, and the volume of interest (VOI) extraction, are conducted to remove the non-lung region, normalize the image spacing, and divide LDCT image into numerous VOIs. Then, the VOIs are fed into the 3-D OSAF-YOLOv3 model, to detect the suspicious nodules. The proposed model is constructed by integrating the 3-D YOLOv3 with the one-shot aggregation module (OSA), the receptive field block (RFB), and the feature fusion scheme (FFS). Finally, the NMS algorithm is performed to eliminate the duplicated detection generated by the model. In this study, the LUNA-16 dataset composed 1186 nodules from 888 LDCT scans and the competition performance metric (CPM) are used to evaluate our CADe system. In the experiment results, the proposed system can achieve a sensitivities rate of 0.962 with the false positive rate of 8 and complete a CPM value of 0.905. Moreover, according to the ablation study results, the employment of OSA module, RFB, and FFS could improve the detection performance actually. Furthermore, compared to other start-of-the-art (SOTA) models, our detection system could also achieve the higher performance. In this study, a YOLO-based CADe system for nodule detection in CT image system integrating additional modules and scheme is proposed for nodule detection in LDCT. The result indicates that the proposed the modification can significantly improve detection performance.


Synthetic mRNA Reprogramming of Human Fibroblast Cells.
Reprogramming of somatic cells, such as skin fibroblasts, to pluripotency was first achieved by forced expression of four transcription factors using integrating retroviral or lentiviral vectors, which result in integration of exogenous DNA into cellular genome and present a formidable barrier to therapeutic application of induced pluripotent stem cells (iPSCs). To facilitate the translation of iPSC technology to clinical practice, mRNA reprogramming method that generates transgene-free iPSCs is a safe and efficient method, eliminating bio-containment concerns associated with viral vectors, as well as the need for weeks of screening of cells to confirm that viral material has been completely eliminated during cell passaging.


The effect of mindfulness therapy in acromegaly, a pilot study.
Patients with acromegaly have often several comorbidities, including decreased quality of life, mood alterations and chronic pain. Mindfulness is effective at improving mood, quality of life and pain management; however, there is no data available on its effect in patients with acromegaly. We aimed at evaluating changes in quality of life, mood, pain, sleep, self-compassion, life satisfaction, blood pressure and heart rate after a mindfulness program. This was a randomized, multicentre, international clinical trial (Barcelona-BCN and Bergamo-BG) of 60 patients, 30 per centre. The intervention group participated in an 8-week face-to-face group program; the control group followed normal clinical routine. In BG, patients performed a classic Mindfulness Based Stress Reduction program; in BCN they performed an adapted program including elements of mindfulness and compassion with a greater focus on daily life. In the BCN intervention group there was an increase in night-time hours in bed (p = 0.05) after the program. In both centres there was a trend to a reduction of the time to start sleeping (p = 0.06 BCN, p = 0.07 BG). In BCN, the intervention group reduced the pain score compared to the control group (p = .02), and an improvement in self-compassion was found (p = .04). In both centres, heart rate decreased significantly in the intervention group during a single 2-hour session. This was evidenced at the first and the last program session (BCN p = .013 and p = .009; BG < 0.001 and p = .04). A training effect was found in BG, where heart rate fell more in the last session than in the first (p = 002). We have demonstrated for the first time the value of a mindfulness program in patients with acromegaly, analysing possible effects and advantages, and clarifying the usefulness of a specific protocol for the disease.


1 alpha,25-dihydroxyvitamin D3 up-regulates expression of the osteoclast integrin alpha v beta 3.
Osteoclast precursors selectively attach to bone and differentiate into multinucleated cells that function to remodel and resorb it. We have shown previously that attachment of osteoclasts to bone and subsequent resorption are mediated by the integrin alpha v beta 3. 1 alpha,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) enhances osteoclast precursor differentiation in vivo by mechanisms that are still not clearly understood but entail enhanced attachment of cells to bone. This observation raises the possibility that at least one component of vitamin D-induced osteoclast precursor differentiation involves modulation of integrin expression. To test if the steroid modulates the osteoclast integrin alpha v beta 3 (the vitronectin receptor), we examined the effects of 1,25-(OH)2D3 on transcription of the alpha v gene as well as surface expression and function of alpha v beta 3, in chicken osteoclast precursors. Treatment of the cells with 1,25-(OH)2D3 led to a progressive dose-dependent increase in steady state alpha v mRNA levels with enhanced expression evident within 24 h. The effect was receptor-mediated as indicated by the effects of other vitamin D analogs. The increase in alpha v mRNA levels did not reflect decreased message degradation but, as demonstrated by nuclear run-on experiments, was due to accelerated rates of transcription. Most importantly, induction of alpha v mRNA by 1,25-(OH)2D3 was mirrored by higher levels of expression of alpha v beta 3 on the cell surface, as well enhanced attachment to its substrate, vitronectin.


Lactic acid bacteria promoted soil quality and enhanced phytoextraction of Cd and Zn by mustard: A trial for bioengineering of toxic metal contaminated mining soils.
Microbial-assisted phytoremediation provides a green approach for remediation of metal contaminated soils. However, the impacts of mono and co-applications of lactic acid bacteria (LAB) on soil biochemical properties and phytoavailability of toxic metals in contaminated mining soils have not yet been sufficiently examined. Consequently, here we studied the effects of Lactobacillus plantarum (P), Lactobacillus acidophilus (A), and Lactobacillus rhamnosus (R) applications alone and in combination on soil enzyme activities and bioavailability and uptake of Cd and Zn by mustard (Brassica juncea) in a smelter-contaminated soil under greenhouse conditions. Among the studied bacteria, P was the most tolerant to Cd-and-Zn contamination. As compared to control, R increased the fresh and dry weight of mustard plants by 53.5% and 63.2%, respectively. Co-application of P + A increased the chlorophyll content by 28.6%, as compared to control. Addition of LAB to soil increased the activity of soil urease, alkaline phosphatase and β-D glucosidase increased by 1.86-fold (P + R), 1.80-fold (R) and 55.16% (P + R), respectively. Application of P + A + R enhanced catalase activity (19.3%) and superoxide dismutase activity (51.2%), while addition of A alone increased peroxidase activity (POD: 15.7%). Addition of P alone and together with A (P + A) enhanced Cd and Zn phytoextraction by mustard shoots up to 51.5% and 52.5%, respectively. We conclude that the single and/or co-application of LAB decreased soil pH, promoted plant growth, antioxidant and enzyme activities, and enhanced the phytoavailability of Cd and Zn in the studied contaminated soil. These findings might be an aid for enhancing the phytoremediation of Cd and Zn using LAB and mustard as a bioenergy crop, which may offer new ideas for field treatment of toxic metals contaminated soils.


Multi-stage planning of LID-GREI urban drainage systems in response to land-use changes.
Long-term planning of urban drainage systems aimed at maintaining the sustainability of urban hydrology remains challenging. In this study, an innovative multi-stage planning framework involving two adaptation pathways for optimizing hybrid low impact development and grey infrastructure (LID-GREI) layouts in opposing chronological orders was explored. The Forward Planning and Backward Planning are adaptation pathways to increase LID in chronological order based on the initial development stage of an urban built-up area and reduce LID in reverse chronological order based on the final development stage, respectively. Two resilience indicators, which considered potential risk scenarios of extreme storms and pipeline failures, were used to evaluate the performance of optimized layouts when land-use changed and evolved over time. Compared these two pathways, Forward Planning made the optimized layouts more economical and resilient in most risk scenarios when land-use changed, while the layouts optimized by Backward Planning showed higher resilience only in the initial stage. Furthermore, a decentralized scheme in Forward Planning was chosen as the optimal solution when taking costs, reliability, resilience, and land-use changes into an overall consideration. Nevertheless, this kind of reverse optimization order offers a novel exploration in planning pathways for discovering the alternative optimization schemes. More comprehensive solutions can be provided to decision-makers. The findings will shed a light on the exploration of optimized layouts in terms of spatial configuration and resilience performance in response to land-use changes. This framework can be used to support long-term investment and planning in urban drainage systems for sustainable stormwater management.


The presence of immunoreactive growth hormone release-inhibiting hormone in normal cerebrospinal fluid.
Immunoreactive GHRIH is present in normal CSF at a level of 55 +/- 28 pg/ml. Immunoreactivity shows mobility identical to synthetic GHRIH standard on sephadex and thin layer chromatography, and can be removed by antibody conjugated to sepharose.


Effects of 6-hydroxydopamine on rat carotid body chief cells.
Administration of 6-hydroxydopamine (6-OHDA) in concentrations high enough to cause degeneration of perivascular adrenergic nerve terminals has no morphological effect on the catecholamine-storing cells of the rat carotid body. Uptake of 6-OHDA by carotid body chief cells may be more selective than that exhibited by small-intensely-fluorescent cells and other catecholamine-storing cells which are affected by 6-OHDA. Alternatively, the sustentacular cells which envelope the chief cells may provide an effective barrier against the uptake of 6-OHDA.


Occurrence and characterization of inducible clindamycin resistance in canine methicillin-resistant Staphylococcus pseudintermedius.
This study aimed to detect inducible clindamycin (iCLI) resistance in Staphylococcus pseudintermedius isolated from dogs in Thailand using D-zone testing. Strains that were iCLI-resistant were characterized by molecular typing and antibiogram and were detected in 10/200 S. pseudintermedius isolates (5%) from 7/41 dogs (17%). All were methicillin-resistant S. pseudintermedius (MRSP) and demonstrated multidrug resistance. The iCLI-resistant MRSP contained erm(B) and had identical or closely related DNA fingerprint patterns by pulsed-field gel electrophoresis. All iCLI-resistant MRSP strains belonged to the same clonal complex 112 (sequence types 111 and 112) by multilocus sequence typing. To avoid misinterpretation of clindamycin susceptibility, D-zone testing is recommended to promote rational antimicrobial selection and limit the clonal expansion of multidrug resistant bacteria.


Comparison of the functional features of the pump organs of Anopheles sinensis and Aedes togoi.
Mosquitoes act as vectors for severe tropical diseases. Mosquito-borne diseases are affected by various factors such as environmental conditions, host body susceptibility, and mosquito feeding behavior. Among these factors, feeding behavior is affected by the feeding pump system located inside the mosquito head and also depends on the species of mosquito. Therefore, the 3D morphological structures of the feeding pumps of Aedes togoi and Anopheles sinensis were comparatively investigated using synchrotron X-ray microscopic computed tomography. In addition, the feeding behaviors of their pumping organs were also investigated using a 2D X-ray micro-imaging technique. An. sinensis, a malarial vector mosquito, had a larger feeding pump volume than Ae. togoi in the static or resting position. Interestingly, the two species of mosquitoes exhibited different feeding behaviors. Ae. togoi had a higher feeding frequency and expansion ratio than An. sinensis. Ae. togoi also exhibited F-actin localization more clearly. These distinctive variations in feeding volumes and behaviors provide essential insight into the blood-feeding mechanisms of female mosquitoes as vectors for tropical diseases.


Validation of the artificial intelligence-based trauma outcomes predictor (TOP) in patients 65 years and older.
The Trauma Outcomes Predictor tool was recently derived using a machine learning methodology called optimal classification trees and validated for prediction of outcomes in trauma patients. The Trauma Outcomes Predictor is available as an interactive smartphone application. In this study, we sought to assess the performance of the Trauma Outcomes Predictor in the elderly trauma patient. All patients aged 65 years and older in the American College of Surgeons-Trauma Quality Improvement Program 2017 database were included. The performance of the Trauma Outcomes Predictor in predicting in-hospital mortality and combined and specific morbidity based on incidence of 9 specific in-hospital complications was assessed using the c-statistic methodology, with planned subanalyses for patients 65 to 74, 75 to 84, and 85+ years. A total of 260,505 patients were included. Median age was 77 (71-84) years, 57% were women, and 98.8% had a blunt mechanism of injury. The Trauma Outcomes Predictor accurately predicted mortality in all patients, with excellent performance for penetrating trauma (c-statistic: 0.92) and good performance for blunt trauma (c-statistic: 0.83). Its best performance was in patients 65 to 74 years (c-statistic: blunt 0.86, penetrating 0.93). Among blunt trauma patients, the Trauma Outcomes Predictor had the best discrimination for predicting acute respiratory distress syndrome (c-statistic 0.75) and cardiac arrest requiring cardiopulmonary resuscitation (c-statistic 0.75). Among penetrating trauma patients, the Trauma Outcomes Predictor had the best discrimination for deep and organ space surgical site infections (c-statistics 0.95 and 0.84, respectively). The Trauma Outcomes Predictor is a novel, interpretable, and highly accurate predictor of in-hospital mortality in the elderly trauma patient up to age 85 years. The Trauma Outcomes Predictor could prove useful for bedside counseling of elderly patients and their families and for benchmarking the quality of geriatric trauma care.


Analysis of Risk Factors for Gunshot Wound Infection in a Nigerian Civilian Trauma Setting.
Survivors of firearm injury are at risk of wound infection. On average, civilian gunshot wound infection rates in developing countries are relatively high and almost on a par with infection rates in war trauma settings. Overall, there are limited data on civilian gunshot wound infection and its predisposing factors. The aim of this study was to determine the risk factors for gunshot wound infection in a civilian trauma setting of a developing nation. This was a retrospective analysis of data on the entire patients who presented in Federal Teaching Hospital Abakaliki with firearm injury from January 2005 to December 2014. There were 196 patients, and wound infection was a complication in 58 (29.6 %) of them. The significant factors for high wound infection rate in univariate analysis were perforating wound (p < 0.001), high velocity injury (p < 0.001), haematocrit <30 % (p < 0.001), presence of fracture (p < 0.001), hollow viscus injury (p < 0.001) and injury to hospital arrival interval later than 6 h (p < 0.014). Anatomical site of injury correlated with infection rate (p < 0.001), highest rate (40.6 %) in lower extremity and least (9.1 %) in head and neck wounds. Multivariate logistic regression analysis identified haematocrit (p < 0.001), perforating wound (p < 0.021), presence of fracture (p < 0.043) and hollow viscus injury (p < 0.039) as independent predictors of gunshot wound infection. The independent predictors of infection identified in this study call for judicious replacement of blood loss and high priority accorded to perforating wound, fractures and hollow viscus injury in interventions aimed at reducing gunshot wound infection rate.


Abrupt laryngeal engagement during stop plosive-vowel transitions in children with repaired cleft palate and adequate velopharyngeal closure: aerodynamic and sound pressure level evidence.
To determine whether children with repaired cleft palate and adequate velopharyngeal closure exhibit abrupt laryngeal engagement during stop plosive-vowel transitions as compared with children without cleft palate. A prospective group design was used with convenience sampling of patients at a university craniofacial center. PARTICIPANTS were 25 children (15 boys, 10 girls) with repaired cleft palate (mean age = 10.9 years, standard deviation = 1.5 years) and 20 children (10 boys, 10 girls) without cleft palate (mean age = 10.8 years, standard deviation = 1.8 years). All children with cleft palate had adequate velopharyngeal closure as determined by aerodynamic testing. (1) Peak oral airflow was determined during the release of /t/ in the word "two" during a counting task. (2) An index of laryngeal engagement defined as the ratio of the maximum oral airflow declination to peak oral airflow was calculated during the release of /t/. (3) Sound pressure level was determined during the vowel of the word "two." Children with cleft palate exhibited significantly more negative laryngeal engagement ratios (i.e., more abrupt adduction) (P = .002) and greater sound pressure level (P = .049) than controls. There was a significant negative relationship between laryngeal engagement and sound pressure level for all children (r = -.428, P = .003). Children with repaired cleft palate and adequate velopharyngeal function appear to use a strategy of abrupt laryngeal adduction during stop plosive-vowel transitions. This strategy-perhaps learned even prior to palate surgery-may help to achieve either adequate sound pressure level and/or velopharyngeal closure.


Lattice modulation strategies for 2D material assisted epitaxial growth.
As an emerging single crystals growth technique, the 2D-material-assisted epitaxy shows excellent advantages in flexible and transferable structure fabrication, dissimilar materials integration, and matter assembly, which offers opportunities for novel optoelectronics and electronics development and opens a pathway for the next-generation integrated system fabrication. Studying and understanding the lattice modulation mechanism in 2D-material-assisted epitaxy could greatly benefit its practical application and further development. In this review, we overview the tremendous experimental and theoretical findings in varied 2D-material-assisted epitaxy. The lattice guidance mechanism and corresponding epitaxial relationship construction strategy in remote epitaxy, van der Waals epitaxy, and quasi van der Waals epitaxy are discussed, respectively. Besides, the possible application scenarios and future development directions of 2D-material-assisted epitaxy are also given. We believe the discussions and perspectives exhibited here could help to provide insight into the essence of the 2D-material-assisted epitaxy and motivate novel structure design and offer solutions to heterogeneous integration via the 2D-material-assisted epitaxy method.


Spatiotemporal dynamics of Plasmodium falciparum histidine-rich protein 2 and 3 deletions in Peru.
Peru was the first country where pfhrp2 and pfhrp3 gene deletions were detected despite the fact that rapid diagnostics tests are not commonly used for confirmatory malaria diagnosis. This context provides a unique scenario to study the dynamics of pfhrp2 and pfhrp3 gene deletions without apparent RDTs selection pressure. In this study we characterized the presence of pfhrp2 and pfhrp3 genes on 325 P. falciparum samples collected in Iquitos and surrounding communities between 2011 and 2018 in order to understand the dynamics of gene deletion prevalence, potential associations with clinical symptomatology and parasite genetic background. P. falciparum presence was confirmed by microscopy and PCR of 18 s rRNA, pfmsp1 and pfmsp2. Gene deletions were assessed by amplification of exon1 and exon2 of pfhrp2 and pfhrp3 using gene specific PCRs. Confirmation of absence of HRP2 expression was assessed by ELISA of HRP2 and pLDH. Genotyping of 254 samples were performed using a panel of seven neutral microsatellite markers. Overall, pfhrp2 and pfhrp3 dual gene deletions were detected in 67% (217/324) parasite samples. Concordance between pfhrp2 deletion and negligible HRP2 protein levels was observed (Cohen's Kappa = 0.842). Prevalence of gene deletions was heterogeneous across study sites (adjusted p < 0.005) but there is an overall tendency towards increase through time in the prevalence of dual pfhrp2/3-deleted parasites between 2011 (14.3%) and 2016 (88.39%) stabilizing around 65% in 2018. Dual deletions increase was associated with dominance of a single new parasite haplotype (H8) which rapidly spread to all study sites during the 8 study years. Interestingly, participants infected with dual pfhrp2/3-deleted parasites had a significantly lower parasitemias than those without gene deletions in this cohort. Our study showed the increase of pfhrp2/3 deletions in the absence of RDTs pressure and a clonal replacement of circulating lines in the Peruvian Amazon basin. These results suggest that other factors linked to the pfhrp2/3 deletion provide a selective advantage over non-deleted strains and highlight the need for additional studies and continuing surveillance.


Curvilinear MetaSurfaces for Surface Wave Manipulation.
Artificial sheet materials, known as MetaSurfaces, have been applied to fully control both space and surface waves due to their exceptional abilities to dynamically tailor wave fronts and polarization states, while maintaining small footprints. However, previous and current designs and manufactured MetaSurfaces are limited to specific types of surfaces. There exists no general but rigorous design methodology for MetaSurfaces with generic curvature. The aim of this paper is to develop an analytical approach to characterize the wave behavior over arbitrary curvilinear MetaSurfaces. The proposed method allows us to fully characterize all propagating and evanescent wave modes from the MetaSurfaces. We will validate the proposed technique by designing, realizing and testing an ultrathin MetaSurface cloak for surface waves. Good results are obtained in terms of bandwidth, polarization independence and fabrication simplicity.


Differential control of respiratory frequency and tidal volume during exercise.
The lack of a testable model explaining how ventilation is regulated in different exercise conditions has been repeatedly acknowledged in the field of exercise physiology. Yet, this issue contrasts with the abundance of insightful findings produced over the last century and calls for the adoption of new integrative perspectives. In this review, we provide a methodological approach supporting the importance of producing a set of evidence by evaluating different studies together-especially those conducted in 'real' exercise conditions-instead of single studies separately. We show how the collective assessment of findings from three domains and three levels of observation support the development of a simple model of ventilatory control which proves to be effective in different exercise protocols, populations and experimental interventions. The main feature of the model is the differential control of respiratory frequency (fR) and tidal volume (VT); fR is primarily modulated by central command (especially during high-intensity exercise) and muscle afferent feedback (especially during moderate exercise) whereas VT by metabolic inputs. Furthermore, VT appears to be fine-tuned based on fR levels to match alveolar ventilation with metabolic requirements in different intensity domains, and even at a breath-by-breath level. This model reconciles the classical neuro-humoral theory with apparently contrasting findings by leveraging on the emerging control properties of the behavioural (i.e. fR) and metabolic (i.e. VT) components of minute ventilation. The integrative approach presented is expected to help in the design and interpretation of future studies on the control of fR and VT during exercise.


Prenatal Identification of Confined Placental Mosaicism in Pregnant Women with Fetal Growth Restriction.
We examined the influence of confined placental mosaicism (CPM) as a cause of fetal growth restriction (FGR), and whether CPM can be screened using cell-free DNA (cfDNA) analysis of the maternal plasma. We analyzed cfDNA in the maternal plasma of 40 FGR cases with an estimated fetal weight of less than - 2.0 SD using massively parallel sequencing to detect chromosomal aberrations. Fetal and placental genotyping was performed to confirm CPM cases. cfDNA analyses of maternal plasma detected suspected CPM cases with chromosomal aneuploidy or copy number variations in 5 of 40 cases (12.5%). For 4 cases in which the entire placenta consisted of cells with chromosomal abnormalities, fetal growth was severely restricted. CPM can be screened by cfDNA analysis in maternal plasma, accounting for approximately 10% of the causes of moderate or severe FGR, and the higher the proportion of abnormal karyotype cells in the placenta, the more severe the placental dysfunction and FGR.


Effects of the inhibitors of energy metabolism, lonidamine and levamisole, on 5-aminolevulinic-acid-induced photochemotherapy.
The ability of endogenously synthesized protoporphyrin IX (PpIX) to damage Chinese hamster lung fibroblasts of the line V79 by exposure to light was examined. This treatment induced reduction of cellular ATP, GTP, of the NADH/NAD+ ratio and of oxygen consumption. The present results indicate a close relationship between inhibition of respiration of irradiated cells and their ability to survive, e.g. 1 min of light exposure induced 90% inhibition of oxygen consumption and inactivation of approximately 95% of the cells, while the cellular content of ATP was reduced by only 15%. This indicates that the mitochondria are one of the primary targets of 5-aminolevulinic acid (ALA)-mediated photochemotherapy (PCT). In the present study, ALA-PCT was combined with the modulators of the glycolysis and the respiration chain, levamisole (LEV) and lonidamine (LND). A synergistic effect of combining ALA-PCT with non-toxic concentrations of LND was observed when LND was given prior to light exposure. This synergism was observed despite a substantial LND-induced inhibition of PpIX formation. At increasing doses of LND (>0.15 mM) the combination treatment becomes less efficient. This is due to the inhibition of PpIX synthesis induced by LND. A synergistic effect of ALA-PDT and LEV was found when LEV was given prior to light exposure. This was at least partly due to an LEV-stimulated effect on ALA-induced PpIX formation. However, it is not clear from the present results whether LEV may perturb energy metabolism in V79 cells since LEV alone did not reduce the energy charge or the NADH/NAD+ ratio. When LEV or LND were given after ALA-PCT, these 2 treatment modalities acted in an additive or slightly synergistic manner.


The architecture and biological performance of drug-loaded LbL nanoparticles.
Layer-by-Layer (LbL) nanoparticles are an emerging class of therapeutic carriers that afford precise control over key design parameters that facilitate improved drug and carrier pharmacokinetics, and enhanced molecular-targeting capabilities. This paper advances the development of these systems by establishing them as drug carriers, with the means to control drug release in a systemic environment and retard particle clearance from circulation, promoting improved biodistribution of the drug-containing system. Using dual-fluorescent tracking in vivo, this work establishes a robust means of screening libraries of LbL systems generated, affording simultaneous resolution over persistence and biodistribution of both the drug and carrier following systemic administration of a single particle formulation. Employing a PLGA drug-containing core as a substrate for LbL deposition, a range of coated systems were fabricated to investigate the abilities of these films to stabilize drug for delivery as well as to improve the pharmacokinetics of both the drug and carrier. Significant reductions in liver accumulation were observed for different formulations of the layered architectures within the first 30 min of systemic circulation. LbL architectures diminished liver localization of the surrogate drug, cardiogreen, by 10-25% ID/g relative to native PLGA nanoparticles and modulated carrier accumulation in the liver >50% ID/g. Further, enhanced persistence of the drug was observed with the coated systems, significantly increasing the drug half-life from 2 to 3 min for free drug and 1.87 h for the uncoated core to 4.17 h and 4.54 h for the coated systems. These systems provide an exciting, modular platform that improves the pharmacokinetic properties of the therapeutic, reduces bolus release of drug from nanoparticles, and enhances the safety and circulation half-life of the drug in vivo, proving them to be highly clinically-relevant and a promising approach for future development of molecularly-targeted and combination therapeutics.


Independent and combined effects of environmental factors and CYP2C19 polymorphisms on the risk of esophageal squamous cell carcinoma in Fujian Province of China.
The purpose of this study was to explore the effects of CYP2C19 gene polymorphisms and various environmental factors and their interactions on the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population. A 1:2 frequency-matched case control study of 285 patients and 570 controls was conducted from June 2010 to May 2011 in AnXi of Fujian province, China. Environmental factors were investigated using a self-administered questionnaire and genotypes were determined using polymerase chain reaction restriction fragment length polymorphism based methods. Unconditional logistic regression models were used for statistical evaluation. Current or former smoking, consumption of pickled vegetables or hot beverages/food, having a first degree relative with ESCC and history of reflux esophagitis were significantly associated with increased ESCC risk, whereas tea drinking and consumption of fresh vegetables and fruits were significantly associated with decreased risk. The CYP2C19*2 GA/AA genotype was significantly more prevalent in ESCC patients and individuals with at least one copy of the CYP2C19*2 A allele had a 3.19-fold increased risk (adjusted 95% confidence interval (CI): 2.21-4.61, P < 0.001) of ESCC compared with those without this allele. We found no significant associations between CYP2C19*3 genotypes and ESCC. The Cyp2C19*2 polymorphism appeared to have a multiplicative joint effect with tea drinking and hot beverage/food consumption (gene-tea drinking: P(interaction) = 0.042; hot beverage/food consumption: P(interaction) = 6.98 × 10(-6)) and an additive joint effect with pickled vegetable consumption (interaction contrast ratio = 1.96, 95% CI: 0.12-3.80). Our findings suggest that the CYP2C19*2 polymorphism plays an important role in the development of ESCC in the Chinese population, modified by tea drinking and consumption of pickled vegetables or hot beverages/food. Further studies are warranted to confirm our results.


[Pneumopericardium in newborns during artificial ventilation (author's transl)].
During a period of 4 years 5 cases of pneumopericardium were observed among 571 artificially ventilated early- and newborn babies. 4 patients died as result of cardiac tamponade, 3 of them before the pericardiocentesis could be performed. 1 infant survived by puncture of the pericardial cavity. Frequency, pathological mechanism, and diagnosis of the pneumopericardium including quick terapeutical measurements under which pericardiocentesis could be life saving, are discussed.


An index system for comparative parameter weighting in MR imaging.
An analytic method for comparative parameter weighting in magnetic resonance (MR) imaging has been developed using the concept of "fractional sensitivity." This new approach results in easily calculated indexes for T1, T2, and hydrogen weighting. This index system enables quantitative comparisons to be made between MR studies that have been performed at various field strengths, using different pulse sequences and pulse timing intervals.


Emergency carotid artery thrombectomy for postpartum hemiplegia.
The case of a 22-year-old patient who suffered from postpartum hemiplegia due to thrombosis of the internal carotid artery is reported. She was treated aggressively with pentobarbital coma, angiography, and thrombectomy and recovered with minimal deficit.


Ferroportin-1 in the recurrence of hepatic iron overload after liver transplantation.
Hepatic siderosis is frequent in patients with Hepatitis C virus (HCV) chronic hepatitis and considered secondary to advanced liver disease when detected in the explanted liver of cirrhotic patients submitted to transplantation. Here, we document the early recurrence of hepatic iron overload starting from host Kupffer cells and later involving hepatocytes in an Italian male submitted to liver transplantation for HCV-related cirrhosis, whose hemosiderosis was interpreted as related to a primary defect of iron handling by monocytic cells due to decreased Ferroportin-1 expression. He was negative for HFE mutations, had normal liver function, did not drink alcohol and had no erythropoietic defect. He was positive for the (CGG)(8/9) and the IVS1 -24 G>C Ferroportin-1 polymorphisms, associated with non-parenchymal iron overload, and had decreased Ferroportin-1 expression in monocytes. In conclusion, this case report documents the recurrence of progressive liver siderosis, which recalls Ferroportin disease, associated with decreased Ferroportin-1 expression in host monocytes repopulating the donor liver.


Gamma-ray spectrometric dating of late Homo erectus skulls from Ngandong and Sambungmacan, Central Java, Indonesia.
Hominid fossils from Ngandong and Sambungmacan, Central Java, Indonesia, are considered to be the most anatomically derived and youngest representatives of Homo erectus. Nondestructive gamma-ray spectrometric dating of three of these Homo erectus skulls showed that all samples underwent uranium leaching. Nevertheless, we could establish minimum age estimates of around 40ka, with an upper age limit of around 60 to 70ka. This means that the Homo erectus of Java very likely survived the Toba eruption and may have been contemporaneous with the earliest Homo sapiens in Southeast Asia and Australasia.


Biosynthesis of selenium nanoparticles by lactic acid bacteria and areas of their possible applications.
Lactic acid bacteria, being generally recognized as safe, are the preferred choice among other microbial producers of selenium nanoparticles. For successful production of SeNPs, it is necessary to take into account the physiological properties of the bacterium used as a biotransformer of inorganic forms of selenium in Se0. The antimicrobial and antioxidant activity of SeNPs allows to use them in the form of pure nanoparticles or biomass of lactic acid bacteria enriched with selenium in preparation of food, in agriculture, aquaculture, medicine, veterinary, and manufacturing of packing materials for food products. To attract attention to the promising new directions of lactic acid bacteria applications and to accelerate their implementation, the examples of the use of SeNPs synthesized by lactic acid bacteria in the mentioned above areas of human activity are described.


Grafting polymerization of glycidyl methacrylate onto capillary-channeled polymer (C-CP) fibers as a ligand binding platform: Applications in immobilized metal-ion affinity chromatography (IMAC) protein separations.
Immobilized metal-ion affinity chromatography (IMAC) is a valuable method for preparative and analytical-scale protein separations. Nylon 6 capillary-channeled polymer (C-CP) fibers were grafted with glycidyl methacrylate (GMA) as a monomer with ceric ammonium nitrate (in dilute nitric acid) used as the initiator. The polymerization reaction occurs rapidly (15 min) in a residential microwave. Iminodiacetic acid (IDA) is then attached to the grafted GMA polymers by reacting with the reactive terminal epoxide groups. Different parameters regarding the grafting time, initiator concentration and conversion time were investigated to find the optimal conditions for the entire modification process. The resulting nylon-IDA fibers were characterized by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM). The resulting carboxyl density and copper binding capacity were determined to be 612 ± 21 μmol g-1 and 375 ± 12 μmol g-1, respectively. When charged with Cu2+ ions and packed in a column format, the nylon-IDA fibers can be applied as an IMAC stationary phase for the separation of histidine rich proteins. The performance of this novel phase was evaluated through the separation of a mixture of model proteins (cytochrome C, α-chymotrypsinogen A and lysozyme) and a recombinant histidine-tagged protein (his-tagged ubiquitin). Despite multi-step modifications, columns of the modified fibers still maintain the anticipated high levels of throughput and efficiency, with binding capacities of 6.89 ± 0.56 mg lysozyme g-1 fiber and 6.32 ± 0.12 mg His-tagged ubiquitin g-1 fiber.


Payment to gamete donors: equality, gender equity, or solidarity?
Regulation of payment to gamete donors varies substantially across countries. The development of an ethically sustainable governance system of payments in gamete donation demands that the preferences of different stakeholders be heard. This study intends to contribute to improving the understanding of payment to gamete donors by analysing the views of donors and recipients about the preferred form of payment and its associations with their sociodemographic characteristics. This cross-sectional study included 70 donors and 172 recipients recruited at the Portuguese Public Bank of Gametes (July 2017-June 2018). Participants completed a self-reported questionnaire. Views about the preferred form of payment were collected through a multiple-choice question and an open-ended item. Associations were quantified through χ2 tests; content analysis was conducted with the open-ended answers. Both donors (48.6%) and recipients (40.7%) considered that reimbursement is the preferred form of payment to ensure solidarity-based motivations to donate. This option was followed by compensation for non-financial losses (41.4% of donors; 33.7% of recipients) based on gender equity. Preference for a fixed reward (22.7% of recipients; 8.6% of donors) was less frequent among younger donors and married/living with a partner or employed recipients, being based on the promotion of equality. In the context of the search for cross-border reproductive care and gamete circulation across countries, the findings from this study claim for the need to create solutions for payment to gamete donors that take into account gender equity and are simultaneously sensitive to donor's actual expenses and further health complications.


Molecular characterization of three L-type lectin genes from channel catfish, Ictalurus punctatus and their responses to Edwardsiella ictaluri challenge.
L-type lectins have a leguminous lectin domain and can bind to high-mannose type oligosaccharides. In the secretory pathway, L-type lectins play crucial roles in selective protein trafficking, sorting and targeting. Three L-type lectins were cloned in the channel catfish, Ictalurus punctatus, the 53 kDa endoplasmic reticulum ER-Golgi intermediate compartment protein (ERGIC-53), the vesicular integral protein of 36 kDa (VIP36) and VIP36-like. Phylogenetic analysis indicated that the catfish genes are orthologous to their counterparts in other species. Southern blot analysis demonstrated that all three L-type lectin genes are likely single-copy genes in the catfish genome. Analysis of expression in healthy tissues using quantitative real time RT-PCR indicated that all three genes are expressed widely in all tested tissues, but with strong tissue preference of expression: ERGIC-53 was found to be abundantly expressed in the liver, VIP36 was found to be abundantly expressed in the head-kidney, whereas VIP36-like was found to be abundantly expressed in the brain. Upon infection with Edwardsiella ictaluri, expressions of the three genes all had significant up-regulation in the head-kidney, but had distinct expression patterns: ERGIC-53 was gradually induced with the highest expression 7 days after challenge in the head-kidney, but was down-regulated in the liver, spleen, and brain. VIP36 was highly induced in the head-kidney, and 3 days after challenge in the brain, but was not up-regulated in any other tissues or timepoints after challenge. Expression levels of the catfish VIP36-like gene appeared to also respond to infection, albeit with differing patterns among the tested tissues. Taken together, our results indicate that all three L-type lectin genes may be involved in the immune responses of catfish after infection with E. ictaluri.


Transient hypercalciuria after commencing total intravenous nutrition.
A study of 28 patients receiving a standard regimen of total intravenous nutrition (I.V.N.) for periods of > 14 days has shown the transient development of hypercalciuria in 14 patients (50%). The peak incidence of hypercalciuria occurred in 11 patients (39%) after 1 week of I.V.N. and hypercalciuria persisted for 1-4 weeks. In only one patient was hypercalciuria present at the end of the treatment period. Urine calcium (Ca) and nitrogen (N) excretion rates correlated significantly (r = 0.48 p < 0.001) and urine N excretion varied from week to week in parallel with urine Ca excretion in the hypercalciuric group of patients. There was no significant difference in urine Ca excretion between 12 patients who received 3.75 mmol Ca/day and 16 patients who received 8.75 mmol Ca/day. It is concluded that transient hypercalciuria may be related to increased protein catabolism and N excretion and that it probably does not indicate a major problem in mineral metabolism.


Mechanism of action of hydroxychloroquine as an antirheumatic drug.
The antimalarial agents chloroquine and hydroxychloroquine have been used widely for the treatment of rheumatoid arthritis and systemic lupus erythematosus. These compounds lead to improvement of clinical and laboratory parameters, but their slow onset of action distinguishes them from glucocorticoids and nonsteroidal antiinflammatory agents. Chloroquine and hydroxychloroquine increase pH within intracellular vacuoles and alter processes such as protein degradation by acidic hydrolases in the lysosome, assembly of macromolecules in the endosomes, and posttranslation modification of proteins in the Golgi apparatus. It is proposed that the antirheumatic properties of these compounds results from their interference with "antigen processing" in macrophages and other antigen-presenting cells. Acidic cytoplasmic compartments are required for the antigenic protein to be digested and for the peptides to assemble with the alpha and beta chains of MHC class II proteins. As a result, antimalarials diminish the formation of peptide-MHC protein complexes required to stimulate CD4+ T cells and result in down-regulation of the immune response against autoantigenic peptides. Because this mechanism differs from other antirheumatic drugs, antimalarials are well suited to complement these other compounds in combination drug therapy.


Adherence to appointments for gestational diabetes testing and experiences with two-hour postprandial glucose test: a mixed-methods study in Ghana.
Failure to attend scheduled appointments is a common problem in healthcare. In obstetrics, diagnostic and treatment protocols for gestational diabetes mellitus (GDM) require client booking, test preparations, management and follow-up reviews. We identified the socio-demographic, obstetric and medical drivers influencing adherence to appointments for GDM testing and experiences of pregnant women's regarding performing oral glucose tolerance test (OGTT). A convergent parallel mixed-methods study comprising a cross-sectional survey and an explorative qualitative descriptive design were used. We recruited 817 women in their first trimester of pregnancy from the antenatal clinics of primary, secondary and tertiary health facilities in Ghana. After obtaining their demographic and health history, we scheduled them for 2-h OGTT between 24 and 28 gestational weeks and estimated the odds of returning for the test. In the qualitative phase, we called 166 participants to ascertain why they failed to report. Also, we had in-depth and focused group discussions with 60 postpartum women who performed the OGTT to explore their experiences with the test. Out of 817 pregnant women scheduled, 490 (59.97%) reported of which 54.59, 54.33 and 53.24% completed fasting plasma glucose, 1-h and 2-h OGTT, respectively. Maternal age above 35 years (OR: 3.56, 95% CI:1.49-8.47), secondary education (OR: 3.21, 95% CI: 1.19-8.69), formal sector employment (OR: 2.02, 95% CI: 1.16-3.51) and having same-sex children (OR: 4.37, 95% CI: 1.98-9.66) increased odds of appointment adherence whereas healthcare in a tertiary hospital (OR:0.46, 95% CI:0.22-0.96), rural residence (OR: 0.53, 95% CI: 0.34-0.85) and being overweight (OR: 0.45, 95% CI: 0.25-0.78) decreased the likelihood. Experiences were thematized into feelings about test procedure, acceptability of test, skillfulness of the health workers and information on the test. Despite the apprehension and discomforts associated with the test, the desire to know one's disease status was the chief motivation. Empathy, reassurance and receiving ample information on the test procedures eased anxiety and improved test compliance. Although 40% of participants scheduled did not return, the test was generally acceptable. Socio-cultural underpinnings influenced the health-seeking behaviors, meaning that health worker interactions on test procedures need to be sensitive to the woman's situation.


Isolated central nervous system relapse of multiple myeloma post autologous stem cell transplant- A rare presentation.
•CNS relapse in multiple myeloma after ASCT without medullary relapse is uncommon.•Isolated CNS relapse is extremely rare with only 7 cases reported in literature.•Prognosis is poor with very short median survival after detection of CNS relapse.•Management is based on IMiD's and intrathecal therapy with radiation.


The quest for mammalian Polycomb response elements: are we there yet?
A long-standing mystery in the field of Polycomb and Trithorax regulation is how these proteins, which are highly conserved between flies and mammals, can regulate several hundred equally highly conserved target genes, but recognise these targets via cis-regulatory elements that appear to show no conservation in their DNA sequence. These elements, termed Polycomb/Trithorax response elements (PRE/TREs or PREs), are relatively well characterised in flies, but their mammalian counterparts have proved to be extremely difficult to identify. Recent progress in this endeavour has generated a wealth of data and raised several intriguing questions. Here, we ask why and to what extent mammalian PREs are so different to those of the fly. We review recent advances, evaluate current models and identify open questions in the quest for mammalian PREs.


Phytohormones and volatile organic compounds, like geosmin, in the ectomycorrhiza of Tricholoma vaccinum and Norway spruce (Picea abies).
The ectomycorrhizospheric habitat contains a diverse pool of organisms, including the host plant, mycorrhizal fungi, and other rhizospheric microorganisms. Different signaling molecules may influence the ectomycorrhizal symbiosis. Here, we investigated the potential of the basidiomycete Tricholoma vaccinum to produce communication molecules for the interaction with its coniferous host, Norway spruce (Picea abies). We focused on the production of volatile organic compounds and phytohormones in axenic T. vaccinum cultures, identified the potential biosynthesis genes, and investigated their expression by RNA-Seq analyses. T. vaccinum released volatiles not usually associated with fungi, like limonene and β-barbatene, and geosmin. Using stable isotope labeling, the biosynthesis of geosmin was elucidated. The geosmin biosynthesis gene ges1 of T. vaccinum was identified, and up-regulation was scored during mycorrhiza, while a different regulation was seen with mycorrhizosphere bacteria. The fungus also released the volatile phytohormone ethylene and excreted salicylic and abscisic acid as well as jasmonates into the medium. The tree excreted the auxin, indole-3-acetic acid, and its biosynthesis intermediate, indole-3-acetamide, as well as salicylic acid with its root exudates. These compounds could be shown for the first time in exudates as well as in soil of a natural ectomycorrhizospheric habitat. The effects of phytohormones present in the mycorrhizosphere on hyphal branching of T. vaccinum were assessed. Salicylic and abscisic acid changed hyphal branching in a concentration-dependent manner. Since extensive branching is important for mycorrhiza establishment, a well-balanced level of mycorrhizospheric phytohormones is necessary. The regulation thus can be expected to contribute to an interkingdom language.


Stretch reflex modulation during a cyclic elbow movement.
Small torque pulses were delivered to the forearm in order to test the stretch reflex of the brachialis and triceps arm muscles in 11 normal subjects performing a cyclic movement about the elbow in the horizontal plane. The flexion-extension movement was paced by a metronome and performed under various loading conditions. Reflexes for each muscle were tested either in each 50 msec segment of the 2 sec cycle period, or in a smaller number of selected phases. A late reflex, appearing at a latency of about 60 msec (measured from the onset of the torque increment), was modulated extensively during the movement cycle. The amplitude of the late reflex increased markedly at the onset of a muscle contraction. In many of the subjects reflex responsiveness began to increase as early as 200 msec prior to the onset of voluntary muscle activity. Peak reflex responses were elicited by stimuli delivered 100-150 msec prior to the peak rate of increase of dynamic load (composed of inertial, viscous and elastic forces). The increase in responsiveness was followed by a drop which was generally coincident in time with the peak rate of increase of the load opposing muscle contraction. The modulation of the late reflex is appropriately timed for reflex-generated tension to help counteract dynamic loads, intrinsic to the movement.


The Human Monitoring Laboratory's new lung counter: calibration and comparison with the previous system and the Cameco Corporation's lung counter.
The Human Monitoring Laboratory has replaced its lung counting system with four large area (85 mm x 30 mm) HPGe detectors, electronics, and software. The system has been calibrated with the same lung set and phantom that was used to calibrate the Human Monitoring Laboratory's previous lung counting system and the Cameco Corporation's mobile lung counter. The performance characteristics (efficiency and sensitivity) of all three systems are compared, with the Human Monitoring Laboratory's new system being more sensitive than the other systems by factor of 1.3. The large area detectors highlight the design deficiency of the Lawrence Livermore National Laboratory's torso phantom, namely short lungs, as the lower two detectors are over inactive tissue (approximately 40%). As a result, both a two-detector and a three-detector array are actually more sensitive than a four-detector array in certain circumstances. This is, however, an unrealistic finding as human lungs are much longer (approximately 10 cm) than the Lawrence Livermore National Laboratory's phantom's lungs. The dosimetric implications of the new system's minimum detectable activities are put into perspective using (57)Co, (235)U, (238)U, (239)Pu, (241)Am, and natural uranium as example radionuclides.


Functional Movement Patterns and Body Composition of High-Level Volleyball, Soccer, and Rugby Players.
Sports practice leads athletes to develop a specific body composition, coordination patterns, and basic motor skills based on the different tactical and physical needs. To present and compare a wide range of functional movement patterns and body composition (BC) parameters of high-level male athletes playing different sports and to determine if there was a relationship between the parameters examined. Cross-sectional study. Team facilities. A total of 30 volleyball, 25 soccer, and 30 rugby players (age = 25.9 [5.0] y and body mass index = 25.6 [4.1] kg/m2). Functional movement patterns and anthropometric measurements were collected by a physician specifically trained. Body mass index, fat mass, fat-free mass, upper-arm muscle and fat area, calf muscle and fat area, thigh muscle and fat area, and functional movement screen (FMS) scores. In addition to considering the FMS total score, the authors separated the screen into 3 parts: FMSmove, FMSflex, and FMSstab. The rugby players showed a higher number of asymmetrical and dysfunctional movements than the other athletes (P < .01), while the highest scores in FMSflex were obtained by the volleyball players (P < .01). In addition, most of the asymmetrical and painful movements in the athletes were measured on the shoulder mobility test. Muscle and fat areas differed significantly among the athletes (P < .05). Significant associations were found between movement patterns and several BC variables. In particular, large negative correlations were measured between percentage of fat mass (r = -.616; P < .01), upper-arm fat area (r = -.519; P < .01), and FMS total score. Functional movement patterns and BC differ in athletes according to the sport practiced. Furthermore, reaching an optimal BC is essential to achieve a satisfactory quality of movement.


System maps for retention of neutral organic compounds under isocratic conditions on a reversed-phase monolithic column.
The solvation parameter model is used to create systems maps for the separation of neutral organic compounds on a Chromolith Performance RP-18e octadecylsiloxane-bonded silica-based monolithic column for water-acetonitrile and water-methanol mobile phase compositions from 10 to 70% (v/v) organic solvent. These results demonstrate that the retention properties of the monolithic column are similar to those of conventional octadecylsiloxane-bonded silica particle-packed columns. It is further shown that the selectivity for the monolithic column falls within the selectivity range for typical particle-packed columns at two mobile phase compositions for which a direct comparison is possible.


UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis.
Emerging evidences have demonstrated that ubiquitin-associated domain-containing protein 2 (UBAC2) is closely related to the occurrence and development of malignant tumors. However, the functions and underlying molecular mechanisms of UBAC2 in bladder cancer (BC) development have not been defined. In this study, we found that both UBAC2 mRNA and protein levels were upregulated in BC tissues and cell lines, and knockdown of UBAC2 inhibited BC cells proliferation both in vitro and in vivo. Meanwhile, Kaplan-Meier survival plots of 406 BC cases from TCGA database showed that higher expression of UBAC2 in BC patients was associated with lower survival rate. Mechanistic studies revealed that knockdown of UBAC2 increased the expression of p27 by posttranscriptional regulation. Our previous study indicated that circular RNA BCRC-3 (BCRC-3) promoted the expression of p27 through interacting with miR-182-5p, and reversed miR-182-5p-induced inhibition of p27 3'UTR activity. In the present study, we found that UBAC2 could bind to BCRC-3, and subsequently affected the interaction of BCRC-3 with miR-182-5p to inhibit the expression of p27. Furthermore, knockdown of BCRC-3 partly reversed the upregulation of p27 expression induced by knockdown of UBAC2. Our findings highlight a novel mechanism of UBAC2 in regulating p27 through affecting the function of BCRC-3, and provide a research basis for the diagnostic and therapeutic application of BC.


Pupillary responses and attentional allocation problems on the backward masking task in schizophrenia.
Early visual information processing impairment has consistently been found on the backward masking task in patients with schizophrenia, but the nature of this impairment remains unclear. Pupillometry was used to measure attentional allocation during visual backward masking task performance in patients with schizophrenia (n=16) and nonpsychiatric controls (n=16). The extent of pupil dilation recorded during a cognitive task reflects the processing load placed on the nervous system by the task. Schizophrenia patients detected significantly fewer targets than controls only when the stimulus onset asynchrony (SOA) between targets and masks reached 317 ms. For both groups, peak pupil dilation responses were also significantly larger in the 317 ms SOA condition relative to a no-mask condition, suggesting that the processing load of the 317 SOA masking condition was greater than the no-mask condition. In addition, a principal components analysis of pupillary response waveforms identified time-related factors that appeared to differentially index attentional allocation to targets vs. masks. Patients with schizophrenia showed less dilation than controls on a middle factor that appeared to index attentional allocation to targets, but patients showed greater dilation than controls on a late factor that appeared to index attentional allocation to masks. That is, controls attended more to targets than to masks, but patients attended more to masks than to targets. These findings suggest that masking impairments at SOA intervals greater than 100-200 ms may be due abnormalities in attentional allocation mechanisms.


Mapping DNA Methylation in Mammals: The State of the Art.
A complete understanding of the dynamics and function of cytosine modifications in mammalian biology is lacking. Central to achieving this understanding is the availability of techniques that permit sensitive and specific genome-wide mapping of DNA modifications in mammalian DNA. The last decade has seen the development of a vast arsenal of novel profiling approaches enabling epigeneticists to tackle research questions that were previously out of reach. Here, we review the techniques currently available for profiling DNA modifications in mammals, discuss their strengths and weaknesses, and speculate on the future direction of DNA modification profiling technologies.


Refined mapping of loss of heterozygosity on 1q31.1-32.1 in sporadic colorectal carcinoma.
To explore precise deleted regions and screen the candidate tumor suppressor genes related to sporadic colorectal carcinoma. Six markers on 1q31.1-32.1 were chosen. These polymorphic microsatellite markers in 83 colorectal cancer patients tumor and normal DNA were analyzed via PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for Loss of heterozygosity (LOH) scanning and analysis. Comparison between LOH frequency and clinicopathological factors was performed by c2 test. 1q31.1-32.1 exhibited higher LOH frequency in colorectal carcinoma. The average LOH frequency of 1q31.1-32.1 was 23.0%, with the highest frequency of 36.7% (18/49) at D1S2622, and the lowest of 16.4% (11/67) at D1S412, respectively. A minimal region of frequent deletion was located within a 2 cM genomic segment at D1S413-D1S2622 (1q31.3-32.1). There was no significant association between LOH of each marker on 1q31.1-32.1 and the clinicopathological data (patient sex, age, tumor size, growth pattern or Dukes stage), which indicated that on 1q31.1-32.1, LOH was a common phenomenon in all kinds of sporadic colorectal carcinoma. Through our refined deletion mapping, the critical and precise deleted region was located within 2 cM chromosomal segment encompassing 2 loci (D1S413, D1S2622). No significant association was found between LOH and clinicopathologic features in 1q31.1-32.1.


Simultaneous ipsilateral fractures of distal and proximal ends of the radius.
We treated a patient with a rare combination of ipsilateral fractures of the distal and proximal ends of the radius. A woman aged 52 years had simultaneous fractures of the distal and proximal ends of the radius (radial head and neck) after she fell from a high place. The fracture of the radial head was treated by open fixation with a cancellous bone screw, and the fractured distal end of the radius was treated by bone graft, with the subsequent application of an external fixator. At the 1-year follow up, the patient had minor residual limitation of forearm pronation and elbow joint extension, but she had no pain on movement, and had a good result based on Cooney's score (90 points).


Variability in blue carbon storage related to biogeochemical factors in seagrass meadows off the coast of the Korean peninsula.
Coastal vegetated habitats such as mangroves, salt marshes, and seagrasses, referred to as blue carbon ecosystems, play an important role in climate change mitigation by an effective CO2 capture from atmosphere and water columns and long-term organic carbon (Corg) storage in sediments. Although seagrass meadows are considered intense carbon sinks, information on regional variability in seagrass blue carbon stock and factors influencing its capacity still remain sparse. In the present study, seagrass blue carbon storage by measuring Corg stocks in sediments and living seagrass biomass, and carbon accumulation rates (CARs) in seagrass meadows were estimated along the Korean coast. Factors affecting variability in Corg stocks were also analyzed using partial least squares (PLS) regression and principal component analysis (PCA). Projected Corg stocks in sediment, extrapolated to a depth 1 m, exhibited substantial variability among sites, ranging from 49.91 to 125.71 Mg C ha-1. The majority of Corg (96-99%) was stored in sediments, whereas the contribution of living biomass was minor. PLS regression and PCA indicated that Corg stocks in seagrass meadows are strongly associated with sediment characteristics such as dry bulk density and water and mud content. Among seagrass traits, above- to below-ground biomass ratio was significantly related to the quantity of Corg stocks in seagrass meadows. Because of the high spatial variability in Corg stocks and CARs, local and regional differences in seagrass blue carbon storage should be considered to accurately assess the climate change mitigation potential of seagrass ecosystems.


Chlamydia pneumoniae infection in Italian patients.
Of 91 adult patients with respiratory tract infections, 13 (14%) had serological evidence of recent infection with Chlamydia pneumoniae. The clinical picture was consistent with asthmatic bronchitis in three patients, whilst exacerbations of chronic obstructive pulmonary disease were present in five subjects and, pneumonia was diagnosed in the remaining five. Our findings provide evidence of an aetiological association between C. pneumoniae and respiratory infections in our region (Bari, South Italy).


Changes in incidence of hospitalization for cardiovascular diseases during the COVID-19 pandemic in The Netherlands in 2020.
This population-based cohort study aimed to describe changes in incidence of cardiovascular disease (CVD) hospital diagnoses during the COVID-19 pandemic in The Netherlands compared with the pre-pandemic period. We used Dutch nationwide statistics about hospitalizations to estimate incidence rate ratios (IRR) of hospital diagnoses of CVD during the first and second COVID-19 waves in The Netherlands in 2020 versus the same periods in 2019. Compared with 2019, the incidence rate of a hospital diagnosis of ischemic stroke (IRR 0.87; 95% CI 0.79-0.95), major bleeding (IRR 0.74; 95% CI 0.68-0.82), atrial fibrillation (IRR 0.73; 95% CI 0.65-0.82), myocardial infarction (IRR 0.78; 95% CI 0.72-0.84), and heart failure (IRR 0.74; 95% CI 0.65-0.85) declined during the first wave, but returned to pre-pandemic levels throughout 2020. However, the incidence rate of a hospital diagnosis of pulmonary embolism (PE) increased during both the first and second wave in 2020 compared with 2019 (IRR 1.30; 95% CI 1.15-1.48 and IRR 1.31; 95% CI 1.19-1.44, respectively). In conclusion, we observed substantial declines in incidences of CVD during the COVID-19 pandemic in The Netherlands in 2020, especially during the first wave, with an exception for an increase in incidence of PE. This study contributes to quantifying the collateral damage of the COVID-19 pandemic.


Dopamine and serotonin neurotransmission in the reinforcing effects of alcohol and apomorphine.
To determine the role of dopamine and 5-hydroxytryptamine (5-HT; serotonin) in the reinforcing effects of alcohol and apomorphine. Experimental study. Department of Biochemistry, University of Karachi from September to November 2004. The study was conducted on 24 male albino Wistar rats. Reinforcing effects were monitored in a conditioned place preference (CPP) paradigm using a light-dark activity box. Slicing and punching method was used to collect dorsal and ventral striatum. Neurochemical estimations were done by HPLC-EC. Withdrawal from repeated administration of ethanol (1g/kg/day) as well as apomorphine (1 mg/kg/day) elicited reinforcement that could be monitored in a CPP paradigm. CNS depressant effects of ethanol were not altered on repeated administration but CNS stimulatory effects of apomorphine increased. Reinforcing effects of ethanol but not apomorphine were associated with a decrease in dopamine metabolism in the ventral striatum. A decrease in the activity of dopaminergic neurons following withdrawal from repeated administration is involved in the compulsive use of abused drugs.


Rodent models of adaptive decision making.
Adaptive decision making affords the animal the ability to respond quickly to changes in a dynamic environment: one in which attentional demands, cost or effort to procure the reward, and reward contingencies change frequently. The more flexible the organism is in adapting choice behavior, the more command and success the organism has in navigating its environment. Maladaptive decision making is at the heart of much neuropsychiatric disease, including addiction. Thus, a better understanding of the mechanisms that underlie normal, adaptive decision making helps achieve a better understanding of certain diseases that incorporate maladaptive decision making as a core feature. This chapter presents three general domains of methods that the experimenter can manipulate in animal decision-making tasks: attention, effort, and reward contingency. Here, we present detailed methods of rodent tasks frequently employed within these domains: the Attentional Set-Shift Task, Effortful T-maze Task, and Visual Discrimination Reversal Learning. These tasks all recruit regions within the frontal cortex and the striatum, and performance is heavily modulated by the neurotransmitter dopamine, making these assays highly valid measures in the study of psychostimulant addiction.


The risk of pulmonary adverse drug reactions of rebamipide and other drugs for acid-related diseases: An analysis of the national pharmacovigilance database in South Korea.
The objective of this case/non-case study was to detect rebamipide-related pulmonary adverse events (AE) compared with other drugs for acid-related disorders based on population-level data. From 2009 to 2018, AE reports on drugs for acid-related disorders, which are anatomical therapeutic chemical code A02B drugs, in the Korea Adverse Events Reporting System (KAERS) database were examined. The reporting odds ratio (ROR) was calculated, and the odds of reporting pulmonary AE for rebamipide and all other A02B drugs were compared. Furthermore, a stratified analysis according to patients' age and sex was conducted. Altogether 13 (0.05%) and 157 (0.11%) cases of pulmonary AE were reported for rebamipide and all other A02B drugs, respectively. The risk of reporting pulmonary AE was significantly lower for rebamipide than for all other A02B drugs (ROR 0.49, 95% confidence interval [CI] 0.28-0.87). The number of reports of pulmonary AE for rebamipide was significantly higher among patients aged ≥65 years than those aged <65 years (ROR 19.36, 95% CI 2.50-149.97). Rebamipide was less often reported for pulmonary AE. However, healthcare professionals need to be aware of the risk of pulmonary AE in elderly patients.


Management in the febrile, neutropenic patient with cancer: therapeutic considerations.
Infection is the principal cause of death in neutropenic children and adults with neoplastic diseases. Various antibiotic regimens have been studied in clinical trials in an attempt to reduce this mortality. Recent trials have compared newer combinations of antibacterial agents (double beta-lactams) or monotherapy with the standard aminoglycoside-beta-lactam combinations. No significant differences are demonstrated in these trials with regard to efficacy. Emphasis has been on the reduction of toxicity. Although nephrotoxicity, ototoxicity, and hypokalemia have been of concern in the past and continue to be important, newer problems have emerged that involve disorders of coagulation, for example, prolongation of prothrombin time, disorders of platelet function, and clinical bleeding. Superinfection and the emergence of resistance during therapy have also been problematic. Cost must be considered an important factor in determining the selection of an antibacterial regimen. The combination of an aminoglycoside and a beta-lactam antibiotic remains the standard against which future combinations or monotherapy must be judged in clinical trials involving the febrile, neutropenic patient with cancer.


Nervous system involvement in Farber disease.
A 30 months-old boy with Farber disease developed nystagmus 12 months after hematopoietic stem cell transplantation (HSCT). At 40 months, gait ataxia was evident, and brain MRI showed increased size of pericerebellar sulci and 4th ventricle. EMG showed denervation in the tongue and upper limb muscles, consistent with motor neuron disease. HSCT improves the peripheral manifestations of Farber disease, but may not prevent the progressive neurological deterioration.


Dcf1 deletion presents alterations in gut microbiota of mice similar to Parkinson's disease.
The gut-brain communication is increasingly being recognized as a profound effector on Parkinson's disease (PD). Gut microbiota changes have become the focus of attention. However, the mechanism leading to changes in the gut microbiota is not clear. In the present study, we found that knockout of Dcf1 (Dcf1-/-) caused changes in the gut microbiota in mice. Results indicated that the increased Proteobacteria (phylum-level) and decreased Prevotellaceae (family-level) in the microbiota composition of Dcf1-/- (KO) mice, which is consistent with the situation of PD patients. On species-level, Prevotellaceae_UCG-001 and Helicobacter_ganmani were significantly different between KO and WT mice, suggesting glycolipid metabolism disorders and inflammatory lesions in KO mice. In the behavior of Y-maze and Open field test, KO mice showed typical PD symptoms such as memory deficits, slowness of movement and anxiety. Further Nissl staining of brain tissue sections confirmed that the deletion of Dcf1 caused damage to amygdala neurons. These results provide a new mechanism for understanding gut microbiota changes, and provide a new basis for PD treatment from a new perspective of Gut-brain axis.


Can daily dietary arginine supplement affect the function and subpopulation of lymphocytes in patients with advanced gastric cancer? Wu C-W, Chi C-W, Chiu C-C, Liu W-Y, P'eng F-K and Wang S-R. Digestion 1993; 54: 118-124.
The effect of arginine on lymphocyte proliferation in vitro was studied in patients with advanced gastric cancer. Patients who were ambulatory, normally nourished and consuming a normal diet, received a daily supplement of 30 g arginine for 7 days. There was no change in total lymphocyte count, T B cell ratio in peripheral blood, or an enhancement of lymphocyte proliferation in response to mitogen stimulation. Arginine ingestion did not impair liver function and had no detectable side effects except transient nausea in one patient. An in vitro study on the effect of arginine on phytohaemagglutination-stimulated lymphocyte proliferation showed that lymphocytes from gastric cancer patients had poorer responses than obtained from normal subjects despite the supplement in the culture medium with normal serum, patient serum, or fetal bovine serum. These results indicate that dietary arginine supplementation appears safe but does not stimulate lymphocyte function in these advanced gastric cancer patients. The suppressed immune function may be the results of their intrinsic lymphocyte defect.


Increased chromosome damage in pediatric heart catheterization patients after diagnostic fluoroscopy and cineangiography.
Chromosome damage (CD) and sister chromatid exchange (SCE) levels were studied in lymphocytes from 30 pediatric heart catheterization patients receiving radiation during diagnostic fluoroscopy and cineangiography procedures. Forty-eight-hour CD and 72-hr SCE cultures were prepared from sequential samples taken from each patient: samples 1-3 via the catheter the same day (1) before exposure, (2) after fluoroscopy, and (3) after cineangiography; and sample 4 by venipuncture the next morning. Significant increases in CD (dicentrics, rings, and fragments), but not SCE, were observed. From a mean base level of 0.4% cells with CD, the CD levels increased 2-3-fold in samples 3 and 4 (p = .001). Rings only occurred in samples 3 and 4. While increased CD levels also correlated with increasing age, body surface area, and weight, partial correlations controlling for these factors clearly indicate that the CD effects are principally attributable to the radiological procedures (p = .001). Increased CD levels correlated with both the roentgen dose of cineangiography exposure (p = .002) and the volume of contrast medium (p = .000); however, partial correlations, controlling for either factor, indicate that the contrast medium was the principal factor (p = .006).


The Role of Mu-Opioids for Reward and Threat Processing in Humans: Bridging the Gap from Preclinical to Clinical Opioid Drug Studies.
Opioid receptors are widely expressed in the human brain. A number of features commonly associated with drug use disorder, such as difficulties in emotional learning, emotion regulation and anhedonia, have been linked to endogenous opioid signalling. Whereas chronic substance use and misuse are thought to alter the function of the mu-opioid system, the specific mechanisms are not well understood. We argue that understanding exogenous and endogenous opioid effects in the healthy human brain is an essential foundation for bridging preclinical and clinical findings related to opioid misuse. Here, we will examine psychopharmacological evidence to outline the role of the mu-opioid receptor (MOR) system in the processing of threat and reward, and discuss how disruption of these processes by chronic opioid use might alter emotional learning and reward responsiveness. In healthy people, studies using opioid antagonist drugs indicate that the brain's endogenous opioids downregulate fear reactivity and upregulate learning from safety. At the same time, endogenous opioids increase the liking of and motivation to engage with high reward value cues. Studies of acute opioid agonist effects indicate that with non-sedative doses, drugs such as morphine and buprenorphine can mimic endogenous opioid effects on liking and wanting. Disruption of endogenous opioid signalling due to prolonged opioid exposure is associated with some degree of anhedonia to non-drug rewards; however, new results leave open the possibility that this is not directly opioid-mediated. The available human psychopharmacological evidence indicates that the healthy mu-opioid system contributes to the regulation of reward and threat processing. Overall, endogenous opioids can subtly increase liking and wanting responses to a wide variety of rewards, from sweet tastes to feelings of being connected to close others. For threat-related processing, human evidence suggests that endogenous opioids inhibit fear conditioning and reduce the sensitivity to aversive stimuli, although inconsistencies remain. The size of effects reported in healthy humans are however modest, clearly indicating that MORs play out their role in close concert with other neurotransmitter systems. Relevant candidate systems for future research include dopamine, serotonin and endocannabinoid signalling. Nevertheless, it is possible that endogenous opioid fine-tuning of reward and threat processing, when unbalanced by e.g. opioid misuse, could over time develop into symptoms associated with opioid use disorder, such as anhedonia and depression/anxiety.


Triterpene saponins from Guo-gang-long attenuate collagen-induced arthritis via regulating A20 and inhibiting MAPK pathway.
The stems of Entada phaseoloides (L.) Merr commonly named "Guo-gang-long", is a traditional Chinese folk medicine that has been used clinically in China for the treatment of arthritis. Our previous study described that triterpene saponins isolated from "Guo-gang-long" could inhibit the inflammatory response. However, the potential mechanism of "Guo-gang-long" on treatment of arthritis, and whether the triterpene saponins responsible for its anti-arthritic effect are unclear. To investigate the function and mechanisms of the triterpene saponins from E. phaseoloides (ES) in collagen-induced arthritis (CIA) rats. The chemical components of ES were analyzed by HPLC. Anti-arthritic activity of ES was investigated in CIA rats, which was established by immunization with bovine type II collagen. Three doses of ES (25, 50 and 100 mg/kg) were administrated using oral gavage to CIA rats daily for 3 weeks. The anti-arthritic activity of ES was evaluated by clinical arthritis scoring, paw swelling and mechanical sensitivity, as well as histological changes in CIA rats. The impacts of ES on the regulation of the ubiquintin-editing enzyme A20 and MAPK signaling pathway, and production of pro-inflammatory cytokines in CIA rats were examined by Western blot, quantitative real-time PCR, ELISA, and immunohistochemical staining, respectively. ES treatment relieved the paw swelling, hyperalgesia and joint destruction, and prevented the progression of arthritis in CIA rats. Meanwhile, ES suppressed the excessive mRNA levels and protein expression of TNF-α and IL-17 in synovial tissues and hind paw joints, and reduced the production of IL-1β, TNF-α and IL-17 in serum. Furthermore, ES up-regulated A20 and suppressed the phosphorylation of p38 and ERK1/2 in hind paw joints, as well as inhibiting the activation of spinal p38 in CIA rats. ES could relieve rheumatic symptoms and prevent the development of rheumatoid arthritis. The effects of ES may be mediated by reducing proinflammatory cytokine levels, up-regulating A20 expression, reducing p38 and ERK1/2 activation in periphery, and inhibiting of phospho-p38 in spinal cord.


Generation of integration free hiPSCs clones, NSi001-A, NSi001-B, and NSi001-C from peripheral blood mononuclear cells of an individual with down syndrome having Robertsonian translocation.
Human-induced pluripotent stem cells (hiPSCs) clones NSi001-A, NSi001-B, and NSi001-C were generated from a female individual of Indian origin having Robertsonian translocation down syndrome (DS) by reprogramming peripheral blood mononuclear cells (PBMCs) using integration-free Sendai viral vectors. The established hiPSCs clones had karyotype similar to the patient sample with Robertsonian translocation [46, XX rob (14;21)], normal ES-like morphology, expression of pluripotency markers, and potential for three germ layer differentiation, i.e., ectoderm, mesoderm, and endoderm.


The morphology of cirrhosis. Recommendations on definition, nomenclature, and classification by a working group sponsored by the World Health Organization.
This memorandum provides guidelines on the definition, nomenclature, and classification of cirrhosis, chronic hepatitis, and hepatic fibrosis. These are considered according to morphological characteristics and aetiology. It is hoped that this system will serve as a standard for diagnostic, research, and epidemiological purposes. The relationship of cirrhosis to liver cell carcinoma is briefly discussed and the possible morphological markers of an increased risk of malignancy are defined.


Inhibition of O6-alkylguanine-DNA-alkyltransferase by metals.
The activity of the DNA-repair protein O6-alkylguanine-DNA-alkyltransferase was found to be strongly inhibited by a number of metal ions. Cd2+ was the most active followed by Cu2+, Hg2+, Zn2+ and Ag2. This inhibition is likely to result from the interaction of the metals with the cysteine-acceptor residue on the protein since the inhibition was reduced by increasing the concentration of dithiothreitol in the assay buffer. These results raise the possibility that exposure to Cd2+ could increase the mutagenicity and carcinogenicity of alkylating agents by retarding the rate of repair of alkylated DNA. However, other metals or metallic compounds which are known to be carcinogenic (such as compounds containing arsenic, lead, nickel or chromium) did not interfere with DNA repair by this protein.


Role of chemokines in HPV-induced cancers.
Human papillomaviruses (HPVs) cause cancers of the uterine cervix, oropharynx, anus, and vulvovaginal tract. Low-risk HPVs, such as HPV6 and 11, can also cause benign mucosal lesions including genital warts, and in patients with recurrent respiratory papillomatosis, lesions in the larynx, and on occasion, in the lungs. However, both high and less tumorigenic HPVs share a striking commonality in manipulating both innate and adaptive immune responses in HPV- infected keratinocytes, the natural host for HPV infection. In addition, immune/inflammatory cell infiltration into the tumor microenvironment influences cancer growth and prognosis, and this process is tightly regulated by different chemokines. Chemokines are small proteins and exert their biological effects by binding with G protein-coupled chemokine receptors (GPCRs) that are found on the surfaces of select target cells. Chemokines are not only involved in the establishment of a pro-tumorigenic microenvironment and organ-directed metastases but also involved in disease progression through enhancing tumor cell growth and proliferation. Therefore, having a solid grasp on chemokines and immune checkpoint modulators can help in the treatment of these cancers. In this review, we discuss the recent advances on the expression patterns and regulation of the main chemokines found in HPV-induced cancers, and their effects on both immune and non-immune cells in these lesions. Importantly, we also present the current knowledge of therapeutic interventions on the expression of specific chemokine and their receptors that have been shown to influence the development and progression of HPV-induced cancers.


Confucian bioethics and cross-cultural considerations in health care decision-making.
This article discusses the similarities and differences between Beauchamp and Childress's principlism and Confucian bioethics in terms of autonomy, beneficence, nonmaleficence, and justice. The author presents sensitive approaches for culturally diverse groups in health care areas and cautions against dichotomy in cross-cultural studies, which ignores the dynamic nature and intravariations of cultures. As a way of health care providers to become engaged in cultural diversity in nursing practice and research, the author suggests that they do not only have a general knowledge about the theoretical differences among groups through "normative analysis" but also learn to appreciate each individual's particular beliefs and values through narratives of morality. Health care providers as well as legal professionals need to cultivate "cultural humility," which is the willingness to explore the similarities and differences between their own and each client's priorities and values and to develop courses of action with patients.


Extrapleural pneumonectomy for early stage malignant pleural mesothelioma: a harmful procedure.
The effects on long-term post-operative quality of life (QoL) and disease-control in malignant pleural mesothelioma (MPM) of extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) are compared. Seventy-seven patients affected by early-stage MPM received EPP (40) or P/D (37) associated with multimodal treatment between 1998 and 2009 at our institution. The last consecutive 39 (19 EPP and 20 P/D) were asked to answer the EORTC-QLQ-C30 questionnaire at baseline and at 6- and 12-months after treatment completion to evaluate the impact on QoL of both procedures. QoL evaluation was stopped at recurrence demonstration. Twenty-five (62%) EPP vs 9 (24%) P/D patients (p = 0.002) had in-hospital major complications, and 2/40 (5%) EPP vs no one P/D patients died after surgery. Both procedures caused a significant impairment of all the considered variables of the EORTC-QLQ-C30 questionnaire after treatment completion; only P/D patients returned at baseline levels after 12 months. EPP patients had a worse long-term post-operative QoL when compared with P/D. Median post-operative disease-free period was longer for EPP patients (14 vs 11 months) whereas the residual life to death period after recurrence detection was significantly longer for P/D patients (13 vs 9 months) (p = 0.01). Median long-term survival was longer, even not significant, for P/D patients (25 vs 20 months). MPM patients submitted to EPP had a higher post-operative complication rate, a worse long-term QoL, a shorter residual life time after recurrent disease, despite a similar long-term survival when compared to P/D.


Selective deacetylation of zaluzanin D using transformed Escherichia coli cultures.
The use of conventional and unconventional reaction methodology for the hydrolysis of the acetate group in zaluzanin D resulted in hydration of the 11,13 exocyclic bond along with deacetylation. But the microorganism E. coli selectively cleaved the acetate group to yield zaluzanin C.


[Nerve and artery lesions after irradiation (author's transl)].
Recent studies relating to soft tissue lesions following irradiation have been concerned with those involving nerves and arteries: Nerve root myelopathies--Brown-sequard's syndrome--spasmodic paraparesis Peripheral neuropathies--plexal disorders--peripheral lesions Carotid stenosis.


Autonomic modulation following exercise is impaired in HIV patients.
The autonomic modulation in HIV patients undergoing highly active antiretroviral therapy (HAART) was investigated. The heart rate variability (HRV) was assessed in 13 HIV patients (43±2 years) and 10 healthy controls (31±5 years) at rest, during exercise, and recovery. All time (standard deviation of NN intervals, SDNN; root mean of squared sum of successive differences, rMSSD; relative number of pairs of adjacent RR intervals differing more than 50 ms, pNN50) and frequency (Low Frequency, LF; High Frequency, HF) HRV components were lower in HIV patients at rest [SDNN (HIV: 44.2±3.9 ms vs. 65.5±9.8 ms; P=0.04); rMSSD (HIV: 27.2±3.6 ms vs. 49.3±8.3 ms; P=0.02); pNN50 (HIV: 8.8±2.9% vs. 26.5±7.0%; P=0.02); LF (HIV: 502.4±80.5 ms2 vs. 1302.8±446.4 ms2; P=0.04); HF (HIV: 296.4 ± 62.3 ms2 vs. 986.3±280.6 ms2; P=0.01)] and post-exercise [SDNN (HIV: 32.3±3.5 ms vs. 55.8±5.9 ms; P=0.002); rMSSD (HIV: 17.4±3.1 ms vs. 36.6±4.6 ms; P=0.002); pNN50 (HIV: 2.9±1.2% vs. 14.7±3.4%; P=0.001); LF (HIV: 404.9±102.6 ms2 vs. 910.1±214.2 ms2; P=0.03); HF (HIV: 147.6 ± 40.1 ms vs. 554.5±135.0 ms2; P=0.004)]. No between-group differences were found during exercise (P>0.05 for all comparisons). In conclusion, HIV patients showed impaired autonomic modulation, with reduced parasympathetic activity at rest and during post-exercise recovery.


Quality evaluation based on color grading: quality discrimination of the Chinese medicine Corni Fructus by an E-eye.
'Quality evaluation based on color grading' is one of the features used in Chinese medicine discrimination. In order to assess the feasibility of electronic eye (E-eye) in implementing 'quality evaluation based on color grading', the present study applied an IRIS VA400 E-eye to test 58 batches of Corni Fructus samples. Their optical data were acquired and combined with their corresponding classes. A total of four quality discrimination models were produced according to discrimination analysis (DA), least squares support vector machine (LS-SVM), partial least squares-discrimination analysis (PLS-DA), and principal component analysis-discrimination analysis (PCA-DA). The accuracy rate of the aforementioned 4 cross evaluation models were 86.21%, 89.66%, 81.03% and 91.38%, respectively. Therefore, the PCA-DA method was used to build the final discrimination model for classifying Corni Fructus or discriminating its quality.


Identifying the Unique Aspects of Adolescent and Young Adult Palliative Care: A Case Study to Propel Programmatic Changes in Pediatric Hospitals.
Using a case study, in this article we seek to highlight how the distinct developmental needs of adolescent and young adult patients facing a life-threatening condition require a different approach to patient care by pediatric health care workers. The case underscores pitfalls in using a pediatric construct of care in areas of pain management, social stressors, and advanced care planning, and suggests programs to implement for improvement, including partnership with psychiatry, substance abuse, and palliative care specialists.


Recent advances in the genetics of frontotemporal dementia.
In this review we highlight recent advances in the human genetics of frontotemporal dementia (FTD). In addition to providing a broad survey of genes implicated in FTD in the last several years, we also discuss variation in genes implicated in both hereditary leukodystrophies and risk for FTD (e.g., TREM2, TMEM106B, CSF1R, AARS2, NOTCH3). Over the past five years, genetic variation in approximately 50 genes has been confirmed or suggested to cause or influence risk for FTD and FTD-spectrum disorders. We first give background and discuss recent findings related to C9ORF72, GRN and MAPT, the genes most commonly implicated in FTD. We then provide a broad overview of other FTD-associated genes and go on to discuss new findings in FTD genetics in East Asian populations, including pathogenic variation in CHCHD10, which may represent a frequent cause of disease in Chinese populations. Finally, we consider recent insights gleaned from genome-wide association and genetic pleiotropy studies. Recent genetic discoveries highlight cellular pathways involving autophagy, the endolysosomal system and neuroinflammation, and reveal an intriguing overlap between genes that confer risk for leukodystrophy and FTD.


Generalized giant axonal neuropathy-a case with features of Fazio-Londe disease.
We present the 8th case so far published of generalized giant axonal neuropathy. Many features of the neurological picture of this 8 year 8 month old boy were suggestive of progressive bulbar paralysis of childhood. Muscle and sural nerve biopsies disclosed typical nodular axonal swellings measuring between 10--29 nm. Ultrastructure of the inflated portions of the axon consisted almost exclusively of 10 nm filaments. Normally appearing constituents were found in the non-dilated portions of the axons with this particularity that glycogen and mitochondria were aggregated. Previous clinical and pathological evidence indicates that this rare disorder not only affects the peripheral nerves but also the whole CNS. Our case differs from the others reported in literature by its rapidly deteriorating course and by the prominent involvement of some brain-stem motor functions; we offer the theory that a link might be implicated between this entity and Fazio-Londe disease.


Online mental health care during the COVID-19 pandemic.
Identify users, services, and reasons for seeking online mental health care during the COVID-19 pandemic. A descriptive, retrospective study, with documentary analysis of medical records of users served between April and July 2020. Of the 258 accesses, 159 were complete, and 99 were offline messages. Although there were 61 (38.36%) consultations in May, in April, there were 49 (30.82%) in 18 days of reception. More than 89% of accesses were women between 40 and 59 years. Among the motivations in the search for care, anxiety, fear, depression, sadness, crying, stress, and suicidal ideation stand out. Chat is a quick, early and short-wait intervention opportunity for people in need of mental health care. Therefore, the study emphasizes the importance of investing in the training of nursing professionals to act in mental health.


Novel biomarkers in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths and the fifth most common cancer worldwide. Most of these patients are seen with advanced disease at the time of presentation. In spite of its high prevalence, there are not many therapeutic options available for patients with advanced-stage HCC. There is an urgent need for improving early detection and prognostication of patients with HCC. In addition, the development of new therapies targeting specific pathways involved in the pathogenesis of HCC should be a major goal for future research, with the objective of improving outcomes of patients with HCC. Biomarkers represent a relatively easy and noninvasive way to detect and estimate disease prognosis. In spite of the numerous efforts to find molecules as possible biomarkers, there is not a single ideal marker in HCC. Many new findings have shown promising results both in diagnosing and treating HCC. In this review, we summarized the most recent and relevant biomarkers in HCC.


Validation of the STOP-Bang Questionnaire in Greek Patients Suffering from Obstructive Sleep Apnea.
Obstructive sleep apnea (OSA) is a sleep disorder with high prevalence and significant health consequences. The aim of this study was to validate the STOP-Bang Questionnaire, a widely used screening tool for OSA besides polysomnography, in Greek patients. A hundred and two (102) patients with OSA, aged [mean (SD)] 59.16 (8.53) years, and 102 healthy adults, aged [mean (SD)] 54.67 (9.36) years, were assessed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for different cut-off values. The Epworth Sleepiness Scale (ESS) was also used to examine predictive validity. Patients with OSA showed higher scores than healthy controls (p < 0.001). The resulting specificity, sensitivity, PPV, and NPV were 98%, 60%, 71%, 97%, (cut-off 3), 96%, 81%, 84%, 95% (cut-off 4), and 86%, 97%, 97%, 88% (cut-off 5), respectively. This study has demonstrated that the Greek version of STOP-Bang can be used in the clinical setting to differentiate patients with OSA from healthy individuals with high accuracy and at low cost.


Introduction of automated systems to evaluate touch-pressure, vibration, and thermal cutaneous sensation in man.
Systems for automatic assessment of cutaneous touch-pressure, vibratory, and thermal sensation have been developed. These systems use stimuli which are quantified and reproducible, a two-alternative forced-choice technique, and programmed steps to test, score, and report. If normal responses from series of healthy persons have been measured, percentile values specific for test, site, age, and sex can be determined. Abnormality, as in neurological disease, can then be defined as the response which has a value greater than that of the 95th (or other) percentile. These systems may be used to detect and validate abnormalities of sensation in neurological disease and in persons at risk from new medications or from industrial toxins, and to monitor worsening or improvement of sensation in follow-up of a patient or in evaluation of therapeutic regimens.