The high efficient Sb(III) removal by cauliflower like amorphous nanoscale zero-valent iron (A-nZVI).
In this study, cauliflower like amorphous nanoscale zero-valent iron (A-nZVI) was prepared and its performance on the removal of Sb(III) was investigated and compared with that of nZVI. The results indicated that the removal of Sb(III) by nZVI and A-nZVI followed the pseudo-second-order kinetic model and Langmuir isotherm model, but the removal of Sb(III) by A-nZVI was more stable and its removal capacity (558.2 mg/g) is much higher than that of nZVI (91.3 mg/g). Moreover, the effects of initial Sb(III) concentration, initial pH and anions such as Cl-, NO3-, SO42-, PO43-, and AsO43- were also investigated. A-nZVI showed extremely high selectivity towards Sb(III) in that 500 mg/L of AsO43- and PO43- shows little impact on its removal, while the removal of Sb(III) by nZVI was almost inhibited under the same condition. The combination of SEM-EDS, XPS, XRD and FTIR revealed the removal of Sb(III) by nZVI and A-nZVI were synergistic effects of oxidation and adsorption, but less Sb(III) (39.5%) was oxidized by A-nZVI. More γ-FeOOH and γ-Fe2O3 were formed at the surface of A-nZVI during the reaction. Both oxides have high affinity toward Sb(III), which might cause the higher removal capacity and selectivity for the removal of Sb(III) by A-nZVI. In conclusion, A-nZVI showed great potential for the remediation of Sb(III) in groundwater.


The Management of Heterotopic Pregnancy with Transvaginal Ultrasound-Guided Local Injection of Absolute Ethanol.
The aim of the study is to present five cases of heterotopic pregnancy (HP) patients who received transvaginal ultrasound-guided local injection of absolute ethanol (AE). This was a case series and literature review in Reproductive Medicine Center of the 105th Hospital of the People's Liberation Army. Five primary infertile women who underwent assisted reproductive technology were diagnosed with HP and treated with local injection of AE (1.0-2.5 ml) under transvaginal ultrasound guidance. The size of intrauterine (IU) and ectopic sacs and the level of serum beta-human chorionic gonadotropin as well as pregnancy outcomes were monitored after treatment. Not applicable. Four of five cases presented with lack of Doppler flow in the injected area after AE injection. Meanwhile, IU pregnancy proceeded well after treatment and delivered a normal newborn. One case received emergency surgery 3 h after local injection of 2.5 ml AE because of the rupture of ectopic gestational sac (GS). An early abortion was identified 7 days after the surgery. Transvaginal ultrasound-guided local injection of AE is an alternative nonsurgical treatment for HP, yet overdose injection of AE will increase the risk of ectopic GS rupture.


Direct inhibitory effects of some 'calcium-antagonists' and trifluoperazine on the contractile proteins in smooth muscle.
1 Taenia preparations from the guinea-pig caecum were treated with Triton X-100 and glycerol to disrupt the plasma membrane. Disruption of the sarcolemma was confirmed by electronmicroscopy. The preparations contracted in response to low concentration of Ca2+ (10-40 microM) and the contractions were dependent upon exogenous adenosine triphosphate (ATP). 2 Nifedipine (100 microM), verapamil (100 microM) and diltiazem (100 microM) did not inhibit Ca2+-induced activation of the contractile proteins. 3 In contrast, fendiline (100 microM), cinnarizine (100 microM), flunarizine (100 microM), pimozide (100 microM) and trifluoperazine (100 microM) significantly inhibited Ca2+-induced contractions. The effects of cinnarizine (100 microM) were reversible. 4 These findings disclose further differences between calcium-antagonists and suggest that certain of these agents have an intracellular site of action.


Automated 3-D registration of MR and CT images of the head.
This paper discusses the application of voxel similarity measures in the automated registration of clinically acquired MR and CT data of the head. We describe a novel single-start multi-resolution approach to the optimization of these measures, and the issues involved in applying this to data having a range of different fields of view and sampling resolution. We compare four proposed measures of voxel similarity using the same optimization scheme when presented with 10 pairs of images with a range of initial misregistrations. The registration estimates are compared with those provided by manual point-based registration and evaluated by visual inspection to give an assessment of the robustness and accuracy of the different measures. One full-volume CT image set is used to investigate the performance of each measure when used to align truncated images from different regions in the head. The soft tissue correlation and mutual information measures were found to provide the most robust measures of misregistration, providing results comparable to or better than those from manual point-based registration for all but the most truncated image volumes.


Skills and procedures in emergency medicine: room for controversy.
To examine patterns of consensus and divergence of opinion about whether, and under what conditions, residency-trained emergency physicians use certain skills and perform procedures, directors of 35 emergency medicine, 28 surgery and 30 internal medicine residency programs were surveyed. The directors reacted to a list of 30 skills modified from the condition/skills list compiled by the Certification Task Force of the American College of Emergency Physicians representing a consensus on the core-knowledge for emergency medicine, as determined by both practicing and university-based emergency physicians. The responses indicate a wide variation of opinion about which skills are within the realm of residency-trained emergency physicians, and under what circumstances a procedure should be performed. The skills of greatest concern among emergency medicine directors include axillary and intravenous lidocaine blocks, bronchoscopy, burr holes, closed reduction of dislocated hips, Swan-Ganz catheterization, and cardiopulmonary by-pass. In contrast, slightly more than one third of the procedures on the modified list were clearly agreed upon by over 80% of the directors as procedures performed by trained emergency physicians.


Airway management in paediatric emergencies outside of an intensive care setting: a quality improvement project using Lean/Six Sigma methodology.
Use of a Lean/Six Sigma methodology in a quality improvement project to reduce variation and improve safety in airway management outside of the intensive care environment in a tertiary paediatric hospital.


Regulatory T-cell development and function are impaired in mice lacking membrane expression of full length intercellular adhesion molecule-1.
To further investigate the contribution of intercellular adhesion molecule-1 (ICAM-1) to adaptive immune responses, we analysed T-cell development and function in mice lacking full-length ICAM-1 (ICAM-1(tm1Jcgr) ). Compared with wild-type (ICAM-1(WT) ) mice, ICAM-1(tm1Jcgr) mice have impaired thymocyte development. Proportions and numbers of double negative, double positive, mature CD4(+) and CD8(+) thymocytes, as well as of regulatory T (Treg) cells were also significantly decreased. In the periphery, ICAM-1(tm1Jcgr) mice had significantly decreased proportions and numbers of naive and activated/memory CD4(+) and CD8(+) T cells, as well as of Treg cells, in lymph nodes but not in the spleen. In vitro activation of CD4(+) and CD8(+) T cells from ICAM-1(tm1Jcgr) mice with anti-CD3 antibodies and antigen-presenting cells (APCs) resulted in a significantly weaker proliferation, whereas proliferation induced with anti-CD3 and anti-CD28 antibody-coated beads was normal. In vivo immunization of ICAM-1(tm1Jcgr) mice resulted in normal generation of specific effector and memory immune responses that protect against a viral challenge. However, contrary to ICAM-1(WT) mice, immunization-induced specific effectors could not eradicate immunogen-expressing tumours. Treg cells from ICAM-1(tm1Jcgr) mice have abnormal activation and proliferation induced by anti-CD3 antibody and APCs, and have markedly decreased suppressive activity in vitro. In contrast to ICAM-1(WT) mice, they were unable to control experimentally induced colitis in vivo. Hence, our results further highlight the pleiotropic role of ICAM-1 in T-cell-dependent immune responses, with a major role in Treg cell development and suppressive function.


Legionnaires' disease in a patient with rheumatoid arthritis treated with cyclosporine.
We report a patient with long-standing rheumatoid arthritis (RA) treated with cyclosporine A; she developed a flare of her arthritis and evidence of vasculitis, cavitary pulmonary disease, nephritis and hepatitis, and was found to have Legionella pneumophila serotype I infection. Cyclosporine is a relatively new and investigational therapy in RA. Thus, it is important that any unusual complications in patients with RA treated with cyclosporine should be documented.


Effect of the crystalline environment on the third-order nonlinear optical properties of L-arginine phosphate monohydrate: a theoretical study.
A supermolecular approach combined with an iterative electrostatic scheme was employed to investigate the nonlinear optical properties of the hybrid L-arginine phosphate monohydrate crystal, the procedure being aided by DFT calculations. The supermolecular scheme basically treated the molecules surrounding the unit cell as point charges; this approximation results in rapid convergence, making it a feasible method. DFT functionals of different flavors were considered: B3LYP, B2PLYP, CAM-B3LYP, ωB97, and M06HF, utilizing the 6-311 + G(d) basis set. All functionals gave sufficiently accurate values for the dipole moment (μ) with respect to the experimental value 32(2) D. For the average linear polarizability ([Formula: see text]) and the total first hyperpolarizability (β tot), good agreement was observed between the DFT-calculated values and MP2-derived results reported in the literature. For the second hyperpolarizability, both static and dynamic regimes were considered. The point-charge embedding approach led to an attenuation of the second hyperpolarizability γ for all frequencies considered. Excitations of γ were not observed for frequencies smaller than 0.1 a.u. For the second hyperpolarizability (both static and dynamic), computational results showed that L-arginine phosphate monohydrate exhibits a large nonlinear optical effect, which implies the occurrence of microscopic third-order NLO behavior.


Body composition is associated with tacrolimus pharmacokinetics in kidney transplant recipients.
A population pharmacokinetic (popPK) model may be used to improve tacrolimus dosing and minimize under- and overexposure in kidney transplant recipients. It is unknown how body composition parameters relate to tacrolimus pharmacokinetics and which parameter correlates best with tacrolimus exposure. The aims of this study were to investigate which body composition parameter has the best association with the pharmacokinetics of tacrolimus and to describe this relationship in a popPK model. Body composition was assessed using bio-impedance spectroscopy (BIS). Pharmacokinetic analysis was performed using nonlinear mixed effects modeling (NONMEM). Lean tissue mass, adipose tissue mass, over-hydration, and phase angle were measured with BIS and then evaluated as covariates. The final popPK model was evaluated using goodness-of-fit plots, visual predictive checks, and a bootstrap analysis. In 46 kidney transplant recipients, 284 tacrolimus concentrations were measured. The base model without body composition parameters included age, plasma albumin, plasma creatinine, CYP3A4 and CYP3A5 genotypes, and hematocrit as covariates. After full forward inclusion and backward elimination, only the effect of the phase angle on clearance (dOFV = - 13.406; p < 0.01) was included in the final model. Phase angle was positively correlated with tacrolimus clearance. The inter-individual variability decreased from 41.7% in the base model to 34.2% in the final model. The model was successfully validated. The phase angle is the bio-impedance spectroscopic parameter that correlates best with tacrolimus pharmacokinetics. Incorporation of the phase angle in a popPK model can improve the prediction of an individual's tacrolimus dose requirement after transplantation.


Age, sex and regional brain volumes predict perceptual-motor skill acquisition.
Neural mechanisms of skill acquisition across the lifespan are largely unknown. Neuroimaging in younger adults and research on neurodegenerative disorders suggests that perceptual-motor learning relies on the striatum, cerebellum, and prefrontal cortex. Our objective in this study was to explore whether individual differences in regional brain volumes modify the effects of age and sex on the acquisition of a perceptual-motor skill in healthy adults. The participants (N = 85, age 22-80) performed five 5-trial blocks of a mirror-drawing task on three separate days (for a total of 25 trials). Index of performance was time to completion and number of errors committed. All participants improved with practice, but younger adults performed better than their older counterparts, and women performed better than men. Four brain regions--lateral prefrontal cortex (LPFC), hippocampus (HC), cerebellar hemispheres (Cb) and the caudate nucleus (Cd)--were selected on the basis of the relevant literature and measured on MRI scans. All regional volumes were negatively associated with age, although the magnitude of association differed from LPFC (the strongest) to Cd (the weakest). Larger lateral PFC was associated with better performance on the mirror drawing task, and this link was stronger in the older participants and was strengthened at the later stages of learning. Larger caudate was related to better performance, especially at later learning, among men, but among women the link was evident only during early learning. Thus, mirror-drawing represents a task that, despite its visual-spatial nature, favors women, and may exhibit sexually dimorphic brain substrates.


Progressive multifocal leukoencephalopathy in a lung transplant recipient.
Progressive multifocal leukoencephalopathy (PML) is a sub-acute, demyelinating disease of the brain caused by a human polyomavirus. We describe a patient with the onset of PML 7 months after lung transplantation. The patient was treated with immunosuppressive modulation and cidofovir, a new anti-viral therapy for PML, with stabilization of the symptoms. We also review the 4 additional reports in the literature of PML after heart and lung transplantation. Progressive multifocal leukoencephalopathy may become more prevalent as the population of heart and lung transplantation recipients increases.


The Rho-family guanine nucleotide exchange factor GEFT enhances retinoic acid- and cAMP-induced neurite outgrowth.
The Rho GTPases are important regulators of neurite outgrowth and pathfinding. We have recently reported that a Rho-family guanine nucleotide exchange factor, GEFT, modulates dendrite spine morphology and basal neurite outgrowth in primary hippocampal neurons and Neuro2A cells, respectively. Here we demonstrate that GEFT protein is highly expressed in all regions of the brain and is highly up-regulated upon treatment of Neuro2A cells with retinoic acid and dibutyric cAMP, which promote dendrite and axon-like neurite extensions, respectively. Within retinoic acid-induced neurite extensions, GEFT is localized to actin-enriched regions in the primary neurites, with little or no expression from secondary branches. Dibutyric cAMP-induced neurite extensions are highly concentrated for GEFT at the actin-rich distal tip of the growth cone. Additionally, we demonstrate that GEFT promotes neurite outgrowth in undifferentiated as well as differentiated Neuro2A cells. Together, our data provide new evidence suggesting that GEFT is an important regulator of multiple processes involved in axon and dendrite formation.


qpure: A tool to estimate tumor cellularity from genome-wide single-nucleotide polymorphism profiles.
Tumour cellularity, the relative proportion of tumour and normal cells in a sample, affects the sensitivity of mutation detection, copy number analysis, cancer gene expression and methylation profiling. Tumour cellularity is traditionally estimated by pathological review of sectioned specimens; however this method is both subjective and prone to error due to heterogeneity within lesions and cellularity differences between the sample viewed during pathological review and tissue used for research purposes. In this paper we describe a statistical model to estimate tumour cellularity from SNP array profiles of paired tumour and normal samples using shifts in SNP allele frequency at regions of loss of heterozygosity (LOH) in the tumour. We also provide qpure, a software implementation of the method. Our experiments showed that there is a medium correlation 0.42 ([Formula: see text]-value=0.0001) between tumor cellularity estimated by qpure and pathology review. Interestingly there is a high correlation 0.87 ([Formula: see text]-value [Formula: see text] 2.2e-16) between cellularity estimates by qpure and deep Ion Torrent sequencing of known somatic KRAS mutations; and a weaker correlation 0.32 ([Formula: see text]-value=0.004) between IonTorrent sequencing and pathology review. This suggests that qpure may be a more accurate predictor of tumour cellularity than pathology review. qpure can be downloaded from https://sourceforge.net/projects/qpure/.


Dynein interacts with the neural cell adhesion molecule (NCAM180) to tether dynamic microtubules and maintain synaptic density in cortical neurons.
Cytoplasmic dynein is well characterized as an organelle motor, but dynein also acts to tether and stabilize dynamic microtubule plus-ends in vitro. Here we identify a novel and direct interaction between dynein and the 180-kDa isoform of the neural cell adhesion molecule (NCAM). Optical trapping experiments indicate that dynein bound to beads via the NCAM180 interaction domain can tether projecting microtubule plus-ends. Live cell assays indicate that the NCAM180-dependent recruitment of dynein to the cortex leads to the selective stabilization of microtubules projecting to NCAM180 patches at the cell periphery. The dynein-NCAM180 interaction also enhances cell-cell adhesion in heterologous cell assays. Dynein and NCAM180 co-precipitate from mouse brain extract and from synaptosomal fractions, consistent with an endogenous interaction in neurons. Thus, we examined microtubule dynamics and synaptic density in primary cortical neurons. We find that depletion of NCAM, inhibition of the dynein-NCAM180 interaction, or dampening of microtubule dynamics with low dose nocodazole all result in significantly decreased in synaptic density. Based on these observations, we propose a working model for the role of dynein at the synapse, in which the anchoring of the motor to the cortex via binding to an adhesion molecule mediates the tethering of dynamic microtubule plus-ends to potentiate synaptic stabilization.


Corpus callosum abnormalities associated with greater externalizing behaviors in subjects at high risk for alcohol dependence.
Subjects at high risk for alcoholism have a greater propensity for externalizing behaviors and brain volume reductions of possible neurodevelopmental origin. Morphometric deficits in the corpus callosum (CC), which might reflect this neurodevelopmental abnormality, have been reported in other externalizing disorders such as attention deficit hyperactivity disorder, but not in subjects at high risk for alcoholism. The objective of the current study was to evaluate the CC morphometry in subjects at high risk for alcoholism. Magnetic resonance images of the CC in high-risk subjects (n=20) were compared with those of low-risk subjects matched to the high-risk subjects for age, sex, and handedness (n=20). Mid-sagittal areas of the CC, genu, body, isthmus and splenium were measured based on Witelson's method with good inter- and intra-rater reliability. Externalizing behaviors were assessed using the Semi-Structured Assessment for Genetics of Alcoholism-II. Total CC, genu and isthmus areas were significantly smaller in high-risk than low-risk subjects after controlling for age and intracranial area. The total externalizing symptoms score had a significant negative correlation with genu and isthmus areas. Smaller CC areas and their negative association with externalizing behaviors may represent yet another marker of susceptibility to alcoholism in high-risk subjects.


Copper induces microglia-mediated neuroinflammation through ROS/NF-κB pathway and mitophagy disorder.
The epidemiological correlation between copper exposure and higher risk of Parkinson disease (PD) has been recognized for a long time, and microglia-mediated neuroinflammation has reported to be an important component of the pathogenesis of PD. The present study aimed to investigate the role of microglial activation and neuroinflammation in copper neurotoxicity and the underlying mechanism of copper-induced activation of microglia. Based on the inflammatory changes in mouse brain tissues, the activation of microglia, the loss of dopaminergic neurons and the aggregation of α-syn were found in the substantia nigra. In this study we found that copper significantly caused inflammatory activation of BV2 cells. Importantly, copper increased the level of reactive oxygen species (ROS) in BV2 cells, and then activated the NF-κB pathway which acted as an early survival signal. Further study indicated that sustained copper accumulation in BV2 cells led to the decrease of mitochondrial membrane potential, reduction of Parkin and PINK1 expression, increase of P62 expression and LC3BⅡ/I ratio, as well as upregulation of NLRP3/caspase1/GSDMD axis proteins. In addition, the increased release of inflammatory factors was rescued by redox agent, NF-κB pathway inhibitor and mitophagy inducer. This work illustrated that copper exposure activates microglia to secrete inflammatory products, resulting in the pyroptosis of dopaminergic neurons, which was related to the early activation of ROS/NF-κB pathway and subsequent mitophagy disorder in BV2 cells.


Relationship between spontaneous abortion and presence of antibody to Toxoplasma gondii.
Five hundred and twenty-three pregnant women were screened to determine whether a relationship existed between spontaneous abortion, and the presence of antibody to Toxoplasma gondii. The percentage of women with this antibody and a past history of spontaneous miscarriage was not statistically different from the percentage of women without antibody and a past history of spontaneous abortion.


The factors that influence care home residents' and families' engagement with decision-making about their care and support: an integrative review of the literature.
As care homes play an important role in the lives of an increasing number of older people, it is pivotal to understand how residents' and their families engage in decision-making about their care and support. Internationally, there is an increasing emphasis in long-term care settings on the right of residents to be actively involved in all aspects of decision-making about their care and support. However, the steps necessary to achieving a culture of shared decision-making in long-term care settings remain unclear. The aim of this literature review is to summarise what is known in the literature about the factors that influence care home residents' and families' engagement with decision-making about their care and support. An integrative literature reviews was carried out, guided by the methodological framework proposed by Whittemore and Knafl (2005). CINAHL, Medline Ovid and ProQuest Health and Medical databases were searched for relevant articles from 2011 to 2021. A three-step method was used, including the use of reference and citation management software to manage search results and identify duplicate citations. Abstracts and full texts were reviewed by two reviewers. Details of the selected articles were then extracted using the Data Extraction Form. In total, 913 articles were located and 22 studies were included in the final analysis. The thematic analysis identified three main themes that illustrate the complexities of shared decision-making in care homes: (a) a positive culture of collaborative and reciprocal relationships; (b) a willingness to engage and a willingness to become engaged; and (c) communicating with intent to share and support rather than inform and direct. The implementation of shared decision-making in care homes is highly dependent on the support and nurturing of collaborative and reciprocal relationships between residents, families, and staff. Part of this process includes ascertaining the willingness of residents and families to become engaged in shared decision-making. Communication skills training for staff and guided approaches that view decision-making as a supportive process rather than a once off event are essential prerequisites for implementation.


Population-based comparison of two feeding tube approaches for head and neck cancer patients receiving concurrent systemic-radiation therapy: is a prophylactic feeding tube approach harmful or helpful?
The purpose of this study is to compare patient outcomes between a therapeutic versus a prophylactic gastrostomy tube (GT) placement approach in patients treated with concurrent systemic and radiation (SRT) therapy for head and neck cancer (HNC). Outcomes were compared between all HNC patients treated with concurrent SRT from January 2001 to June 2009 from a center that only places GTs therapeutically when clinically necessary (center A) versus a center that generally places them prophylactically (center B). A total of 445 patients with HNC were identified, with 63 % from center A. As anticipated, GTs were placed less commonly in center A compared to B (31 versus 88 %; p < 0.001). Center B had a significantly higher number of GT complications (p < 0.001), including infection (16 versus 5 %), leakage (10 versus 2 %), and blockage (3 versus 1 %). Conversely, center A had a higher admission rate (27 versus 13 %, p = 0.001), most prominent for GT-related issues (15 versus 6 %). Center B had higher GT dependence at 90 days post-radiation therapy (34 versus 12 %; p < 0.001), but not at 1 year (11 versus 10 %; p = 0.74). There was no significant difference in the proportion of head and neck patients who had a 10 % weight loss at 1 year (compared to baseline) between centers A and B (42 versus 53 %, p = 0.07). There was no significant difference in the overall survival (A versus B, HR = 0.99; p = 0.96). A prophylactic GT approach results in exposing higher number of patients to GT complications. The higher rate of hospitalizations using a therapeutic approach suggests that patients are sicker when GTs are required. Given the similar weight loss and survival, a therapeutic approach at an earlier stage of need may be a preferable approach, when access to prompt GT placement is available.


In vitro and in vivo cardiac toxicity of flavored electronic nicotine delivery systems.
The usage of flavored electronic nicotine delivery systems (ENDS) is popular, specifically in the teen and young adult age-groups. The possible cardiac toxicity of the flavoring aspect of ENDS is largely unknown. Vaping, a form of electronic nicotine delivery, uses "e-liquid" to generate "e-vapor," an aerosolized mixture of nicotine and/or flavors. We report our investigation into the cardiotoxic effects of flavored e-liquids. E-vapors containing flavoring aldehydes such as vanillin and cinnamaldehyde, as indicated by mass spectrometry, were more toxic in HL-1 cardiomyocytes than fruit-flavored e-vapor. Exposure of human induced pluripotent stem cell-derived cardiomyocytes to cinnamaldehyde or vanillin-flavored e-vapor affected the beating frequency and prolonged the field potential duration of these cells more than fruit-flavored e-vapor. In addition, vanillin aldehyde-flavored e-vapor reduced the human ether-à-go-go-related gene (hERG)-encoded potassium current in transfected human embryonic kidney cells. In mice, inhalation exposure to vanillin aldehyde-flavored e-vapor for 10 wk caused increased sympathetic predominance in heart rate variability measurements. In vivo inducible ventricular tachycardia was significantly longer, and in optical mapping, the magnitude of ventricular action potential duration alternans was significantly larger in the vanillin aldehyde-flavored e-vapor-exposed mice than in controls. We conclude that the widely popular flavored ENDS are not harm free, and they have a potential for cardiac harm. More studies are needed to further assess their cardiac safety profile and long-term health effects.NEW & NOTEWORTHY The use of electronic nicotine delivery systems (ENDS) is not harm free. It is not known whether ENDS negatively affect cardiac electrophysiological function. Our study in cell lines and in mice shows that ENDS can compromise cardiac electrophysiology, leading to action potential instability and inducible ventricular arrhythmias. Further investigations are necessary to assess the long-term cardiac safety profile of ENDS products in humans and to better understand how individual components of ENDS affect cardiac toxicity.


Upregulation and secretion of kallikrein-related peptidase 6 (KLK6) in gastric cancer.
KLK6 encoding kallikrein-related peptidase 6, a trypsin-like serine protease, has been shown to be upregulated in several cancers, although the tumorigenic role of KLK6 has not been elucidated. In this study, KLK6 was identified as a highly upregulated gene in gastric cancer; therefore, the possibility that KLK6 might be a suitable candidate tumor marker was examined. RT-PCR and immunohistochemical analysis showed overexpression of KLK6 in gastric cancer tissues compared to nontumor regions. Sera from gastric cancer patients had a 1.7-fold increase in KLK6 (373.1 μg/L, P = 0.048) compared to healthy individuals (214.2 μg/L), although there was no significant difference among patients with various tumor stages. Cellular invasiveness decreased by 45% in cells transfected with KLK6-specific small interfering RNA. Exogenous overexpression of KLK6 led to decreased activity of the E-cadherin promoter. This study shows that KLK6 is significantly upregulated and secreted in gastric cancer tissues and sera, suggesting that KLK6 might be used as a potential biomarker and therapeutic target for gastric cancer.


Toward kingdom-wide analyses of gene expression.
Gene expression data for Archaeplastida are accumulating exponentially, with more than 300 000 RNA-sequencing (RNA-seq) experiments available for hundreds of species. The gene expression data stem from thousands of experiments that capture gene expression in various organs, tissues, cell types, (a)biotic perturbations, and genotypes. Advances in software tools make it possible to process all these data in a matter of weeks on modern office computers, giving us the possibility to study gene expression in a kingdom-wide manner for the first time. We discuss how the expression data can be accessed and processed and outline analyses that take advantage of cross-species analyses, allowing us to generate powerful and robust hypotheses about gene function and evolution.


Porcine Parkin: molecular cloning of PARK2 cDNA, expression analysis, and identification of a splicing variant.
Parkin, encoded by the PARK2 gene, is an E3 ligase which functions as an integral component of the cytoplasmic ubiquitin/proteasomal protein degradation pathway. Mutations in the PARK2 gene, resulting in the loss of parkin function, leads to autosomal recessive juvenile Parkinsonism (AR-JP). This work reports the cloning and characterization of the porcine (Sus scrofa) PARK2 cDNA (SsPARK2) and splicing variants hereof. The PARK2 cDNA was amplified by the reverse transcriptase polymerase chain reaction (RT-PCR) using oligonucleotide primers derived from in silico sequences. The porcine PARK2 cDNA codes for a protein of 461 amino acids which shows a high similarity to orangutan (91%), human (86%), and to rat (82%) parkin. A splicing variant of the porcine PARK2 with a complete deletion of exon 9 was also identified. Expression analysis by quantitative real-time RT-PCR revealed presence of PARK2 transcript in all examined organs and tissues. Differential expression was observed, with very high levels of PARK2 mRNA in cerebellum, heart, and kidney. In addition, expression analysis showed that porcine PARK2 transcripts could be detected early in embryo development in different brain regions. The porcine PARK2 orthologue was mapped to chromosome 1p24-25. Single nucleotide polymorphism (SNP) analysis revealed seven SNPs in the porcine PARK2 gene, one missense and one silent mutation in exon 7 and five SNPs in intron 7.


Breast cancer with an initial gastrointestinal presentation: a case report and literature review.
The most common sites of breast cancer metastasis are the lymph nodes, lungs, bones, and liver. Gastrointestinal (GI) metastasis is relatively rare and often occurs within several years after a breast cancer diagnosis. Most patients experience abdominal pain, anorexia, bleeding, vomiting, and other digestive system symptoms, symptoms which are difficult to distinguish from primary gastric cancer. There is no characteristic change seen under a digestive tract endoscopy, and the difference in morphology under the pathological microscope from that of primary poorly differentiated gastric adenocarcinoma is so small that it can easily cause a misdiagnosis. This paper reports the case of 46-year-old female patient whose first symptom was GI discomfort. She was hospitalized for GI surgery with an unknown medical history, but, during the preoperative examination, multiple breast masses were found on both sides, which were proved by pathology to be invasive lobular cancer. According to the medical literature, bilateral breast cancer with gastric metastasis is very rare, and, so far, this is the first reported case. Despite it being a rare phenomenon, it is necessary to be aware of the possibility of metastatic lobular carcinoma in the diagnosis of poorly differentiated gastric adenocarcinoma by biopsy.


Effect of ascorbic acid (vitamin C) on the ESR spectra of the red and black hair: pheomelanin free radicals are not always present in red hair.
Increased incidence of melanoma in the population with red hair is conditioned by synthesis of pheomelanin pigments in the skin and their phototoxic properties. The recent research has shown that free radicals of pheomelanin are produced not only by the influence of UV irradiation, but also in UV-independent pathways of oxidative stress. It has been ascertained, that the color of the hair is not always determinant of the amount of pheolemanin radicals in red hair. Therefore, in order to evaluate the risk of melanoma in different individuals, it is necessary to define the amount of free radicals of pheomelanin in red hair using ESR spectroscopy method. Besides, it is very important to find effective antioxidant, capable of neutralizing free radicals of pheomelanin. It was proved that ascorbic acid neutralizes free radicals of pheomelanin very effectively. The main goal of our research was to define the presumably optimal concentration of ascorbic acid as an antioxidant and study the kinetics of the influence of this concentration on red and black hair. It has been found out, that ascorbic acid influences the free radicals of red and black hair, and its appropriate optimal concentration is 10 mM. The obtained results can be considered in dermatology and cosmetology.


Deconvolution of bulk tumors into distinct immune cell states predicts colorectal cancer recurrence.
Predicting colorectal cancer recurrence after tumor resection is crucial because it promotes the administration of proper subsequent treatment or management to improve the clinical outcomes of patients. Several clinical or molecular factors, including tumor stage, metastasis, and microsatellite instability status, have been used to assess the risk of recurrence, although their predictive ability is limited. Here, we predicted colorectal cancer recurrence based on cellular deconvolution of bulk tumors into two distinct immune cell states: cancer-associated (tumor-infiltrating immune cell-like) and noncancer-associated (peripheral blood mononuclear cell-like). Prediction model performed significantly better when immune cells were deconvoluted into two states rather than a single state, suggesting that the difference in cancer recurrence was better explained by distinct states of immune cells. It indicates the importance of distinguishing immune cell states using cellular deconvolution to improve the prediction of colorectal cancer recurrence.


New electrocardiographic criteria for predicting the site of coronary artery occlusion in inferior wall acute myocardial infarction.
In patients with inferior wall acute myocardial infarction (AMI), the site of the culprit lesion is an important determinant of outcome. Patients with right ventricular infarction have a poor prognosis, whereas those with occlusion of the left circumflex coronary artery (LCx) have a good prognosis. Therefore, we assessed whether standard 12-lead electrocardiograms obtained on admission could identify the site of coronary artery occlusion, (i.e., a site proximal to the origin of the right ventricular branch of the right coronary artery [RCA], a site distal to the origin of the right ventricular branch of the RCA, or a site in the LCx). The ratio of ST depression in lead V3 to ST elevation in lead III (V3/III ratio) was evaluated immediately before coronary angiography in 152 patients with a first inferior wall AMI confirmed by coronary angiography within 12 hours after the onset of symptoms. For occlusion of the proximal RCA, distal RCA, and LCx, V3/III ratio was 0.2+/-0.3, 0.8+/-0.5, and 2.5+/-2.5 (p = 0.0001), respectively. The V3/III ratio <0.5 identified proximal RCA occlusion, 0.5 <V3/III ratio < or = 1.2 identified distal RCA occlusion, and 1.2 <V3/III ratio identified LCx occlusion with sensitivities of 91%, 84%, and 84%, and specificities of 91%, 93%, and 95%, respectively. We conclude that the V3/III ratio is useful in predicting the site of coronary artery occlusion in patients with inferior wall AMI.


Gender influence on ocular manifestations and their outcome in Behcet's Disease. A long-term follow-up of up to 20 years.
It is of general belief that males are prone to more frequent, more severe manifestations, and less favorable outcome. We evaluated this hypothesis in ophthalmological manifestations (OM) of Behcet's Disease (BD). Visual acuity (VA), anterior uveitis, posterior uveitis (PU), and retinal vasculitis (RV) were checked, according to Ben Ezra, in 1,515 patients with eye lesions. The data at baseline and last visit were compared. Male/female ratio was 1.2 in the BD registry (6,500 patients) and 1.51 for OM patients (Chi(2) = 98.962, p < 0.0001). The patients-year-follow-up was 4,987. All parameters improved significantly from the baseline. Mean VA improved from 4.87 to 5.35 for males (p < 0.0001) and from 5.20 to 5.74 for females (p < 0.0001). Difference between males/females at baseline was not significant (p = 0.60). The mean improvement for males/females was statistically non-significant (p = 0.58). Percent improvement of eyes for males/females was 47.1%/48.8% (p = 0.41). Mean PU improved from 1.83 to 0.71 for males (p < 0.0001) and from 1.66 to 0.49 for females (p < 0.0001). Difference between males/females at baseline was significant (p = 0.01). The mean improvement for males/females was statistically non-significant (p = 0.45). Percent improvement of eyes for males/females was 75.4%/81.0% (p = 0.004). Mean RV improved from 2.05 to 1.16 for males (p < 0.0001) and from 1.97 to 0.99 for females (p < 0.0001). Difference between males/females at baseline was not significant (p = 0.42). The mean improvement for males/females was statistically non-significant (p = 0.47). Percent improvement of eyes for males/females was 62%/64.4% (p = 0.33). Male gender is more prone to ocular manifestations. The severity of lesions at baseline was the same for VA and RV. For PU, the difference was statistically significant, but was not clinically relevant. The therapeutic outcome (mean improvement and percent of improved eyes) was the same for all parameters.


Draft Genome Sequence of Streptococcus thermophilus C106, a Dairy Isolate from an Artisanal Cheese Produced in the Countryside of Ireland.
The lactic acid bacterium Streptococcus thermophilus is widely used for the fermentation of dairy products. Here, we present the draft genome sequence of S. thermophilus C106 isolated from an artisanal cheese produced in the countryside of Ireland.


Predictors of changes in body image concerns of Chinese adolescents.
This nine-month prospective study tested the extent to which risk factors implicated in recent accounts of body dissatisfaction predicted changes in body image concerns of adolescent boys and girls in China. A sample of 593 Chinese adolescents (217 boys, 376 girls) completed measures of weight esteem, appearance esteem and physical stature concern in addition to demographics, internalization of attractiveness ideals, negative affect, and appearance pressure, teasing, and comparison at baseline and nine-month follow-up. For girls, initial levels of social comparison, and internalized attractiveness ideals predicted decreases in body esteem over time. Time 1 negative affect contributed to changes in both appearance esteem and weight esteem for boys. Baseline level of stature concerns and reported height were the only predictors of later stature concerns within each sex. In sum, this study suggests specific factors previously implicated in Western accounts also have utility for understanding body image concerns of adolescents in China.


Effects of valerian on the severity and systemic manifestations of dysmenorrhea.
To evaluate the impact of valerian-a herb with sedative effects and antispasmodic effects on smooth muscles-on the severity of dysmenorrhea. In a double-blind, randomized, placebo-controlled trial, 100 students were randomly assigned to receive valerian (n=49) or placebo (n=51). Valerian (dose 255 mg) was given 3 times daily for 3 days beginning at the onset of menstruation, for 2 consecutive menstrual cycles. At baseline and during the intervention cycles, the pain severity was evaluated with a visual analog scale and the systemic manifestations were assessed using a multidimensional verbal scale. The pain severity at baseline did not differ significantly between the groups. After the intervention, the pain severity was significantly reduced in both groups (P<0.001), but the extent of the reduction was larger in the valerian group, with the difference between the 2 groups being statistically significant (P<0.05). The total scores of the systemic manifestations associated with dysmenorrhea decreased after the intervention, but there was no significant difference between the groups, with the exception for syncope (P<0.05). Valerian seems to be an effective treatment for dysmenorrhea, probably because of its antispasmodic effects.


Chemoreceptor stimulation and hypoxic pulmonary vasoconstriction in conscious dogs.
Dogs with electromagnetic flow probes implanted on their left (QL) and main (QT) pulmonary arteries, catheters in their left atria and external jugular veins, and chronic tracheostomies were trained to accept Carlens dual-lumen endotracheal tubes into their tracheostomies, thus allowing separate ventilation of the two lungs. Swan-Ganz catheters were inserted through the jugular vein catheters. Pneumotachographs measured air flow to each lung. During bilateral ventilation with room air or O2, QL was about 36% of QT. When the left lung was ventilated with N2 while the right remained on O2, PAO2 was above 90 mmHg and QL fell to about 25% of QT. When the left lung was ventilated with N2 and the right with room air, PAO2 fell below 40 mm Hg and QL increased to control levels. This increase in perfusion of the hypoxic lung during systemic hypoxemia was not seen in dogs after surgical deafferentation of the systemic arterial chemoreceptors, indicating that stimulation of the arterial chemoreceptors may interfere with the hypoxic pulmonary vasoconstriction.


k-space filtering in 2D gradient-echo breath-hold hyperpolarized 3He MRI: spatial resolution and signal-to-noise ratio considerations.
In this work some of the factors that can influence the signal-to-noise ratio (SNR) and spatial resolution in MR images of inhaled hyperpolarized gases are systematically addressed. In particular, the effects of RF depletion of longitudinal polarization and image gradient diffusion dephasing were assessed in terms of their contribution to a k-space filter. By means of theoretical simulations and a novel method of experimental validation using a variable transverse magnetization of the 1H signal, systematic quantitative and qualitative investigations of the effects of k-space filtering intrinsic to imaging of hyperpolarized gas were made. A 2D gradient-echo image is considered for a range of flip angles with centric, sequential, and half-Fourier Cartesian phase-encoding strategies, and the results are assessed in terms of SNR and spatial resolution in the reconstructed images. Centric phase encoding was found to give the best SNR at higher flip angles, with a trade-off in spatial resolution compared to sequential phase encoding. A half-Fourier approach potentially offers increased SNR through the use of higher flip angles without compromising the spatial resolution, which is comparable to that achieved with sequential encoding.


Bio-ethanol production by a novel autochthonous thermo-tolerant yeast isolated from wastewater.
It has been known for years that ethanol is a bio-fuel to replace fossil fuels. The ethanol industry requires the utilization of micro-organisms capable production with stresses. The purpose of present study was to isolate and characterize ethanologenic yeast with high potential application at high temperature to produce bio-ethanol. To isolate ethanologenic yeasts, wastewater samples from a starch producer plant in Varamin, Iran were used. The isolates were identified by molecular characterization. Characteristics of the isolated strains were determined at 30, 35, 40 and 45°C for 48 hours. 50 yeast strains capable of growing well in agar plates in a temperature range of 30-45°C were isolated. Out of the isolated strains, only three strains were screened for their ability to grow at 45°C. Selected yeast, designated as AT-3 strain which showed efficient flocculation capabilities with higher ethanol production and grew faster as compared to the rest of strains in media with 180 g/L glucose at 35°C. The selected yeast was identified as a new strain of Saccharomyces cerevisiae and submitted to the Gene-Bank database. Its' optimum growth temperature was between 35 and 40°C. The results showed that during the bio-ethanol production 2.5 × 10(10) and 8.5 × 10(9) (CFU/mL) were a good indication of strain capability in heat tolerance. Also, ethanol produced at a raise of 6.9% and 6.85% (w/v) at 35 and 40°C, respectively, whereas glucose-to-ethanol conversion yield was about 75% of the theoretical value. Results emphasized that the isolated strain identified as Saccharomyces cerevisiae. This specific strain has thermo-tolerant, osmo-tolerant, flocculating capabilities with potential for application in developing a low cost ethanol industry.


Expression of the Sonic hedgehog pathway in squamous cell carcinoma of the skin and the mucosa of the head and neck.
Activation of the hedgehog pathway may contribute to carcinogenesis. This study characterizes the expression pattern in squamous cell carcinoma of the skin and the head and neck. Tissue microarrays were constructed with samples of squamous cell carcinoma of the skin and the head and neck. All tissue samples were immunohistochemically stained for 7 Hedgehog pathway molecules. Significant (p < .0001) overexpression of all evaluated molecules could be observed in the tumor samples compared with healthy control tissues. Expression of Gli-2 showed significant upregulation and that of Smoothened and Patched significant downregulation in head and neck compared with skin carcinoma. High expression of Sonic hedgehog correlates significantly (p = .001) with poor overall survival in patients with head and neck cancer. Hedgehog signaling is differentially regulated in squamous cell carcinomas of the skin and the head and neck. Sonic hedgehog expression may serve as a prognostic factor in patients with head and neck cancer.


CircSNX25 mediated by SP1 promotes the carcinogenesis and development of triple-negative breast cancer.
Circular RNAs (circRNAs), according to a growing body of research, are thought to be important in the initiation and development of a number of cancers. However, more research is needed to fully understand how circRNAs work at the molecular level in triple-negative breast cancer (TNBC). RNA sequencing was conducted on four sets of TNBC samples and their corresponding adjacent noncancerous tissues (ANTs). The circSNX25 expression was assessed using quantitative real-time PCR in TNBC tissues and cells. Several in vitro and in vivo experiments were conducted in order to examine the function of circSNX25 in TNBC carcinogenesis. Through luciferase reporter and chromatin immunoprecipitation (ChIP) assays, we also investigated the potential regulation of circSNX25 biogenesis by specificity protein 1 (SP1). To further validate the relationship between circSNX25 and COPI coat complex subunit beta 1 (COPB1) in TNBC, we conducted circRNA pull-down and RNA immunoprecipitation (RIP) assays using the MS2/MS2-CP system. Online databases were analyzed to examine the clinical implications and prognostic value of COPB1 in TNBC. A higher circSNX25 expression levels were observed in tissues and cells of TNBC. Silencing circSNX25 notably inhibited TNBC cell proliferation, triggered apoptosis, and hindered tumor growth in vivo. Conversely, upregulation of circSNX25 had the opposite effects. Mechanistically, circSNX25 was found to physically interact with COPB1. Importantly, we identified that SP1 may enhance circSNX25 biogenesis. COPB1 levels were markedly higher in TNBC cells. Analysis of online databases revealed that TNBC patients with elevated COPB1 levels had a poorer prognosis. Our findings demonstrate that SP1-mediated circSNX25 promotes TNBC carcinogenesis and development. CircSNX25 may therefore serve as both a diagnostic and therapeutic biomarker for TNBC patients.


Resveratrol mediates its anti-cancer effects by Nrf2 signaling pathway activation.
Cancer represents a major health problem with an exceedingly high toll on the patients, their families, and the economy. Cancers are also associated with high mortality rates. Existing therapies for cancer are generally ineffective with many side effects. A search was conducted on Pubmed, Google Scholar, Scopus, and web of science databases, and articles related to anticancer effects of resveratrol were collected. Resveratrol is a natural compound that can activate the Nrf2 transcription factor. Nfr2 translocates to the nucleus and induces antioxidant gene expression. In different cell lines, resveratrol can increase apoptosis and inhibit the proliferation of cancer cells. We found that resveratrol shows efficacy for the treatment of cancer, but due to high controversy on the Nrf2 signaling pathway and mechanisms of resveratrol action, additional studies should be conducted to better characterize its mode-of-action in cancer.


Clinical Characterization of HCC/CCA Mixed Cancers in a Population-based Cohort.
Primary liver cancer (PLC) ranks among of the most common cancers worldwide. Within this group, a minority of cases displays characteristics of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), known as combined hepatocellular cholangiocarcinoma (cHCC- CCA). Currently, there is no specific standardized therapy for these mixed tumors. Therefore, the aim of our study was to analyze the clinical course, treatment and outcome of cHCC-CCA patients in a European population-based registry. We investigated 9,144 patients with PLC (6,622 HCC, 2,356 iCCA, and 166 cHCC-CCA) diagnosed between 2009 and 2020. All data were obtained from Clinical Cancer Registry of Baden-Württemberg (BW), Germany. In all three groups patients were predominantly male (82%, 57%, and 68% for HCC, iCCA and cHCC-CCA groups, respectively). 48% of cHCC-CCA patients were diagnosed as stage IV cancers, which was more than for HCC (31%) but less compared to CCA (64%). Overall median survival of cHCC-CCA patients was worse compared to HCC (9-13 months vs. 15.5 months, p<0.001) and rather comparable to CCA (11.8 months). Our data demonstrated that cHCC-CCA tumors appear to have a distinct clinical course with worse overall survival compared to HCC. Thus, identification of these cancers by histopathology is essential in order to further characterize this tumor entity and to provide accurate treatment to these patients.


Immune capacity of the chicken bursectomized at 60 hours of incubation: failure to produce immune, natural, and autoantibodies in spite of immunoglobulin production.
Chickens surgically bursectomized at 60 hr of incubation were immunized at the ages of 6, 7, 8, and 9 weeks with Escherichia coli lipopolysaccharide, levan, tetanus toxoid, and dinitrophenyl-bovine serum albumin. All antigens were given on each occasion. All embryonically bursectomized (BX) chickens had detectable concentrations of serum IgM, IgG, and IgA. On the whole, the IgG level was markedly decreased and the levels of IgM and IgA were normal. Concentrations of serum immunoglobulins did not change during immunization in the BX chickens. In spite of the production of serum immunoglobulins the BX chickens were unable to respond to the immunization by production of specific antibodies, whereas the control (CO) chickens produced good antibody response to each antigen used. The BX chickens also lacked both natural antibodies to phosphorylcholine, fecal bacteria, rabbit red blood cells (RRBC), and MHC antigens and autoantibodies to the liver, kidney, and thyroidea. Neither were any antibodies to the bursal structures observed. These results support the hypothesis that the bursal influence is not necessary for isotype switch, but is essential for the production of specific antibodies.


Vulnerable Hospitals and Cancer Surgery Readmissions: Insights into the Unintended Consequences of the Patient Protection and Affordable Care Act.
Penalties from the Hospital Readmission Reduction Program can push financially strained, vulnerable patient-serving hospitals into additional hardship. In this study, we quantified the association between vulnerable hospitals and readmissions and examined the respective contributions of patient- and hospital-related factors. A total of 110,857 patients who underwent major cancer operations were identified from the 2004-2011 State Inpatient Database of California. Vulnerable hospitals were defined as either self-identified safety net hospitals (SNHs) or hospitals with a high percentage of Medicaid patients (high Medicaid hospitals [HMHs]). We used multivariable logistic regression to determine the association between vulnerable hospitals and readmission. Patient and hospital contributions to the elevation in odds of readmission were assessed by comparing estimates from models with different subsets of predictors. Of the 355 hospitals, 13 were SNHs and 31 were HMHs. After adjusting for Hospital Readmission Reduction Program variables, SNHs had higher 30-day (odds ratio [OR] = 1.32; 95% CI, 1.18-1.47), 90-day (OR = 1.28; 95% CI, 1.18-1.38), and repeated readmissions (OR = 1.33; 95% CI, 1.18-1.49); HMHs also had higher 30-day (OR = 1.18; 95% CI, 1.05-1.32), 90-day (OR = 1.28; 95% CI, 1.16-1.42), and repeated readmissions (OR = 1.24; 95% CI, 1.01-1.54). Compared with patient characteristics, hospital factors accounted for a larger proportion of the increase in odds of readmission among SNHs (60% to 93% vs 24% to 39%), but a smaller proportion among HMHs (9% to 15% vs 60% to 115%). Vulnerable status of hospitals is associated with higher readmission rates after major cancer surgery. These findings reinforce the call to account for socioeconomic variables in risk adjustments for hospitals who serve a disproportionate share of disadvantaged patients.


Changes in monoclonal antibody productivity of recombinant BHK cells immobilized in collagen gel particles.
Animal cell perfusion high density culture is often adopted for the production of biologicals in industry. In high density culture sometimes the productivity of biologicals has been found to be enhanced. Especially in immobilized animal cell culture, significant increase in the productivity has been reported. We have found that the specific monoclonal antibody (MAb) productivity of an immobilized hybridoma cell is enhanced more than double. Several examples of enhancing productivities have been also shown by collagen immobilized cells. Immobilized cells involve some different points from non-immobilized cells in high density culture: In immobilized culture, some cells are contacted together, resulting in locally much higher cell concentration more than 10(8) cells/ml. Information originating from a cell can be easily transduced to the others in immobilized culture because the distance between cells is much nearer. Here we have performed collagen gel immobilized culture of recombinant BHK cells which produce a human IgG monoclonal antibody in a protein-free medium for more than three months. In this high density culture a stabilized monoclonal antibody production was found with around 8 times higher specific monoclonal antibody productivity compared with that in a batch serum containing culture. No higher MAb productivity was observed using a conditioned medium which was obtained from the high density culture, indicating that no components secreted from the immobilized cells work for enhancing monoclonal antibody production. The MAb productivity by the non-immobilized cells obtained by dissolving collagen using a collagenase gradually decreased and returned to the original level in the batch culture using a fresh medium. This suggests that the direct contact of the cells or a very close distance between the cells has something to do with the enhancement of the MAb productivity, and the higher productivity is kept for a while in each cell after they are drawn apart.


Extraskeletal mesenchymal chondrosarcoma arising from soft tissues: A rare case report.
Chondrosarcomas are an exceedingly rare form of cancer, impacting only a few individuals per million. Among chondrosarcomas, a small fraction belongs to the mesenchymal sub-type. Furthermore, only one-third of mesenchymal chondrosarcomas manifest in extraskeletal locations. A 38-year-old woman was referred by a midwife after experiencing pain in the right upper quadrant of her right breast for 2 months. The mass had been palpable for 1 week before the initial assessment. According to radiological evaluations, the tumor is outside breast tissue and not connected to the bones. Hence, a biopsy of the mass is done. The biphasic morphology of the tumor during pathological evaluation, in addition to immunohistochemistry testing, confirms the diagnosis of extraskeletal mesenchymal chondrosarcoma (EMCS). Finally, the mass was surgically removed, and 6 months of chemotherapy were administered to the patient. Given the tumor's rarity and the lack of established guidelines, diagnosing EMCS can be challenging and prone to errors. As such, meticulous sampling, along with precise pathological and imaging investigations, is imperative to accurately establish the diagnosis of these tumors.


Splicing factors of SR and hnRNP families as regulators of apoptosis in cancer.
SR and hnRNP proteins were initially discovered as regulators of alternative splicing: the process of controlled removal of introns and selective joining of exons through which multiple transcripts and, subsequently, proteins can be expressed from a single gene. Alternative splicing affects genes involved in all crucial cellular processes, including apoptosis. During cancerogenesis impaired apoptotic control facilitates survival of cells bearing molecular aberrations, contributing to their unrestricted proliferation and chemoresistance. Apparently, SR and hnRNP proteins regulate all levels of expression of apoptotic genes, including transcription initiation and elongation, alternative splicing, mRNA stability, translation, and protein degradation. The frequently disturbed expressions of SR/hnRNP proteins in cancers lead to impaired functioning of target apoptotic genes, including regulators of the extrinsic (Fas, caspase-8, caspase-2, c-FLIP) and the intrinsic pathway (Apaf-1, caspase-9, ICAD), genes encoding Bcl-2 proteins, IAPs, and p53 tumor suppressor. Prototypical members of SR/hnRNP families, SRSF1 and hnRNP A1, promote synthesis of anti-apoptotic splice variants of Bcl-x and Mcl-1, which results in attenuation of programmed cell death in breast cancer and chronic myeloid leukemia. SR/hnRNP proteins significantly affect responses to chemotherapy, acting as mediators or modulators of drug-induced apoptosis. Aberrant expression of SRSF1 and hnRNP K can interfere with tumor responses to chemotherapy in pancreatic and liver cancers. Currently, a number of splicing factor inhibitors is being tested in pre-clinical and clinical trials. In this review we discuss recent findings on the role of SR and hnRNP proteins in apoptotic control in cancer cells as well as their significance in anticancer treatments.


Inhibitory effect of kassinin on salt intake induced by different natriorexigenic treatments in the rat.
Pulse intracerebroventricular (i.c.v.) injection of kassinin, 100-500 ng/rat, potently inhibits salt intake induced by sodium depletion. The effect appears to be selective since the same doses of kassinin do not inhibit milk intake or solid food intake. When given by continuous i.c.v. infusion kassinin elicits a clear anti-natriorexic effect at doses of 1-10 ng/min/rat. Kassinin not only suppresses sodium depletion-induced salt appetite, but it also inhibits sodium intake induced by pulse i.c.v. injection of renin or by subcutaneous (s.c.) deoxycorticosterone. Finally it also suppresses the elevated need-free intake of 1.5% NaCl in multidepleted female rats, which is not mediated by the renin-angiotensin-aldosterone system. These findings show that kassinin exerts a general suppressive effect on salt intake, irrespective of the natriorexigenic treatment. The present study suggests that the kassinin-like peptides that are endogenous to the rat brain may be involved in the behavioral regulation of extracellular body fluids in the rat by inhibiting sodium intake.


Factors associated with the perception of parents and children regarding obesity-related terminology used by healthcare professionals in a sample of Korean children and adolescents with obesity.
This study aimed to compare how children with overweight or obesity and their parents perceive the obesity-related terms used by healthcare professionals and investigate the factors associated with these perceptions. Children and adolescents aged 8-16 years with overweight or obesity (n = 192) and their parents participated in the cross-sectional study by responding to a 5-point Likert-scale questionnaire on 10 obesity-related terms, including "chubby," "weight problem," "weight," "overweight," "BMI," "obese," "heavy," "fleshy," "fat," and "severely obese." For both children and parents, "chubby" was the most desirable term (mean ± standard deviation: 3.50 ± 1.12 and 2.95 ± 0.83, respectively), and "severely obese" was the least acceptable term (2.83 ± 1.17 and 2.02 ± 1.02, respectively). Although the parents preferred all the terms less than the children did (p < 0.001), "weight problem" was considered most motivating for a child to lose weight (3.93 ± 0.94). Among children, older age and a larger self-perceived body size were associated with a more positive response towards obesity-related terms, whereas having internalized or externalized problems were negatively associated with these terms. Parents with a history of cardiovascular disease considered "severely obese" (β = -0.419, [95% CI: -0.739, -0.099]) and "fat" (β = -0.457, [95% CI: -0.750, -0.164]) less desirable. Children and adolescents had a higher preference for obesity-related terms than their parents and preferred that healthcare professionals use euphemistic terms such as "chubby," or neutral terms such as "weight problem." Children with larger self-perceived body sizes or older age had a higher preference for obesity-related words. The terms used by healthcare professionals to describe excess weight must be motivating and respectful for all family members participating in the treatment.


Sucrose-induced changes in VLDL- and LDL-B apoprotein removal rates.
Dietary sucrose has been shown to increase triglyceride transport in very-low-density lipoproteins (VLDL), but it is not known whether the metabolism of the entire particle is affected. Measurements were therefore carried out on VLDL-B apoprotein flux and removal rate before and after the consumption of high sucrose diets (55% of calories). Autologous 125I-labeled VLDL were injected and the specific activity-time curves analyzed by two-pool kinetics. Two kinds of response to sucrose were seen. In two subjects, the pool of VLDL-B apoprotein decreased by 20% and 14% (despite increased fluxes) due to substantial increases in removal rates of 42% and 116%. In four subjects, pool size expanded by 154%, 426%, 50% and 105%, primarily as the result of decreased removal rates (decreases of 55%, 67%, 30%, and 43%). Changes in flux were inconstant, suggesting that accumulation of VLDL particles was related to delayed clearance rather than to increased formation. This may reflect the longer time required to remove the larger load of triglyceride from each particle. The catabolic rate of low-density lipoprotein (LDL) was also measured in five subjects: in four, the clearance of LDL increased with sucrose and was associated with decreases in LDL-B apoprotein and plasma cholesterol.


On Macdonald's model for schistosomiasis.
An attempt is made to reconstruct the specifics of the model in Macdonald's 1965 paper based on some manuscripts. The resulting model is not conclusive as discrepancies occur between this formulation and Macdonald's results. Assuming the formulation is adequate, the values of parameters yielding Macdonald's standard situation are provided. A way of studying the equilibrium behaviour of the model is outlined. The mathematical nature of the properties observed by Macdonald is studied. The model is altered to admit aggregated distributions of worms in hosts and to permit different death rates of infected and uninfected snails. The dynamics are found to depend strongly on the death rate of infected snails.


The dynamics of extracellular gadolinium-based contrast agent excretion into pleural and pericardial effusions quantified by T1 mapping cardiovascular magnetic resonance.
Excretion of cardiovascular magnetic resonance (CMR) extracellular gadolinium-based contrast agents (GBCA) into pleural and pericardial effusions, sometimes referred to as vicarious excretion, has been described as a rare occurrence using T1-weighted imaging. However, the T1 mapping characteristics as well as presence, magnitude and dynamics of contrast excretion into these effusions is not known. To investigate and compare the differences in T1 mapping characteristics and extracellular GBCA excretion dynamics in pleural and pericardial effusions. Clinically referred patients with a pericardial and/or pleural effusion underwent CMR T1 mapping at 1.5 T before, and at 3 (early) and at 27 (late) minutes after administration of an extracellular GBCA (0.2 mmol/kg, gadoteric acid). Analyzed effusion characteristics were native T1, ΔR1 early and late after contrast injection, and the effusion-volume-independent early-to-late contrast concentration ratio ΔR1early/ΔR1late, where ΔR1 = 1/T1post-contrast - 1/T1native. Native T1 was lower in pericardial effusions (n = 69) than in pleural effusions (n = 54) (median [interquartile range], 2912 [2567-3152] vs 3148 [2692-3494] ms, p = 0.005). Pericardial and pleural effusions did not differ with regards to ΔR1early (0.05 [0.03-0.10] vs 0.07 [0.03-0.12] s- 1, p = 0.38). Compared to pleural effusions, pericardial effusions had a higher ΔR1late (0.8 [0.6-1.2] vs 0.4 [0.2-0.6] s- 1, p < 0.001) and ΔR1early/ΔR1late (0.19 [0.08-0.30] vs 0.12 [0.04-0.19], p < 0.001). T1 mapping shows that extracellular GBCA is excreted into pericardial and pleural effusions. Consequently, the previously used term vicarious excretion is misleading. Compared to pleural effusions, pericardial effusions had both a lower native T1, consistent with lesser relative fluid content in relation to other components such as proteins, and more prominent early excretion dynamics, which could be related to inflammation. The clinical diagnostic utility of T1 mapping to determine quantitative contrast dynamics in pericardial and pleural effusions merits further investigation.


Extracting Multiple Worries From Breast Cancer Patient Blogs Using Multilabel Classification With the Natural Language Processing Model Bidirectional Encoder Representations From Transformers: Infodemiology Study of Blogs.
Patients with breast cancer have a variety of worries and need multifaceted information support. Their accumulated posts on social media contain rich descriptions of their daily worries concerning issues such as treatment, family, and finances. It is important to identify these issues to help patients with breast cancer to resolve their worries and obtain reliable information. This study aimed to extract and classify multiple worries from text generated by patients with breast cancer using Bidirectional Encoder Representations From Transformers (BERT), a context-aware natural language processing model. A total of 2272 blog posts by patients with breast cancer in Japan were collected. Five worry labels, "treatment," "physical," "psychological," "work/financial," and "family/friends," were defined and assigned to each post. Multiple labels were allowed. To assess the label criteria, 50 blog posts were randomly selected and annotated by two researchers with medical knowledge. After the interannotator agreement had been assessed by means of Cohen kappa, one researcher annotated all the blogs. A multilabel classifier that simultaneously predicts five worries in a text was developed using BERT. This classifier was fine-tuned by using the posts as input and adding a classification layer to the pretrained BERT. The performance was evaluated for precision using the average of 5-fold cross-validation results. Among the blog posts, 477 included "treatment," 1138 included "physical," 673 included "psychological," 312 included "work/financial," and 283 included "family/friends." The interannotator agreement values were 0.67 for "treatment," 0.76 for "physical," 0.56 for "psychological," 0.73 for "work/financial," and 0.73 for "family/friends," indicating a high degree of agreement. Among all blog posts, 544 contained no label, 892 contained one label, and 836 contained multiple labels. It was found that the worries varied from user to user, and the worries posted by the same user changed over time. The model performed well, though prediction performance differed for each label. The values of precision were 0.59 for "treatment," 0.82 for "physical," 0.64 for "psychological," 0.67 for "work/financial," and 0.58 for "family/friends." The higher the interannotator agreement and the greater the number of posts, the higher the precision tended to be. This study showed that the BERT model can extract multiple worries from text generated from patients with breast cancer. This is the first application of a multilabel classifier using the BERT model to extract multiple worries from patient-generated text. The results will be helpful to identify breast cancer patients' worries and give them timely social support.


Impaired microcirculation in mild-to-moderate essential arterial hypertension.
The aim of this study was to correlate capillary morphology and erythrocyte velocity to blood pressure in mild-to-moderate essential arterial hypertension. Ambulatory blood pressure measurement may provide more precise information about a patient's mean blood pressure than office measurements. Fifteen patients with recently diagnosed, previously untreated mild-to-moderate essential hypertension underwent 24-h ambulatory blood pressure recording and a capillaroscopic examination of finger microcirculation. Erythrocyte velocity was determined by the flying spot technique. Both mean 24-h ambulatory systolic blood pressure (SBP) and mean 24-h ambulatory diastolic blood pressure (DBP) were significantly inversely correlated with capillary erythrocyte velocity. However, the correlation between erythrocyte velocity and office SBP and office DBP was less significant. Capillary length was related to 24-h ambulatory DBP but not to office DBP. Capillary number was not related to any blood pressure parameter. These results indicate that, in patients with mild-to-moderate essential hypertension, erythrocyte velocity is significantly lower than for matched controls. It is also inversely related to mean 24-h ambulatory SBP and 24-h ambulatory DBP.


Reliability and validity of the Child Behavior Checklist Obsessive-Compulsive Scale.
This study examined the psychometric properties of the Obsessive-Compulsive Scale (OCS) of the Child Behavior Checklist (CBCL). Participants included 48 youth with obsessive-compulsive disorder (OCD), 41 with a non-OCD internalizing disorder, and 101 with an externalizing disorder. Confirmatory factor analysis of the 8-item OCS did not result in an adequate fit. Exploratory factor analysis identified a 1-factor model consisting of 6 items. Adequate internal consistency for the revised OCS (OCS-R) was obtained, and convergent validity was supported by moderate relationships with other OCD indices. The OCS-R had stronger associations with measures of OCD symptoms than with measures of depression and externalizing behaviors. Youth with OCD had significantly higher OCS-R scores than those with internalizing and externalizing disorders. Suggestions for cutoff scores are provided using results from ROC analyses. Overall, these findings suggest that the OCS-R is a reliable and valid instrument for the assessment of pediatric OCD.


Health inequalities in hypertension and diabetes management among the poor in urban areas: a population survey analysis in south Korea.
This study investigated whether the prevalence, awareness, treatment, and control of hypertension and diabetes differed by residential areas. In addition, the rate of good hypertension or diabetes control was examined separately in men and women, and in urban and rural areas. This study used Korea National Health and Nutrition Examination V (2010-2012) data, a nationwide cross-sectional survey of general South Korean population. Residential areas were categorized into urban and rural areas. To examine differences between the residential areas in terms of prevalence, awareness, treatment, and control of hypertension and diabetes we performed a multivariate logistic regression adjusting for age, body mass index, physical activity, alcohol use, smoking, marital status, monthly income, and educational level. To investigate control of hypertension or diabetes within each residential area, we performed a subgroup analysis in both urban and rural areas. The prevalence of hypertension is higher among men in urban areas than among those in rural areas (OR = 0.80; 95 % CI = 0.67-0.96, reference group = urban areas). However, the subgroups did not differ in terms of diabetes prevalence, awareness, treatment, and control. Regardless of both sex and residential area, participants in good control of their hypertension and diabetes were younger. Inequality in good control of hypertension was observed in men who lived in urban (≤Elementary school, OR 0.74, 95 % CI 0.60-0.92) and rural areas (≤Elementary school, OR 0.67, 95 % CI 0.46-0.99). Inequality in health status was found in women who resided in urban areas (≤Elementary school, OR 0.53, 95 % CI 0.37-0.75). Good control of diabetes also showed inequalities in health status for both men (≤Elementary school, OR 0.61, 95 % CI 0.40-0.94; Middle/High school, OR 0.69, 95 % CI 0.49-0.96) and women in urban areas (≤1 million won, OR 0.56, 95 % CI 0.33-0.93) (Reference group = '≥College' for education and '>3 million' Korean won for income). After correction for individual socioeconomic status, differences by residential area were not observed. However, when the participants with good disease control were divided by region, inequality was confirmed in urban residents. Therefore, differentiated health policies to resolve individual and regional health inequalities are necessary.


Cystometrical evaluation of bladder instability in rats with infravesical outflow obstruction.
Cystometries were performed in normal rats and in rats with bladder hypertrophy due to infravesical outflow obstruction. Investigations were performed in the presence and absence of anesthesia. pentobarbital anesthesia depressed spontaneous contractile activity in the bladder and the micturition reflex, thereby making measurements of other variables, such as bladder capacity and residual volume, impossible. In conscious animals infravesical outflow obstruction led to development of increased bladder capacity, marked residual volume, and unstable detrusor contractions. The model seems to be well suited for further evaluation of the mechanisms involved in the development of detrusor instability and the responses to pharmacological treatment.


Bidirectional crosstalk between epithelial-mesenchymal plasticity and IFNγ-induced PD-L1 expression promotes tumour progression.
Epithelial-mesenchymal transition (EMT) and immunoevasion through upregulation of programmed death-ligand 1 (PD-L1) are important drivers of cancer progression. While EMT has been proposed to facilitate PD-L1-mediated immunosuppression, molecular mechanisms of their interaction remain obscure. Here, we provide insight into these mechanisms by proposing a mathematical model that describes the crosstalk between EMT and interferon gamma (IFNγ)-induced PD-L1 expression. Our model shows that via interaction with microRNA-200 (miR-200), the multi-stability of the EMT regulatory circuit is mirrored in PD-L1 levels, which are further amplified by IFNγ stimulation. This IFNγ-mediated effect is most prominent for cells in a fully mesenchymal state and less strong for those in an epithelial or partially mesenchymal state. In addition, bidirectional crosstalk between miR-200 and PD-L1 implies that IFNγ stimulation allows cells to undergo EMT for lower amounts of inducing signal, and the presence of IFNγ accelerates EMT and decelerates mesenchymal-epithelial transition (MET). Overall, our model agrees with published findings and provides insight into possible mechanisms behind EMT-mediated immune evasion, and primary, adaptive, or acquired resistance to immunotherapy. Our model can be used as a starting point to explore additional crosstalk mechanisms, as an improved understanding of these mechanisms is indispensable for developing better diagnostic and therapeutic options for cancer patients.


Histopathological discrepancy between biopsy and Mohs micrographic surgery in keratinocyte carcinoma: A 464 case series in an Australian population.
Therapeutic approaches to keratinocyte carcinoma rely on the accuracy of the biopsy to correctly identify, grade or subtype the tumour. Several studies have investigated the frequency and nature of histopathological discordance between the biopsy and final excision specimen. We analysed information extracted from an Australian Mohs micrographic surgery (MMS) database and compared similar studies. An Australian MMS database was retrospectively reviewed for a period of one year. Correlation was made between the preoperative lesion diagnosis based on the formal pathology report and the histopathological results reported at the time of MMS. A systematic PubMed review of similar articles was also performed. A total of 464 cancers (406 BCC and 58 SCC) in 399 patients were included. The overall discrepancy rate in the histopathological classification of keratinocyte carcinoma in our study (42.2%) and the proportion of cases in which the biopsy underestimated the aggressiveness of the tumour (12.9%) were consistent with those found in similar studies. The percentage of biopsies that failed to identify an aggressive BCC subtype (31.6%), and that of biopsy-proven superficial BCC that demonstrated an invasive component in MMS (79.3%), were higher in our study than in comparable studies. The high prevalence of mixed histopathological subtypes, especially amongst BCC with discordant histopathological results, appeared as an important contributing factor. Despite subtle differences, the results from this Australian study support the results from similar studies and highlight that the biopsy report should be carefully interpreted in combination with the clinical findings.


In vivo haematopoietic potential of human neural stem cells.
The fetal sheep model was used to compare the in vivo haematopoietic potential of human neural stem cells (NSC) versus bone marrow (BM)-derived haematopoietic stem cells (HSC). To this end, sheep were transplanted with either 8 x 10(5) NSC (n = 11) or HSC, CD34(+)Lin(-) (n = 5), and subsequently analysed for haematopoietic chimaerism. While HSC-transplanted sheep displayed robust donor-derived haematopoiesis starting at less than 2 months post-transplant, NSC recipients exhibited haematopoietic engraftment at much later time points. Nevertheless, chimaerism persisted in both groups throughout the course of this study. Transplantation of secondary recipients with human CD45(+)/HLA-DR(+) cells from the BM of NSC primary recipients at 14 and 16 months post-transplant demonstrated that long-term engrafting HSC were present in these animals. At 6 months post-transplant, both NSC- and HSC-transplanted sheep were mobilised with granulocyte colony-stimulating factor. In contrast to HSC-transplanted animals, levels of human blood cells in peripheral blood of NSC-transplanted sheep remained low throughout mobilisation. Our results show that, although human NSC were able to give rise to multilineage haematopoiesis in our model, the levels, timing of blood cell production and the ability to respond to cytokine mobilisation were different, suggesting that human NSCs latent haematopoietic potential is inherently different from that of true HSC.


Steady-state level of messenger RNA and immunolocalization of aquaporins 3, 7, and 9 during in vitro growth of ovine preantral follicles.
Aquaporins (AQPs) are a well-conserved family of small (approximately 30 kDa) membrane channel proteins that facilitate rapid movement of fluids and have a unique tissue-specific pattern of expression. These proteins have been found in the female reproductive systems of humans, rats, and mice. However, the expression and cellular localization of AQPs have not extensively been studied in the female reproductive system of sheep. Therefore, this study aimed to evaluate, by real-time polymerase chain reaction and immunohistochemistry respectively, the levels of messenger RNA and the immunolocalization of AQP3, AQP7, and AQP9 in large isolated ovine secondary follicles over a period of IVC. Our analysis revealed that AQP3 and AQP9 were present predominately in follicles that exhibited antrum formation, suggesting a crucial role of these AQPs in the formation of the antrum. Interestingly, AQP7 was only expressed in follicles that had not formed an antrum by Day 12 of culture. In conclusion, the presence of protein channels (AQP3 and AQP9) seems to be essential for the formation of the antrum in isolated ovine secondary follicles cultured in vitro and thus plays an important role during folliculogenesis in this species.


Anal endosonography in children with chronic constipation.
Hypertrophy of the internal anal sphincter may be apparent in some children, but its significance has not yet been determined. To assess anal endosonographic findings in children with chronic constipation. Materials and methods. We performed anal endosonography in 46 children with chronic constipation and compared the results with values considered normal. We did not find a significant relationship between age and thickness of the internal or external anal sphincters. The clinical response to medical management did not differ between patients with or without sphincter hypertrophy. Although we did not find a significant correlation between sphincter hypertrophy and constipation or age, further studies may clarify its place amongst other techniques which are used in the investigation of anorectal pathology.


Novel candidate genes AuxRP and Hsp90 influence the chip color of potato tubers.
Potato (Solanum tuberosum L.) tubers exhibit significant variation in reducing sugar content directly after harvest, cold storage and reconditioning. Here, we performed QTL analysis for chip color, which is strongly influenced by reducing sugar content, in a diploid potato mapping population. Two QTL on chromosomes I and VI were detected for chip color after harvest and reconditioning. Only one region on chromosome VI was linked with cold-induced sweetening. Using the RT-PCR technique, we showed differential expression of the auxin-regulated protein (AuxRP) gene. The AuxRP transcript was presented in light chip color parental clone DG 97-952 and the RNA progeny of the bulk sample consisting of light chip color phenotypes after cold storage. This amplicon was absent in dark chip parental clone DG 08-26/39 and the RNA bulk sample of dark chip progeny. Genetic variation of AuxRP explained up to 16.6 and 15.2 % of the phenotypic variance after harvest and 3 months of storage at 4 °C, respectively. Using an alternative approach, the RDA-cDNA method was used to recognize 25 gene sequences, of which 11 could be assigned to potato chromosome VI. One of these genes, Heat-shock protein 90 (Hsp90), demonstrated higher mRNA and protein expression in RT-qPCR and western blotting assays in the dark chip color progeny bulk sample compared with the light chip color progeny bulk sample. Our study, for the first time, suggests that the AuxRP and Hsp90 genes are novel candidate genes capable of influencing the chip color of potato tubers.


Efficacy and safety of thermal ablation for autonomously functioning thyroid nodules: a systematic review and meta-analysis.
Although thermal ablation has been regarded as an alternative treatment option for autonomously functioning thyroid nodules (AFTNs), the efficacy of this treatment in patients with AFTNs has not yet been systematically evaluated. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of thermal ablation in the treatment of AFTN, and identify the factors affecting the effectiveness of the treatment. Ovid-MEDLINE and Embase databases were searched for studies reporting the efficacy and safety of thermal ablation for patients with AFTN published up until January 6, 2020. Data extraction and quality assessment were performed by two radiologists according to PRISMA guidelines. The primary and secondary outcomes were to yield the pooled proportions of thyroid-stimulating hormone (TSH) normalization and pooled estimates of volume reduction rate (VRR), respectively. Subgroup analyses were performed to identify factors affecting the treatment efficacy. This systematic review identified 411 AFTNs treated by thermal ablation in 391 patients in 14 studies. TSH normalization was achieved in 71.2% of patients and the volume reduction rate was 69.4% at a mean follow-up period of 12.8 months. No patients experienced hypothyroidism or a life-threatening complication during follow-up. Subgroup analyses according to nodule volume did not find a significant difference in TSH normalization (p = 0.54) or VRR (p = 0.94). Thermal ablation is an effective and safe treatment method for patients with AFTNs. The nodule volume did not affect the efficacy of thermal ablation, and this result should be considered in future thermal ablation guidelines. • Thermal ablation has good efficacy and safety in the treatment of autonomously functioning thyroid nodule. • The efficacy of thermal ablation was not affected by nodule volume.


Updates on the Management of Pilonidal Disease.
This article reviews the current practices and evidence on the management of pilonidal disease in the pediatric population. Medical management, use of laser epilation, and minimally invasive surgical options are highlighted with a brief review of more invasive surgical options for refractory disease.


Pantoprazole and omeprazole in the treatment of reflux oesophagitis: a European multicentre study.
Pantoprazole is a new substituted benzimidazole which inhibits gastric H+,K(+)-ATPase. In this double-blind, multicentre study, pantoprazole 40 mg once daily was compared with omeprazole 20 mg once daily in the treatment of grade II and III (Savary-Miller) reflux oesophagitis. Endoscopy was repeated after 4 weeks of treatment, and also after 8 weeks in patients unhealed at 4 weeks. The primary efficacy variable was ulcer healing; after 4 weeks, 81/103 (78.6%) patients in the pantoprazole group and 83/105 (79.0%) patients in the omeprazole group had healed completely. After 8 weeks, the cumulative healing rates were 94.2% and 91.4% in the pantoprazole and omeprazole groups, respectively (P > 0.05 at 4 weeks and 8 weeks). Both groups experienced rapid relief of the key symptoms: heartburn, acid regurgitation and pain on swallowing. The time course of relief of the individual symptoms was similar in both groups after 2 and 4 weeks (P > 0.05). Both treatments were well tolerated, with only three patients withdrawing owing to adverse events. Pantoprazole has been shown to be as effective as omeprazole in the treatment of reflux oesophagitis.


Teratoid Wilms' tumour: a report of two cases.
We report two cases of Wilms' tumour in which the degree of heterologous differentiation was sufficient to warrant the diagnosis of teratoid Wilms' tumour. The first description of neural elements in this Wilms' variant and the first cytogenetic analysis of teratoid Wilms' tumour are presented.


Platelet-mimicking supramolecular nanomedicine with precisely integrated prodrugs for cascade amplification of synergistic chemotherapy.
Camptothecin (CPT) and cisplatin (Pt) have shown synergistic effects on a variety of cancers during preclinical and clinical studies. However, the ratio of the two drugs often could not be precisely regulated in different delivery systems, which hinders the desired synergistic effect. In addition, the low delivery efficiency of the two drugs to the tumor further impedes the ideal therapeutic outcomes. Herein, we report that a platelet-mimicking supramolecular nanomedicine (SN) could precisely control of the ratio of CPT and Pt with a high tumor accumulation rate for cascade amplification of synergistic chemotherapy. The SN was fabricated via the host-guest interaction between cucurbit[7]uril conjugated hyaluronic acid (HA-CB[7]) and adamantane (ADA) respectively functionalized CPT- and Pt-based prodrugs. The ratio of CPT and Pt in the SN could be facilely regulated by simply controlling the loading ratio, based on the strong binding affinity between CB[7] and ADA, and SN60 with 60% CPT and 40% Pt showed the highest synergistic effects on 4T1 cells. To improve the tumor accumulation efficiency of SN, 5,6-dimethylxanthenone-4-acetic acid (DMXAA, a tumor vasculature-disruptive agent) was loaded into the optimized SN and then coated with platelet membrane to yield platelet-mimicking supramolecular nanomedicine (D@SN-P). D@SN-P could first passively accumulate in tumors owing to the enhanced permeability and retention (EPR) effect after intravenous administration. The initially release of DMXAA from D@SN-P could induce tumor vascular disruption, and the resultant epithelial collagen exposure around the disrupted tumor vasculature provided a target for further recruitment of platelet-mimicking SN, leading to cascade amplification of tumor accumulation with synergistic chemotherapy. Hence, this platelet-mimicking supramolecular nanomedicine presents a universal supramolecular strategy to finely regulate the ratio of loaded pro-drugs, and improve the accumulation efficiency to amplify chemotherapy via platelet-mimics.


Plasmapheresis for Rescue in Severe Encephalopathy and Multiorgan Failure from Fulminant Influenza (H3N2) Infection.
We are presenting a case of 4-years-old previously healthy male with coma, severe acute hepatitis and multiorgan failure in presence of Influenza infection. Literature review highlighted an immune-mediated pathophysiology for such presentations so the child underwent a trial of plasmapheresis which resulted in a rapid clinical improvement and child was discharge in his baseline neurologic status by day 14.


On the conditional equivalence of chemical loading and mechanical loading on articular cartilage.
Osmotic pressure loading of articular cartilage has been customarily invoked to be equivalent to mechanical loading. In the literature, this equivalence is defined by the amount of water squeezed from the tissue, i.e. if the amount of water content lost by these two modes of loading are the same, it has been generally regarded that the two loadings are equivalent. This assumption has never been proven. Using the water content lost concept, in this paper, we derived the exact conditions under which an osmotic pressure loading of cartilage can be considered to be equivalent to a mechanical loading. However, the mechanical loading condition satisfying this equivalency criterion, i.e. an isotropic loading delivered via a porous permeable rigid platen uniformly applied all around the specimen, is not practically achievable. Moreover, even if this were achieved experimentally, the interstitial fluid pressure caused by the two loading conditions are not the same. This result has important ramifications for interpretation of experimental data from mechanical stimulations of cartilage explant studies.


Burst firing of rat septal neurons induced by 1S,3R-ACPD requires influx of extracellular calcium.
We have demonstrated that burst firing in rat dorsolateral septal nucleus neurons is a specific response following activation of metabotropic glutamate receptors. Now we report that the burst firing induced by 1S,3R-ACPD (1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid), a selective agonist, is blocked by inorganic calcium channel blockers. Our data suggest that influx of external calcium is required for this metabotropic glutamate response. Intracellular second messenger pathways coupled to the metabotropic glutamate receptor may be more complex than releasing calcium from IP3-sensitive internal stores as is currently hypothesized.


A Single-Institutional Comparative Analysis of Advanced Versus Standard Snare Removal of Inferior Vena Cava Filters.
To investigate differences in procedure time, radiation exposure, and periprocedural complications associated with advanced inferior vena cava (IVC) filter retrieval compared with standard snare retrieval. A total of 378 patients underwent standard or advanced IVC filter retrieval over a 5-year period. Technical success, retrieval techniques, fluoroscopy time, radiation dose, and complications were analyzed. All retrieval procedures with techniques other than a "snare-and-sheath" method were categorized as advanced, including failed standard attempts requiring intraprocedural conversion to advanced techniques. A total of 462 filter retrieval attempts were made in 378 patients (57% female). Success rates for standard and advanced retrieval attempts were 86.8% (317 of 365) and 91.8% (89 of 97), respectively. The rate of periprocedural complications was significantly higher in the advanced retrieval group (P = .006). Complication rates for standard and advanced retrievals were 0.6% (2 of 318; all minor) and 5.2% (5 of 97; 3 minor [3.1%] and 2 major [2.1%]), respectively. The 2 major complications during advanced retrievals included filter fracture and embolization. Average fluoroscopy time for advanced retrievals was significantly higher than for standard retrievals (23.1 min vs 4.3 min; P < .001). Average radiation dose for advanced retrievals was also significantly higher than for standard retrievals (557.2 mGy vs 156.9 mGy; P < .001). Use of general anesthesia was also significantly more common in advanced retrievals compared with standard retrievals (6.2% vs 0.9%; P = .002). Advanced filter retrieval results in a similarly high rate of technical success compared with standard snare retrieval but is associated with greater fluoroscopy time, anesthesia requirements, and radiation exposure.


Collagen- and laminin-containing gels impede peripheral nerve regeneration through semipermeable nerve guidance channels.
Semipermeable guidance channels were filled with saline, collagen-, or laminin-containing gels and used to repair a 4-mm sciatic nerve gap in mice. After 12 weeks, nerve cables regenerated in gel-filled channels displayed fewer myelinated axons than saline-filled channels. Remnants of the exogenous substrates were still in evidence, in amounts related to the initial collagen or laminin gel concentration. The impairment of nerve regeneration by collagen or laminin-containing gels suggests that the regenerative environment created within semipermeable channels is not improved by the addition of growth substrates in a gel form.