Zoledronic acid exerts antitumor effects in NB4 acute promyelocytic leukemia cells by inducing apoptosis and S phase arrest.
The aim of this study was to investigate the antitumor effect of zoledronic acid (ZOL) in the NB4 human acute promyelocytic leukemia (APL) cell line and explore the potential mechanism of action of this compound. NB4 cells were exposed to various concentrations (0-200μM) of ZOL. Cell viability was measured by MTS assay. The extent of cell apoptosis and distribution of cells in the different phases of the cell cycle were analyzed with flow cytometry. The expression of apoptosis- and cell cycle-related proteins was assayed by Western blot. The combined effect of ZOL and arsenic trioxide (ATO) on the proliferation of NB4 cells was also determined. The results of this study indicate that ZOL inhibits cell proliferation in a time- and dose-dependent fashion and also induces apoptosis and S phase arrest in a dose-dependent manner. The Western blot analysis confirmed the induction of apoptosis and S phase arrest, revealing that the pro-apoptosis proteins Bax, Puma and activated caspase-9 were upregulated and the anti-apoptosis proteins Bcl-2 and Bcl-xL were downregulated. ZOL at a concentration of 50μM synergized with 0.5μM ATO on the growth inhibition of NB4 cells. Taken together, our data indicate that ZOL exerts a potent antitumor effect on NB4 cells by inducing apoptosis and cell cycle arrest, and that ZOL can synergize with the traditional chemotherapy drug ATO.


Calcium antagonists.
Calcium antagonists were introduced for the treatment of hypertension in the 1980s. Their use was subsequently expanded to additional disorders, such as angina pectoris, paroxysmal supraventricular tachycardias, hypertrophic cardiomyopathy, Raynaud phenomenon, pulmonary hypertension, diffuse esophageal spasms, and migraine. Calcium antagonists as a group are heterogeneous and include 3 main classes--phenylalkylamines, benzothiazepines, and dihydropyridines--that differ in their molecular structure, sites and modes of action, and effects on various other cardiovascular functions. Calcium antagonists lower blood pressure mainly through vasodilation and reduction of peripheral resistance. They maintain blood flow to vital organs, and are safe in patients with renal impairment. Unlike diuretics and beta-blockers, calcium antagonists do not impair glucose metabolism or lipid profile and may even attenuate the development of arteriosclerotic lesions. In long-term follow-up, patients treated with calcium antagonists had development of less overt diabetes mellitus than those who were treated with diuretics and beta-blockers. Moreover, calcium antagonists are able to reduce left ventricular mass and are effective in improving anginal pain. Recent prospective randomized studies attested to the beneficial effects of calcium antagonists in hypertensive patients. In comparison with placebo, calcium antagonist-based therapy reduced major cardiovascular events and cardiovascular death significantly in elderly hypertensive patients and in diabetic patients. In several comparative studies in hypertensive patients, treatment with calcium antagonists was equally effective as treatment with diuretics, beta-blockers, or angiotensin-converting enzyme inhibitors. From these studies, it seems that a calcium antagonist-based regimen is superior to other regimens in preventing stroke, equivalent in preventing ischemic heart disease, and inferior in preventing congestive heart failure. Calcium antagonists are also safe and effective as first-line or add-on therapy in diabetic hypertensive patients. Heart rate-lowering calcium antagonists (verapamil, diltiazem) may have an edge over the dihydropyridines in post-myocardial infarction patients and in diabetic nephropathy. Thus, calcium antagonists may be safely used in the management of hypertension and angina pectoris.


AARC Clinical Practice Guidelines: Artificial Airway Suctioning.
Artificial airway suctioning is a key component of airway management and a core skill for clinicians charged with assuring airway patency. Suctioning of the artificial airway is a common procedure performed worldwide on a daily basis. As such, it is imperative that clinicians are familiar with the most-effective and efficient methods to perform the procedure. We conducted a systematic review to assist in the development of evidence-based recommendations that pertain to the care of patients with artificial airways. From our systematic review, we developed guidelines and recommendations that addressed questions related to the indications, complications, timing, duration, and methods of artificial airway suctioning. By using a modified version of the RAND/UCLA Appropriateness Method, the following recommendations for suctioning were developed for neonatal, pediatric, and adult patients with an artificial airway: (1) breath sounds, visual secretions in the artificial airway, and a sawtooth pattern on the ventilator waveform are indicators for suctioning pediatric and adult patients, and an acute increase in airway resistance may be an indicator for suctioning in neonates; (2) as-needed only, rather than scheduled, suctioning is sufficient for neonatal and pediatric patients; (3) both closed and open suction systems may be used to safely and effectively remove secretions from the artificial airway of adult patients; (4) preoxygenation should be performed before suctioning in pediatric and adult patients; (5) the use of normal saline solution should generally be avoided during suctioning; (6) during open suctioning, sterile technique should be used; (7) suction catheters should occlude < 70% of the endotracheal tube lumen in neonates and < 50% in pediatric and adult patients, and suction pressure should be kept below -120 mm Hg in neonatal and pediatric patients and -200 mm Hg in adult patients; (8) suction should be applied for a maximum of 15 s per suctioning procedure; (9) deep suctioning should only be used when shallow suctioning is ineffective; (10) routine bronchoscopy for secretion removal is not recommended; and (11) devices used to clear endotracheal tubes may be used when airway resistance is increased due to secretion accumulation.


Blinking suppression in CdSe/ZnS single quantum dots by TiO2 nanoparticles.
The photoluminescence of semiconductor quantum dots and fluorescence of single molecules intermittently turn ON and OFF, a phenomenon referred to as blinking. In quantum dots, blinking occurs as a result of intermittent Auger ionization, which results in the formation of positively charged quantum dots. Due to strong Coulombic interactions, successive photoactivation of a charged quantum dot results in nonradiative carrier recombination, inducing long-lived OFF states in the intensity trajectories. Blinking is an undesirable property with respect to applications of quantum dots toward single-molecule imaging and single-photon logic devices. Here we report significant blinking suppression for CdSe/ZnS single quantum dots in the presence of TiO(2) nanoparticles. In this work, we continuously recorded photoluminescence intensity trajectories of single quantum dots with and without TiO(2) nanoparticles. Interestingly, the intensity trajectory of a single quantum dot that was covalently tethered on a cover glass and dipped in water resulted in near-complete blinking suppression as soon as a TiO(2) nanoparticle solution was introduced. The blinking suppression was associated with a decrease in the photoluminescence intensity but without considerable changes in the photoluminescence lifetime, indicating that nonradiative carrier recombination in quantum dots was channeled into electron transfer to TiO(2) nanoparticles and back electron transfer to quantum dots. On the basis of these experiments and recent reports on photoinduced electron transfer from quantum dots to TiO(2) nanoparticles, we hypothesize that blinking of a quantum dot can be suppressed by increasing the rate of nonradiative regeneration of its neutral state by interfacing with a well-defined charge carrier trap such as an electron acceptor, which accepts an electron during Auger ionization and neutralizes the charged quantum dot by back electron transfer. Correlation between blinking suppression and electron transfer in a quantum dot-TiO(2) nanoparticle system may have important implications, for the preparation of nonblinking quantum dot for incessant and on-demand light emission, donor-acceptor systems for efficient solar energy harvesting, and hybrid semiconductor materials for quantum optical devices.


Temporal Lobe Encephaloceles: A Potentially Curable Cause of Seizures.
Temporal lobe encephaloceles are characterized by protrusion of brain parenchyma through a structural defect in the floor of the middle fossa. They have been reported to cause cerebrospinal fluid (CSF) leaks, conductive hearing loss, meningitis, and seizures. The association between temporal encephaloceles and epileptiform activity is particularly rare. All patients who presented to a single tertiary referral center between 2011 and 2014 with intractable seizures and radiographic evidence of a middle cranial fossa encephalocele were evaluated. Five patients from this subset who underwent surgical repair of their encephalocele are presented. Middle cranial fossa approach for encephalocele repair. Postoperative epileptiform activity. Five patients underwent a craniotomy for resection of a temporal lobe encephalocele with repair of a middle fossa floor defect. After surgery, CSF rhinorrhea resolved, when present, and all patients remained seizure-free through their last available follow-up. Range of follow-up time was 3.5 months to 4 years. Average follow-up time was 19.7 months. Temporal lobe encephaloceles are an infrequent cause of seizures. Given that these lesions can be missed with standard imaging modalities, they are likely underdiagnosed upon initial medical evaluation. This diagnosis should be considered in patients with intractable seizures. If an encephalocele is found, focused resection of epileptogenic tissue associated with herniation and repair of the temporal floor defect can provide definitive treatment.


[The diagnostic value of hysterosalpingography in the diagnosis of tubal disease].
To present an overview of trials and discussion focused on the diagnostic value of hysterosalpingography in the diagnosis of tubal disease. Review article. Sanatorium Pronatal, Prague. Hysterosalpingography may be a screening test for tubal patency. Data demonstrates high specificity of hysterosalpingography for diagnosis of proximal tubal occlusion or hydrosalpinx and low sensitivity in cases with peritubal adhesions. Routine use of diagnostic laparoscopy should be delayed for asymptomatic women. It is expected hysteroscopy and transvaginal hydrolaparoscopy for asymptomatic women may decrease indications for diagnostic laparoscopy with complete visualization of the pelvic cavity.


Role of histone deacetylase expression in intrahepatic cholangiocarcinoma.
Histone deacetylase (HDAC) plays an important role in chromatin remodeling and gene expression, and in regulating cell cycle progression and differentiation. Furthermore, hypoxic conditions in the malignant tumor enhance HDAC function and increased HDAC activity is closely involved in worse malignant behavior through hypoxia inducible factor (HIF) activation. The aim of this study was to elucidate the correlation between HDAC expression and tumor malignant behavior including HIF-1α expression in intrahepatic cholangiocarcinoma (IHCC). Thirty-five patients with IHCC who underwent hepatic resection were evaluated. HDAC1 and HIF-1α expressions were determined immunohistochemically, and the patients were divided into 2 groups: the HDAC1 positive group (n = 21) and the HDAC1 negative group (n = 14). Clinicopathologic variables including HIF-1α expression were compared between the 2 groups. HDAC1 expression correlated significantly with higher stage carcinoma, lymph node metastasis, and vascular invasion. The prognosis in the HDAC1 positive group was poorer than in the HDAC1 negative group (5-year survival: 78% vs 8%, P = .001). Furthermore, disease free survival rate in the HDAC1 positive group had significantly worse than that in the HDAC1 negative group (P = .0003). In the multivariate analysis, HDAC1 positive expression was identified as the only independent prognostic factor for disease free survival (Hazard Ratio: 7.194, P = .0018). Furthermore, there was a significant correlation between HDAC1 expression and HIF-1α expression (P = .007). These findings suggested that HDAC1 positive expression was a potential new prognostic indicator of IHCC, and a possible promising molecular target through the regulation of HIF-1α.


Challenging the "jolly fat" hypothesis among older adults: High body mass index predicts increases in depressive symptoms over a 5-year period.
Several investigators have observed lowered risk of depression among obese older adults, coining the "jolly fat" hypothesis. We examined this hypothesis using baseline and a 5-year follow-up body mass index, depressive symptoms, and covariates from 638 community-based older adults. High objectively measured body mass index and functional limitations predicted increased future depressive symptoms. However, symptoms did not predict future body mass index. Self-reported body mass index showed similar associations despite underestimating obesity prevalence. Results did not differ on the basis of gender. Results for this study, the first longitudinal reciprocal risk analysis between objectively measured body mass index and depressive symptoms among older adults, do not support the "jolly fat" hypothesis.


[Usefulness of arterio-portal shunt in 40% hepatectomized and hepatic artery-occluded model].
We performed an experimental study in dogs with 40% hepatectomy to prove the efficacy and safety of arterio-portal shunt (APS). Forty-two adult mongrel dogs were used for the experiments. After dearterialization of all the collateral arteries to the liver, the dogs were divided into 3 groups. In Group 1, dearterialization of the hepatic artery, 40% hepatectomy and APS were performed; in Group 2, only 40% hepatectomy was performed, and in Group 3, dearterialization of the hepatic artery and 40% hepatectomy were performed. APS was constructed by anastomosing the common hepatic artery with the portal vein. The hepatic hemodynamics, oxygen delivery and consumption were evaluated, and biochemical and histological studies were carried out in each group. The study consisted of a short-term (48-hour; Experiment 1) and a medium-term (4-weeks; Experiment 2) observations. In Experiment 2, liver regeneration was additionally examined. In Experiment 1, Group 1 and Group 2 showed almost the same findings in all the 4 examination points. However, in Group 3, postoperative oxygen delivery and consumption significantly decreased, and biochemical and histological examinations evidenced the significant liver failure. These results show that APS is capable of preventing postoperative liver failure during the short-term observation period and can substitute for reconstruction of the hepatic artery. Experiment 2 was intended for a longer follow-up of Experiment 1. However, Group 3 did not survive longer than 1 week and was thus excluded. In Group 1 and Group 2, findings on the 4 examinations remained alike for p.o. 4 weeks. And, the two groups regained the preoperative liver weight, respectively, at p.o. 4 weeks. The number of PCNA (proliferating cell nuclear antigen)-positive hepatocytes significantly increased at p.o. 1 week in both groups. These findings revealed that regeneration of the liver in Group 1 with APS was equivalent to that in Group 2 with mere hepatectomy for p.o. 4 weeks at least. These results indicate that liver failure can be averted by constructing APS in hepatectomy cases where reconstruction of the hepatic artery is impossible.


Importance of plant- and microbe-driven metabolic pathways for plant defence.
Expression of plant phenotypes can depend on both plant genomes and interactions between plants and the microbes living in, on and near their roots. We understand a growing number of the mechanistic links between plant genotypes and phenotypes, such as defence against herbivory (see brief review in Hubbard et al., ), yet the links between root microbiomes and the comprehensive swathe of plant phenotypes they affect (Friesen et al., ) remain less clear. In this issue of Molecular Ecology, Hubbard et al. () follow microbe- and plant-driven changes in plant defence against hervibory from molecular underpinnings to ecological consequences, contrasting both the metabolites affected and the magnitude of defensive impact. Naively, we might expect plant genomes to drive more variation in phenotype than the root microbiome, but Hubbard et al. () find the opposite, implying profound consequences for plant trait evolution and ecological interactions.


Efficacy of steroid injection on idiopathic sudden sensorineural hearing loss.
To evaluate the effectiveness of transtympanic steroid injection on patients with idiopathic sudden sensorineural hearing loss (ISSNHL) compared with patients who receive oral steroids alone. Retrospective chart review. Patients with a history of ISSNHL and failed oral steroid therapy were included. Audiograms were performed and patients were included if SNHL of more than 20 dB occurred over less than 72 hours. Patients who received transtympanic steroid injection were compared with those who received oral steroids alone. Sixty-one patients met inclusion criteria and were included in the study. The number of patients with improvement in pure tone average in the injection group was 9 (30%) compared with 5 (17%) in the oral group. Twelve (38.7%) of the injected patients did have improvement in speech discrimination scores of greater than 15% compared with only 3 (10%) in the oral steroid group. Our study revealed that patients with ISSNHL who have failed oral steroid therapy obtain better hearing results with transtympanic steroids in comparison to oral steroids. B-3b.


Rumination's effect on suicide ideation through grit and gratitude: A path analysis study.
The current study documents the relationship between suicide ideation, grit and gratitude, and rumination subtypes of brooding and reflection. The relationship between rumination and suicide ideation has been well documented and previous research has demonstrated that grit and gratitude are protective factors against suicide. We hypothesized that both subtypes of rumination would have an indirect effect on suicide ideation through levels of grit and gratitude. Results of a conditional indirect effects path analysis indicated that brooding was indirectly related to suicide ideation through gratitude. Brooding interacted with grit such that it only predicted suicide ideation at low levels of grit. Reflection interacted with gratitude to predict levels of grit. Results suggest that brooding may impact suicide risk and resilience through its effect on gratitude, indicating important cognitive-behavioral targets for suicide prevention strategies. These results extend the literature about the relationship between well known risk factors for suicide and protective factors.


Methylcellulose/agarose hydrogel loaded with short electrospun PLLA/laminin fibers as an injectable scaffold for tissue engineering/3D cell culture model for tumour therapies.
This research aimed at designing and fabricating a smart thermosensitive injectable methylcellulose/agarose hydrogel system loaded with short electrospun bioactive PLLA/laminin fibers as a scaffold for tissue engineering applications or 3D cell culture models. Considering ECM-mimicking morphology and chemical composition, such a scaffold is capable of ensuring a hospitable environment for cell adhesion, proliferation, and differentiation. Its viscoelastic properties are beneficial from the practical perspective of minimally invasive materials that are introduced to the body via injection. Viscosity studies showed the shear-thinning character of MC/AGR hydrogels enabling the potential injection ability of highly viscous materials. Injectability tests showed that by tuning the injection rate, even a high amount of short fibers loaded inside of hydrogel could be efficiently injected into the tissue. Biological studies showed the non-toxic character of composite material with excellent viability, attachment, spreading, and proliferation of fibroblasts and glioma cells. These findings indicate that MC/AGR hydrogel loaded with short PLLA/laminin fibers is a promising biomaterial for both tissue engineering applications and 3D tumor culture models.


Genetic correlations between traits associated with hyperuricemia, gout, and comorbidities.
Hypertension, obesity, chronic kidney disease and type 2 diabetes are comorbidities that have very high prevalence among persons with hyperuricemia (serum urate > 6.8 mg/dL) and gout. Here we use multivariate genetic models to test the hypothesis that the co-association of traits representing hyperuricemia and its comorbidities is genetically based. Using Bayesian whole-genome regression models, we estimated the genetic marker-based variance and the covariance between serum urate, serum creatinine, systolic blood pressure (SBP), blood glucose and body mass index (BMI) from two independent family-based studies: The Framingham Heart Study-FHS and the Hypertension Genetic Epidemiology Network study-HyperGEN. The main genetic findings that replicated in both FHS and HyperGEN, were (1) creatinine was genetically correlated only with urate and (2) BMI was genetically correlated with urate, SBP, and glucose. The environmental covariance among the traits was generally highest for trait pairs involving BMI. The genetic overlap of traits representing the comorbidities of hyperuricemia and gout appears to cluster in two separate axes of genetic covariance. Because creatinine is genetically correlated with urate but not with metabolic traits, this suggests there is one genetic module of shared loci associated with hyperuricemia and chronic kidney disease. Another module of shared loci may account for the association of hyperuricemia and metabolic syndrome. This study provides a clear quantitative genetic basis for the clustering of comorbidities with hyperuricemia.


Estimating chromatographic enantioselectivity (α) from gradient enantioselective chromatography data.
Calculation of chromatographic enantioselectivity (α) is critically important in enantioselective chromatographic method development studies. The fact that α can only be calculated from isocratic elution conditions, whereas gradient elution conditions are predominantly used in method development screening, presents some problems for the use of α as a scoring indicator for automated, intelligent enantioselective chromatography method development systems. In this study, an empirical algorithm was developed to estimate α at isocratic conditions based upon information collected from a gradient elution. The algorithm was validated for SFC applications and has been shown to accurately predict enantioselectivity for a wide variety of racemic test analytes eluted on different chiral column and mobile phase conditions.


[Arthroscopy of the wrist].
Arthroscopy of the wrist has gained popularity among hand and wrist surgeons for diagnosing and treating wrist pathologies. In general, it is a minimally-invasive procedure which can be performed in day care surgery. It has a higher diagnostic accuracy compared to conventional imaging modalities such as CT or MRI. Simultaneous therapeutic intervention can be performed such as ligament repair, fracture reduction, ganglion cyst removal or synovectomy of the wrist. Recent studies have shown better functional outcomes and fewer complications compared to open surgical interventions. Prospective studies are still needed to confirm effectiveness and safety of wrist arthroscopy for several indications. Nonetheless, wrist arthroscopy has shown to be an important asset in the repertoire of the hand and wrist surgeon.


A scanning electronic microscopy study of the action of different desensitizing agents on bovine dentin.
This study sought to use scanning electronic microscopy (SEM) to evaluate the dentinal tubule occlusion potential of different desensitizing agents. Ten slices of bovine dentin were divided into six fragments, cleaned (using ultrasound), and etched for 15 seconds with a 35% phosphoric acid solution. All but one of the groups received a different desensitizing agent; the sixth group served as a control and received no additional treatment. After the agents were applied, the dentin specimens were analyzed by SEM and scores were assigned based on the extent of tubular obliteration. Only three agents demonstrated tubular sealing that was significantly different from that of the control group.


Fumigant toxicity of basil oil compounds and related compounds to Thrips palmi and Orius strigicollis.
This study was aimed at assessing the fumigant toxicity to adult Thrips palmi (a serious insect pest) and Orius strigicollis (a beneficial predator insect) of basil (Ocimum basilicum) essential oil compounds and structurally related compounds using vapour-phase toxicity bioassays. Against adult T. palmi, linalool (LD50 0.0055 mg cm(-3) ) was the most toxic fumigant and was 15.2-fold more effective than dichlorvos (0.0837 mg cm(-3) ). Strong fumigant toxicity was also observed in pulegone (0.0095 mg cm(-3) ), (±)-camphor (0.0097 mg cm(-3) ) and 1,8-cineole (0.0167 mg cm(-3) ). Moderate toxicity was produced by camphene, 3-carene, (-)-menthone, (+)-α-pinene, (+)-β-pinene, α-terpineol and (-)-α-thujone (0.0215-0.0388 mg cm(-3) ). Against adult O. strigicollis, dichlorvos (LD50 9.0 × 10(-10) mg cm(-3) ) was the most toxic fumigant, whereas the LD50 values of these compounds ranged from 0.0127 to >0.23 mg cm(-3) . Based upon the selective toxicity ratio, the compounds described are more selective than dichlorvos. The basil oil compounds described merit further study as potential insecticides for control of T. palmi in greenhouses because of their generally lower toxicity to O. strigicollis and their greater activity as a fumigant than dichlorvos.


[Screening of three straw-cellulose degrading microorganism].
The aim of this study was to screen straw-cellulose degrading microorganisms and to investigate their degradation ability of straw-cellulose. The methods used to screen the high effect straw-cellulose degrading microorganism included the traditional isolation methods of straw-cellulose degrading microorganism such as holes observation method on filter paper sheet, disintegration test of filter paper scrip, hydrolysis spot diameter measurement method of CMC-Na, weight lose assay method of straw, measurement method of cellulose decomposition rate, measurement method of extracellular enzyme activity. We isolated 3 fungi with cellulose degrading ability, of which 98MJ was identified as Penicillium oxalicum, W3 as Trichoderma sp., and W4 as Penicillium expansum. Strain W4 possessed high straw-cellulose degrading ability with straw-cellulose degrading rate of 56.3%, cellulose 59.06%, hemicellulose 78.75% and lignin 33.79% in 10 days. Strain W4 was a cellulase-producing strain with broad development potential.


Association between Hepatitis C Virus Infection, p53 Phenotypes, and Gene Variants of Adenomatous Polyposis Coli in Hepatocellular Carcinomas.
To investigate the clinical value of p53 codon 72 single nucleotide polymorphisms (SNPs) and variants of adenomatous polyposis coli (APC) in hepatocellular carcinomas (HCCs). DNA and RNA from 51 HCCs and their matching, uninvolved liver tissues were analyzed for p53 mutations, and the methylation and expression of APC variants were determined. Proliferation of each HCC was assessed by Ki67 immunohistochemistry. The results were correlated with the demographic and clinicopathologic features and patient survival. Of 51 HCCs, 12% exhibited missense p53 mutations. SNP analysis of p53 codon 72 demonstrated the highest prevalence of the Arg/Arg (56%) phenotype, followed by Arg/Pro (33%) and Pro/Pro (11%). Four of five cases with the Pro/Pro phenotype were African Americans (AAs). All five cases with the Pro/Pro phenotype had hepatitis C virus (HCV) infections, a high Ki67 index, and lower median survival (15.5 months) compared to those with Arg/Arg or Arg/Pro phenotypes (32 months). The overall frequency of APC methylation was 31%, which was found predominantly in Caucasians. There was lower mRNA expression of APC variants-2 and -3 in both HCCs and corresponding adjacent, uninvolved liver tissues as compared to APC variant-1. The expression of APC variant-3, but not variants-1 and -2, was lower in HCCs relative to uninvolved tissues. Expression of all APC variants was lower in HCCs with APC methylation relative to HCCs without APC methylation, and low expression of APC variant-2 was associated with the Pro/Pro phenotype. These findings suggest that, for AA patients with HCCs, the p53 Pro/Pro phenotype and low expression of APC variant-2 are associated with aggressive tumor behavior, HCV infection, and poor clinical outcome.


The Hypoxia-Related Gene COL5A1 Is a Prognostic and Immunological Biomarker for Multiple Human Tumors.
Collagen type V alpha 1 chain (COL5A1) is a hypoxia-related gene (a collagen family protein) and participates in the formation of the extracellular matrix. Although some evidence supports a significant role for COL5A1 in the progression of several cancers, a pan-cancer analysis of COL5A1 is not currently available. Herein, we aimed to assess the prognostic value of COL5A1 in 33 human cancers and to investigate its underlying immunological function. Through multiple bioinformatics methods, we analyzed the data from Oncomine, TCGA, CCLE, HPA, DNMIVD, and cBioPortal database to explore the potential underlying carcinogenic effect of COL5A1, including the relevance of COL5A1 to the outcome, DNA methylation, tumor microenvironment, immune cells infiltration, and drug sensitivity in 33 human cancers. The effects of COL5A1 on glioma cell proliferation, migration, and invasion were verified in cellular experiments. Our findings indicated that COL5A1 was expressed at high levels in 13 cancers and was negatively related to the prognosis of 11 cancers. Additionally, COL5A1 was coexpressed with genes encoding the major histocompatibility complex, immune activators, immune suppressors, chemokines, chemokine receptors, mismatch repair genes, and immune checkpoints. We also identified different roles for COL5A1 in the immunocyte infiltration in different cancers. The correlation between COL5A1 and drug sensitivity was found in several cancers. COL5A1 potentially influenced the tumor progression through immune-related pathways, negative regulation of immune system processes, chemokine signaling pathways, JAK-STAT pathways, T cell receptor pathways, lymphocyte migration, and antigen processing and presentation, among other processes. Based on our study, COL5A1 may be employed as a prognostic marker in different malignancies because of its impact on tumorigenesis and immune cell infiltration and have implications for cancer immune checkpoint inhibitors and chemotherapy.


Validation of the digital photographic assessment to diagnose traumatic dental injuries.
Alternatives for monitoring dental trauma in epidemiological surveys may be useful, as data collection of epidemiological investigation can be jeopardized due to several conditions. To investigate the validity of standard digital photographs to determine the occurrence of anterior dental trauma compared to the clinical examination in an epidemiological survey. Participants were children aged 8-12 years old attending both private and public schools; children were clinically evaluated for the assessment of dental trauma, and standard photographs were taken from maxillary and mandibular permanent incisors of each child. Validity was determined by calculating the percentages and respective 95% confidence interval of sensitivity, specificity, positive predictive value, and negative predictive value. Cohen's kappa statistic was also used. A total of 412 children were included, totaling 3296 teeth assessed for dental trauma presence. The prevalence of dental trauma was 11.2% (95% CI 8.29-14.61) and 10.2% (95% CI 7.45-13.53), respectively, for the clinical examination and the photographic method. Agreement between the gold standard and the photographic diagnosis was good: 0.64 for the prevalence of dental trauma and 0.66 for diagnosis of dental trauma on a tooth basis. The diagnosis through the photographic method had higher specificity (96.7%) than sensitivity (65.2%). High positive likelihood ratio and low negative likelihood ratio were also observed. The photographic assessment method of dental trauma was valid and reliable as compared to the oral clinical examination.


[Fetal risks related to the administration of anti-arrhythmia drugs during pregnancy].
The major concern about the administration of antiarrhythmic drugs during pregnancy is related to their effect on fetal well-being. Even if teratogenic risks are higher during organogenesis in the first 8 weeks of pregnancy, after this period undesirable effects may include depression of uterine blood flow, interference with fetal growth and development, and interference with labor and delivery. Most drugs are secreted in the mother's milk, a fact that raises concern about the nursing infants. In this report we review the fetal risks related to the management of maternal arrhythmias during pregnancy showing that most patients can be treated with an excellent result for their babies.


Membrane raft domains and remodeling in aging brain.
Lipids are the fundamental structural components of biological membranes. For a long time considered as simple barriers segregating aqueous compartments, membranes are now viewed as dynamic interfaces providing a molecular environment favorable to the activity of membrane-associated proteins. Interestingly, variations in membrane lipid composition, whether quantitative or qualitative, play a crucial role in regulation of membrane protein functionalities. Indeed, a variety of alterations in brain lipid composition have been associated with the processes of normal and pathological aging. Although not establishing a direct cause-and-effect relationship between these complex modifications in cerebral membranes and the process of cognitive decline, evidence shows that alterations in membrane lipid composition affect important physicochemical properties notably impacting the lateral organization of membranes, and thus microdomains. It has been suggested that preservation of microdomain functionality may represent an effective strategy for preventing or decelerating neuronal dysfunction and cerebral vulnerability, processes that are both aggravated by aging. The working hypothesis developed in this review proposes that preservation of membrane organization, for example, through nutritional supplementation of docosahexaenoic acid, could prevent disturbances in and preserve effective cerebral function.


Construction of iridium and rhodium cyclometalated macrocycles based on p-carborane and N,N'-donor bridging ligands.
Six tetranuclear half-sandwich iridium and rhodium complexes bridged by neutral N,N'-donor pyridyl-imine ligands and 1,12-dicarbadodecaborane(12)-1,12-dicarboxylate (p-CDC) were controllably synthesized and fully characterized. The results revealed that the precursors, binuclear complexes [(Cp*M)2{1,4-bis(2-pyridylmethyleneamino)benzene}Cl2][OTf]2 (Cp* = η(5)-pentamethylcyclopentadienyl, M = Ir (2a), Rh (2b)), have different preferential configurations, and tetranuclear complexes [(Cp*M)4{1,4-bis(2-pyridylmethyleneamino)benzene}2(p-CDC)2][OTf]4 (M = Ir (3a), Rh (3b)), which were prepared using monodentate p-carborane dicarboxylate and 2a or 2b, showed highly twisted backbones. Likewise, homologous regular rectangular compounds [(Cp*M)4{1,4-{(2-C5H4N)HC=N}2-2,3,5,6-Me4C6}2(p-CDC)2][OTf]4 (M = Ir (4a), Rh (4b)) and [(Cp*M)4{1,4-{(2-C5H4N)HC=N}2-1,5-naphthalene}2(p-CDC)2][OTf]4 (M = Ir (5a), Rh (5b)) were obtained following a similar synthetic route. X-ray determination confirmed that 4b and 5b have stacking channels as well.


A Context-Aware Accurate Wellness Determination (CAAWD) Model for Elderly People Using Lazy Associative Classification.
Wireless Sensor Network (WSN) based smart homes are proving to be an ideal candidate to provide better healthcare facilities to elderly people in their living areas. Several currently proposed techniques have implementation and usage complexities (such as wearable devices and the charging of these devices) which make these proposed techniques less acceptable for elderly people, while the behavioral analysis based on visual techniques lacks privacy. In this paper, a context-aware accurate wellness determination (CAAWD) model for elderly people is presented, where behavior monitoring information is extracted by using simple sensor nodes attached to household objects and appliances for the analysis of daily, frequent behavior patterns of elderly people in a simple and non-obtrusive manner. A contextual data extraction algorithm (CDEA) is proposed for the generation of contextually comprehensive behavior-training instances for accurate wellness classification. The CDEA presents an activity's spatial-temporal information along with behavioral contextual correlation aspects (such as the object/appliance of usage and sub-activities of an activity) which are vital for accurate wellness analysis and determination. As a result, the classifier is trained in a more logical manner in the context of behavior parameters which are more relevant for wellness determination. The frequent behavioral patterns are classified using the lazy associative classifier (LAC) for wellness determination. The associative nature of LAC helps to integrate spatial-temporal and related contextual attributes (provided by CDEA) of elderly behavior to generate behavior-focused classification rules. Similarly, LAC provides high accuracy with less training time of the classifier, includes minimum-support behavior patterns, and selects highly accurate classification rules for the classification of a test instance. CAAWD further introduces the ability to contextually validate the authenticity of the already classified instance by taking behavioral contextual information (of the elderly person) from the caregiver. Due to the consideration of spatial-temporal behavior contextual attributes, the use of an efficient classifier, and the ability to contextually validate the classified instances, it has been observed that the CAAWD model out-performs currently proposed techniques in terms of accuracy, precision, and f-measure.


Effect of probiotics on pro-inflammatory cytokines and NF-kappaB activation in ulcerative colitis.
To demonstrate the therapeutic effect of probiotics in patients with ulcerative colitis (UC), and their effect on inflammatory mediators and nuclear factor (NF)-kappaB activation in these patients. Thirty patients with mild to moderate UC were randomly classified into two groups: sulfasalazine group, who received sulfasalazine 2400 mg/d; and probiotic group, who received sulfasalazine 2400 mg/d with probiotic. The patients were investigated before and after 8 wk of treatment with probiotic (Lactobacillus delbruekii and Lactobacillus fermentum). Colonic activity of myeloperoxidase (MPO) was assayed with UV spectrophotometry, the colonic content of interleukin (IL)-6 was determined by enzyme-linked immunosorbent assay (ELISA), fecal calprotectin was determined by ELISA, and expression of NF-kappaB p65 and tumor necrosis factor (TNF)-alpha proteins in colonic tissue was identified by immunohistochemistry and reverse transcription polymerase chain reaction, respectively. At the start of the study, colonic mucosal injury and inflammation were demonstrated in UC patients by hematoxylin and eosin staining, and an increase in colonic MPO activity, fecal calprotectin, and expression of colonic TNF-alpha and NF-kappaB p65 proteins. The use of probiotic for 8 wk significantly ameliorated the inflammation by decreasing the colonic concentration of IL-6, expression of TNF-alpha and NF-kappaB p65, leukocyte recruitment, as demonstrated by a decrease in colonic MPO activity, and the level of fecal calprotectin compared to sulfasalazine group and the control group (P < 0.05). Oral supplementation with probiotics could be helpful in maintaining remission and preventing relapse of UC.


Parental attitudes towards and perceptions of their children's participation in clinical research: a developing-country perspective.
Paediatric clinical research faces unique challenges that compromise optimal recruitment of children into clinical trials. A main barrier to enrolment of children is parental misconceptions about the research process. In developing countries, there is a knowledge gap regarding parental perceptions of and attitudes towards their children's participation in clinical trials. To explore such perceptions and attitudes in Lebanese parents. 33 in-depth interviews were conducted with parents with and without previous research experience. Interviews were tape-recorded, transcribed in colloquial Arabic, and later subjected to thematic analysis. Benefit/risk ratio assessment was a major determinant of parental consent. Fear of adverse events or painful procedures in research was a recurring theme in most interviews. Whereas perception of direct benefit to the child, trust in the physician or institution, financial gains or having a positive previous experience in research facilitated consent, a complex informed consent form and misunderstanding of the term 'randomisation' hindered parental approval of participation. Lebanese parents have perceptions of and attitudes towards children's participation in clinical trials that are similar to those reported from the industrialised world. Improving communication with parents and building trust between researchers and parents is important for successful recruitment. Investigators planning to conduct paediatric trials in developing countries need to simplify consent forms and devise new ways to explain randomisation.


Cancer and non-cancer health risk assessment of occupational exposure to 1,3-butadiene in a petrochemical plant in Iran.
1,3-Butadiene is classified as carcinogenic to humans by inhalation. This study aimed to assess cancer and non-cancer risk following occupational exposure to 1,3-butadiene. This cross-sectional study was conducted in a petrochemical plant producing acrylonitrile butadiene styrene copolymer in Iran. Occupational exposure to 1,3-butadiene was measured according to the National Institute for Occupational Safety and Health 1024 method. Cancer and non-cancer risk assessment were performed according to the United States Environmental Protection Agency method. The average occupational exposure to 1,3-butadiene during work shifts among all participants was 560.82 ± 811.36 µg m-3. The average lifetime cancer risk (LCR) in the present study was 2.71 × 10-3; 82.2% of all exposed workers were within the definite carcinogenic risk level. Also, the mean non-cancer risk (hazard quotient (HQ)) among all participants was 10.82 ± 14.76. The highest LCR and HQ were observed in the safety and fire-fighting station workers with values of 7.75 × 10-3 and 36.57, respectively. The findings revealed that values of carcinogenic and noncarcinogenic risk in the majority of participants were within the definitive and unacceptable risk levels. Therefore, corrective measures are necessary to protect these workers from non-cancer and cancer risks from 1,3-butadiene exposure.


Antioxidant Activity of Lawsonia inermis Extracts Inhibits Chromium(VI)-Induced Cellular and DNA Toxicity.
Hexavalent chromium Cr(VI) is a very strong oxidant which consequently causes high cytotoxicity through oxidative stress. Prevention of Cr(VI)-induced cellular damage has been sought in this study in aqueous and methanolic extracts of Lawsonia inermis Linn. (Lythraceae), commonly known as Henna. The extracts showed significant (P < .05) potential in scavenging free radicals (DPPH(•) and ABTS(•+)) and Fe(3+), and in inhibiting lipid peroxidation. DNA damage caused by exposure of pBR322 to Cr(VI)-UV is markedly inhibited by both extracts in varying degrees. A distinct decline in Cr(VI)-induced cytotoxicity was noticed in MDA-MB-435S (human breast carcinoma) cells with an increase in dosage of both extracts individually. Furthermore, both extracts proved to contain a high content of phenolic compounds which were found to have a strong and significant (P < .05) positive correlation to the radical scavenging potential, lipid peroxidation inhibition capacity and cyto-protective efficiency against Cr(VI)-induced oxidative cellular damage. HPLC analysis identified some of the major phenolic compounds in both extracts, which might be responsible for the antioxidant potential and the properties of DNA and cyto-protection. This study contributes to the search for natural resources that might yield potent therapeutic drugs against Cr(VI)-induced oxidative cell damage.


Segregation distortion of isozyme loci in cherimoya (Annona cherimola Mill).
The allelic segregation of 13 isozyme loci in hand-fertilized heterozygous cherimoya trees (Annona cherimola Mill.) has been studied. We analyzed 63 locus x progeny combinations and found non-Mendelian segregation in 12 cases. The sequential Bonferroni method revealed only eight cases of non-Mendelian segregation; these have been investigated with several chi-square tests to discover what processes were involved. Gametic selection appears to be the main contributor, although zygotic selection seems also to play a part.


Internal carotid artery reconstruction using multiple fenestrated clips for complete occlusion of large paraclinoid aneurysms.
Although surgical techniques for clipping paraclinoid aneurysms have evolved significantly in recent times, direct microsurgical clipping of large and giant paraclinoid aneurysms remains a formidable surgical challenge. We review here our surgical experiences in direct surgical clipping of large and giant paraclinoid aneurysms, especially in dealing with anterior clinoidectomy, distal dural ring resection, optic canal unroofing, clipping techniques, and surgical complications. Between September 2001 and February 2012, we directly obliterated ten large and giant paraclinoid aneurysms. In all cases, tailored orbito-zygomatic craniotomies with extradural and/or intradural clinoidectomy were performed. The efficacy of surgical clipping was evaluated with postoperative digital subtraction angiography and computed tomographic angiography. Of the ten cases reported, five each were of ruptured and unruptured aneurysms. Five aneurysms occurred in the carotid cave, two in the superior hypophyseal artery, two in the intracavernous, and one in the posterior wall. The mean diameter of the aneurysms sac was 18.8 mm in the greatest dimension. All large and giant paraclinoid aneurysms were obliterated with direct neck clipping without bypass. With the exception of the one intracavenous aneurysm, all large and giant paraclinoid aneurysms were occluded completely. The key features of successful surgical clipping of large and giant paraclinoid aneurysms include enhancing exposure of proximal neck of aneurysms, establishing proximal control, and completely obliterating aneurysms with minimal manipulation of the optic nerve. Our results suggest that internal carotid artery reconstruction using multiple fenestrated clips without bypass may potentially achieve complete occlusion of large paraclinoid aneurysms.


Left ventricular global longitudinal strain in acute myocardial infarction--with special reference to neurohormonal activation, in-hospital heart failure and prognosis.
Systolic dysfunction, clinical heart failure and elevated levels of neurohormonal peptides are major predictors of adverse outcome after acute myocardial infarction (MI). In the present thesis we evaluated global longitudinal strain (GLS) in patients with acute MI in relation to neurohormonal activation, in-hospital heart failure and prognosis with specific attention to the group of patients with preserved LVEF that currently do not meet the criteria for anti remodeling therapies. GLS was found to be significantly associated with neurohormonal activation as assessed by NT-proBNP levels and that this association was present also in patients with preserved LVEF. Patients with clinical HF during hospitalization for acute MI had significantly poorer GLS compared to controls and this relationship was robust when adjusting for known factors associated with elevated LV filling pressure such as left atrial volume and E/e' ratio. Furthermore, measurement of GLS attenuated the value of NT-proBNP in relation to in-hospital HF in patients with preserved LVEF. Finally, GLS was related to outcome in the largest ever echocardiographic deformation study of patients with acute MI and relatively preserved LVEF. We found that GLS predicted mortality and heart failure admissions and that the effect on mortality was driven by a significantly increased risk of cardiac death in patients with impaired GLS. In conclusion, the results of this thesis demonstrate that GLS as a measure of LV systolic function is significantly related to elevated neurohormonal activation, early hemodynamic deterioration and predict adverse outcome in a low risk population without indications for anti remodeling therapies. Early measurement of GLS in this population could be used as a risk stratification tool for added monitoring and clinical trials.


Prognostic comparison of the proliferation markers (mitotic activity index, phosphohistone H3, Ki67), steroid receptors, HER2, high molecular weight cytokeratins and classical prognostic factors in T₁₋₂N₀M₀ breast cancer.
The proliferation factors: mitotic activity index (MAI), phosphohistone H3 (PPH3) and Ki67 have strong prognostic value in early breast cancer but their independent value to each other and other prognostic factors has not been evaluated. In 237 T₁₋₂N₀M₀ breast cancers without systemic adjuvant treatment, formalized MAI assessment and strictly standardized, fully automated quantitative immunohistochemistry (IHC) for Ki67, PPH3, estrogen (ER) and progesterone receptor (PR), HER2, cytokeratins-5/6 and -14, and automated digital image analysis (DIA) for measuring PPH3 and Ki67 were performed. Section thickness was measured to further control IHC measurements. All features were measured in the periphery of tumors. The different proliferation assessments and other well-established clinicopathological and biomarker prognostic factors were compared. DIA-Ki67 added prognostically to PPH3. None of the other biomarkers or clinicopathological variables added prognostically to this PPH3/Ki67 combination. However, when PPH3 is replaced by MAI the prognostic value is nearly the same. In early operable node negative breast cancer without adjuvant systemic treatment, Ki67 with a threshold of 6.5% assessed by digital image analysis in the periphery of the tumor is prognostically strong. The combination of either PPH3/Ki67 or MAI/Ki67 overshadowed the prognostic value of all other features including Ki67 alone.


A New Multiple Hypothesis Tracker Using Validation Gate with Motion Direction Constraint.
In multi-target tracking scenarios with dense and heterogeneous clutter, there is a substantial increase in the false measurements that originated from the clutter within the validation gate, and consequently, the number of measurement-to-track association hypothesis grows rapidly in traditional multiple hypothesis tracker (MHT), leading to a sharp decrease in data association accuracy and tracking performance. A new multiple hypothesis tracker using validation gate with motion direction constraint (MHT-MDC) is proposed to solve these problems. In the MHT-MDC, a motion direction constraint (MDC) gate is designed by considering the prior target maneuvering information, which effectively reduces the volume of validation gate and, thus, diminishes the number of false measurements in the gate when the innovation covariance is large. Subsequently, the clutter density in the MDC gate is adaptively estimated by the conditional mean estimator of clutter density (CMECD), based on which the score functions in the MDC gate can be calculated. The MHT-MDC is compared with the MHT algorithm in simulations, and the experimental results demonstrate its superior tracking performance for weakly maneuvering targets in high clutter density scenarios.


Hepatocyte growth factor upregulates alpha2beta1 integrin in Madin-Darby canine kidney cells: implications in tubulogenesis.
It has been well established that hepatocyte growth factor (HGF) induces branching tubule formation of Madin-Darby canine kidney (MDCK) cells cultured in collagen gel. Tubulogenesis per se requires the involvement of cell proliferation, migration, focalization proteolysis, cell-cell interaction and differentiation. However, signaling pathways and proteins involved in HGF-induced tubulogenesis by MDCK cells have not been thoroughly studied. Because cell-matrix interactions play important roles in tubulogenesis, we analyzed whether HGF altered the expression of extracellular matrix receptor (alpha2, alpha3, beta1 and alphavbeta3 integrin). We found that among those proteins examined, alpha2beta1 integrin levels were enhanced by HGF. HGF-induced upregulation of alpha2beta1 integrin was mediated via upregulation of alpha2 integrin mRNA abundance. Cycloheximide blocked the HGF-induced increase in alpha2 integrin mRNA expression. To understand the signaling pathways leading to an HGF-induced increase in alpha2beta1 integrin levels, PD98059 (MEK1 inhibitor), LY294002 (PI3-kinase inhibitor), and GF109203X (PKC inhibitor) were used. We found that PD98059 blocked the HGF-induced increase in alpha2beta1 integrin expression. Furthermore, 5E8 (specific anti-alpha2beta1 integrin antibody) was employed to elucidate the potential role of HGF-induced upregulation of alpha2beta1 integrin in branching morphogenesis. 5E8 did not alter HGF-induced scattering effects but disrupted HGF-induced branching tubulogenesis in collagen gel via inhibition of cell-cell interactions and growth. Taken together, HGF upregulates alpha2beta1 integrin expression via an indirect pathway, the results of which contribute to the regulation of cell-cell interactions and cell growth during branching morphogenesis in collagen gel.


Response to Ibrutinib of a Refractory IgA Lymphoplasmacytic Lymphoma Carrying the MYD88 L265P Gene Mutation.
In 2014 a 66-year-old woman presented with anemia and an IgAk monoclonal spike. Bone marrow (BM) biopsy showed 80% lymphocytes and lymphoplasmacytoid cells. Computed Tomography (CT) scan documented neither adenopathy nor splenomegaly. Diagnosis of IgA lymphoplasmacytic lymphoma was made. After three lines of treatment, progressive disease with adenopathies, splenomegaly, and ascites were documented on a CT scan. Our patient developed thrombocytopenia, transfusion-dependent anemia, and clinical deterioration. We performed genetic studies of peripheral blood lymphocytes with the NGS approach. Given the identification of MYD88 L265P mutation, in February 2018 our patient started ibrutinib off-label. Hb and PLT improved from day +35. In July 2018 no ascites and 50% reduction of adenopathies and spleen were shown on a CT scan. In April 2019 the patient was still on ibrutinib with transfusion independence and good performance status.


[Automated analyzer of enzyme immunoassay].
Automated analyzers for enzyme immunoassay can be classified by several points of view: the kind of labeled antibodies or enzymes, detection methods, the number of tests per unit time, analytical time and speed per run. In practice, it is important for us consider the several points such as detection limits, the number of tests per unit time, analytical range, and precision. Most of the automated analyzers on the market can randomly access and measure samples. I will describe the recent advance of automated analyzers reviewing their labeling antibodies and enzymes, the detection methods, the number of test per unit time and analytical time and speed per test.


Evaluation of an in-house cat scratch disease IgM ELISA to detect Bartonella henselae in a routine laboratory setting.
Cat scratch disease (CSD) is caused by Bartonella henselae infection and is a common cause of regional lymphadenopathy. The diagnosis of CSD largely depends on serology, but detection of B. henselae in an affected lymph node by PCR is also an important diagnostic tool. We evaluated an IgM in-house ELISA protocol and analyzed its performance in routine CSD serology. Serum samples from PCR-positive patients (n = 126), PCR-negative patients (n = 123), and age-matched controls (n = 126) were used for evaluation. The sensitivity of the IgM ELISA was only 56%, showing that the performance of B. henselae serology under routine laboratory settings is low, probably caused by the wide variability in disease duration in patients suspected of CSD whose samples were submitted to our laboratory. Most patients (46%) with a positive IgM response were between 0 and 20 years of age. We conclude that the serodiagnosis of B. henselae is hampered by the low sensitivity and specificity of the assays when used in a routine laboratory setting. For this reason, a negative IgM or PCR result can never exclude CSD, especially with late sample collection.


The effect of short-duration, high-intensity electromagnetic pulses on fresh ulnar fractures in rats.
Pulsed electromagnetic fields (PEMFs) have been found to be beneficial to a wide variety of biological phenomena. In particular, PEMFs have been shown to be useful in the promotion of healing of ununited fractures. Conflicting information exists regarding the benefit of using PEMFs to accelerate the healing of fresh fractures. This paper reports on the evaluation of the effect of a new PEMF generator (PAP IMI) on the healing of fresh ulnar fractures in rats. This device is unique by virtue of the extremely high power output of each of the pulses it generates. Ulnar fractures were created in rats by using a bone cutter, thus producing a 2-3 mm bone defect. Rats were then randomly divided into treatment and control groups. The treatment group underwent periodic treatments with the PAP IMI, and the control group received no treatment. Radiographs of rats from both groups were taken at 1-week intervals. Histological evaluation was performed at the end of the study. Radiographic and histopathological evaluations were scored, and scores were used to assess both rate and quality of healing. The radiographic results demonstrated gradual bridging callus formation in both control and treatment groups, however, the healing process was faster in rats that were not treated by PEMF. Histological evaluation demonstrated that the fibrous content of the callus in rats belonging to the treatment group was significantly higher than that in rats belonging to the control group. The results of this study do not support the claim that PEMF generated by the PAP-IMI stimulate osteogenesis and bone healing after the creation of fresh ulnar fractures in rats.


Increase in Central Retinal Edema after Subthreshold Diode Micropulse Laser Treatment of Chronic Central Serous Chorioretinopathy.
Purpose. Subthreshold diode micropulse laser (SDM) treatment is believed to be safe method of treating clinical entities involving retinal edema. We present a case of serous edematous reaction of the retina to SDM treatment. Methods. Results. A patient with chronic central serous chorioretinopathy (CSCR) was treated with SDM Yellow multispot laser. Procedure had been preceded by careful titration of the laser power, which after achieving of the threshold parameter was decreased by 50%. The follow-up visit two days after treatment revealed significant central retinal edema and subretinal fluid. Fundus autofluorescence image showed thermal reaction from the RPE in the form of small spots of hyperfluorescence corresponding to the laser multispot pattern used for treatment. Retinal edema resolved after topical bromfenac and single intravitreal bevacizumab injection. Slight pigmentary reaction from the RPE persisted. Conclusion. In the treatment of CSCR, there is a need to significantly reduce threshold SDM power parameters or simply use very low power without titration.


[Totally endocardial surgical ablation of atrial fibrillation combined with mitral valve surgery. Our experience with the Cardioablate pen].
Atrial fibrillation (AF) is the most common arrhythmia found in mitral valve (MV) disease, occurring in 30 to 85% of patients. Since 1999, AF has been ablated using monopolar epicardial-endocardial radiofrequency. In this study, we describe our own endocardial experience of using the Cardioablate monopolar radiofrequency irrigated pen for the ablation of AF in patients undergoing MV surgery and an analysis of the short and mid-term results. From August 2002 to February 2004, a monopolar radiofrequency pen was used to ablate AF in 29 patients undergoing MV replacement or repair (24 females, 82.7%). Preoperative AF was paroxysmal in 27.6% of the patients, persistent in 13.8%, and permanent in 58.6%. The mean left atrial diameter was 65.8 +/- 11.4 mm (range 40-92 mm). In all the patients the ablation lines were created under conditions of extracorporeal circulation and aortic cross-clamping and carried out according to the Alfieri's set. The left atrial appendage was resected or excluded. Endocardial ablation increased the duration of the operation by a mean time of 14.8 +/- 2.7 min with an average time of 7.3 +/- 1.4 min for radiofrequency application. All patients left the operating room with ginus rhythm (SR) or with atrioventricular pacing. Perioperative AF was common, affecting 51.7% of patients. Six patients required electrical cardioversion. Both early postoperative death (2 patients, 6.8%) and complications were not procedure-related. At discharge, all patients were in SR. The mean follow-up was 14.8 +/- 5.2 months (range 7-25 months). Only 3 patients (11.1%) lost SR within the first 6 months of follow-up but it was recovered in all cases through the use of electrical cardioversion (2 patients) or antiarrhythmic drugs. The totally endocardial monopolar radiofrequency pen facilitates a quick and safe AF ablation in patients with MV disease. Its only theoric limitation concerns the transmurality of the lesions. Perioperative AF is common and should be treated aggressively. By 6 months postoperatively, 100% of patients are free of AF or atrial flutter with recovery of normal atrial contraction. More patients and longer follow-up are necessary to document the long-term results of this simple procedure.


Observations on structural features and characteristics of biological apatite crystals. 6. Observation on lattice imperfection of human tooth and bone crystals. I.
In a series of studies to investigate the basic structural features and characteristics of the biological apatite crystals, using an electron microscope, we examined the ultrastructure of the human enamel, dentin, and bone crystals at near atomic resolution and showed the configuration of the hydroxyapatite structure through the cross and longitudinal sections of the crystals. Subsequently, based on the results of the observations by the authors of the ultrastructure of the tooth and bone, using the same approach, we have been able to directly examine the images of the lattice imperfections in the human enamel, dentin, and bone crystals, such as the point defect structures and dislocations in the crystals. In this report, we describe the image of the point defect structures and line defect structures obtained, using the same approach from the sections of the human enamel, dentin, and bone crystals. The materials used for this study were the noncarious enamel and dentin from the freshly extracted human erupted lower first molars, and bone tissue obtained from the alveolar compact bone. The small cubes of the material were fixed in glutaraldehyde and osmium tetroxide and embedded in epoxy resin using the routine methods. The ultrathin sections were cut with a diamond knife without decalcification. The sections were examined with the HITACHI H-800 H and H-9000 types of transmission electron microscopes operated at 200 kV and 300 kV. Each crystal was observed at the initial magnification of 300,000-500,000 times and at the final magnification of 10,000,000 times and over. We sincerely believe that the electron micrographs shown in this report are the first to show the images of the lattice imperfections in the human enamel, dentin, and bone crystals, such as the point defect and line defect structures, at near atomic resolution.


Phylogenetic Analysis and Epidemic History of Hepatitis C Virus Genotype 2 in Tunisia, North Africa.
HCV genotype 2 (HCV-2) has a worldwide distribution with prevalence rates that vary from country to country. High genetic diversity and long-term endemicity were suggested in West African countries. A global dispersal of HCV-2 would have occurred during the 20th century, especially in European countries. In Tunisia, genotype 2 was the second prevalent genotype after genotype 1 and most isolates belong to subtypes 2c and 2k. In this study, phylogenetic analyses based on the NS5B genomic sequences of 113 Tunisian HCV isolates from subtypes 2c and 2k were carried out. A Bayesian coalescent-based framework was used to estimate the origin and the spread of these subtypes circulating in Tunisia. Phylogenetic analyses of HCV-2c sequences suggest the absence of country-specific or time-specific variants. In contrast, the phylogenetic grouping of HCV-2k sequences shows the existence of two major genetic clusters that may represent two distinct circulating variants. Coalescent analysis indicated a most recent common ancestor (tMRCA) of Tunisian HCV-2c around 1886 (1869-1902) before the introduction of HCV-2k in 1901 (1867-1931). Our findings suggest that the introduction of HCV-2c in Tunisia is possibly a result of population movements between Tunisia and European population following the French colonization.


The Flavor of Dairy Products from Grass-Fed Cows.
The milks used for manufacturing bovine dairy products are not all equal. The feeding regimen of lactating cows can widely vary, giving rise to remarkable compositional differences. Recently, grass-fed/based milk and transformed products are being taken into great consideration due to their more favorable nutritional characteristics and better sustainability over those from intensive systems. Besides these well-established aspects, the existence of differences in flavor is highly debated. The "cheese story tellers" consider it as a proven fact and tend to directly link the aroma of grass-based dairy products to the plants the animals ate. Unfortunately, this claim is not yet supported by scientific data. Actually, there is sufficient evidence of the presence of a distinctive aroma in milk from grass-fed cows, but the connection with specific aroma-active compounds is still in progress. In addition to this, the role of some compounds deriving from cow's metabolism seems to be much more important than that of other compounds that directly derive from feed. The situation in transformed products, in particular cheese, is even more complicated due to the overlapping of flavor compounds originating from technological operations, microbial metabolism and enzyme activities during storage or ripening. Further work is still needed to answer the question, but the increasing application of a flavoromics approach to the studies should rapidly bring about a decisive contribution to the knowledge.


Medicare and Medicaid programs; organ procurement organizations and organ procurement protocols--HCFA. Final rule.
This rule sets forth the following: A requirement for hospitals to have, as a condition of participation in the Medicare and Medicaid programs, written protocols to identify potential organ donors; Requirements for participation in the Medicare and Medicaid programs for hospitals that perform organ transplants; and Requirements that an organ procurement organization must meet to be designated by Medicare for payment and to remain so designated. The rule implements section 1138 of the Social Security Act, as added by section 9318(a) of the Omnibus Budget Reconciliation Act of 1986 and as the effective date was modified by section 102(c) of the Balanced Budget and Emergency Deficit Control Reaffirmation Act of 1987 and section 4009(g) of the Omnibus Budget Reconciliation Act of 1987. This rule is intended to enhance the organ procurement process.


Evaluation of different cochlear implants in unilateral hearing patients during word listening tasks: A brain connectivity study.
Advanced methodologies used for the biomedical signal interpretation allow using cerebral signals to assess important cognitive functions in humans. In the present study, as parameter of cerebral effort, has been employed the isolated effective coherence, in order to estimate the effective connectivity and network organization. The hypothesis was that the lower the number of inter-connections engaged, the lower the cerebral effort induced by the experimental condition. In the present research this index has been applied to test the reaction to the use of different cochlear implant processors (Freedom, CP810 and CP910 - Cochlear Ltd), with the aim to identify the most performing device during a word in noise recognition task. Results support the capability of identifying the device eliciting less brain area connections. In particular, the CP910 was the processor inducing the lower number of inter-connections among the tested ones. This investigation appeared to be worthy, since representing a tool to identify devices that would make available user's cognitive resources for additional tasks, a matter susceptible of generalization to various fields of application. The employment of the cerebral signals therefore open the way to the evaluation of the impact of different sensors and prosthetic devices, also using connectivity measures.


Biocontrol of Phyllosticta citricarpa by Bacillus spp.: biological and chemical aspects of the microbial interaction.
Citrus fruits are the most produced fruits in the world, but they are threatened by several pathogens, including the fungus Phyllosticta citricarpa, the causal agent of citrus black spot (CBS). The fungus affects most citrus species and the infection results in economic losses in citrus-producing areas. This disease causes the aesthetic depreciation of fresh fruit, impairing its commercialization. As an alternative to the use of synthetic fungicides to control the pathogen, the biological control, using bacteria of the genus Bacillus, is highlighted. Such microorganisms enable biocontrol by the production of volatile organic compounds (VOC) or non-volatile. Therefore, this work aimed to evaluate the production of VOC by isolates of Bacillus spp. grown in different culture media; to evaluate the effects of these compounds on the evolution of CBS lesions in orange fruits; to study the effects of VOC on resistance induction in orange fruits; to evaluate the effects of VOC on P. citricarpa morphology in CBS lesions, and to identify the produced VOC. Tryptone soya agar (TSA) and tryptone soya broth (TSB) media used to culture the bacterium resulted in up to 73% pathogen inhibition by VOC. Volatile compounds from Bacillus spp. ACB-65 and Bacillus spp. ACB-73 when cultured in TSB culture medium provided 86% inhibition of freckles that evolved to hard spots. The volatile fractions produced by the bacteria were identified as alcohols, ketones, amines, ethers, aldehydes and carboxylic acids that can serve as arsenal against the phytopathogen. The present work demonstrated the potential of VOC produced by Bacillus spp. in the control of P. citricarpa.


Two-photon chloride imaging in neurons of brain slices.
Two-photon laser scanning microscopy has been used successfully for imaging activity-dependent changes of intracellular calcium and sodium levels. Here we introduce a simple technique for two-photon chloride imaging in intact neurons. It involves the use of the membrane-permeable Cl(-) indicator dye MQAE [N-(6-methoxyquinolyl) acetoethyl ester]. Brief incubation with MQAE produced a robust loading of cells in slices from various brain regions including hippocampus, cortex and cerebellum. In contrast to conventional fluorescence measurements using MQAE, two-photon imaging was not affected in a major way by dye bleaching and phototoxic damage. Instead, it allowed prolonged recordings of time-resolved changes in intracellular chloride concentration in somata and dendrites. As an example of an application we imaged GABA-mediated Cl(-) transients in pyramidal cells of cortical and hippocampal slices as well as in cerebellar Purkinje neurons. By combining Cl(-) imaging with the gramicidin-based perforated-patch-clamp technique we showed that changes in MQAE fluorescence are proportional to the magnitudes of GABA-evoked transmembrane Cl(-) fluxes. Thus, MQAE-based two-photon microscopy promises to be a valuable technique for many applications requiring chloride imaging in single cells.


Cell membrane-anchored MUC4 promotes tumorigenicity in epithelial carcinomas.
The cell surface membrane-bound mucin protein MUC4 promotes tumorigenicity, aggressive behavior, and poor outcomes in various types of epithelial carcinomas, including pancreatic, breast, colon, ovarian, and prostate cancer. This review summarizes the theories and findings regarding MUC4 function, and its role in epithelial carcinogenesis. Based on these insights, we developed an outline of the processes and mechanisms by which MUC4 critically supports the propagation and survival of cancer cells in various epithelial organs. MUC4 may therefore be a useful prognostic and diagnostic tool that improves our ability to eradicate various forms of cancer.


[Problematization of gender relations at the first Brazilian Eugenics Conference: the status of women, determination of biological gender and reproductive control].
This article problematizes gender relations during the first Brazilian Eugenics Conference, held in Rio de Janeiro in 1929. Seen as the largest public manifestation of the eugenics movement in Brazil, the Atas e Trabalhos do Congresso (Conference Minutes and Proceedings) were analyzed in terms of gender issues expressed through the spectrum of intrinsic conceptions of hereditarianism and reproduction. The problematizations make an effort to discuss, through the works of several participants in the conference, the role and status of women in Brazilian eugenics, reproductive control in Brazil and the relationship between studies involving determination of biological gender and improvement of the human race.


The efficacy of micropulse laser combined with ranibizumab in diabetic macular edema treatment: study protocol for a randomized controlled trial.
At present, intraocular injection of anti-VEGF (vascular endothelial growth factor) drugs has replaced traditional laser therapy as the first-line treatment for DME (diabetic macular edema). However, ranibizumab, a commonly used anti-VEGF drug, is expensive and requires multiple intraocular injections. It places a heavy economic burden on patients with DME. Micropulse laser is safer than conventional laser and can reduce edema. Combined treatment with anti-VEGF may reduce the number of intraocular injections. This study will compare the efficacy of micropulse laser combined with ranibizumab treatment to ranibizumab monotherapy in the treatment of DME, providing a new regimen for future DME treatment. This study is a prospective randomized double-blind controlled clinical trial (RCT) in patients with DME. After 1-year follow-up, visual acuity and macular edema regression will be compared between micropulse laser combined with ranibizumab group and ranibizumab monotherapy group to determine whether the efficacy of micropulse laser combined with ranibizumab treatment was not lower than that of ranibizumab monotherapy in the treatment of DME. Visual acuity measured by the ETDRS chart is the primary outcome measure. The secondary outcome measures are CMT (central macular thickness) measured by OCT (optical coherence tomography) and the number of injections of two groups. Changes in visual acuity and CMT of the two groups will be compared at 12-month follow-up. Before patients are recruited, we provide them with informed consent, in which we explain to them the purpose and process of the study. Micropulse laser combined with anti-VEGF drugs in the treatment of DME can reduce the number of intravitreal anti-VEGF injections, not only relieve the pain of the patients, but also ease the economic and psychological burden of patients, bringing great benefits. However, there is no treatment consensus for the parameters and specific methods of micropulse laser treatment for DME. There is a lack of clinical research data reference of micropulse laser combined with anti-VEGF therapy in clinical practice. This study intends to provide a new direction for clinical DME treatment and also provide a realistic consideration for the application of micropulse laser in DME treatment. ClinicalTrials.gov NCT03690947. Registered on 1 October 2018.


[Helicopter transport of patients from Croatian Adriatic Islands and coastal area in the period from 1996 to 2002].
For most of the Croatian Adriatic islands and coastal area, helicopter is the fastest, and for some remote areas the only effective way of patient transport. In Croatia, most of the aeromedical transports are performed by helicopters of 95th Air Force Base. During the post-war period, the number of civilian patients transported with those helicopters increased from 56 in 1996 to 311 in 2002, this trend continuing in 2003. The majority of these transports were performed in the third trimester of the year, the largest number of patients were transported from the Island of Hvar, and the most common medical indication for aeromedical trasport was trauma. The lack of competent medical escort may have unfavourable impact on patient health and flight safety. The increasing trend in requesting aeromedical transport would obviously justify the foundation of a specialized commercial service to provide both safe transport and competent medical escort.


Acquisition of High Spectral Resolution Diffuse Reflectance Image Cubes (350-2500 nm) from Archaeological Wall Paintings and Other Immovable Heritage Using a Field-Deployable Spatial Scanning Reflectance Spectrometry Hyperspectral System.
There is growing interest in bringing non-invasive laboratory-based analytical imaging tools to field sites to study wall paintings in order to collect molecular information on the macroscale. Analytical imaging tools, such as reflectance imaging spectrometry, have provided a wealth of information about artist materials and working methods, as well as painting conditions. Currently, scientific analyses of wall paintings have been limited to point-measurement techniques such as reflectance spectroscopy (near-ultraviolet, visible, near-infrared, and mid-infrared), X-ray fluorescence, and Raman spectroscopy. Macroscale data collection methods have been limited to multispectral imaging in reflectance and luminescence modes, which lacks sufficient spectral bands to allow for the mapping and identification of artist materials of interest. The development of laboratory-based reflectance and elemental imaging spectrometers and scanning systems has sparked interest in developing truly portable versions, which can be brought to field sites to study wall paintings where there is insufficient space or electrical power for laboratory instruments. This paper presents the design and testing of a simple hyperspectral system consisting of a 2D spatial spot scanning spectrometer, which provides high spectral resolution diffuse reflectance spectra from 350 to 2500 nm with high signal to noise and moderate spatial resolution (few mm). This spectral range at high spectral resolution was found to provide robust chemical specificity sufficient to identify and map many artists' materials, as well as the byproducts of weathering and conservation coatings across the surface of ancient and Byzantine Cypriot wall paintings. Here, we present a detailed description of the hyperspectral system, its performance, and examples of its use to study wall paintings from Roman tombs in Cyprus. The spectral/spatial image processing workflow to make maps of pigments and constituent painting materials is also discussed. This type of configurable hyperspectral system and the imaging processing workflow offer a new tool for the field study of wall paintings and other immovable heritage.


Australian young people's awareness of headspace, beyondblue and other mental health organizations.
Objective: The aim of this paper is to assess young people's awareness of mental health organizations supporting their age group. Of particular interest was awareness of headspace, which was created in 2006 to provide youth-oriented mental health services, and of beyondblue, which aims to raise community awareness of depression, anxiety and related disorders. Method: A telephone survey was carried out on a national sample of young people who were part of a 2-year follow-up study of youth mental health literacy. Data were analysed for those aged 13-25 years. Results: Awareness was highest for beyondblue and telephone helplines; headspace had established some awareness, particularly in areas where its services operate. However, awareness was unrelated to the participant's psychological symptoms in the past year. Conclusions: If youth-oriented services are to be successful, young people need to know about them. Awareness campaigns need to be targeted at the sub-group who have greatest need for these services, namely those with mental health problems.


High-frequency tortuosity relaxation in open-cell foams.
Propagation of ultrasounds through open-cell polymeric foams is studied using air-coupled ultrasound and Fourier spectral analysis (both phase and magnitude) in the frequency range 0.1 to 6 MHz. A detailed micrographic study is first performed to determine struts dimensions and cell geometry, hence, a unit cell model to describe these foams is proposed. Ultrasound phase velocity and transmission loss were then measured. Variation of these magnitudes with the frequency follows the shape of a sigmoid growth. This behavior of the phase velocity can be explained by introducing an apparent tortuosity with a relaxation-like behavior, which can be explained by considering a probabilistic tortuous walk, as it has recently been performed for other kind of foams. However and unlike in previous studies, the present one shows the whole transition of this sigmoid growth for all studied foams. This is achieved by a precise selection of the foam samples and by the fabrication of new air-coupled transducers that enlarge the experimental working frequency range to lower frequencies. The study of the measured sigmoid growth is used to determine the probability function, required by the probabilistic tortuous walk model, which best describes the variation of the apparent tortuosity.


The UCL low-density lipoprotein receptor gene variant database: pathogenicity update.
Familial hypercholesterolaemia (OMIM 143890) is most frequently caused by variations in the low-density lipoprotein receptor (LDLR) gene. Predicting whether novel variants are pathogenic may not be straightforward, especially for missense and synonymous variants. In 2013, the Association of Clinical Genetic Scientists published guidelines for the classification of variants, with categories 1 and 2 representing clearly not or unlikely pathogenic, respectively, 3 representing variants of unknown significance (VUS), and 4 and 5 representing likely to be or clearly pathogenic, respectively. Here, we update the University College London (UCL) LDLR variant database according to these guidelines. PubMed searches and alerts were used to identify novel LDLR variants for inclusion in the database. Standard in silico tools were used to predict potential pathogenicity. Variants were designated as class 4/5 only when the predictions from the different programs were concordant and as class 3 when predictions were discordant. The updated database (http://www.lovd.nl/LDLR) now includes 2925 curated variants, representing 1707 independent events. All 129 nonsense variants, 337 small frame-shifting and 117/118 large rearrangements were classified as 4 or 5. Of the 795 missense variants, 115 were in classes 1 and 2, 605 in class 4 and 75 in class 3. 111/181 intronic variants, 4/34 synonymous variants and 14/37 promoter variants were assigned to classes 4 or 5. Overall, 112 (7%) of reported variants were class 3. This study updates the LDLR variant database and identifies a number of reported VUS where additional family and in vitro studies will be required to confirm or refute their pathogenicity.


Evaluating the Health SmartLibrary.
The Health SmartLibrary (HSL), supported by the National Library of Medicine (Information Systems grant # 1 G08 LM07051-01A1), is a web-based system designed to target resources relevant to the users' information needs. Faculty and librarians collaborated to build tools that would make access to information resources easy and efficient. These tools include current awareness; a metasearch engine; a file cabinet; personalization features; and discipline-based resource collections.


Characterization of a plant glutamate receptor activity.
Bioinformatic approaches have allowed the identification of twenty genes, grouped into three subfamilies, encoding for homologues of animal ionotropic glutamate receptors (iGLRs) in the Arabidopsis thaliana model plant. Indirect evidence suggests that plant iGLRs function as non-selective cation channels. In the present work we provide biochemical and electrophysiological evidences for the chloroplast localization of glutamate receptor(s) of family 3 (iGLR3) in spinach. A specific antibody, recognizing putative receptors of family 3 locates iGLR3 to the inner envelope membrane of chloroplasts. In planar lipid bilayer experiments, purified inner envelope vesicles from spinach display a cation-selective electrophysiological activity which is inhibited by DNQX (6,7-dinitroquinoxaline-2,3-dione), considered to act as an inhibitor on both animal and plant iGLRs. These results identify for the first time the intracellular localization of plant glutamate receptor(s) and a DNQX-sensitive, glutamate-gated activity at single channel level in native membrane with properties compatible with those predicted for plant glutamate receptors.


[Capsule endoscopy: evidence-based indications in 2020.]
Videocapsule endoscopy is, by far, one of the most important milestones in the technological development of endoscopy in the last twenty years. The introduction and spread of videocapsule endoscopy in clinical practice revolutionized the management of small bowel's diseases, allowing a high-quality, extensive examination of its whole mucosal surface. Because of its technical features, videocapsule endoscopy does not allow any direct therapeutic interventions but, compared to other techniques, it is minimally invasive, radiation-free and has an excellent safety profile. The most common indication for videocapsule endoscopy is suspected small bowel bleeding, although other conditions (such as coeliac disease, hereditary polyposis syndromes and, above all, Crohn's disease) may benefit from its use, as highlighted by several studies in recent years. The aim of this paper is to provide a wide overview on indications, limitations and future perspectives of videocapsule endoscopy: by 2020, this technique has become a valuable and irreplaceable tool for the study of the small bowel, changing the patients' management in many clinical scenarios.


Synthesis and evaluation of different fatty acid esters formulated into Precirol ATO-Based lipid nanoparticles as vehicles for topical delivery.
A series of isopropyl fatty esters having different chain length (C(13)-C(23)) were synthesized and formulated in lipid nanoparticles based on Precirol ATO to evaluate their effect on the physicochemical properties of these latter. Moreover, drug loading and skin permeation of Econazole nitrate, chosen as a lipophilic model drug, were evaluated as well. The obtained nanosystems, prepared by high shear homogenization method, had a mean diameter ranging from 180 to 280 nm and showed an encapsulation efficiency of about 100%. Ex vivo permeation results demonstrated a parabolic correlation between permeation effect and chain length of the fatty esters present in the lipid nanoparticles formulated in hydrophilic gels. The maximum flux of drug was observed for the nanoparticles containing esters with 17 and 19 carbon atoms, suggesting that these formulations may constitute a potential carrier for topical delivery of econazole nitrate.


The Role of Parental Beliefs About Anxiety and Attachment on Parental Accommodation of Child Anxiety.
This study examined: 1) the relationship between negative parental beliefs about child anxiety (i.e., it is harmful), insecure parental attachment and parental accommodation of child anxiety; 2) whether parental attachment insecurity moderates the effect of negative beliefs about anxiety on parent accommodation; and 3) a path model of parental factors affecting accommodation and child anxiety severity. Participants were 139 parents of children (6-18 years) with a primary anxiety disorder. Parents completed measures of parental accommodation of their child's anxiety, beliefs about child anxiety, and attachment security. Child anxiety diagnosis and severity was determined using semi-structured clinical interviews. Negative beliefs about child anxiety were directly associated with levels of parental accommodation. There was no direct relationship between insecure attachment and accommodation; however anxious attachment moderated the effect of parental beliefs about anxiety on parental accommodation. Among parents with more secure attachment, negative beliefs about anxiety were associated with greater parental accommodation. However, among parents with less secure attachment, accommodation was high regardless of beliefs about anxiety. A path model suggested that negative beliefs about anxiety was related to increased parental accommodation, which in turn was related to increased child anxiety severity. Psychoeducation about the nature of anxiety is likely to be beneficial in helping to reduce accommodation among parents with more secure attachment styles. However, among those with greater anxious attachment, psychoeducation may need to be tailored to focus on corrective information about the impact of treatment processes on the parent-child relationship.


Robust 2D Otsu's Algorithm for Uneven Illumination Image Segmentation.
Otsu's algorithm is one of the most well-known methods for automatic image thresholding. 2D Otsu's method is more robust compared to 1D Otsu's method. However, it still has limitations on salt-and-pepper noise corrupted images and uneven illumination images. To alleviate these limitations and improve the overall performance, here we propose an improved 2D Otsu's algorithm to increase the robustness to salt-and-pepper noise together with an adaptive energy based image partition technology for uneven illumination image segmentation. Based on the partition method, two schemes for automatic thresholding are adopted to find the best segmentation result. Experiments are conducted on both synthetic and real world uneven illumination images as well as real world regular illumination cell images. Original 2D Otsu's method, MAOTSU_2D, and two latest 1D Otsu's methods (Cao's method and DVE) are included for comparisons. Both qualitative and quantitative evaluations are introduced to verify the effectiveness of the proposed method. Results show that the proposed method is more robust to salt-and-pepper noise and acquires better segmentation results on uneven illumination images in general without compromising its performance on regular illumination images. For a test group of seven real world uneven illumination images, the proposed method could lower the ME value by 15% and increase the DSC value by 10%.


Evaluation of between-methods agreement of extracellular water measurements in adults and children.
Extracellular water (ECW), a relevant molecular level component for clinical assessment, is commonly obtained by 2 methods that rely on assumptions that may not be possible to test at the time the measurements are made. The aim of the current study was to evaluate the degree of agreement between ECW assessment by the sodium bromide dilution (ECW(NaBr)) and total body potassium (TBK; whole-body (40)K counting) to total body water (TBW; isotope dilution) methods (ECW(TBK-TBW)) in an ethnically mixed group of children and adults. ECW was measured with the ECW(NaBr) and ECW(TBK-TBW) methods in 526 white and African American males and females (86 nonobese children, 193 nonobese adults, and 247 obese adults). Fat mass was assessed with dual-energy X-ray absorptiometry. Multiple regression analysis was used to examine the variables related to between-ECW method differences. Significant but generally small group mean (+/-SD) differences in ECW were found in the obese adults (1.28 +/- 2.54 kg) and children (-0.71 +/- 1.78 kg). The magnitude of the differences was related to mean ECW in obese adults, children, and nonobese adults, and the relations between these variables were modified by sex for nonobese adults. ECW differences were also dependent on age, weight, sex, and race or on interactions between these variables. Overall, although good between-method agreement was found across the 3 groups, the degree of agreement varied according to subject characteristics, particularly at the extremes of ECW and body weight. We advance a possible mechanism that may link subject characteristics with the degree of agreement between ECW measurement methods and their underlying assumptions.


[Hormesis effect of cadmium on Lonicera japonica].
A hydroponic experiment was conducted to study the growth characteristics of Lonicera japonica under the stress of different concentrations (0, 0.5, 2.5, 5, 10, and 25 mg L-1 ) cadmium (Cd), aimed to explore the hormesis effect of low concentrations Cd on L. japonica. At < or =5 mg L-1 of Cd, the maximum root length, plant dry biomass, and the contents of chlorophyll a, chlorophyll b, and carotenoid of L. japonica increased significantly, with the increment being 13. 6%, 11.7%, 14. 0% ,10. 8%, and 54. 5%, respectively, as compared with the control. <5 mg L-1 of Cd also had a definite positive effect on the leaf water content. At> or = 10 mg L-1 of Cd, the growth of L. japonica was inhibited significantly. When exposed to 25 mg L-1 of Cd, the shoot Cd concentration of L. japonica reached 622. 93 mg kg-1 , suggesting that L. japonica had a strong capacity of Cd-hyperaccumulation. The dose range of the hormesis effect of Cd on L. japonica was 0.5-5 mg L-1 of Cd.


Retinol-binding protein-deficient mice: biochemical basis for impaired vision.
We reported previously that mice lacking plasma retinol-binding protein (RBP) are phenotypically normal except that they display impaired vision at the time of weaning. This visual defect is associated with greatly diminished eyecup levels of retinaldehyde and is reversible if the mutants are maintained for several months on a vitamin A-sufficient diet. Here we provide a biochemical basis for the visual phenotype of RBP-deficient mice. This phenotype does not result from inadequate milk total retinol levels since these are not different for RBP-deficient and wild-type mice. The eye, unlike all other tissues that have been examined, takes up dietary retinol very poorly. Moreover, compared to other tissues, the eye displays a strong preference for retinol uptake when retinol is delivered bound to RBP. The poor uptake of dietary retinol by the eye coupled with its marked ability to take up retinol from RBP, we propose, provides a basis for the impaired vision observed in weanling RBP-deficient mice. Further study of the mutants suggests that the impaired vision is reversible because the eyes of mutant mice slowly acquire sufficient retinol from the low levels of retinol present in their circulation either bound to albumin or present in lipoprotein fractions. Thus, the eye is unlike other tissues in the body in that it shows a very marked preference for acquiring retinol needed to support vision from the retinol-RBP complex and is unable to meet adequately its retinol need through uptake of recently absorbed dietary retinol. This provides an explanation for the impaired vision phenotype of RBP-deficient mice.


Cognitive profiles and neuropsychiatric symptoms in Korean early-onset Alzheimer's disease patients: a CREDOS study.
Early-onset Alzheimer's disease (EOAD, onset age < 65 years) may differ from late-onset Alzheimer's disease (LOAD) in terms of cognitive profiles and neuropsychiatric symptoms. There have been few studies for Korean EOAD patients using well-structured databases. Previous studies focusing on cognitive profiles between the two groups had a variety of demographic data and comparability. The purpose of this study was to identify the unique profiles of cognitive functions and neuropsychiatric symptoms in Korean EOAD patients that differentiate from LOAD. Through propensity score matching, a total of 435 patients with EOAD and a total of 435 patients with LOAD were included in this nationwide, multicenter, hospital-based study. Each patient underwent comprehensive neurological examination, interview for caregiver, neuropsychological tests, and brain magnetic resonance imaging. Neuropsychological test results showed worse performances on frontal/executive functions, visuospatial function, and visual memory in EOAD patients as compared to LOAD patients. In terms of neuropsychiatric symptoms, apathy was more common in EOAD patients, while delusions were more prevalent in LOAD patients. The differences in neuropsychiatric symptoms between the two groups were most pronounced in patients with the APOE ε4 allele, suggesting that neuropsychiatric symptoms in AD may be influenced by the APOE genotype. Our results suggested that EOAD may be an important phenotype, fronto-parietal dysfunction, in the spectrum of AD, and this finding can provide for early diagnosis of EOAD patients.