Continuous Intraoperative Nerve Monitoring in Thyroid Surgery: Can Amplitude Be a Standardized Parameter?
The objective of this study is to evaluate electromyographic waveforms related to vagus monitoring. We collected data from patients undergoing thyroidectomy with CIONM, regardless of vocal cord response amplitude initially measured. We divided data of 193 nerves into three groups, according to initial amplitude value: ≥500 µV (Group 1,110 pt.), between 100 and 500 µV (Group 2, 79 pt.), and <100 µV (Group 3, 4 pt.). ROC curve showed a high diagnostic accuracy of final amplitude absolute value in vocal cord paralysis detection in both groups (89 and 86%). An increase of vocal cord paralysis risk was associated with progressive amplitude reduction (Group 1: OR=1.05, CI=1.02-1.09, p=0.001; Group 2: OR=1.05, CI=1.02-1.08, p=0.002). Cut-off values for amplitude reduction with optimal sensitivity and specificity were -77% in Group 1 and -15% in Group 2. In Group 3 signals showed an amplitude <100 µV for all monitoring, with no loss of a recognizable signal and normal postoperative cordal functionality. The use of a strict amplitude signal cut-off value ≥500 µV could be too restrictive. Also, signal with baseline amplitude <500 µV may be considered equally adequate. Setting the alarm for a reduction of 77% in patients with initial amplitude ≥500 µV and of 15% for those <500 µV could make monitoring safe and an effective aid for surgeons. In conclusion, there are cases in which initial amplitude is lower than that considered as adequate by current literature but with well recognizable and stable EMG waveforms. How those cases should be approached and what should the surgeon's attitude be are a matter of discussion.


Identification and characterization of a novel PRR of fibrinogen-related protein in Apostichopus japonicus.
Fibrinogen-related proteins (FREPs) play important roles in innate immunity by recognizing pathogen associated molecular patterns on pathogenic bacteria surfaces via conserved fibrinogen-like domain (FBG). In this paper, the full-length cDNA of Apostichopus japonicus FREP (designated as AjFREP) was cloned combined with rapid amplification of cDNA ends (RACE) and transcriptome sequencing. The full-length cDNA of AjFREP was of 2110 bp with an open reading frame (ORF) of 1659 bp. SMART analysis revealed that the AjFREP contained a typical signal peptide of 19 amino acid residues, a FBG and two unusual epidermal growth factor-like domains (EGFs). Multiple sequence alignments suggested that FBG domain shared a remarkably high structural conservation in polypeptide binding site and Ca2+ binding site. Tissue distribution analysis revealed that AjFREP was constitutively expressed in all examined tissues with the largest magnitude in coelomocytes, indicating AjFREP might play an important role in immune defense. The mRNA level of AjFREP in coelomocytes was sharply up-regulated by Vibrio splendidus challenge, and reached its peak expression at 48 h. Knock-down AjFREP by specific siRNA could significantly repress the coelomocyte phagocytosis rate. Meantime, the survival number of V. splendidus in the coelomic fluid was promoted. All these current results indicated that AjFREP might be involved in pathogen clearance through mediating coelomocytes phagocytosis activity.


The Swedish telephone herpes helpline.
To increase the accessibility of qualified and anonymous advice on herpes infections in Sweden, a telephone counselling service was initiated in November 1994. The nucleus of the service is an answering machine that works around the clock. A caller can choose one of 3 different messages dealing with labial or genital herpes infection or herpes zoster--each message is approximately 3 min long. Those wanting written information can register and have material sent to them. For 2 h daily, 4 days a week, calls pass directly to the staff of the sexually transmitted diseases clinic of the University Hospital in Uppsala, Sweden--the caller pays only a single telephone unit charge. The personal calls deal with all aspects of herpes infections. During the first 3 months of the counselling service more than 4,500 calls were received.


Nasopharyngeal carcinoma: treatments and outcomes in the 20th century.
Nasopharyngeal carcinoma (NPC), although rare in Europe and North America, is not uncommon in parts of Asia such as southern China and Hong Kong. Consequently, very few oncologists in the Western world have extensive experience in treating this neoplasm. Treatment using external beam therapy and/or brachytherapy evolved greatly during the 20th century and is still evolving, particularly with the use of adjunctive chemotherapy regimes. Diagnosis of NPC has also improved with the availability of CT and MRI. This worldwide review is divided into historical, transitional and modern eras, with the latter concerning 1971-2000. Currently, the most controversial aspects of NPC are recommendations for treatment of recurrent disease and the role of chemotherapy in the overall framework of treatment. Comparison of results from different centres is not possible without an understanding of the various staging systems that are, and have been, used; a comparison is given in this review. In the future, early diagnosis, adequate radiation dose to the primary with boost to bulky disease, and regular follow-up with biopsy of any suspicious residual or recurrent disease, are likely to become key issues to improve outcome. Also, apart from direct/indirect nasopharyngoscopy, the role of follow-up CT needs to be studied for early detection of residual or recurrent disease. More clinical trials on chemo-radiation are also required, in order to study optimum doses and agents.


The care of older people with a delirium in acute care settings.
This article suggests that nurses should play a major part in the screening, assessment and management of delirium in older people in acute settings.


CLONING AND EXPRESSING TRYPSIN MODULATING OOSTATIC FACTOR IN Chlorella desiccata TO CONTROL MOSQUITO LARVAE.
The insect peptide hormone trypsin modulating oostatic factor (TMOF), a decapeptide that is synthesized by the mosquito ovary and controls the translation of the gut's trypsin mRNA was cloned and expressed in the marine alga Chlorella desiccata. To express Aedes aegypti TMOF gene (tmfA) in C. desiccata cells, two plasmids (pYES2/TMOF and pYDB4-tmfA) were engineered with pKYLX71 DNA (5 Kb) carrying the cauliflower mosaic virus (CaMV) promoter 35S(2) and the kanamycin resistant gene (neo), as well as, a 8 Kb nitrate reductase gene (nit) from Chlorella vulgaris. Transforming C. desiccata with pYES2/TMOF and pYDB4-tmfA show that the engineered algal cells express TMOF (20 ± 4 μg ± SEM and 17 ± 3 μg ± SEM, respectively in 3 × 10(8) cells) and feeding the cells to mosquito larvae kill 75 and 60% of Ae. aegypti larvae in 4 days, respectively. Southern and Northern blots analyses show that tmfA integrated into the genome of C. desiccata by homologous recombination using the yeast 2 μ circle of replication and the nit in pYES2/TMOF and pYDB4-tmfA, respectively, and the transformed algal cells express tmfA transcript. Using these algal cells it will be possible in the future to control mosquito larvae in the marsh.


Nonlinear correlations impair quantification of episodic memory by mesial temporal BOLD activity.
Episodic memory processes can be investigated using different functional MRI (fMRI) paradigms. The purpose of the present study was to examine correlations between neuropsychological memory test scores and BOLD signal changes during fMRI scanning using three different memory tasks. Twenty-eight right-handed healthy subjects underwent three paradigms, (a) a word pair, (b) a space-labyrinth, and (c) a face-name association paradigm. These paradigms were compared for their value in memory quantification and lateralization by calculating correlations between the BOLD signals in the mesial temporal lobe and behavioral data derived from a neuropsychological test battery. As expected, group analysis showed left-sided activation for the verbal, a tendency to right-sided activation for the spatial, and bilateral activation for the face-name paradigm. No linear correlations were observed between neuropsychological data and activation in the temporo-mesial region. However, we found significant u-shaped correlations between behavioral memory performance and activation in both the verbal and the face-name paradigms, that is, BOLD signal changes were greater not only among participants who performed best on the neuropsychological tests, but also among the poorest performers. The figural learning task did not correlate with the activations in the space-labyrinth paradigm at all. We interpreted the u-shaped correlations to be due to compensatory hippocampal activations associated with low performance when people try unsuccessfully to remember presented items. Because activation levels did not linearly increase with memory performance, the latter cannot be quantified by fMRI alone, but only be used in conjunction with neuropsychological testing.


Degradation of azoxystrobin, methoxyfenozide, and propyzamide by ultrasound treatment.
Ultrasound as a green and efficient process gains special attention in wastewater treatment. The ultrasound-assisted degradation of azoxystrobin, methoxyfenozide, and propyzamide as widely used pesticides for vine treatment was investigated. A wide range of ultrasonic power (40 to 140 W) and a single frequency (20 kHz) were applied. Degradation experiments were carried out according to the parameters set by a central composite design (CCD) under response surface methodology (RSM) via JMP software. The treatment efficiency was quantified using degradation rates and hydrogen peroxide (H2O2) measurements. Results indicated that the pesticide's degradation was negligible at 40 W but by increasing the power setting from 80 to 140 W, the degradation rate constants of azoxystrobin, methoxyfenozide, and propyzamide increased from 3.6 × 10-2 min-1 to 0.2 min-1, from 6.1 × 10-2 min-1 to 0.3 min-1, and from 3.1 × 10-2 min-1 to 0.1 min-1, respectively. The hydrogen peroxide (H2O2) measurements confirmed this trend. Besides, electric energy per order of pollutant removal (EE/O) was also evaluated for the same treatment duration and results revealed that treatment conditions of 20 kHz and 140 W were the less energy-guzzling. Finally, profiles obtained with RSM illustrated linear degradation kinetics for azoxystrobin and propyzamide. Indeed, treatment efficiency increased when increasing both studied parameters. However, both linear and quadratic degradation kinetics occurred for methoxyfenozide degradation indicating a parameter threshold beyond which the trend is reversed. Overall, this study confirms the effectiveness of ultrasound for the degradation of pesticides in aqueous medium.


Correlation between the gut microbiome and neurodegenerative diseases: a review of metagenomics evidence.
A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis. As a contributing factor, microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota's diverse microorganisms, and for both neuroimmune and neuroendocrine systems. Here, we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases, with an emphasis on multi-omics studies and the gut virome. The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated. Finally, we discuss the role of diet, prebiotics, probiotics, postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.


Gingiva-Derived Mesenchymal Stem Cell-Extracellular Vesicles Activate Schwann Cell Repair Phenotype and Promote Nerve Regeneration.
Peripheral nerve injuries (PNIs) are common and debilitating, usually resulting in considerable long-term disability and remaining an unmet clinical need. Even though the combination of mesenchymal stem cells (MSCs) and the state-of-the-art tissue engineering technologies has shown promising therapeutic potentials for PNI, there is still not a single licensed stem cell-based product for peripheral nerve repair/regeneration. Emerging evidence indicates that MSC-derived extracellular vesicles (EVs) are comparably effective as MSCs in the therapy of a variety of disease models or pathological conditions. This report shows that local delivery of gingiva-derived mesenchymal stem cell (GMSC)-derived EVs could obviously promote axonal regeneration and functional recovery of injured mice sciatic nerves. Importantly, the findings suggest that GMSC-derived EVs promoted the expression of Schwann cell dedifferentiation/repair phenotype-related genes in vitro, particularly c-JUN, a key transcription factor that drives the activation of repair phenotype of Schwann cells during PNI and regeneration.


Metrics for network comparison using egonet feature distributions.
Identifying networks with similar characteristics in a given ensemble, or detecting pattern discontinuities in a temporal sequence of networks, are two examples of tasks that require an effective metric capable of quantifying network (dis)similarity. Here we propose a method based on a global portrait of graph properties built by processing local nodes features. More precisely, a set of dissimilarity measures is defined by elaborating the distributions, over the network, of a few egonet features, namely the degree, the clustering coefficient, and the egonet persistence. The method, which does not require the alignment of the two networks being compared, exploits the statistics of the three features to define one- or multi-dimensional distribution functions, which are then compared to define a distance between the networks. The effectiveness of the method is evaluated using a standard classification test, i.e., recognizing the graphs originating from the same synthetic model. Overall, the proposed distances have performances comparable to the best state-of-the-art techniques (graphlet-based methods) with similar computational requirements. Given its simplicity and flexibility, the method is proposed as a viable approach for network comparison tasks.


The Affordable Care Act and suicide incidence among adults with cancer.
Patients with cancer are at an increased suicide risk, and socioeconomic deprivation may further exacerbate that risk. The Affordable Care Act (ACA) expanded insurance coverage options for low-income individuals and mandated coverage of mental health care. Our objective was to quantify associations of the ACA with suicide incidence among patients with cancer. We identified US patients with cancer aged 18-74 years diagnosed with cancer from 2011 to 2016 from the Surveillance, Epidemiology, and End Results database. The primary outcome was the 1-year incidence of suicide based on cumulative incidence analyses. Difference-in-differences (DID) analyses compared changes in suicide incidence from 2011-2013 (pre-ACA) to 2014-2016 (post-ACA) in Medicaid expansion relative to non-expansion states. We conducted falsification tests with 65-74-year-old patients with cancer, who are Medicare-eligible and not expected to benefit from ACA provisions. We identified 1,263,717 patients with cancer, 812 of whom died by suicide. In DID analyses, there was no change in suicide incidence after 2014 in Medicaid expansion vs. non-expansion states for nonelderly (18-64 years) patients with cancer (p = .41), but there was a decrease in suicide incidence among young adults (18-39 years) (- 64.36 per 100,000, 95% CI = - 125.96 to - 2.76, p = .041). There were no ACA-associated changes in suicide incidence among 65-74-year-old patients with cancer. We found an ACA-associated decrease in the incidence of suicide for some nonelderly patients with cancer, particularly young adults in Medicaid expansion vs. non-expansion states. Expanding access to health care may decrease the risk of suicide among cancer survivors.


The isolation of Actinomyces naeslundii from sound root surfaces and root carious lesions.
The isolation of Actinomyces naeslundii from sound, exposed root surfaces (n = 56) and soft and leathery root carious lesions (n = 71) was investigated. Root carious lesions were sampled after the removal of overlying plaque. Supragingival plaque or carious dentine was sampled using a sterile excavator, the samples were disaggregated and cultured on both selective and non-selective media. A. naeslundii isolates were identified to the genospecies using specific antisera. Significantly greater numbers and proportions of A. naeslundii genospecies 2 than A. naeslundii genospecies 1 were isolated from all sites sampled. There was no significant difference between the numbers and proportions of the two genospecies isolated from leathery and soft lesions. The relationship between the presence of A. naeslundii genospecies and aciduric and acidogenic organisms was investigated. Those sound exposed root surfaces from which A. naeslundii genospecies 1 and/or 2 were isolated yielded significantly lower numbers of lactobacilli and yeasts than the surfaces from which A. naeslundii were not isolated. This difference was also found in leathery lesions but not soft root carious lesions. The microflora of soft root carious lesions was found to comprise primarily gram-positive pleomorphic rods which formed 70+/-7.8% of the flora, while in plaque from exposed root surfaces and in infected dentine from leathery lesions the gram-positive pleomorphic rods represented only 35% of the flora.


Bladder cancer in Taiwan: relationship to trihalomethane concentrations present in drinking-water supplies.
The objective of this study was to evaluate whether exposure to disinfection by-products (DBP) is associated with bladder cancer. A matched case-control study was used to investigate the relationship between the risk of death from bladder cancer and exposure to total trihalomethanes (TTHM) in drinking water in 65 municipalities in Taiwan. All bladder cancer deaths of the 65 municipalities from 1996 through 2005 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth,and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water in study municipalities were collected from the Taiwan Environmental Protection Administration. The municipality of residence for cancer cases and controls was assumed to be the source of the subject's TTHM exposure via drinking water. The adjusted odds ratios for bladder cancer death for those with high TTHM concentrations in their drinking water were 1.8 (1.18-2.74) and 2.11 (1.43-3.11) compared to the lowest group. The results of this study show that there was a significant positive correlation between the concentration of TTHM in drinking water and risk of death from bladder cancer.


The effects of general anesthesia on human peripheral immune cell distribution and cytokine production.
Anesthetic agents are believed to have an adverse effect on human immune defense mechanisms. We investigated changes in peripheral immune cell numbers such as natural killer (NK) cells, B cells, and T lymphocyte subpopulations (CD4+ and CD8+ cells) and differences in cytokine production after stimulation with different mitogens before and during narcosis. We studied 30 patients undergoing elective orthopedic surgery. Stimulatory experiments were performed with the mitogens lipopolysaccharide, phytohemagglutinin A, and inactivated Newcastle disease virus. During general anesthesia with fentanyl, thiopental, and isoflurane, there was a significant decrease of circulating NK cells in the peripheral blood accompanied by a significant increase of B cells and CD8+ T lymphocytes. We detected a significant anesthesia-associated increase of interferon (IFN)-gamma, IFN-alpha, tumor necrosis factor-alpha, and soluble interleukin-2 receptor (sIL-2R) synthesis after stimulation with different mitogens while interleukin (IL)-1 beta and IL-6 protein did not change significantly. After the beginning of surgery, CD8-positive cells showed a return to control values and NK cell number increased slightly. These findings suggest that general anesthesia interferes with immune cell number and immune cell response. This may explain the clinically well-recognized disturbance of human immunity after surgery and general anesthesia.


X-ray absorption spectroscopic characterization of the molybdenum site of Escherichia coli dimethyl sulfoxide reductase.
Structural studies of dimethyl sulfoxide (DMSO) reductases were hampered by modification of the active site during purification. We report an X-ray absorption spectroscopic analysis of the molybdenum active site of Escherichia coli DMSO reductase contained within its native membranes. The enzyme in these preparations is expected to be very close to the form found in vivo. The oxidized active site was found to have four Mo-S ligands at 2.43 A, one Mo=O at 1.71 A, and a longer Mo-O at 1.90 A. We conclude that the oxidized enzyme is a monooxomolybdenum(VI) species coordinated by two molybdopterin dithiolenes and a serine. The bond lengths determined for E. coli DMSO reductase are very similar to those determined for the well-characterized Rhodobacter sphaeroides DMSO reductase, suggesting similar active site structures for the two enzymes. Furthermore, our results suggest that the form found in vivo is the monooxobis(molybdopterin) species.


Characterization of vinyl-substituted, carbon-carbon double bonds by GC/FT-IR analysis.
Vapor-phase infrared spectra allow the determination of the stereochemistry of carbon-carbon double bonds conjugated with a vinyl group. Cis and trans isomers of unsubstituted 1,3-alkadienes can be differentiated on the basis of the differences observed in the 900-1000 cm-1 region (spectra of cis isomers show two bands at 993 and 906 cm-1, while those of trans compounds show three absorptions at 998, 949, and 902 cm-1) and the 1590-1650 cm-1 region (the C=C stretch bands are observed at 1595 and 1642 cm-1 for cis compounds and at 1604 and 1650 cm-1 for trans compounds). Compounds bearing CH2=CHC(CH3)=CHCH2- and CH2=CHC(=CH2)-CH2- structural moieties, referred to as alpha- and beta-type compounds, are frequently encountered as natural products. For compounds bearing alpha-type groups, the cis/trans configuration of the trisubstituted double bond can be determined unambiguously. An absorption at 3095-3091 cm-1, for the =CH2 stretch vibration, is common to both of these groups; however, due to the presence of two =CH2 groups, the relative intensity of the band is much higher for beta-type compounds. For alpha-type compounds, a cis configuration at the C-3 carbon atom is characterized by a =CH2 wag absorption at 907-906 cm-1. For beta-type compounds and 3E-alpha-type compounds, this band appears at 899-897 cm-1. In addition, a wavy "fingerprint" pattern with two minima at 1632 (low intensity) and 1595-1594 cm-1 (high intensity) is characteristic for beta-type compounds. Our generalizations are based on spectra of cis and trans ocimene, myrcene, and dehydration products of many 3-methyl-1-alken-3-ols. Six isomers of farnesene can be characterized by GC/FT-IR. Furthermore, gas-phase IR allows the determination of the configuration of the trisubstituted double bond at C-3 in alpha-type farnesene congeners. For example, the homo- and bishomofarnesene isomers from Myrmica ants were shown to include a 3Z bond.


Quantitative Proteomics of All 14 Renal Tubule Segments in Rat.
Previous research has used RNA sequencing in microdissected kidney tubules or single cells isolated from the kidney to profile gene expression in each type of kidney tubule epithelial cell. However, because proteins, not mRNA molecules, mediate most cellular functions, it is desirable to know the identity and amounts of each protein species to understand function. Recent improvements in the sensitivity of mass spectrometers offered us the ability to quantify the proteins expressed in each of 14 different renal tubule segments from rat. We manually dissected kidney tubules from rat kidneys and subjected samples to protein mass spectrometry. We used the "proteomic ruler" technique to estimate the number of molecules of each protein per cell. Over the 44 samples analyzed, the average number of quantified proteins per segment was 4234, accounting for at least 99% of protein molecules in each cell. We have made the data publicly available online at the Kidney Tubule Expression Atlas website (https://esbl.nhlbi.nih.gov/KTEA/). Protein abundance along the renal tubule for many commonly studied water and solute transport proteins and metabolic enzymes matched expectations from prior localization studies, demonstrating the overall reliability of the data. The site features a "correlated protein" function, which we used to identify cell type-specific transcription factors expressed along the renal tubule. We identified and quantified proteins expressed in each of the 14 segments of rat kidney tubules and used the proteomic data that we obtained to create an online information resource, the Kidney Tubule Expression Atlas. This resource will allow users throughout the world to browse segment-specific protein expression data and download them for their own research.


Inducing weight loss in native ponies: is straw a viable alternative to hay?
Obesity is a growing problem in UK equine population. Achieving weight loss in obese horses and ponies at risk of laminitis is an important but often challenging objective. We hypothesised that supplementing poor winter pasture with a mix of barley straw and hay (50:50) rather than hay alone (group B) would lead to weight loss in grazing equids over winter. For this purpose, a group of 40 horses were fed either the straw mix (group A) or hay alone (group B) over winter. Over the study period, all animals in group A (n=25) lost weight with a mean weight change of -27±17 kg, while in group B (n=15) only 3 out of 15 lost weight (20 per cent), and overall, group B gained weight (+6±18 kg). This study suggests that straw is a cost-effective and low-energy roughage, which may be a useful alternative to hay alone when trying to induce weight loss in grazing equids over winter. There were no episodes of colic or laminitis during the study period in either group.


IL-33 activates mTORC1 and modulates glycolytic metabolism in CD8+ T cells.
Interleukin (IL)-33, a member in the IL-1 family, plays a central role in innate and adaptive immunity; however, how IL-33 mediates cytotoxic T-cell regulation and the downstream signals remain elusive. In this study, we found increased mouse IL-33 expression in CD8+ T cells following cell activation via anti-CD3/CD28 stimulation in vitro or lymphocytic choriomeningitis virus (LCMV) infection in vivo. Our cell adoptive transfer experiment demonstrated that extracellular, but not nuclear, IL-33 contributed to the activation and proliferation of CD8+ , but not CD4+ T effector cells in LCMV infection. Importantly, IL-33 induced mTORC1 activation in CD8+ T cells as evidenced by increased phosphorylated S6 ribosomal protein (p-S6) levels both in vitro and in vivo. Meanwhile, this IL-33-induced CD8+ T-cell activation was suppressed by mTORC1 inhibitors. Furthermore, IL-33 elevated glucose uptake and lactate production in CD8+ T cells in both dose- and time-dependent manners. The results of glycolytic rate assay demonstrated the increased glycolytic capacity of IL-33-treated CD8+ T cells compared with that of control cells. Our mechanistic study further revealed the capacity of IL-33 in promoting the expression of glucose transporter 1 (Glut1) and glycolytic enzymes via mTORC1, leading to accelerated aerobic glucose metabolism Warburg effect and increased effector T-cell activation. Together, our data provide new insights into IL-33-mediated regulation of CD8+ T cells, which might be beneficial for therapeutic strategies of inflammatory and infectious diseases in the future.


Syndecan-1 (CD138) modulates triple-negative breast cancer stem cell properties via regulation of LRP-6 and IL-6-mediated STAT3 signaling.
Syndecan-1 (CD138), a heparan sulfate proteoglycan, acts as a coreceptor for growth factors and chemokines and is a molecular marker associated with epithelial-mesenchymal transition during development and carcinogenesis. Resistance of Syndecan-1-deficient mice to experimentally-induced tumorigenesis has been linked to altered Wnt-responsive precursor cell pools, suggesting a potential role of Syndecan-1 in breast cancer cell stem function. However, the precise molecular mechanism is still elusive. Here, we decipher the functional impact of Syndecan-1 knockdown using RNA interference on the breast cancer stem cell phenotype of human triple-negative MDA-MB-231 and hormone receptor-positive MCF-7 cells in vitro employing an analytical flow cytometric approach. Successful Syndecan-1 siRNA knockdown was confirmed by flow cytometry. Side population measurement by Hoechst dye exclusion and Aldehyde dehydrogenase-1 activity revealed that Syndecan-1 knockdown in MDA-MB-231 cells significantly reduced putative cancer stem cell pools by 60% and 27%, respectively, compared to controls. In MCF-7 cells, Syndecan-1 depletion reduced the side population by 40% and Aldehyde dehydrogenase-1 by 50%, repectively. In MDA-MB-231 cells, the CD44(+)CD24(-/low) phenotype decreased significantly by 6% upon siRNA-mediated Syndecan-1 depletion. Intriguingly, IL-6, its receptor sIL-6R, and the chemokine CCL20, implicated in regulating stemness-associated pathways, were downregulated by >40% in Syndecan-1-silenced MDA-MB-231 cells, which showed a dysregulated response to IL-6-induced shifts in E-cadherin and vimentin expression. Furthermore, activation of STAT-3 and NFkB transcription factors and expression of a coreceptor for Wnt signaling, LRP-6, were reduced by >45% in Syndecan-1-depleted cells compared to controls. At the functional level, Syndecan-1 siRNA reduced the formation of spheres and cysts in MCF-7 cells grown in suspension culture. Our study demonstrates the viability of flow cytometric approaches in analyzing cancer stem cell function. As Syndecan-1 modulates the cancer stem cell phenotype via regulation of the Wnt and IL-6/STAT3 signaling pathways, it emerges as a promising novel target for therapeutic approaches.


[Citrate (CG-120) therapy for urolithiasis. 1. Clinical effects].
Urinary citrate is an important determinant for crystallization of calcium salts, and recently oral administration of citrate has been suggested to be clinically useful in the management of renal stone disease. The effect of CG-120, a citrate compound (potassium citrate, sodium citrate and citric acid) produced by Dr. Madaus (Germany), on upper urinary tract stones was investigated in 398 patients in this study group. The patients were treated with 3 or 4 g CG-120 daily. Two hundred thirty-one of them were treated accurately according to the protocol of the study for more than 32 weeks. The cumulative percentage of positive clinical effect for the stone (disappearance, passage or decrease in size) was 30.3% (70/231). There were no differences in the clinical effect between the group of 3 g/day and the group of 4 g/day. CG-120 seemed to be more effective in the cases of ureteral stone, young patients and females, but was less effective in the recurrent stone formers. Although there were 45 episodes of side effects in 38 patients in this study, no serious side effects attributed to CG-120 were experienced. CG-120 was proved as a useful drug in the treatment of upper urinary tract calculi as well as its prevention.


Comparison of Neonatal Outcomes With and Without Prophylaxis With Indomethacin in Premature Neonates.
Historically, prophylactic indomethacin (pINDO) has been used in some institutions for patent ductus arteriosus (PDA) in extremely low birthweight neonates while other institutions have used it as prophylaxis for intraventricular hemorrhage (IVH). The objective of this study was to evaluate the incidence of IVH and PDA with or without pINDO in premature neonates. This was a retrospective, single-center study comparing neonatal outcomes in neonates weighing 1250 grams or less who received pINDO (pINDO group) to those who did not (No pINDO group) after our institution discontinued its routine use. A total of 399 infants were included for analysis (pINDO, n = 141; No pINDO, n = 258). No difference was found between pINDO and No pINDO groups in incidence of any IVH (18% vs 14%, respectively) or severe IVH (7% vs 3%, respectively) when adjusting for gestational age and antenatal corticosteroids. Although the incidence of moderate-to-large PDA was lower in the pINDO group (13% vs 23%, respectively, adjusted p = 0.002), there was no significant difference for PDA requiring surgery (4% vs 3%, respectively). Results demonstrated a higher incidence of bronchopulmonary dysplasia (BPD) in the pINDO group (55% vs 41%, respectively, adjusted p = 0.014). No difference in the incidence of IVH, severe IVH, or PDA requiring surgery was observed between groups, whereas an increase in BPD was seen with use of pINDO. These data support our institutional practice change to discontinue routine use of pINDO in premature neonates. Further research is needed to guide clinical practice.


Transition metals and mitochondrial metabolism in the heart.
Transition metals are essential to many biological processes in almost all organisms from bacteria to humans. Their versatility, which arises from an ability to undergo reduction-oxidation chemistry, enables them to act as critical cofactors of enzymes throughout the cell. Accumulation of metals, however, can also lead to oxidative stress and cellular damage. The importance of metals to both enzymatic reactions and oxidative stress makes them key players in mitochondria. Mitochondria are the primary energy-generating organelles of the cell that produce ATP through a chain of enzymatic complexes that require transition metals, and are highly sensitive to oxidative damage. Moreover, the heart is one of the most mitochondrially-rich tissues in the body, making metals of particular importance to cardiac function. In this review, we focus on the current knowledge about the role of transition metals (specifically iron, copper, and manganese) in mitochondrial metabolism in the heart. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism".


Tuning the Spin Coupling Interactions in the Nitroxide-Based Bisphenol-Like Diradicals.
The intramolecular spin coupling interactions of bisphenol-like trinary-bridged diradicals [nitroxide-(para/meta)phenylene-X-phenylene(para/meta)-nitroxide, X=C=CH2 , O, BH, NH and SO2 ] were explored with an emphasis on the tuning role of the X coupler at the (U)B3LYP/6-311++G(d,p) level. Our results indicate that all designed trinary-bridged diradicals featuring a V-type structure with a bending angle of 104-130° and torsional angles of two phenylene rings being 20-90° exhibit different diradical character and magnetism, depending on the structures and properties of the X bridges. More interestingly, although meta/para-phenylene supports a ferromagnetic (FM)/antiferromagnetic (AFM) coupling, their combinations by using X as a trinary bridge can mediate spin coupling, but the coupling magnitude strongly depends on X. In general, a para/para or meta/meta combination with X leads to an open-shell singlet ground state and thus AFM, but the meta/meta combination considerably decreases the spin coupling interaction. In contrast, a para/meta combination with X produces a triplet ground state and FM. Their combination with a single-electron conjugation end coupler (C=CH2 ) leads to an inverse coupling regularity. All results can be reasonably explained by the spin alternation rule, molecular structures, and properties. In particular, detailed spin coupling mechanisms are suggested to involve cooperative through-space and through-bond pathways with different levels of cooperativity. This is rationalized with the X-induced bending of the diradicals not only modifying the through-bond (extended π conjugation) pathway but also provididng a through-space (face-to-face vs. side-to-side π-π interaction) possibility for spin coupling, in conjunction with twisting of the phenylene rings. Different contributions of the through-space and through-bond couplings are quantitatively distinguished and depend on the structure and property of the X coupler. Clearly, this work reports interesting aspects of the trinary bridged diradicals and also provides important information for the design of molecules for functional magnetic materials and tuning their magnetic properties.


Identification of fermented tea (Camellia sinensis) polyphenols and their inhibitory activities against amyloid-beta aggregation.
Thirty-three phenolic compounds were identified from the extract of fermented tea (Camellia sinensis L.), including three undescribed flavonoids, namely quamoreokchaside I-II and kamoreokchaside I, along with thirty known compounds. All isolates were tested to evaluate their inhibitory effects against amyloid-beta (Aβ) aggregation through thioflavin-T (ThT) fluorescence-based assay and transmission electron microscopy (TEM). Among the isolates, three tea polyphenols, including (-)-catechin gallate (CG), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG), significantly decreased Aβ aggregation at a concentration of 10 μg ml-1, compared to the positive control, Aβ alone. The anti-Aβ aggregation effects of CG, ECG, and EGCG were confirmed again via TEM, which were consistent with the ThT fluorescence-based assay. Moreover, CG and ECG provided stronger protection on SH-SY5Y cells against Aβ-induced cytotoxicity than EGCG. Remarkably, CG showed more potent inhibitory activity than EGCG, the best-known anti-Aβ aggregation agent from tea products.


Enhancing the Nutritive Value of Corn Whole Stillage for Pigs via Pretreatment and Predigestion.
Corn DDGS is poorly digested by pigs. Pretreatment or predigestion of whole stillage (WS; slurry material from which DDGS is derived) can potentially improve corn DDGS digestibility. Thus, a study was conducted to determine the effects of pretreating WS with heat (160 °C and 70 psi for 20 min) alone or in combination with citric acid (10 g/L; CA), sulfuric acid (90 mM; H2SO4), or ammonia (1%), without or with subsequent multienzymatic hydrolysis for 24 h, on porcine digestibility. Dried untreated, heat-pretreated, CA-pretreated, H2SO4-pretreated, and ammonia-pretreated WS contained 23, 21, 12 19, and 18% total nonstarch polysaccharides, respectively. Pretreatment increased in vitro digestibility of dry matter of WS by ∼11 (CA) to ∼15% units (ammonia). Multienzyme hydrolysis increased in vitro digestibility of dry matter of WS by ∼6 (ammonia-treated WS) to ∼18% units (untreated WS). Thus, pretreatment or predigestion can improve the digestibility of WS and hence the resulting DDGS.


Activation of HIV-specific ribozyme activity by self-cleavage.
A hammerhead ribozyme designed to cleave in trans the R region of HIV-1 RNA was inserted into a eukaryotic expression vector. This ribozyme was studied in vitro using the T3 RNA polymerase promoter located upstream of the eukaryotic promoter. The ribozyme showed no activity against its specific target sequence under any condition tested. To decrease the influence of potential cis inhibitory sequences in such a ribozyme transcript, a specific target sequence was inserted upstream of the ribozyme-coding sequence. This insertion allowed the release by cis cleavage of a short RNA bearing ribozyme activity and able to cleave in trans an external RNA target. The cis cleavage reaction generated two RNA molecules: the shorter RNA species, which included the catalytic domain, showed a trans cleavage reaction. This self-cleavable ribozyme was active in vitro at 37 degrees C against three distinct HIV-1 transcripts sharing the specific target sequence. Ribozyme activity was thus attained by self-cleavage of the ribozyme-containing sequence from the longer vector transcript.


[Models of peer support in psychiatric care].
In the past decades, psychiatric care has changed from the traditional medical model to a more person-centered and recovery-focused approach. In this process, peer support workers are essential, because with their lived experience of crisis and recovery they are able to spread hope.This article gives an overview of the recent literature describing the current change model of peer support, reporting the evidence of peer support, as well as the current stage of implementation of peer support in different psychiatric contexts.An overview of the current state of research, selected by the authors, based on repeated systematic literature searches in peer support research projects, is given. Additionally, some examples of user involvement from the Hamburg EX-IN Curriculum, trialogs between sufferers, relatives and professionals, as well as the so-called psychosis seminars are described in more detail.Peer support has shown promising results in one-to-one and group settings, case management, crisis interventions, and the reduction of coercive measures.Although there are promising results of peer support in various clinical contexts, multiple challenges in the implementation of peer support are reported. They need to be overcome by the inclusion of all staff members in the change process of the system in order to further develop user-oriented and recovery-oriented psychiatric care.


Aiming at the heart: the capsid protein of dengue virus as a vaccine candidate.
Dengue fever remains as a health problem worldwide. Although Dengvaxia®, was registered in several countries, the results after the immunization of people suggest an increase of risk in non-immune persons and children younger than 9 years old. No other vaccine is registered so far, thus the development of a safe and effective vaccine continues to be a priority for the WHO and the scientific community. This work reviews the structural and antigenic properties of the capsid protein of Dengue virus, along with results of studies performed to assess the immunogenicity and protective capacity in animals of vaccine candidates based on this protein. The generation of a memory cellular immune response alone, after vaccination against Dengue virus, could be advantageous, as there would not be risk of increasing viral infectivity through sub-neutralizing antibodies. However, it is improbable to achieving sterilizing immunity. In this scenario, an infection could stablished but without the appearance of the severe disease. The cell-mediated immunity should keep the virus at bay. The capsid protein induces a protective immune response in animals without the induction of virus-binding antibodies. Vaccine candidates based on this protein could be an attractive strategy to induce protection against the severe Dengue disease.


Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis.
Acetaminophen (APAP) is one of the most widely used drugs. Though safe at therapeutic doses, overdose causes mitochondrial dysfunction and centrilobular necrosis in the liver. The first studies of APAP metabolism and activation were published more than 40 years ago. Most of the drug is eliminated by glucuronidation and sulfation. These reactions are catalyzed by UDP-glucuronosyltransferases (UGT1A1 and 1A6) and sulfotransferases (SULT1A1, 1A3/4, and 1E1), respectively. However, some is converted by CYP2E1 and other cytochrome P450 enzymes to a reactive intermediate that can bind to sulfhydryl groups. The metabolite can deplete liver glutathione (GSH) and modify cellular proteins. GSH binding occurs spontaneously, but may also involve GSH-S-transferases. Protein binding leads to oxidative stress and mitochondrial damage. The glucuronide, sulfate, and GSH conjugates are excreted by transporters in the canalicular (Mrp2 and Bcrp) and basolateral (Mrp3 and Mrp4) hepatocyte membranes. Conditions that interfere with metabolism and metabolic activation can alter the hepatotoxicity of the drug. Recent data providing novel insights into these processes, particularly in humans, are reviewed in the context of earlier work, and the effects of altered metabolism and reactive metabolite formation are discussed. Recent advances in the diagnostic use of serum adducts are covered.


A stable tRNA-like molecule is generated from the long noncoding RNA GUT15 in Arabidopsis.
The Arabidopsis GUT15 RNA belongs to a class of noncoding RNAs that are expressed from the intergenic regions of protein-coding genes. We show that the RNA polymerase II transcribed GUT15 transcript serves as a precursor for two stable RNA species, a tRNA-like molecule and GUT15-tRF-F5, which are both encoded by the final intron in the GUT15 gene. The GUT15-encoded tRNA-like molecule cannot be autonomously transcribed by RNA polymerase III. However, this molecule contains a CCA motif, suggesting that it may enter the tRNA maturation pathway. The GUT15-encoded tRNA-like sequence has an inhibiting effect on the splicing of its host intron. Moreover, we demonstrate that the canonical tRNA genes nested within introns do not affect the splicing patterns of their host protein-coding transcripts.


Critical decision-making in radiotherapy for early stage breast cancer in a neo-adjuvant treatment era.
In breast cancer management, the role of adjuvant radiation therapy (RT) has been the subject of intense controversy over the past several years, due to the improvement in neoadjuvant chemotherapy (NACT) prescription. One of the most controversial questions regarding indication for adjuvant RT is whether or not RT is essential in patients with early stage disease at diagnosis. The value of adjuvant RT remains highly debatable in those patients with clinically negative nodes at the completion of NACT. Areas covered: This review is focused on this gray area and is intended to assist with clinical decision-making. We provide a comprehensive review using PubMed and meeting proceedings of San Antonio Breast Cancer Symposium, European Society for Radiotherapy & Oncology, European Society of Medical Oncology and American Society of Clinical Oncology. Expert commentary: The identification of potential prognostic factors may lead to novel adjuvant RT indications. Phase III clinical trials are underway and their results will help guide treatment decisions.


Weight reduction does not induce an undesirable decrease in muscle mass, muscle strength, or physical performance in men with obesity: a pilot study.
To date, there have been no reports on whether weight reduction causes decreases in muscle mass, muscle strength, or physical performance that could lead to health problems. Thus, in this pilot study, we investigated the appropriateness of the changes in muscle mass, muscle strength and physical performance after weight reduction. Obese men who completed a weight reduction program to decrease and maintain a body mass index (BMI) of less than 25 kg/m2 for one year were recruited for the study. One year after the completion of a weight reduction program, the participants' muscle mass, muscle strength, and physical performance were compared with those in a reference group composed of individuals whose BMI was less than 25 kg/m2. Whole-body scanning was performed using dual-energy X-ray absorptiometry to analyze muscle mass. Handgrip strength and knee extensor strength were measured to evaluate arm and leg muscle strength, respectively. For physical performance, a jump test was employed. The results showed that the biceps, triceps, subscapular, and suprailiac areas of professional fashion models were significantly thinner than those of women in general (p<.001), and that their waist size was also significantly smaller (p<.001). However, hip circumference showed no significant difference. Body mass index, waist-to-hip ratio, and body fat (%) in professional fashion models were significantly lower than those in women in general (p<.001), while the body density in professional fashion models was significantly greater (p<0.001). Weight reduction participants showed an average reduction in body weight of -16.47%. Normalized arm muscle mass and handgrip strength were significantly greater in the weight reduction group than in the reference group; however, no significant differences were detected between the two groups with respect to the other variables. After one year, there were no significant differences between the two groups.


Alterable grating fiber-optic switch.
This paper describes a solid state high speed fiber-optic switch based on dynamically alterable magnetic stripe domains that occur naturally in epitaxial films of rare-earth iron garnet. The array of stripe domains acts collectively as a Faraday effect phase diffraction grating that deflects visible and infrared radiation. Electrically derived magnetic fields in the plane of the film steer incident light from an input fiber to one of several output fibers. Reciprocity and wavelength sensitivity can be exploited for systems applications. Both theoretical and experimental results are presented.


Gene regulation during dedifferentiation in Dictyostelium discoideum.
During development of Dictyostelium discoideum, cells acquire the capacity to rapidly recapitulate morphogenesis. Therefore, when cells at the loose aggregate stage are disaggregated and challenged to reaggregate, they do so in a tenth of the original time. If loose aggregate cells are disaggregated and resuspended in buffered dextrose solution (erasure medium), they retain the capacity of rapid recapitulation for 80 min, then completely lose this capacity in a single, synchronous step referred to as the "erasure event." The erasure event sets in motion a program of dedifferentiation during which cells lose developmentally acquired characteristics at different times. The erasure event is inhibited by the addition of 10(-4) M cAMP to erasure medium. The synthesis of 33 growth-associated polypeptides, the synthesis of 53 development-associated polypeptides, and the level of 2 development-associated RNAs have been monitored during the erasure program and in cultures inhibited from erasing by the addition of 10(-4) M cAMP. Growth-associated polypeptides begin to be resynthesized and development-associated polypeptides exhibit dramatic decreases in rate of synthesis at different times throughout the first 240 min in erasure medium. Inhibiting the erasure event with cAMP has no major effect in the resynthesis of the majority of growth-associated polypeptides. Only one growth-associated polypeptide, V28, is completely inhibited by cAMP, suggesting that it may play a role in the erasure process. In contrast, inhibiting the erasure event with cAMP has a marked effect on the synthesis of development-associated polypeptides, causing a dramatic reduction in the rate at which synthesis decreases for 6 polypeptides, and completely inhibits the decrease in the synthetic rate of 8 polypeptides. The two development-associated RNAs, 16G1 and 10C3, exhibit two distinctly different patterns of loss during erasure, but in both cases cAMP added at time zero of the erasure process dramatically retards or inhibits loss. In addition, when cAMP is added just prior to the erasure event, it inhibits the erasure event and stimulates a rapid increase in the level of 16G1 RNA back to the developmental level. The level of 16G1 RNA then remains at this level for at least 400 min. When cAMP is added after the erasure event, it causes a low, transient increase in the level of 16G1 RNA. These results are considered both in relation to the program of erasure, and in relation to the role of cAMP in the expression of developmental genes during the forward program of development.


Optimising refugee children's health/wellbeing in preparation for primary and secondary school: a qualitative inquiry.
Children from refugee backgrounds are less likely to access appropriate health and social care than non-refugee children. Our aim was to identify refugee children's health/wellbeing strengths and needs, and the barriers and enablers to accessing services while preparing for primary and secondary school, in a low socio-economic multicultural community in Australia. Ten focus groups were facilitated with Arabic-speaking refugee parents of children aged 2-5 years (n = 11) or in first year secondary school (n = 22); refugee adolescents starting high school (n = 16); and key service providers to refugee families (n = 27). Vignettes about a healthy child and a child with difficulties guided the discussions. Data was thematically analysed and feedback sought from the community via the World Café method. Personal resilience and strong family systems were identified as strengths. Mental health was identified as a complex primary need; and whilst refugees were aware of available services, there were issues in knowing how to access them. Opportunities for play/socialisation were recognised as unmet adolescent needs. Adults spoke of a need to support integration of "old" and "new" cultural values. Parents identified community as facilitating health knowledge transfer for new arrivals; whilst stakeholders saw this as a barrier when systems change. Most parents had not heard of early childhood services, and reported difficulty accessing child healthcare. Preschooler parents identified the family "GP" as the main source of health support; whilst parents of adolescents valued their child's school. Health communication in written (not spoken) English was a significant roadblock. Differences in refugee family and service provider perceptions were also evident. Refugee families face challenges to accessing services, but also have strengths that enable them to optimise their children's wellbeing. Culturally-tailored models of care embedded within GP services and school systems may assist improved healthcare for refugee families.


Serum microRNA profiling in patients with glioblastoma: a survival analysis.
Because circulating microRNAs (miRNAs) have drawn a great deal of attention as promising novel cancer diagnostics and prognostic biomarkers, we sought to identify serum miRNAs significantly associated with outcome in glioblastoma patients. To do this, we performed global miRNA profiling in serum samples from 106 primary glioblastoma patients. The study subjects were randomly divided into two sets: set one (n = 40) and set two (n = 66). Using a Cox regression model, 3 serum miRNAs (miR-106a-5p, miR-182, and miR-145-5p) and 5 serum miRNAs (miR-222-3p, miR-182, miR-20a-5p, miR-106a-5p, and miR-145-5p) were identified significantly associated with 2-year patient overall survival and disease-free survival (P < 0.05) in both sets and the combined set. We then created the miRNA risk scores to assess the total impact of the significant serum miRNAs on survival. The high risk scores were associated with poor patient survival (overall survival: HR = 1.92, 95% CI: 1.19, 10.23, and disease-free survival: HR = 2.03, 95%CI: 1.24, 4.28), and were independent of other clinicopathological factors. Our results suggest that serum miRNAs could serve as prognostic predictors of glioblastoma.


[Association between indoor coal-burning pollutants associated with asthmatic susceptible genetic polymorphisms in childhood asthma].
To determine the level of exposure to indoor pollutants (PM4, SO2, CO) produced by burning coal in home of asthmatic children in Guiding County, Guizhou Province, and to observe the distribution frequencies of ACE gene and the 16th and 27th loci of beta2 adrenergic receptor (beta2-AR) gene in the children, and to reveal the association between the pollutants and the susceptible genes in childhood asthma. Case-only study, an epidemiologic method, was employed. PCR was used to examine the polymorphisms at the 16th and 27th loci of beta2-AR gene and the insertion/deletion (ID) polymorphisms of angiotensin converting enzyme (ACE) gene in 231 children suffered from asthma. PM4, SO2 and CO concentrations of indoor air in the children's homes were measured. The distribution frequencies of the polymorphisms were calculated. And the possible interaction of multiplication model between the pollutants and the polymorphisms was determined. Rate of exposure to coal-burning air pollutants was 87.4% (202 children) among the children suffered from asthma. The distribution frequencies of the Arg/Arg and Gly/Gly homozygotes and the Arg/Gly heterozygote at the 16th locus of beta2-AR gene were 13.9%, 13.4% and 72.7%, respectively, and the frequencies of the Gln/Gln and Glu/Glu homozygotes and the Glu/Glu heterozygote at the 27th locus were 13.9%, 4.3% and 81.8%, respectively, and the frequencies of the II, DD and ID genotypes of ACE gene were 49.3%, 20.0% and 30.7%, respectively; and an interaction of multiplication model could exist between the air pollutants, PM4 , SO2, and CO, and the beta2-AR and ACE polymorphisms for the occurrence of childhood asthma (P < 0.05 for all indicators). The problem of air pollution from burning coal maybe serious in the local rural area. The distribution frequencies of the three susceptible polymorphisms for asthma could have their individual characteristics. And the air pollutants, PM4, SO2 and CO, interacted with the Gly/Gly genotype at the 16th locus of beta2-AR gene or the DD genotype of ACE gene maybe increases the risk for asthma in children.


{2-(4-Hy-droxy-phen-yl)-2-[(3-meth-oxy-2-oxidobenzyl-idene)amino-κO,N]propanoato-κO}(1,10-phenanthroline-κN,N')copper(II) dihydrate.
In the title complex, [Cu(C(17)H(15)NO(5))(C(12)H(8)N(2))]·2H(2)O, the central Cu(II) ion is five-coordinate, bound to one N atom and two O atoms from the Schiff base ligand and by two N atoms from a 1,10-phenanthroline ligand in a distorted square-pyramidal configuration. In the crystal, inter-molecular O-H⋯O and C-H⋯O hydrogen bonds form a two-dimensional network parallel to (001).


New Assessments and Treatments in ASD.
The assessment of autism spectrum disorder (ASD) is complex and remains clinical, despite advances in basic research. In this chapter, we review new and updated clinical tools, such as screening and diagnostic tests, and discuss the DSM-5 criteria introduced in 2013. We provide an algorithm to guide clinical evaluation and referrals. We also review non-behavioral treatments and summarize recent research. Current conventional treatment of ASD in children includes intensive behavioral interventions (known as applied behavioral analysis or ABA), rehabilitative services such as speech therapy, occupational therapy, physical therapy, social skills training, and counseling. We present new validated information and provide clinical guidance for the evaluation and treatment of young children and youth with ASD.


Nutritional management of lactose intolerance: the importance of diet and food labelling.
Worldwide, 70% of the adult population has limited expression of lactase enzyme with a wide variation among different regions and countries. Lactase deficiency may lead to lactose intolerance (LI). Depending both on the amount of lactose ingested and on the lactase activity, people who suffer from lactose malabsorption might experience numerous gastrointestinal and extra-intestinal symptoms and manifestations. Treatment of LI mainly consists of reducing or eliminating lactose from the diet until the symptoms disappear as well as supplementing lactase, and inducing colon microbiome adaptation by probiotics. Cow's milk is one of the major source of calcium and several other vitamins and minerals. Thus, a complete exclusion of dairy products may favor the development of bone diseases such as osteopenia and osteoporosis. Therefore, the dietetic approach has a crucial role in the management of LI patients. Additionally, the use of lactose and milk-derived products in non-dairy products (e.g., baked goods, breakfast cereals, drinks, and processed meat) has become widespread in the modern industry (the so-called "hidden lactose"). In this regard, a strict adherence to the lactose-free diet becomes challenging for LI patients, forced to continuous check of all products and food labels. In fact, lactose-free product labeling is still controversial. Considering that nowadays a specific cut-off value establishing "lactose-free" labeling policy is lacking and that there is no universal law regulating the production and commercialization of "delactosed" products, identification of specific safe and suitable products with a well-recognized lactose-free logo might help consumers. This narrative review aims to identify the dietary management for lactose intolerant people, avoiding symptoms and nutrients deficiencies, helped by the use of specific labelling to guide them to choose the safer product on the market.


Association of miR-196a-2 and miR-499 variants with ulcerative colitis and their correlation with expression of respective miRNAs.
MicroRNAs are small non-coding RNAs that play an important role in regulating the gene expression of their target genes. SNP miR-196a-2 rs11614913 and miR-499 rs3746444 are reported to have association with the risk and prognosis of multiple-types of inflammatory diseases including IBD. This study was conducted to show if any association of SNP miR-196a-2rs11614913 and miR-499 rs3746444 exists with ulcerative colitis (UC) patients of north Indian population and how these polymorphisms modulate the expression profile of the respective miRNAs. A total of 638 participants including 197 UC patients and 441 controls were included in this study. Polymorphisms were genotyped by PCR-RFLP and the miRNA expression was measured using qRT-PCR. Genotypes and allele frequencies were calculated using SPSS 16 software. MiR-196a-2 rs11614913 (C>T) and miR-499 rs3746444 (T>C) were found to be associated with UC. TT genotype of miR-196a-2 rs11614913 (p = 0.03) was negatively associated with UC whereas the heterozygous TC genotype of miR-499 rs3746444 (p = 0.003) was showing positive association with UC. Patients having a combination of both SNPs, developed disease at older age and they suffered from severe disease extent. Genotype that showed association with the disease also showed correlation with the changes in miRNA expression. In this study we found miR-196a-2 rs11614913 and miR-499 rs3746444 were associated with UC in north Indian population. We found the genotype that showed association with UC also altered the expression of respective miRNA in the patient harboring the genotype. There was correlation between associated genotype and altered miRNA expression.


The influence of the Ebola outbreak on presumptive and active tuberculosis in Bombali District, Sierra Leone.
Setting: Bombali District, rural Sierra Leone. Objective: To compare the number of patients with presumptive tuberculosis (TB), the number of patients registered with TB (including testing for the human immunodeficiency virus [HIV] and initiation on antiretroviral therapy [ART]) and treatment outcomes during the pre-Ebola, Ebola and post-Ebola disease outbreak periods between 2013 and 2016. Design: This was a cross-sectional study and retrospective cohort analysis of treatment outcomes. Results: The mean monthly number of patients with presumptive TB before, during and post-Ebola was respectively 169, 145 and 210. The mean monthly number of registered TB cases was respectively 57, 57 and 96. Smear-positive TB was the most frequent type of TB, at 75%, 66% and 77%. The proportion of TB patients tested for HIV was 82% pre-Ebola, 74% Ebola and 99% post-Ebola. The proportion of HIV-positive patients with TB initiated on ART was respectively 46%, 85% and 100%. Treatment success among TB patients was 71% in the pre-Ebola period and 89% in the Ebola period (P < 0.001). Conclusion: During the Ebola outbreak, there were decreases in the number of presumptive TB patients and in the proportions of patients diagnosed with smear-positive TB and tested for HIV. The initiation of ART in HIV-infected TB patients and treatment outcomes remained acceptable. Pre-emptive actions are needed to maintain adequate control activities in future outbreaks.


Direct imaging of mechanical and chemical gradients across the thickness of graded organosilicone microwave PECVD coatings.
The characterization of variations in the chemical composition and ensuing mechanical properties across the thickness of coatings with continuously varying compositions through their thickness (graded coatings) presents considerable challenges for current analytical techniques in materials science. We report here the direct imaging of nanomechanical and chemical gradients across cross-sections of an organosilicone coating fabricated via microwave plasma enhanced chemical vapor deposition (PECVD). Cross-sectional nanoindentation was used to determine the mechanical properties of uniform and graded organosilicone coatings. Both hardness and modulus across the coatings were directly measured. Additionally, "modulus mapping" on cross-sections was used to map the complex modulus. For the graded coating, it was found that variations in the complex modulus was predominantly due to varying storage modulus. It was observed that at the interface with the substrate there was a low storage modulus, which linearly increased to a relatively high storage modulus at the surface. It is proposed that the increase in stiffness, from the substrate interface to the outer surface, is due to the increasing content of a cross-linked O-Si-O network. This mechanical gradient has been linked to a change in the Si:O ratio via direct compositional mapping using ToF-SIMS. Direct mapping of the mechanical and compositional gradients across these protective coatings provides insight into the changes in properties with depth and supports optimization of the critical mechanical performance of PECVD graded coatings.


Effect of different chemical bonds in pegylation of zinc protoporphyrin that affects drug release, intracellular uptake, and therapeutic effect in the tumor.
Pegylated zinc protoporphyrin (PEG-ZnPP) is a water-soluble inhibitor of heme oxygenase-1. In this study, we prepared two types of PEG-ZnPP conjugates with different chemical bonds between PEG and ZnPP, i.e., ester bonds and ether bonds, where both conjugates also contain amide bonds. Cleavability of these bonds in vitro and in vivo, especially cancer tissue, and upon intracellular uptake, was investigated in parallel with biological activities of the conjugates. Each conjugate showed different cleavability by plasma esterases and tumor proteases, as revealed by HPLC analyses. PEG-ZnPP with ester bond (esPEG-ZnPP) was more sensitive than PEG-ZnPP with ether bond (etPEG-ZnPP) for cleavage of PEG chains. etPEG-ZnPP showed no cleavage of PEG chains and had lower intracellular uptake and antitumor activity than did esPEG-ZnPP. The degradation of esPEG-ZnPP appeared to be facilitated by both serine and cysteine proteases in tumor tissues, whereas it was significantly slower in normal organs except the liver. Depegylated products such as free ZnPP had higher intracellular uptake than did intact PEG-ZnPP. We also studied hydrolytic cleavage by blood plasma of different animal species; mouse plasma showed the fastest cleavage whereas human plasma showed the slowest. These results suggest that ester-linked conjugates manifest more efficient cleavage of PEG, and greater yield of the active principle from the conjugates in tumor tissues than in normal tissues. More efficient intracellular uptake and thus an improved therapeutic effect with ester-linked conjugates are thus anticipated with fain stability, particularly in human blood.


Effect of diabetes mellitus on thyrotropin release from isolated rat thyrotrophs.
The effect of streptozotocin-induced diabetes on thyrotropin (TSH) secretion was studied in vitro in male rats, using purified thyrotrophs isolated by centrifugal elutriation. The development of diabetes was associated with a significant fall in serum T4 (4.9 +/- 1.5 vs. 1.2 +/- 0.7 micrograms/dl, control vs. diabetic), T3 (59 +/- 16 vs. 20 +/- 9 ng/dl) and TSH (53 +/- 22 vs. 23 +/- 18 microU/ml). In vitro, basal TSH release was lower in cells from diabetic rats (1570 +/- 248 microU/10(6) cells) than in controls (2612 +/- 765 microU/10(6) cells) after 48 h in culture. Furthermore, thyrotropin-releasing hormone (TRH)-induced TSH release was decreased about 30% and the intracellular TSH content was also reduced 45% in diabetic rat thyrotrophs compared with controls. The addition of 200 microU/ml of insulin in the incubation media did not change the TRH-stimulated TSH release, but it decreased the basal TSH release by 42%. Preincubation of thyrotrophs with glucose (25 mM) did not impair the basal or TRH-stimulated TSH release. In the same experimental conditions, no effect of insulin or glucose was seen on the basal or TRH-stimulated TSH release from thyrotrophs of diabetic rats. Preincubation of thyrotrophs with 10, 100, or 1000 nM of T4 for 48 h decreased basal TSH release by 27%, 45%, and 48%, respectively, and reduced TRH-induced TSH release by 46%, 48%, and 55%; 100 nM T4 also reduced TRH-induced TSH release from diabetic thyrotrophs.(ABSTRACT TRUNCATED AT 250 WORDS)


Efficacy and safety of dual antiplatelet therapy after percutaneous coronary drug-eluting stenting: A network meta-analysis.
To evaluate the efficacy and safety of dual antiplatelet regimens after coronary drug-eluting stenting by network meta-analysis (NMA). PubMed, The Cochrane Library, Embase, and Web of Science databases were electronically searched to collect randomized controlled trials (RCTs) of the comparison of different dual antiplatelet regimens after coronary drug-eluting stenting from inception to September 1st, 2021. Two reviewers independently screened literature, extracted data, and assessed the risk bias of included studies. Stata 16.0 software was used for NMA. A total of 27 RCTs involving 79,880 patients were included. The results of NMA: in terms of myocardial infarction (MI), other 3 interventions were higher than the long-term dual antiplatelet therapy (L-DAPT) (the standard dual antiplatelet therapy [Std-DAPT] [odds ratio [OR] = 1.82, 95%confidence interval [CI]: 1.49-2.21), the aspirin monotherapy after short-term dual antiplatelet therapy (S-DAPT + As) (OR = 2.06, 95%CI: 1.57-2.70), the P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy (S-DAPT + P2Y12) (OR = 1.71, 95%CI: 1.29-2.28)]. In terms of stent thrombosis, other 3 interventions were higher than L-DAPT [Std-DAPT (OR = 2.18, 95%CI: 1.45-3.28), S-DAPT + As (OR = 2.32, 95%CI: 1.52-3.54), S-DAPT + P2Y12 (OR = 2.31, 95%CI: 1.22-4.36)]. There was no statistically significant difference among the 4 interventions in prevention of stroke and all-cause mortality (P > .05). In terms of cardiovascular and cerebrovascular adverse events, other 3 interventions were higher than L-DAPT (Std-DAPT [OR = 1.28, 95%CI: 1.12-1.45], S-DAPT + As [OR = 1.27, 95%CI: 1.09-1.48], S-DAPT + P2Y12 [OR = 1.24, 95%CI: 1.01-1.52]). In terms of safety, bleeding rate of other 3 interventions were lower than L-DAPT (Std-DAPT [OR = 0.67, 95%CI: 0.52-0.85], S-DAPT + As [OR = 0.51, 95%CI: 0.39-0.66], S-DAPT + P2Y12 [OR = 0.36, 95%CI: 0.26-0.49]). Two interventions were lower than L-DAPT (S-DAPT + As [OR = 0.77, 95%CI: 0.65-0.90], S-DAPT + P2Y12 [OR = 0.54, 95%CI: 0.44-0.66]). S-DAPT + As was higher than L-DAPT (OR = 1.42, 95%CI: 1.10-1.83). S-DAPT + P2Y12 has the lowest bleeding risk, while L-DAPT has the highest bleeding risk. In the outcome of MI, stent thrombosis, and cardiovascular and cerebrovascular adverse events, L-DAPT has the best efficacy. In the outcome of stroke and all-cause mortality, the 4 interventions were equally effective.


A waterborne polyurethane 3D scaffold containing PLGA with a controllable degradation rate and an anti-inflammatory effect for potential applications in neural tissue repair.
Currently, implanting tissue engineering scaffolds is one of the treatment methods for the regeneration of damaged tissues. The matching of the degradation rate of the scaffolds with the regeneration rate of the damaged zone is a big challenge in tissue engineering. Here, we have synthesized a series of biodegradable waterborne polyurethane emulsions and fabricated three-dimensional (3D) connected porous polyurethane scaffolds by freeze-drying. The degradation rate of the scaffolds was controlled by adjusting the relative ratio of poly-ε-caprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) in the soft segment. The degradation rate of the scaffolds gradually accelerated with the increase of the relative proportion of PLGA. By co-culture with BV2 microglia, the scaffolds promoted the differentiation of BV2 into an anti-inflammatory M2 phenotype rather than a pro-inflammatory M1 phenotype as the proportion of PLGA increases. When the BV2 cells were stimulated with lipopolysaccharide (LPS), the scaffolds with a higher PLGA ratio showed a much stronger anti-inflammatory effect. Then, we demonstrated that the scaffolds could promote the PC12 neurons to differentiate into neurites. Therefore, we believe that the polyurethane scaffolds have a promising potential application in neural tissue repair.


Inpatient versus Outpatient Management of TIA or Minor Stroke: Clinical Outcome.
The management of patients with acute transient ischemic attack (TIA) or minor stroke is highly variable. Whether hospitalization of such patients significantly improves short-term clinical outcome is unknown. We assessed the short-term clinical outcome associated with inpatient versus outpatient management of patients with TIA or minor stroke. We evaluated a consecutive series of patients with acute TIA or minor ischemic stroke (NIH Stroke Scale score ≤ 3) presenting to a single emergency department (ED). We randomized patients to either hospital-based or outpatient-based management. All patients underwent interview and examination 7-10 days following the index event. This study included 100 patients, 41 with TIA and 59 with minor stroke. Nineteen (46%) of the TIA patients and 29 (49%) of the minor stroke patients randomized to hospital management, and the remaining 22 TIA patients and 30 minor stroke patients randomized to outpatient-based management. In the patients with a minor stroke, neurologic worsening occurred in 6 out of 29 (21%) in the inpatient arm compared with 3 out of 30 (10%) in the outpatient arm (p = 0.3). In none of these cases was acute interventional therapy or need for urgent admission considered medically appropriate. In the patients with a TIA, recurrence of a TIA occurred in 2 out of 19 (11%) in the inpatient arm compared with 2 out of 22 (9%) in the outpatient arm (p = 1). None of the patients with a TIA randomized to the inpatient arm experienced a stroke compared with 1 out of 22 in the outpatient arm (p = 1). There were no deaths in either group. Routine hospitalization of all patients with TIA or minor ischemic stroke may not positively affect short-term clinical outcome.


Healing Potential of Propolis Extract-Passiflora edulis Seed Oil Emulgel Against Excisional Wound: Biochemical, Histopathological, and Cytokines Level Evidence.
Propolis is rich in natural bioactive compounds, and considering its importance for many skin therapies, emulgel was prepared. This study examines how a propolis extract (PE) and Passiflora edulis seed (PS) oil emulgel affect rat deep skin wound healing. Based on preset criteria of maximum drug content and optimum drug permeation through the stratum corneum along with drug retention in the skin layers, an optimized emulgel formula based on Box-Behnken factorial design was prepared and used for subsequent in vitro and in vivo evaluations. In vivo wound-healing activities of emulgel and control treatments were investigated in a rat model. The optimized emulgel formula exhibited superior healing activity compared with plain PE suspension-treated rats on day 14 of wounding. Histopathological investigations of hematoxylin and eosin and Masson's Trichrome-stained skin sections supported this effect. Emulgel promotes cutaneous wound healing through a variety of mechanisms, including anti-inflammatory through modulation of cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 production, and promotion of collagen fiber formation, all of which contribute to tissue remodeling. Furthermore, when compared with propolis suspension, emulgel showed significant antioxidant and anti-inflammatory effects. Emulgel significantly increased the skin's hydroxyproline level, antioxidant potential, wound contraction, increased penetration, and localized propolis deposition across the skin. Incorporation of PS oil into the emulgel accelerates the tissue regeneration process. The findings suggest that 5% propolis emulgel could be used as an alternative to treat wounds.


[Myocarditis and dilated cardiomyopathy. New methods in diagnosis and therapy].
In 20% of cases, acute myocarditis can progress to dilated cardiomyopathy as a result of persistence of intramyocardial inflammation or of a virus genome. Both acute myocarditis (10-year survival rate 45%) and dilated cardiomyopathy (leading indication for cardiac transplantation) have a grave prognosis. Etiopathogenic differentiation of dilated cardiomyopathy was made possible for the first time by the use of immunohistochemical and molecular-biological diagnostic procedures applied to endomyocardial biopsy material. In addition to conventional treatment of heart failure, initial randomized studies have shown immunosuppression and antiviral immunomodulation to be effective measures and harbingers of a new era of rational therapeutic concepts in the treatment of dilated cardiomyopathy.


Effect of primaquine standard dose (15 mg/day for 14 days) in the treatment of vivax malaria patients in Thailand.
Primaquine (8-aminoquinoline), the only effective drug to prevent relapses of the persistent liver forms of Plasmodium vivax and Plasmodium ovale, can induce hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The severity varies considerably among affected individuals. Three hundred and sixty-four Plasmodium vivax cases (342 G6PD-normal and 22 G6PD-deficient) were given a 3-day course of chloroquine (total dose 1,500 mg) followed by primaquine 15 mg a day for 14 days and completed a 28-day follow-up. All G6PD-deficient patients were male; there were no relapses or serious adverse events during the study. Although a significant decrease in hematocrit levels and an increase in the percent reduction of hematocrit levels were observed on day 7 (34.9+/-5.0 vs 26.7+/-5.4; (-1.2)+/-14.4 vs (-24.5) +/-13.9 respectively) and on day 14 (35.7+/-4.3 vs 30.9+/-3.1; 1.6+/-17.8 vs (-11.0) +/-19.3 respectively) blood transfusion was not required. Daily doses of 15 mg of primaquine for 14 days following a full course of chloroquine when prescribed to Thai G6PD deficient patients where Mahidol variant is predominant, are relatively safe.


Perceptions of caring behaviours: A comparison of surgical oncology nurses and patients.
The purpose of this article was to compare surgical oncology nurses caring behaviours to perceptions of their surgical oncology inpatients and determine internal consistency of the CAT-Nurse. Nursing practice at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, FL is guided by Duffy's Quality-Caring Model© . No study using Duffy's model for both oncology nurses and patients has been found. A descriptive correlation design was used adhering to the STROBE guidelines. Data were collected using CAT-Nurse and compared to data from a previous study using CAT (version V). Item responses were compared between nurses and patients using t tests. Patients scored higher on perceptions of caring behaviours. Mutual problem solving was an area for improvement. The CAT-Nurse demonstrated internal consistency reliability. Results from this study can make nurses more aware of the caring perceptions that are not as strong as others, and therefore may have the ability to promote transformation. The results can serve as foundational knowledge for action plans aimed at increasing nurse comfort addressing lower scoring caring behaviours that would then result in improving patient perceptions which could be linked to patient satisfaction and reimbursement.


Efficacy and safety of biapenem against lower respiratory tract infections in elderly Chinese patients and optimal dosing regimen based on pharmacokinetic/pharmacodynamic analysis.
The present study evaluated the efficacy and safety of biapenem in elderly Chinese patients with lower respiratory tract infections (LRTIs) and proposed optimal dosage regimen on the basis of pharmacokinetic/pharmacodynamic (PK/PD) analysis. The clinical efficacy, bacterial eradication and comprehensive therapeutic effect rates of biapenem were 70.3 (78/111), 68.5 (37/54) and 61.1% (33/54), respectively. Drug-related adverse reactions were seen in 12.6% of patients (14/111). The total protein level, Acute Physiology and Chronic Health Evaluation (APACHE) II score, %fT>MIC, fAUC24/MIC and fCmax/MIC values of patients had significant impacts (P < 0.05) on clinical and bacteriological efficacy. However, logistic regression analysis showed that only %fT>MIC independently influenced comprehensive therapeutic effect (P < 0.01, odds ratio = 1.064). The cut-off value for predicting comprehensive therapeutic effect using %fT>MIC was 75.0%; the sensitivity and specificity were 87.9 and 85.7%, respectively. Monte Carlo simulations revealed that the usual dosage regimen (300 mg every 12 hours, 0.5 hour infusion) was considered to be insufficient to obtain satisfactory therapeutic outcomes against low susceptible pathogens for elderly Chinese patients with LRTIs (CLcr = 70 ml/min).


Campylobacter jejuni-mediated induction of CC and CXC chemokines and chemokine receptors in human dendritic cells.
Campylobacter jejuni is a leading worldwide bacterial cause of human diarrheal disease. Although the specific molecular mechanisms of C. jejuni pathogenesis have not been characterized in detail, host inflammatory responses are thought to be major contributing factors to the resulting typical acute colitis. The intestinal mucosal chemokine response is particularly important in the initial stages of bacterium-induced gut inflammation. Chemokines attract blood phagocytes and lymphocytes to the site of infection and regulate immune cell maturation and the development of localized lymphoid tissues. The production of chemokines by dendritic cells (DCs) following Campylobacter infection has not yet been analyzed. In the current study, we infected human monocyte-derived DCs with C. jejuni to examine the production of key proinflammatory chemokines and chemokine receptors. The chemokines, including CC families (macrophage inflammatory protein 1α [MIP-1α], MIP-1β, RANTES) and CXC families (growth-related oncogene α [GRO-α], IP-10, and monokine induced by gamma interferon [MIG]), were upregulated in Campylobacter-infected DCs. Chemokine receptors CCR6 and CCR7, with roles in DC trafficking, were also induced in Campylobacter-infected DCs. Further, Campylobacter infection stimulated the phosphorylation of P38, P44/42, and stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) mitogen-activated protein kinases (MAPKs) in DCs. NF-κB activation was specifically involved in chemokine induction in DCs infected with C. jejuni. Additionally, STAT3 was significantly increased in Campylobacter-infected DCs compared to that in uninfected DCs. These results suggest that DCs play a significant role in the initiation and modulation of the inflammatory response by enlisting monocytes, neutrophils, and T lymphocytes during human intestinal infection with Campylobacter.


[Hepatitis C and immunoglobulin heavy-chain gene rearrangement].
Hepatitis C virus (HCV) has cytopathogenic effect not only on hepatocytes, however on salivary glands, monocytes of peripheral blood and lymphoid cells, may explain the systemic manifestations of the infection. HCV activates B and T-cells, modifies the immune response, causes lymphoproliferation, leading the development of B-cell non-Hodgkin's lymphoma (NHL). In the majority of B-cell NHLs immunoglobulin heavy chain (IgH) and light chain (IgL) genes are rearranged and expressed on cell surface in the early stage of the ontogenesis. The analyses of IgH rearrangement prove the clonality of lymphoproliferative disorders giving a powerful approach to the B-cell origin identification of cell proliferation. IgH gene rearrangements were examined from the sera of 57 chronic HCV infected patients and 11 HCV-positive cryoglobulinemic patients as well. Cryoglobulinemia was detected in 20% of all chronic hepatitis C virus infected patients and IgH rearrangement was observed in 10.29% (7/68), 4/7 patients (57.14%) suffered from cryoglobulinemia. These results support the hypothesis that IgH gene rearrangement in HCV positive patients can indicate the lymphoproliferative disorder in the HCV infection released B-cell proliferation and lymphoma development.


Follicular lymphoma with bilateral testicular and epididymal involvement: case report and review of the literature.
Testicular involvement with indolent lymphoma is extremely rare, particularly in the absence of transformation to an aggressive histology. We report a case of a 64-year-old man who presented with cervical lymphadenopathy. Staging CT scans revealed extensive lymphadenopathy as well as bilateral testicular and epididymal masses. Histologic examination of lymph node, bone marrow, and testicular/epididymal biopsies revealed involvement with grade I follicular lymphoma. The patient was started on chemotherapy with cyclophosphamide, vincristine, prednisone, and rituximab in addition to intrathecal methotrexate and testicular radiation. He is now 6 months into therapy and responding well. A review of the literature demonstrated this to be the first confirmed case of testicular and epididymal involvement with grade I follicular lymphoma.


Telepsychological Mobile Applications in the Spanish Android Market.
The use of Android mobile applications aimed at addressing users' psychological health is increasing. However, no review has been conducted on public Android commercial telepsychological applications in Spain. A systematic search was carried out in the general applications section of Google Play Store based on 20 keywords in Spanish. Applications in Spanish or English that were relevant from the perspective of the search terms were included in the analysis. Of the 1,000 applications retrieved, only 43.59% (337/773) met the inclusion criteria, of which 49.26% (171/337) were Spanish. Most of them were Self-applied treatment applications (52.96%, 29.59%, Spanish; 23.37%, English). A total of 69.44% (37.38% Spanish; 31.95% English) did not indicate the origin of the information and the academic link was anecdotal (3.25%). The low percentage of relevant applications, high prevalence of self-help applications, absence of references on the origin of the information, absence of academic support, and lack of certifications encouraged us to recommend caution to consumers and professionals in their adoption of these applications for the treatment of any psychological disorder.


Use of the mutual exclusivity assumption by young word learners.
A critical question about early word learning is whether word learning constraints such as mutual exclusivity exist and foster early language acquisition. It is well established that children will map a novel label to a novel rather than a familiar object. Evidence for the role of mutual exclusivity in such indirect word learning has been questioned because: (1) it comes mostly from 2 and 3-year-olds and (2) the findings might be accounted for, not by children avoiding second labels, but by the novel object which creates a lexical gap children are motivated to fill. Three studies addressed these concerns by having only a familiar object visible. Fifteen to seventeen and 18-20-month-olds were selected to straddle the vocabulary spurt. In Study 1, babies saw a familiar object and an opaque bucket as a location to search. Study 2 handed babies the familiar object to play with. Study 3 eliminated an obvious location to search. On the whole, babies at both ages resisted second labels for objects and, with some qualifications, tended to search for a better referent for the novel label. Thus mutual exclusivity is in place before the onset of the naming explosion. The findings demonstrate that lexical constraints enable babies to learn words even under non-optimal conditions--when speakers are not clear and referents are not visible. The results are discussed in relation to an alternative social-pragmatic account.


A unified thermostat scheme for efficient configurational sampling for classical/quantum canonical ensembles via molecular dynamics.
We show a unified second-order scheme for constructing simple, robust, and accurate algorithms for typical thermostats for configurational sampling for the canonical ensemble. When Langevin dynamics is used, the scheme leads to the BAOAB algorithm that has been recently investigated. We show that the scheme is also useful for other types of thermostats, such as the Andersen thermostat and Nosé-Hoover chain, regardless of whether the thermostat is deterministic or stochastic. In addition to analytical analysis, two 1-dimensional models and three typical real molecular systems that range from the gas phase, clusters, to the condensed phase are used in numerical examples for demonstration. Accuracy may be increased by an order of magnitude for estimating coordinate-dependent properties in molecular dynamics (when the same time interval is used), irrespective of which type of thermostat is applied. The scheme is especially useful for path integral molecular dynamics because it consistently improves the efficiency for evaluating all thermodynamic properties for any type of thermostat.


Review of serum lipids and apolipoproteins in risk-assessment of coronary heart disease.
Coronary heart disease (CHD), the leading cause of death in the western world, is multifactorial in nature. Abnormal lipoprotein levels are among the risk factors that cause atherosclerosis and, therefore, have been used as biochemical markers in assessing risk of developing CHD. The measurement of serum cholesterol, lipoprotein cholesterol, and apolipoproteins accurately and reliably has been hampered with technical difficulties. In addition, the interpretation of these tests and the determination of their clinical values have been challenging for both physicians and laboratory scientists. This article addresses and reviews the major current analytical and clinical concerns in the testing of lipids as well as the prevention and treatment of CHD.


[The pharmacopoeia of Father Morin in 1864].
The "pharmacopoeia or collection of divine remedies found in the documents of an old rural priest after his death" is a publication of nearly 400 pages including a long list of diseases with their associated treatments, followed by several recipes for the day to day life (such as: how to preserve wine, how to produce Champagne's wine, recipes for filler paste, etc.). A last part, very unique, is dedicated to evil spells, i.e. to diseases that do not have natural explanations and for which Saint Benoit's medal works wonders, according to the author. This pharmacopoeia of 1864 is a typical example of "incoherent collection" mentioned by Tardieu in 1862 concerning clergy and pharmacy. It is, from that point of view, the archetype that pharmacists wanted to see disappearing after the law of germinal year XI (1803), but that persisted until the beginning of the XXth century: the illegal practice of pharmacy by priests and nuns.


Enhanced expression of endothelial nitric oxide synthase and caveolin-1 in human cirrhosis.
Nitric oxide is synthesized in diverse mammalian tissues by a family of calmodulin-dependent nitric oxide synthases (NOS). Caveolin, the principal structural protein in caveolae, interacts with endothelial NOS (eNOS) leading to enzyme inhibition by a reversible process modulated by Ca++ -calmodulin. The aim of the present study was to examine the localizations of eNOS and caveolin-1 at protein level in normal human liver tissue, and how the expressions are altered in cirrhotic liver. Fresh liver specimens were obtained from hepatic surgeries. Normal portions resected from cases of carcinoma metastasized to the liver were used as control specimens, and cirrhotic portions resected from cases of hepatocellular carcinoma with hepatitis C-related cirrhosis were used as cirrhotic specimens. Anti-eNOS and anticaveolin-1 antibodies were used for immunohistochemistry and Western blotting. Immunoelectron microscopy was conducted on ultra thin sections using immunoglobulin-gold combined with silver staining. Immunohistochemistry revealed that both eNOS and caveolin-1 were sparsely expressed on hepatic sinusoidal lining in normal liver specimens, and these findings were confirmed by Western blot. Both immunohistochemistry and Western blotting demonstrated over-expression of eNOS and caveolin-1 in cirrhotic liver specimens. Morphometric analysis of immunogold particle labeling for eNOS and caveolin-1 was performed on immunoelectron micrographs. In normal liver tissue, hepatic stellate cells and sinusoidal endothelial cells (SEC) expressed low levels of caveolin-1, and SEC expressed a very low level of eNOS. In cirrhotic liver, both caveolin-1 and eNOS expressions were significantly increased by approximately four-fold on SEC compared to normal liver. In cirrhotic human liver, marked increase of caveolin-1 in perisinusoidal cells may promote caveolin-eNOS binding and reduce the activity of eNOS despite an increased eNOS expression, leading to impaired NO production and increased hepatic microvascular tone.


Involvement of the P2X7 purinergic receptor in inflammation: an update of antagonists series since 2009 and their promising therapeutic potential.
The purinergic receptor P2X7 is highly expressed in immune peripheral and central cells suggesting its important role in numerous diseases characterized by inflammatory processes like cancer, or neurodegenerative pathologies in relation with modulation of the immune system. Thereby, antagonization of this receptor may be a hopeful therapeutic strategy to treat a large range of diseases. Indeed, selective P2X7 antagonists display beneficial anti-inflammatory, analgesic, and in some cases, anticancer properties. This article will review the involvement of P2X7 in the immune system, the update of P2X7 antagonists series since 2009 and their promising therapeutic potential for the treatment of several immune- related diseases.


The past, present, and future of remote patient monitoring in spine care: an overview.
Remote patient monitoring (RPM) has revolutionized the landscape of healthcare. From humble beginnings rooted in landline home telephone calls to present-day devices with near instantaneous wireless connectivity, the evolution of technology has ushered in an era of digital medicine and remote care. Presently, a vast array of healthcare data points can be automatically generated, analyzed, and forwarded to providers to supplement clinical decision-making. While RPM originated and was popularized within medicine, its role in orthopedics, and particularly within spine surgery, is evolving. We sought to provide an overview of RPM within orthopedics, with specific attention on spine care, analyzing its origins, present-day form, and prospects. We reviewed the literature to date as it pertains to RPM within healthcare at large, orthopedics, and spine care. We detail the development and clinical use of wearable technology and smart implants, examining the underlying technology and evaluating the spectrum of their present-day and potential applications. Technological advancements are not only reshaping the paradigm of musculoskeletal care but are also redefining the physician-patient relationship as well as reimagining traditional perspectives on healthcare data collection and privacy.


Inelastic ultraviolet scattering from high frequency acoustic modes in glasses.
The dynamic structure factor of vitreous silica and glycerol has been measured as a function of temperature and of the momentum transfer up to Q=0.105 nm(-1) using a novel experimental technique, the inelastic ultraviolet scattering. As in the case of Brillouin light scattering and ultrasonic measurements, the temperature dependence of the acoustic attenuation shows a plateau below the glass transition whose amplitude scales as Q2. Moreover, a slight temperature dependence of attenuation has been found in vitreous silica at about 130 K, which seems to be reminiscent of the peak measured at lower Qs. These two findings strongly support the idea that anharmonicity is responsible for sound attenuation at ultrasonic and hypersonic frequencies. Finally, we demonstrate that the attenuation mechanism should show a change of regime between 0.105 and 1 nm(-1).