"No Alcohol Is Recommended, But . . .": Health Care Students' Attitudes About Alcohol Consumption During Pregnancy.
Canadian findings suggest that health care providers require further training and education to support their work preventing fetal alcohol spectrum disorder (FASD). However, the knowledge and training of health care students in relation to FASD remains largely unexplored. The purpose of this study was to understand the attitudes and beliefs of health care students about alcohol use during pregnancy. Twenty-one health care students participated in a scenario-based vignette about alcohol consumption during pregnancy. Although almost all students recognized that no alcohol consumption during pregnancy is the safest recommendation, many students recounted that this advice is not always conveyed during encounters with their pregnant patients. Three primary themes related to students' attitudes concerning alcohol use during pregnancy were identified. Health care professionals in training need further education about the risks of alcohol consumption during pregnancy and the potential health outcomes associated with prenatal alcohol exposure.


Polymer donors of nitric oxide improve the treatment of experimental solid tumours with nanosized polymer therapeutics.
Polymer carriers based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers with incorporated organic nitrates as nitric oxide (NO) donors were designed with the aim to localise NO generation in solid tumours, thus highly increasing the enhanced permeability and retention (EPR) effect. The NO donors were coupled to the polymer carrier either through a stable bond or through a hydrolytically degradable, pH sensitive, bond. In vivo, the co-administration of the polymer NO donor and HPMA copolymer-bound cytotoxic drug (doxorubicin; Dox) resulted in an improvement in the treatment of murine EL4 T-cell lymphoma. The polymer NO donors neither potentiated the in vitro toxicity of the cytotoxic drug nor exerted any effect on in vivo model without the EPR effect, such as BCL1 leukaemia. Thus, an increase in passive accumulation of the nanomedicine carrying cytotoxic drug via NO-enhanced EPR effect was the operative mechanism of action. The most significant improvement in the therapy was observed in a combination treatment with such a polymer conjugate of Dox, which is characterised by increased circulation in the blood and efficient accumulation in solid tumours. Notably, the combination treatment enabled the development of an anti-tumour immune response, which was previously demonstrated as an important feature of HPMA-based polymer cytotoxic drugs.


The Caenorhabditis elegans JNK signaling pathway activates expression of stress response genes by derepressing the Fos/HDAC repressor complex.
MAP kinases are integral to the mechanisms by which cells respond to a wide variety of environmental stresses. In Caenorhabditis elegans, the KGB-1 JNK signaling pathway regulates the response to heavy metal stress. In this study, we identified FOS-1, a bZIP transcription factor, as a target of KGB-1-mediated phosphorylation. We further identified two transcriptional targets of the KGB-1 pathway, kreg-1 and kreg-2/lys-3, which are required for the defense against heavy metal stress. FOS-1 plays a critical role in the transcriptional repression of the kreg-1 gene by recruiting histone deacetylase (HDAC) to its promoter. KGB-1 phosphorylation prevents FOS-1 dimerization and promoter binding, resulting in promoter derepression. Thus, HDAC behaves as a co-repressor modulating FOS-1-mediated transcriptional regulation. This study describes the direct link from JNK signaling, Fos phosphorylation, and regulation of kreg gene transcription, which modulates the stress response in C. elegans.


Practical lineshape of a laser operating near an exceptional point.
We present a practical laser linewidth broadening phenomenon in the viewpoint of high sensitivity of an exceptional point (EP). A stochastic simulation model is implemented to describe the fluctuations in the cavity resonance frequencies. The linewidth originated from external noises are maximized at the EP. The linewidth enhancement factor behaves similarly to the Petermann factor although the Petermann effect is not considered. In the long coherence time limit, the power spectral density of the laser exhibits a splitting in the vicinity of the EP although the cavity eigenfrequencies coalesce at the EP.


Tricyclic analogues of acyclovir and ganciclovir. Influence of substituents in the heterocyclic moiety on the antiviral activity.
The effect of substitution in the tricyclic moiety of 3,9-dihydro-9-oxo-5H-imidazo[1,2-alpha]purine (1,N-2-ethenoguanine) analogues of acyclovir (1) and ganciclovir (2) on their physical properties and antiherpetic activity was investigated by synthesizing a series of compounds substituted in the 2, 6, or 7 position (6-14). Substitution in the 6-position with phenyl or 4-biphenylyl resulted in fluorescent compounds (7, 9, 13, 14). In general, the substituent in the 6 position potentiated the antiviral activity. The fluorescent 6-phenyl derivatives: 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-6-phenyl-5H-imidaxo[ 1,2-alpha]purine (7) and its 3-[(1,3-dihydroxy-2-propoxy)methyl] congener (13) were the most potent tricyclic analogues of 1 and 2, respectively. Compound 7 was inhibitory to TK+ HSV-1, TK+ HSV-2, and TK+ VZV within the concentration range of 0.2-2.0 micrograms/mL, well below the cytotoxicity threshold (50 to > 100 micrograms/mL). Compound 13 was inhibitory to TK+ HSV-1 and TK+ HSV-2 within the concentration range of 0.005-0.3 microgram/mL and to TK+ and TK- VZV within the concentration range of 0.4-3 micrograms/mL (cytotoxicity threshold > 200 micrograms/mL). Both 7 and 13 seem to be promising candidate compounds for the noninvasive diagnosis of herpesvirus infections.


Effects of a positive thinking program on hope and sleep quality in Iranian patients with thalassemia: a randomized clinical trial.
Thalassemia have a negative impact on the patients' psychological health and sleep quality. This study aimed to determine the effects of a positive thinking training program on hope and sleep quality of patients with thalassemia major. This randomized clinical trial was conducted on 78 patients with thalassemia major including 36 males (46.2%) and 42 females (53.8%) with a mean age of 25.56 ± 29.6 in Iran. Subjects were randomly assigned into experimental and control groups. Experimental group received 16 h training based on positive thinking materials published by Martin Seligman. Control group received only usual programs. Data were collected at baseline, as well as immediately and one month after the intervention, using Snyder's Hope Scale and the Pittsburgh Sleep Quality Index. Data analysis was performed using SPSS Software 18.0; statistical tests included the independent T-test, the Chi-square, Mann Whitney, and Friedman test. Significance level was set at 0.05 in this study. The experimental group had a significantly higher mean hope score compared to the control group immediately (45.38 ± 7.82 vs. 35.32 ± 5.54, P < 0.001) and one month following intervention (44.67 ± 3.47 vs. 35 ± .54, P < 0.001). Moreover, the mean sleep quality scores of the experimental group was significantly greater than that for control group immediately (5.35 ± 2.02 vs. 7 ± 2.4, P = 0.004) and one month after the intervention (4.23 ± 2.2 vs.7.02 ± 3.03, P < 0.001). Since our training program on positive thinking improved hope and quality of sleep in patients with thalassemia major, we recommend the use of such courses as an important step toward promotion of hope and sleep quality among these patients. Trial registration The name of the registry: Iranian Registry of Clinical Trials. IRCT2017010431774N1. URL of the trial registry record: https://en.irct.ir/trial/24923 . Registration Date: 07/03/2017.


Prevalence of Color Vision Deficiency and its Correlation with Amblyopia and Refractive Errors among Primary School Children.
To determine the prevalence of color vision deficiency (CVD) and its correlation with amblyopia and refractive errors among primary school children. In this population-based cross-sectional study, 2160 children were selected from 36 primary schools; 60 students were from each school (10 students in each grade), with equal sex distribution. A complete eye examination including refraction using a photorefractometer, determination of visual acuity (VA) and color vision using a Yang vision tester, and evaluation of ocular media opacity using a direct ophthalmoscope was performed. Children who could not answer at least 4 plates of the Ishihara color test were considered as color vision deficient subjects. Amblyopia was determined if pinhole VA was worse than 0.3 LogMAR (equal to 20/40). The prevalence of CVD was 2.2% (95% CI: 1.5% to 3%) which was higher in male subjects (37 [3.5%] boys vs. 11 [1.0%] girls, P < 0.001). Mean VA was lower among students with CVD as compared to normal color vision children (P = 0.035) and amblyopia was observed in 8.3% (95% CI: 0.2% to 16.4%) of patients with CVD versus 2.1% (95% CI: 1.5% to 2.08%) of children with normal color vision perception (P = 0.005). A statistically significant correlation between lower VA and CVD was observed (P = 0.023). Although CVD was correlated with lower VA and amblyopia, there was no relationship between CVD and the type of amblyopia, refractive error, anisometropia or strabismus.


Differential diagnosis of pleural effusions: clinical usefulness of cell marker quantitation.
Carcinoembryonic antigen (CEA), orosomucoid beta 2 microglobulin, and alpha fetoprotein were quantified in the pleural fluid and serum of 58 hospitalized consecutive patients in order to differentiate malignant from non-malignant effusions. Cytologic examination of the effusions was also performed. The orosomucoid assay was the most helpful in identifying malignant effusions; higher values (greater than 100 mg/100 ml) were found in 74 percent (26/35) of malignant effusions. Quantitation of carcinoembryonic antigen had a high specificity (95 percent) but a low sensitivity (36 percent) for the detection of malignant pleural effusions. The parallel quantitation of CEA and orosomucoid had a higher sensitivity (86 percent) which increased when associated with cytologic examination. The sensitivity of cytology was only 46 percent. The concentrations of orosomucoid in pleural effusions correlated well with serum concentrations. Alpha fetoprotein and beta 2 microglobulin quantitations were of no clinical value for diagnosing malignant effusions. It is suggested the cytologic examination combined with orosomucoid and CEA quantitation in pleural fluid have a considerable clinical value for the diagnosis of pleural effusions.


Complications associated with optical-access laparoscopic trocars.
To investigate the number and type of serious complications associated with optical-access trocars reported by sources other than the medical literature. Optical-access trocars, first introduced in 1994, were designed to decrease the risk of injury to intra-abdominal structures by allowing the surgeon to visualize abdominal wall layers during placement. To date, very few complications with their use have been reported in the medical literature. MEDLINE, the Food and Drug Administration's Medical Device Reporting, and the Manufacturer and User Facility Device Experience databases were searched for reports of complications occurring during the use of optical-access trocars for laparoscopic access. Only two serious complications resulting from the use of optical-access trocars (vena cava injuries) have been reported in the medical literature. However, 79 serious complications using these techniques have been cited in the Medical Device Reporting and Manufacturer and User Facility Device Experience databases since 1994. These include 37 major vascular injuries involving aorta, vena cava, or iliac vessels, 18 bowel perforations, 20 cases of significant bleeding from other sites, three liver lacerations, and one stomach perforation. Four of these complications resulted in patient deaths. Optical-access trocars may be associated with significant injuries despite having the ability to visualize tissue layers during insertion.


A breakdown in the family unit.
In his article, "Autonomy and beneficence in the family," David J. Doukas describes the dynamic relationship between the family and the physician. He points out: "the family covenant spells out the obligations of all parties to give and receive respect and beneficial care within the realm of medical practice".... While this model may provide a framework for ethical discussion under certain circumstances, it falls short in several major respects....


Isolation of Cu Atoms in Pd Lattice: Forming Highly Selective Sites for Photocatalytic Conversion of CO2 to CH4.
Photocatalytic conversion of CO2 to CH4, a carbon-neutral fuel, represents an appealing approach to remedy the current energy and environmental crisis; however, it suffers from the large production of CO and H2 by side reactions. The design of catalytic sites for CO2 adsorption and activation holds the key to address this grand challenge. In this Article, we develop highly selective sites for photocatalytic conversion of CO2 to CH4 by isolating Cu atoms in Pd lattice. According to our synchrotron-radiation characterizations and theoretical simulations, the isolation of Cu atoms in Pd lattice can play dual roles in the enhancement of CO2-to-CH4 conversion: (1) providing the paired Cu-Pd sites for the enhanced CO2 adsorption and the suppressed H2 evolution; and (2) elevating the d-band center of Cu sites for the improved CO2 activation. As a result, the Pd7Cu1-TiO2 photocatalyst achieves the high selectivity of 96% for CH4 production with a rate of 19.6 μmol gcat-1 h-1. This work provides fresh insights into the catalytic site design for selective photocatalytic CO2 conversion, and highlights the importance of catalyst lattice engineering at atomic precision to catalytic performance.


Estimated prevalence of eating disorders in Malaysia based on a diagnostic screen.
Eating disorders (EDs) are debilitating health conditions and common across cultures. Recent reports suggest that about 14.0% of university students in Malaysia are at risk for developing an ED, and that prevalence may differ by ethnicity and gender. However, less is known about the prevalence of EDs in nonuniversity populations. The current study seeks to (1) estimate the prevalence of EDs and ED risk status among adults in Malaysia using an established diagnostic screen; (2) examine gender and ethnic differences between ED diagnostic/risk status groups; and (3) characterize the clinical profile of individuals who screen positive for an ED. We administered the Stanford-Washington University Eating Disorder Screen, an online ED screening tool, to adults in Malaysia in September 2020. ED risk/diagnostic categories were assigned to 818 participants (ages 18-73 years) of which, 0.8% screened positive for anorexia nervosa, 1.4% for bulimia nervosa, 0.1% for binge-ED, 51.4% for other specified feeding or ED, and 4.8% for avoidant/restrictive food intake disorder. There was gender parity in the high risk and the overall ED categories. The point prevalence of positive eating pathology screening among Malays was significantly higher than Chinese but no different from Indians. This is the first study to estimate the prevalence of EDs using a diagnostic screen in a population-based sample of Malaysians. It is concerning that over 50% of Malaysians reported symptoms of EDs. This study highlights the need to invest more resources in understanding and managing eating pathology in Malaysia. This study estimates the prevalence of EDs among adults in Malaysia using an online EDs screen. Over 50% of Malaysians report symptoms of EDs. The study highlights the need for more resources and funding to address this important public health issue through surveillance, prevention, and treatment of EDs in Malaysia.


Changes of human glomerular basement membrane in diabetes mellitus.
Glomerular basement membranes were isolated from kidneys of human diabetics and non-diabetics. Albumin and immunoglobulin G content of glomerular basement membranes as determined after protease digest was higher in the diabetic group while lower values were obtained for heparan sulphate. Nonenzymatic glucosylation of whole glomerular basement membranes and tendon tissue was significantly elevated in diabetic subjects. Correlation of the determined parameters suggest that charge and size selective properties are altered in diabetic glomeruli. Serum albumin and albumin deposited in glomerular basement membranes showed the same content of nonenzymatically bound glucose in a normal and in a diabetic subject, respectively. Thus it would appear that in human diabetes the glucosylated albumin does not underly increased transcapillary transport as was reported in vitro.


Maternal Allergy Status Has No Impact on Neonatal Immune Responses to Allergen Stimuli.
Due to the increasing incidence of allergic diseases, there is a strong need to identify a prognostic marker pointing to increased risk of allergy development allowing introduction of early preventive measures. Cord blood seems to be a good source for searching for such marker. The capacity of cord blood cells to respond to common allergens could point to increased predisposition to later allergy development. In our study, cytokines typical of Th1 (IFN-γ), Th2 (IL-5, IL-13) and Treg (IL-10) immune responses were followed at both the level of gene expression and cytokine secretion in cord blood cells of newborns of healthy mothers (children with relatively low risk of allergy development) and allergic mothers (children with relatively high risk of allergy development) stimulated by allergens (pollen from birch and timothy grass, house dust mite, ovalbumin). We have not observed any difference in the response of cord blood cells of neonates of healthy and allergic mothers to allergen in vitro. Both gene expression and secretion of cytokines in response to allergen stimulation were comparable with the unstimulated controls. It seems that early postnatal events will be more decisive for future allergy development than prenatal sensitization of the foetal immune system with allergen in utero in allergic mothers.


Projecting the Target Quantity of Medical Staff in Taiwan's Administrative Regions by the Theory of Carrying Capacity.
As physicians and nurses are the main medical staff in any healthcare system, an appropriate medical workforce distribution is crucial for an aging society. This study thus applies the theory of carrying capacity and the given demand side to explore the carrying capacity, carrying efficiency, and potential adjustment ratio of medical staff in Taiwan's administrative regions by using the data envelopment analysis (DEA) approach in which a lower carrying efficiency implies a higher shortage ratio. The main findings are as follows. (i) The carrying efficiency of Taiwan's medical staff is weakening year by year, while the carrying efficiency of the country's nurses is lower than that of physicians. (ii) The outlying islands of Taiwan have a more serious shortage of physicians and nurses than the main island. (iii) The central government should encourage more physicians and nurses to work in regions with a low carrying efficiency.


Price and maternal obesity influence purchasing of low- and high-energy-dense foods.
Price can influence food purchases, which can influence consumption. Limited laboratory research has assessed the effect of price changes on food purchases, and no research on individual differences that may interact with price to influence purchases exists. We aimed to assess the influence of price changes of low-energy-density (LED) and high-energy-density (HED) foods on mother's food purchases in a laboratory food-purchasing analogue. Mothers were randomly assigned to price conditions in which the price of either LED or HED foods was manipulated from 75% to 125% of the reference purchase price, whereas the price of the alternative foods was kept at the reference value. Mothers completed purchases for 2 income levels ($15 or $30 per family member). Purchases were reduced when prices of LED (P < 0.01) and HED (P < 0.001) foods were increased. Maternal BMI interacted with price to influence purchases of HED foods when the price of HED foods increased (P = 0.016) and interacted with price to influence purchases of LED foods when the price of HED foods increased (P = 0.008). These results show the relevance of considering price change as a way to influence food purchases of LED compared with HED foods and the possibility that individual differences may influence the own-price elasticity of HED foods and substitution of LED for HED foods.


Changes in the spin state and reactivity of cytochrome C induced by photochemically generated singlet oxygen and free radicals.
This work compares the effect of photogenerated singlet oxygen (O(2)((1)Delta(g))) (type II mechanism) and free radicals (type I mechanism) on cytochrome c structure and reactivity. Both reactive species were obtained by photoexcitation of methylene blue (MB(+)) in the monomer and dimer forms, respectively. The monomer form is predominant at low dye concentrations (up to 8 microm) or in the presence of an excess of SDS micelles, while dimers are predominant at 0.7 mm SDS. Over a pH range in which cytochrome c is in the native form, O(2) ((1)Delta(g)) and free radicals induced a Soret band blue shift (from 409 to 405 nm), predominantly. EPR measurements revealed that the blue shift of the Soret band was compatible with conversion of the heme iron from its native low spin state to a high spin state with axial symmetry (g approximately 6.0). Soret band bleaching, due to direct attack on the heme group, was only detected under conditions that favored free radical production (MB(+) dimer in SDS micelles) or in the presence of a less structured form of the protein (above pH 9.3). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry of the heme group and the polypeptide chain of cytochrome c with Soret band at 405 nm (cytc405) revealed no alterations in the mass of the cytc405 heme group but oxidative modifications on methionine (Met(65) and Met(80)) and tyrosine (Tyr(74)) residues. Damage of cytc405 tyrosine residue impaired its reduction by diphenylacetaldehyde, but not by beta-mercaptoethanol, which was able to reduce cytc405, generating cytochrome c Fe(II) in the high spin state (spin 2).


Structural validation of oral mucosal tissue using optical coherence tomography.
Optical coherence tomography (OCT) is a non-invasive optical technology using near-infrared light to produce cross-sectional tissue images with lateral resolution. The overall aims of this study was to generate a bank of normative and pathological OCT data of the oral tissues to allow identification of cellular structures of normal and pathological processes with the aim to create a diagnostic algorithm which can be used in the early detection of oral disorders. Seventy-three patients with 78 suspicious oral lesions were referred for further management to the UCLH Head and Neck Centre, London. The entire cohort had their lesions surgically biopsied (incisional or excisional). The immediate ex vivo phase involved scanning the specimens using optical coherence tomography. The specimens were then processed by a histopathologist. Five tissue structures were evaluated as part of this study, including: keratin cell layer, epithelial layer, basement membrane, lamina propria and other microanatomical structures. Two independent assessors (clinician and pathologist trained to use OCT) assessed the OCT images and were asked to comment on the cellular structures and changes involving the five tissue structures in non-blind fashion. Correct identification of the keratin cell layer and its structural changes was achieved in 87% of the cohort; for the epithelial layer it reached 93.5%, and 94% for the basement membrane. Microanatomical structures identification was 64% for blood vessels, 58% for salivary gland ducts and 89% for rete pegs. The agreement was "good" between the clinician and the pathologist. OCT was able to differential normal from pathological tissue and pathological tissue of different entities in this immediate ex vivo study. Unfortunately, OCT provided inadequate cellular and subcellular information to enable the grading of oral premalignant disorders. This study enabled the creation of OCT bank of normal and pathological oral tissues. The pathological changes identified using OCT enabled differentiation between normal and pathological tissues, and identification of different tissue pathologies. Further studies are required to assess the accuracy of OCT in identification of various pathological processes involving the oral tissues.


Regioselective Hydrolysis and Transesterification of Dimethyl 3-Benzamidophthalates Assisted by a Neighboring Amide Group.
An efficient, highly regioselective hydrolysis and transesterification of dimethyl 3-benzamidophthalates into the corresponding carboxylic acid monoesters and mixed esters (including tert-butyl esters) under basic conditions is presented. The selectivity is governed by the neighboring 3-benzamido moiety's participation and by the nature of the solvent. In alcohols the reaction occurred exclusively at the ortho-position to the benzamido functionality, in pyridine or acetonitrile at both ester groups. An insight into the mechanistic pathway was obtained from a (1)H NMR study in perdeuteromethanol.


Updated field synopsis and systematic meta-analyses of genetic association studies in cutaneous melanoma: the MelGene database.
We updated a field synopsis of genetic associations of cutaneous melanoma (CM) by systematically retrieving and combining data from all studies in the field published as of August 31, 2013. Data were available from 197 studies, which included 83,343 CM cases and 187,809 controls and reported on 1,126 polymorphisms in 289 different genes. Random-effects meta-analyses of 81 eligible polymorphisms evaluated in >4 data sets confirmed 20 single-nucleotide polymorphisms across 10 loci (TYR, AFG3L1P, CDK10, MYH7B, SLC45A2, MTAP, ATM, CLPTM1L, FTO, and CASP8) that have previously been published with genome-wide significant evidence for association (P<5 × 10(-8)) with CM risk, with certain variants possibly functioning as proxies of already tagged genes. Four other loci (MITF, CCND1, MX2, and PLA2G6) were also significantly associated with 5 × 10(-8)<P<1 × 10(-3). In supplementary meta-analyses derived from genome-wide association studies, one additional locus located 11 kb upstream of ARNT (chromosome 1q21) showed genome-wide statistical significance with CM. Our approach serves as a useful model in analyzing and integrating the reported germline alterations involved in CM.


Coronary Revascularization and Out-of-hospital Cardiac Arrest: Past, Present and Future.
Cardiologists and the cardiac catheter laboratory have key roles to play in the management of patients after out-of-hospital cardiac arrest (OHCA). Although immediate catheter laboratory activation is the standard of care in cardiogenic shock and ST elevation myocardial infarction, the majority of patients will present without these features and with an uncertain diagnosis. Even in the latter, early assessment and invasive management may be beneficial, but this is counterbalanced by significant resource utilization, potential to cause harm and the possibility that any diagnostic or therapeutic gains are offset by a poor neurological outcome. Past consensus on the management of the OHCA patient without ST elevation or cardiogenic shock is being challenged by emerging results from new trials in this field. Further randomized trials are ongoing, and are expected to deliver robust data from over 4,000 patients, allowing us to further refine the optimal management strategy in this challenging cohort. This article describes the benefits and pitfalls of a strategy of immediate coronary angiography in these patients, examines the recently published COACT and TOMAHAWK trials in detail, and describes a framework with which to approach the patient after resuscitated OHCA, based on the available evidence to date.


[Ultrasound-guided microwave ablation with artificial pleural effusion for liver tumor adjacent to diaphragmatic dome].
To explore the value of ultrasound-guided microwave ablation with artificial pleural effusion for liver tumor adjacent to diaphragmatic dome. Methods: A total of 34 patients with liver tumors located at diaphragmatic dome in Hunan Provincial Tumor Hospital were recruited from January 2014 to October 2015. The number of lesions ≤3 or lesion diameter ≤5 cm was in line with the microwave ablation indications. B ultrasound-guided microwave ablation for the liver tumors was undertaken after the artificial pleural effusion being established. 3-4 weeks later after the microwave ablation, all patients were imaged with enhance CT or MRI. The effect of ablation and the complications were evaluated. Results: There were 49 lesions in 34 patients, including 30 cases (88.2%) of complete ablation (CA), 3 cases (8.8%) of partial ablation (PA) and one case with new lesions after ablation (2.9%). Thirty-four patients had (1 580±230.7) mL of pleural effusion volume, while one case had bloody pleural effusion. One case had a diaphragmatic thermal injury, and one case had a biliary tumor infection. All of them showed remission after symptomatic treatment. Conclusion: Combination of ultrasound-guided microwave ablation with artificial pleural effusion is a safe and effective therapy for liver tumor adjacent to diaphragmatic dome.


Bite Mark Analysis in Foodstuffs and Inanimate Objects and the Underlying Proofs for Validity and Judicial Acceptance.
Even though one of the first bite mark cases was Doyle v. State in 1954 (a bitten cheese case), the research has focused on bite marks inflicted in human skin. As published Papers, Case Reports, or Technical Notes can constitute precedents which are relied upon in making the legal arguments and a considerable amount of case law exists in this area, we present a systematic review on bite mark analysis in foodstuffs and inanimate objects and their underlying proofs for validity and judicial acceptance according to Daubert rulings. Results showed that there is vulnerability in these procedures, and it is essential to demand for focus scrutiny on the known error rates when such evidence is presented in trials. These kinds of bite marks are well documented; however, there has been little research in this field knowing that the protocols of analysis and comparison are the responsibility of the forensic odontologists.


A resistance mechanism dependent upon the inhibition of ethylene biosynthesis.
The highly selective auxin-type herbicide quinclorac is widely used to control important dicotyledon and monocotyledon weeds in rice fields. Echinochloa crusgalli var. zelayensis is one of the most troublesome weeds in China, and is very difficult to control in east China due to misuse of herbicides. The JZD -R, JTJ -R, JCW -R and SSX -R biotypes of E. crusgalli var. zelayensis had resistance to quinclorac with resistance levels ranked as JZD -R < JTJ -R < JCW -R < SSX -R. Growth reduction in different biotypes was positively correlated with ethylene production. Stimulated levels of ethylene and 1-aminocyclopropane-1-carboxylic acid (ACC) and activities of ACC synthase and ACC oxidase in resistant biotypes were less than the susceptible biotype, and were negatively correlated with quinclorac resistance levels, suggesting that inhibition of ethylene biosynthesis was positively correlated with resistance levels. Considering the resistance-dependent inhibition in the ethylene biosynthetic pathway, the mechanisms of resistance to quinclorac in E. crusgalli var. zelayensis involved alteration(s) in the ethylene response pathway, consisting of at least alteration in induction of the enzymes activity of ACC synthase and ACC oxidase.


Embracing technology? Using change management strategies to improve the use of continuous lateral rotation therapy.
The purpose of this quality improvement initiative was to improve the utilization of continuous lateral rotation therapy (CLRT) in a nine-bed community hospital ICU within the context of a nurse-driven protocol. Nursing focus groups, analyzed using a strength, weakness, opportunity, threat (SWOT) approach, resulted in the implementation of four interventions over seven weeks. Change management strategies guided all aspects of the project. Results showed a modest increase in the utilization of CLRT. This initiative demonstrates that change management strategies may assist with the incorporation of technology into nursing practice by increasing empowerment and creating an attachment to and responsibility for outcomes.


Determination of urinary succinylacetone by capillary gas chromatography.
The average analytical recovery of succinylacetone added to urine and separated by capillary gas chromatography was 69% for solvent extraction and 72% for anion exchange separation. Treating succinylacetone with hydroxylamine hydrochloride at a pH of less than 5 caused formation of a derivative separated by capillary gas chromatography into two isomers: 3-methyl-5- isoxazole propionate and 5-methyl-3- isoxazole propionate as their trimethylsilyl derivatives (molecular weight 227). In a pH greater than or equal to 5, succinylacetone dioxime was formed and separated into 3 isomers as their trimethylsilyl derivatives (molecular weight 404). Succinylacetone dioxime was converted to 3(5)-methyl-(3)5- isoxazole propionate whenever the pH of the solution was dropped to less than 5. Mass spectra of both derivatives are shown. This study demonstrates that capillary gas chromatography is suitable for use in urinary succinylacetone determination.


PET-CT image co-registration in the thorax: influence of respiration.
Because anatomical information on fluorine-18 fluorodeoxyglucose (FDG) whole-body positron emission tomography (PET) images is limited, combination with structural imaging is often important. In principle, software co-registration of PET and computed tomography (CT) data or dual-modality imaging using a combined PET-CT camera has an important role to play, since "hardware-co-registered" images are thereby made available. A major unanswered question is under which breathing protocol the respiration level in the CT images of a patient will best match the PET images, which represent summed images over many breathing cycles. To address this issue, 28 tumour patients undergoing routine FDG PET examinations were included in this study. In ten patients, PET and CT were performed using a new combined high-performance in-line PET-CT camera without the need for repositioning of the patient, while in 18 patients imaging was performed on separate scanners located close to each other. CT was performed at four respiration levels: free breathing (FB), maximal inspiration (MaxInsp), maximal expiration (MaxExp) and normal expiration (NormExp). The following distances were measured: (a) between a reference point taken to be the anterior superior edge of intervertebral disc space T10-11 and the apex of the lung, (b) from the apex of the lung to the top of the diaphragm, (c) from the apex of the lung to the costo-diaphragmatic recess and (d) from the reference point to the lateral thoracic wall. Differences between CT and corresponding PET images in respect of these distances were compared. In addition, for each of 15 lung tumours in 12 patients, changes in tumour position between PET and CT using the same protocol were measured. CT during NormExp showed the best fit with PET, followed by CT during FB. The mean differences in movement of the diaphragmatic dome on CT during NormExp, FB, MaxInsp and MaxExp, as compared with its level on PET scan, were, respectively, 0.4 mm (SD 11.7), -11.6 mm (13.3), -44.4 mm (25.5) and -9.5 mm (25.6). CT acquired in MaxExp and MaxInsp is not suitable for image co-registration owing to the poor match of images in MaxInsp and because of difficulties with patient performance in MaxExp. With reference to lung lesions, NormExp showed the best results, with a higher probability of a good match and a smaller range of measured values in comparison with FB. Image misregistration in combined PET-CT imaging can be minimized to dimensions comparable to the spatial resolution of modern PET scanners. For PET-CT image co-registration, the use of a normal expiration breath-hold protocol for CT acquisition is recommended, independent of whether combined PET-CT systems or stand-alone systems are used.


Evaluation of hydrophilic permeant transport parameters in the localized and non-localized transport regions of skin treated simultaneously with low-frequency ultrasound and sodium lauryl sulfate.
The porosity (epsilon), the tortuosity (tau), and the hindrance factor (H) of the aqueous pore channels located in the localized transport regions (LTRs) and the non-LTRs formed in skin treated simultaneously with low-frequency ultrasound (US) and the surfactant sodium lauryl sulfate (SLS), were evaluated for the delivery of four hydrophilic permeants (urea, mannitol, raffinose, and inulin) by analyzing dual-radiolabeled diffusion masking experiments for three different idealized cases of the aqueous pore pathway hypothesis. When epsilon and tau were assumed to be independent of the permeant radius, H was found to be statistically larger in the LTRs than in the non-LTRs. When a distribution of pore radii was assumed to exist in the skin, no statistical differences in epsilon, tau, and H were observed due to the large variation in the pore radii distribution shape parameter (3 A to infinity). When infinitely large aqueous pores were assumed to exist in the skin, epsilon was found to be 3-8-fold greater in the LTRs than in the non-LTRs, while little difference was observed in the LTRs and in the non-LTRs for tau. This last result suggests that the efficacy of US/SLS treatment may be enhanced by increasing the porosity of the non-LTRs.


An acute interprofessional simulation experience for occupational and physical therapy students: Key findings from a survey study.
Due to the fast pace and high complexity of managing patients in intensive and acute care units (ICUs), healthcare students often feel challenged and unprepared to practice in this environment. Simulations and standardised patients provide "hands-on" learning experiences that are realistic and help students to gain competence and confidence. This study examined the impact of an intensive case simulation laboratory using a patient simulator and standardised patients on students' perceptions of their confidence and preparedness to work in acute care settings. Second-year Masters of Occupational Therapy (MOT; n = 127) and Doctor of Physical Therapy (DPT; n = 105) students participated in a three-hour intensive care simulation laboratory comprised of four stations that were designed to simulate common ICU patient care scenarios. Data analysed were student pre- and post-simulation surveys and written comments, and clinical instructors' (CIs; n = 51) ratings on DPT students' preparedness and confidence within the first two weeks of their acute care internships obtained after the laboratory. There was a significant increase for DPT (p < 0.0001) and MOT (p < 0.10) students in median ratings of how prepared they felt to practice in acute care settings following the ICU simulation compared to before the laboratory. CIs rated the DPT students as either prepared or very prepared for and moderately confident or very confident in the acute care setting. The use of simulation training using standardised patients and patient simulators was beneficial in increasing student confidence and preparing OT and PT students to practice in the acute care setting. Health professional educators should consider using an interprofessional simulation experience to improve their students' confidence and preparedness to provide appropriate care in the acute setting.


[Clinical study of fuzheng jiangnian capsule in improving pre-thrombosis correlated factors in patients with coronary heart disease].
To explore the effect of Fuzheng Jiangnian Capsule (FZJN) on the pre-thrombosis correlated factors in patients with coronary heart disease (CHD). Ninety patients with CHD complicated with blood hyperviscosity syndrome were treated with conventional treatment and randomly divided into three groups by the additional treatment, i. e. the FZJN group (FZJN, a preparation with action of invigorating Pi, supplementing Shen, and activating blood circulation), the CSDP group [Compound Salviae droplet pill, CSDP) with the action of activating blood circulation to remove blood stasis) and the aspirin (ASP) group, 30 patients in each group. After two months of treatment, clinical efficacy, the levels of endothelin (ET), nitric oxide (NO), coagulation factor I (Fib), D-dimer (DD), thrombocytic granule membranous glucoprotein (CD62p), superoxide dismutase (SOD), high- and low-density lipoprotein-cholesterol (HDL-C, LDL-C) in patients before and after treatment were observed and compared with those in the healthy control group. Compared with the healthy control group, the levels of Fib, DD, ET, CD62p were significantly higher, NO and SOD significantly lower (P<0.05, P<0.01) in all the patients with CHD. Compared with the same group before treatment, the levels of Fib, DD, ET, CD62p, LDL-C in the FZJN group lowered significantly, while NO and SOD raised significantly (P <0.05, P <0.01). ET and CD62p in the CSDP group lowered significantly, while SOD raised significantly (P < 0.05), CD62p in the ASP group lowered significantly (P < 0.05). No statistical difference was found in comparison of DD or ET, though certain improvement was shown. The total effective rate in relieving TCM syndromes and angina pectoris, and the decrease or stop rate of nitrate esters medication were superior in FZJN group to those in the CSDP group and the ASP group, respectively (P <0.05). The rate of electrocardiogram improvement in the FZJN and CSDP group was superior to that in the ASP group (P< 0.05). Increase of Fib, DD, ET, CD62p, and decrease of NO and SOD levels were found in patients with CHD in prethrombosis stage. Compared with ASP, compound Chinese medicinal herbs can act on the prethrombosis manner of CHD patients through multi-paths, multi-links. FZJN showed better efficacy in improving correlated blood molecule markers and clinical syndromes than CSDP, suggesting that the possible mechanism of FZJN might be related to its actions in dilating blood vessels, improving microcirculation, alleviating endothelial cell damage, inhibiting activity of blood platelet, regulating coagulation-fibrolysis balance, improving metabolism of free radicals as well as lowering the level of LDL-C.


[Bronchoplasty and pulmonary arterioplasty for central-type lung cancer].
Bronchoplasty plus pulmonary arterioplasty has become one of the standard surgical operation for central-type lung cancer. The aim of this study is to review the surgical experience of bronchoplasty and pulmonary arterioplasty in treatment of central-type lung cancer. From 1987 to 2005, 56 patients with central-type lung cancer underwent bronchoplasty and pulmonary arterioplasty. There were 45 males and 11 females with a mean age of 56 years. According to pTNM classification, 18 cases were in stage IIB, and 32 in stage IIIA and 6 in stage IIIB. Histologically, there were 35 cases of squamous cell carcinoma, 14 cases of adenocarcinoma, 4 cases of small cell lung cancer and 3 cases of carcinoid. The surgical procedures included sleeve resection of bronchus for 30 cases, wedge resection of bronchus for 26 cases, and sleeve resection of pulmonary artery for 16 cases and wedge resection of pulmonary artery for 40 cases. One patient died in the perioperative period. The overall 1-, 3-, and 5-year survival rate was 79.6% (43/54), 48.1% (25/52) and 34.0% (17/50), respectively. The results suggest that bronchoplasty and pulmonary arterioplasty can decrease the proportions of total pneumonectomy and exploratory thoracotomy and expand the indication of operation. Bronchoplasty and pulmonary arterioplasty can be achieved with satisfactory outcome for central-type lung cancer, especially for those patients with advanced lesions or poor pulmonary function.


Scalable Design of Paired CRISPR Guide RNAs for Genomic Deletion.
CRISPR-Cas9 technology can be used to engineer precise genomic deletions with pairs of single guide RNAs (sgRNAs). This approach has been widely adopted for diverse applications, from disease modelling of individual loci, to parallelized loss-of-function screens of thousands of regulatory elements. However, no solution has been presented for the unique bioinformatic design requirements of CRISPR deletion. We here present CRISPETa, a pipeline for flexible and scalable paired sgRNA design based on an empirical scoring model. Multiple sgRNA pairs are returned for each target, and any number of targets can be analyzed in parallel, making CRISPETa equally useful for focussed or high-throughput studies. Fast run-times are achieved using a pre-computed off-target database. sgRNA pair designs are output in a convenient format for visualisation and oligonucleotide ordering. We present pre-designed, high-coverage library designs for entire classes of protein-coding and non-coding elements in human, mouse, zebrafish, Drosophila melanogaster and Caenorhabditis elegans. In human cells, we reproducibly observe deletion efficiencies of ≥50% for CRISPETa designs targeting an enhancer and exonic fragment of the MALAT1 oncogene. In the latter case, deletion results in production of desired, truncated RNA. CRISPETa will be useful for researchers seeking to harness CRISPR for targeted genomic deletion, in a variety of model organisms, from single-target to high-throughput scales.


Initiating the formalization of theories of cognitive aging.
Although the relevant knowledge base is still impoverished, the time may be appropriate to attempt to develop and investigate formal models of cognitive aging that incorporate explicit mechanisms to account for age differences frequently observed in measures of cognitive functioning. An initial model based on an associative network metaphor is described, in which age declines in fluid or process aspects of cognition are attributed to a reduction in either the number of simultaneously active nodes, the maximum allowable activation, or the rate of propagating activation between nodes. Results from a computer simulation are consistent at a first level of approximation with many cognitive aging phenomena, and the model is shown to provide a plausible account of age differences in an area that has previously resisted explanation. Although this particular model is only one of many that could be formulated at the present time, it is argued that more rapid progress in theoretical understanding of cognitive aging phenomena will be achieved by attempting to specify one's assumptions and hypotheses in a formal and explicit manner.


[Human rhinovirus infection promotes mast cell apoptosis and increases the release of inflammatory cytokines].
Objective To investigate the regulation of innate immune response of HMC-1 mast cells to human rhinovirus (HRV) infection. Methods Virus replication in HMC-1 cells was quantified by real-time quantitative PCR (qRT-PCR). Cell viability and apoptosis were assessed by flow cytometry. The levels of tumor necrosis factor α (TNF-α), interferon α (IFN-α), interleukin 6 (IL-6) and IL-8 produced by HMC-1 cells were measured using ELISA. Results After HRV infected HMC-1 cells, the copy numbers of virus RNA and apoptotic cells increased obviously over time, what's more, the release of TNF-α, IFN-α, IL-6 and IL-8 from HMC-1 cells ascended significantly compared with control groups. Conclusion HRV infection can promote mast cell apoptosis and enhance the release of inflammatory cytokines from mast cells.


Matching sensor ontologies through siamese neural networks without using reference alignment.
Sensors have been growingly used in a variety of applications. The lack of semantic information of obtained sensor data will bring about the heterogeneity problem of sensor data in semantic, schema, and syntax levels. To solve the heterogeneity problem of sensor data, it is necessary to carry out the sensor ontology matching process to determine correspondences among heterogeneous sensor concepts. In this paper, we propose a Siamese Neural Network based Ontology Matching technique (SNN-OM) to align the sensor ontologies, which does not require the utilization of reference alignment to train the network model. In particular, a representative concepts extraction method is presented to enhance the model's performance and reduce the time of the training process, and an alignment refining method is proposed to enhance the alignments' quality by removing the logically conflict correspondences. The experimental results show that SNN-OM is capable of efficiently determining high-quality sensor ontology alignments.


Takayasu's disease and atherosclerosis.
The aortic arch syndrome characterised by diminished or absent pulses in the arteries arising from the aortic arch has many etiologies, such as syphilitic aortitis, dissection of the aorta, atherosclerosis and Takayasu's arteritis. The diagnostic criteria of Takayasu's arteritis often do not mention histological investigations. We observed a case of an aortic arch syndrome, presenting as a classical case of Takayasu's arteritis but caused by a severe form of atherosclerosis.


Acceptability of zinc-fortified, lipid-based nutrient supplements (LNS) prepared for young children in Burkina Faso.
Micronutrient deficiencies are a public health concern among young children in low-income countries, and novel strategies are needed to improve the nutritional status of children at risk. One promising approach is the use of lipid-based nutrient supplements (LNS), which can be added to complementary food at the time of consumption. The optimal amount of zinc to include in LNS is uncertain, and concerns have been expressed about possible adverse effects of zinc on sensory characteristics of LNS. We conducted a series of acceptability studies of LNS containing either 0 or 10 mg of zinc per daily 20 g LNS dose among Burkinabe children 9-15 months old and their mothers. These acceptability studies included observations of children's consumption, maternal and child sensory reaction to the products using a 5-unit hedonic scale, a triangle test for detection of differences and a review of maternal reports of their child-feeding experiences during a 2-week home-feeding trial. The LNS products were well appreciated by the mothers and children during the sensory trials and the 2-week home-feeding trial. The addition of 10 mg zinc to LNS did not affect the consumed proportion of the offered porridge-LNS-mixture (P = 0.43). Results of the triangle test with mothers confirmed that there was no detectable difference between products containing 0 or 10 mg zinc per 20 g LNS dose. Most importantly, interviews and focus groups following the 2-week home-feeding trial indicated good acceptability of the products by mothers and their children.


Polythiophene as a Double-Electrostatic Template for Zinc Oxide and Gold: Multicomponent Nano-Objects for Enhanced Photocatalysis.
Using electrostatic self-assembly and electrostatic nanotemplating, a quaternary nanostructured system consisting of zinc oxide nanoparticles, gold nanoparticles, poly[3-(potassium-4-butanoate)thiophene-2,5-diyl] (PT), and methyltrioctylammonium chloride (MTOA) (PT-MTOA-ZnO-Au) was designed for aqueous photocatalysis. The PT-MTOA hollow sphere aggregates served as an electrostatic template for both individual inorganic nanoparticles controlling their morphology, stabilizing the nanoparticles, and acting as a photosensitizer. The hybrid structures included spherical ZnO nanoparticles with a diameter of d = 2.6 nm and spherical Au nanoparticles with d = 6.0 nm embedded in PT-MTOA hollow spheres with a hydrodynamic radius of RH = 100 nm. The ZnO nanoparticles acted as the main catalyst, while the Au nanoparticles acted as the cocatalyst. As a photocatalytic model reaction, the dye degradation of methylene blue in aqueous solution using the full spectral range from UV to visible light was tested. The photocatalytic activity was optimized by varying the Zn and Au loading ratios and was substantially enhanced regarding the components; for example, it was increased by about 61% using PT-MTOA-ZnO-Au compared to the composite without gold particles. A photocatalytic mechanism of the methylene blue degradation was proposed when catalyzed by these multicomponent nano-objects. Thus, a simple procedure of templating two different nanoparticle species within the same cocatalytically active template has been demonstrated, which can be extended to other inorganic particles, making a variety of task-specific catalysts accessible.


A pilot clinical study of low-intensity transcranial focused ultrasound in Alzheimer's disease.
Increasing attention has been paid to low-intensity transcranial focused ultrasound (tFUS) for its potential therapeutic effects in Alzheimer's disease (AD). While preclinical studies have shown promising therapeutic effects of low-intensity tFUS in AD models, its efficacy and safety remain unclear in humans. In this pilot study, we investigated the effects of low-intensity tFUS on blood-brain barrier opening, the regional cerebral metabolic rate of glucose (rCMRglu), and cognition in patients with AD. After receiving institutional review board approval, four patients with AD received tFUS to the hippocampus immediately after an intravenous injection of a microbubble ultrasound contrast agent. Sonication was delivered at low-intensity, at a pressure level below the threshold for blood-brain barrier opening. Patients underwent brain magnetic resonance imaging, 18F-fluoro-2-deoxyglucose positron emission tomography, and neuropsychological assessments before and after the tFUS procedure. A whole-brain voxel-wise paired t test was conducted to compare rCMRglu before and after tFUS. The sonication, as anticipated, did not show evidence of active blood-brain barrier opening on T1 dynamic contrast-enhanced magnetic resonance imaging. rCMRglu in the superior frontal gyrus (P<0.001), middle cingulate gyrus (P<0.001), and fusiform gyrus increased after tFUS (P=0.001). Patients demonstrated mild improvement in measures of memory, executive, and global cognitive function following tFUS. No adverse events were reported. These results suggest that hippocampal sonication with low-intensity tFUS may have beneficial effects on cerebral glucose metabolism and cognitive function in patients with AD. Further larger studies are needed to confirm the therapeutic efficacy of tFUS in AD.


Indomethacin attenuates mechanical allodynia during the organization but not the maintenance of the peripheral neuropathic pain induced by nervus ischiadicus chronic constriction injury.
The neurochemical mechanisms underlying neuropathic pain (NP) are related to peripheral and central sensitization caused by the release of inflammatory mediators in the peripheral damaged tissue and ectopic discharges from the injured nerve, leading to a hyperexcitable state of spinal dorsal horn neurons. The aim of this work was to clarify the role played by cyclooxygenase (COX) in the lesioned peripheral nerve in the development and maintenance of NP by evaluating at which moment the non-steroidal anti-inflammatory drug indomethacin, a non-selective COX inhibitor, attenuated mechanical allodynia after placing one loose ligature around the nervus ischiadicus, an adaptation of Bennett and Xie's model in rodents. NP was induced in male Wistar rats by subjecting them to chronic constriction injury (CCI) of the nervus ischiadicus, placing one loose ligature around the peripheral nerve, and a sham surgery (without CCI) was used as control. Indomethacin (2 mg/kg) or vehicle was intraperitoneally and acutely administered in each group of rats and at different time windows (1, 2, 4, 7, 14, 21, and 28 days) after the CCI or sham surgical procedures, followed by von Frey's test for 30 min. The data showed that indomethacin decreased the mechanical allodynia threshold of rats on the first, second, and fourth days after CCI (P<0.05). These findings suggested that inflammatory mechanisms are involved in the induction of NP and that COX-1 and COX-2 are involved in the induction but not in the maintenance of NP.


Mid-infrared plasmonic inductors: enhancing inductance with meandering lines.
We present a mid-infrared inductor that when applied to an extraordinary transmission hole array produces a strong redshift of the resonant peak accompanied by an unprecedented enlargement of the operation bandwidth. The importance of the result is twofold: from a fundamental viewpoint, the direct applicability of equivalent circuit concepts borrowed from microwaves is demonstrated, in frequencies as high as 17 THz upholding unification of plasmonics and microwave concepts and allowing for a simplification of structure design and analysis; in practical terms, a broadband funnelling of infrared radiation with fractional bandwidth and efficiency as high as 97% and 48%, respectively, is achieved through an area less than one hundredth the squared wavelength, which leads to an impressive accessible strong field localization that may be of great interest in sensing applications.


Expression and clinical significance of basic transcription factor 3 in nasopharyngeal carcinoma.
Basic transcription factor 3 (BTF3), a transcription factor and modulator of apoptosis, is differentially expressed in carcinoma. To acquire further understanding of the involvement of BTF3 in carcinoma, the present study analyzed the expression of BTF3, as well as its role in cell function in nasopharyngeal carcinoma (NPC). BTF3 transcription rates in human NPC samples (n=46) and adjacent normal tissue samples (n=46) were analyzed using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. BTF3-silencing in NPC cells was performed via specific small interfering RNA molecules. The function of BTF3 was analyzed by proliferation assays and colony forming assays using a Cellomic assay system. The positive expression rates of BTF3 were significantly increased in cancerous tissues compared with those in adjacent tissues (P<0.05). In addition, BTF3-silencing decreased cell proliferation and colony formation (P<0.01) in TCA-8113 and 5-8F cells. BTF3 is overexpressed in NPC, and its silencing is associated with decreased cell proliferation and colony formation, enhanced apoptosis and cell cycle regulation of TCA-8113 and 5-8F cells.


Biomarkers of Endothelial Activation Are Associated with Poor Outcome in Critical Illness.
Endothelial activation plays a role in organ dysfunction in the systemic inflammatory response syndrome (SIRS). Angiopoietin-1 (Ang-1) promotes vascular quiescence while angiopoietin-2 (Ang-2) mediates microvascular leak. Circulating levels of Ang-1 and Ang-2 in patients with SIRS could provide insight on risks for organ dysfunction and death distinct from inflammatory proteins. In this study, we determined if biomarkers of endothelial activation and inflammation exhibit independent associations with poor outcomes in SIRS. We studied 943 critically ill patients with SIRS admitted to an Intensive Care Unit (ICU) of an academic medical center. We measured plasma levels of endothelial markers (Ang-1, Ang-2, soluble vascular cell adhesion molecule-1 (sVCAM-1)) and inflammatory markers (interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte-colony stimulating factor (G-CSF), soluble tumor necrosis factor receptor-1 (sTNFR-1)) within 24 hours of enrollment. We tested for associations between each marker and 28 day mortality, shock, and day 3 sequential organ failure assessment (SOFA) score. For 28 day mortality, we performed sensitivity analysis for those subjects with sepsis and those with sterile inflammation. We used multivariate models to adjust for clinical covariates and determine if associations identified with endothelial activation markers were independent of those observed with inflammatory markers. Higher levels of all biomarkers were associated with increased 28 day mortality except levels of Ang-1 which were associated with lower mortality. After adjustment for comorbidities and sTNFR-1 concentration, a doubling of Ang-1 concentration was associated with lower 28 day mortality (Odds ratio (OR) = 0.81; p<0.01), shock (OR = 0.82; p<0.001), and SOFA score (β = -0.50; p<0.001), while Ang-2 concentration was associated with increased mortality (OR = 1.55; p<0.001), shock (OR = 1.51; p<0.001), and SOFA score (β = +0.63; p<0.001). sVCAM-1 was not independently associated with SIRS outcomes. In critically ill patients with SIRS, early measurements of Ang-1 and Ang-2 are associated with death and organ dysfunction independently of simultaneously-measured markers of inflammation.


An Adolescent in the Emergency Department with Pelvic Pain: Imperforate Hymen.
Imperforate hymen is a cause of pelvic pain in adolescent females who have not reached menarche. There is scant literature on adolescent gynecology for the emergency provider. The literature about the adolescent with imperforate hymen is usually in a case report format. A patient with imperforate hymen is presented in this article. The purpose of this case study was to review the urgent presentation of imperforate hymen. Advanced emergency providers need to consider the possibility of imperforate hymen in the list of differential diagnoses for pelvic pain in adolescent females. Prompt diagnosis of imperforate hymen allows the emergency provider to initiate gynecological referral for definitive treatment.


Oxidoreductase interactions include a role for ERp72 engagement with mutant thyroglobulin from the rdw/rdw rat dwarf.
Newly synthesized thyroglobulin (Tg), the secretory glycoprotein that serves as precursor in thyroid hormone synthesis, normally forms transient covalent protein complexes with oxidoreductases of the endoplasmic reticulum (ER). The Tg-G2320R mutation is responsible for congenital hypothyroidism in rdw/rdw rats, in which a lack of secondary thyroid enlargement (goiter) implicates death of thyrocytes as part of disease pathogenesis. We found that mutant Tg-G2320R was retained within the ER with no detectable synthesis of thyroxine, had persistent exposure of free cysteine thiols, and was associated with activated ER stress response but incomplete ER-associated degradation (ERAD). Tg-G2320R associated with multiple ER resident proteins, most notably ERp72, including covalent Tg-ERp72 interactions. In PC Cl3 thyrocytes, inducible overexpression of ERp72 increased the ability of cells to maintain Tg cysteines in a reduced state. Noncovalent interactions of several ER chaperones with newly synthesized Tg-G2320R diminished over time in parallel with ERAD of the mutant protein, yet a small ERAD-resistant Tg fraction remained engaged in covalent association with ERp72 even 2 days post-synthesis. Such covalent protein aggregates may set the stage for apoptotic thyrocyte cell death, preventing thyroid goiter formation in rdw/rdw rats.


A Colorimetric Immunoassay Based on g-C3N4@Fe3O4 Nanocomposite for Detection of Carcinoembryonic Antigen.
We proposed a colorimetric immunosensor based on g-C3N4@Fe3O4 nanocomposite-mediated transformation strategy for sensitive detection of carcinoembryonic antigen (CEA). The g-C3N4@Fe3O4 nanocomposite was synthesized and characterized by the scanning electron microscope (SEM), energy dispersive X-ray spectra (EDX), X-ray powder diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Fe3+ derived from g-C3N4@Fe3O4 nanocomposite could combine with sodium salicylate to form purple complex products. Based on this color development, the sandwich colorimetric immunoassay was built by utilizing g-C3N4@Fe3O4 nanocomposite as nanolabels on the microplate. With the increasement of CEA concentration, the purple color showed a gradient change. Under optimal conditions, the linearity range is 0.001-50 ng/mL with the detection limit of 0.35 pg/mL for CEA. More importantly, the colorimetric immunoassay has good selectivity, specificity, repeatability, and stability.


Factors Associated With Diabetes Distress Among Patients With Poorly Controlled Type 2 Diabetes.
Examine factors associated with increased diabetes distress (DD) among patients with type 2 diabetes with DD assessed by Diabetes Distress Scale (DDS) total and subscale scores (emotional burden, physician-related distress, regimen-related distress, and interpersonal distress). Cross-sectional analysis of data from veterans with persistently poorly controlled diabetes mellitus. Multivariable linear regression models included baseline patient characteristics (independent variables) and DDS total and subscale scores (dependent variable). The cohort's (N = 248) mean age was 58 years (SD 8.3); 21% were female, 79% were non-White, and 5% were Hispanic/Latinx. Mean hemoglobin A1c (HbA1c) was 9.8%, and 37.5% had moderate to high DD. Hispanic/Latinx ethnicity (β=0.41; 95% CI 0.01, 0.80), baseline HbA1c (0.07; 95% CI 0.01,0.13), and higher Personal Health Questionnaire-8 (PHQ-8) scores (0.07; 95% CI 0.05, 0.09) were associated with higher total DD. Hispanic/Latinx ethnicity (0.79; 95% CI 0.25, 1.34) and higher PHQ-8 (0.05; 95% CI 0.03, 0.08) were associated with higher interpersonal-related distress. Higher HbA1c (0.15; 95% CI 0.06, 0.23) and higher PHQ-8 scores (0.10; 95% CI 0.07, 0.13) were associated with higher regimen-related distress. The use of basal insulin (0.28; 95% CI 0.001, 0.56) and higher PHQ-8 (0.02; 95% CI 0.001, 0.05) were associated with higher physician-related distress. Higher PHQ-8 (0.10; 95% CI 0.07, 0.12) was associated with higher emotional burden. Hispanic/Latinx ethnicity, depressive symptoms, uncontrolled hyperglycemia, and insulin use were associated with higher risk for DD. Future research should explore these relationships, and interventions designed to reduce diabetes distress should consider accounting for these factors.


Comparison of specific expiratory, inspiratory, and combined muscle training programs in COPD.
Respiratory muscle weakness may contribute to dyspnea and exercise limitation in patients with significant COPD. In an attempt to reduce the severity of breathlessness and to improve exercise tolerance, inspiratory muscle training has been applied in many COPD patients. On the other hand, there is a paucity of data related to expiratory muscle performance and training in COPD. Thirty-two patients with significant COPD (ie, mean FEV(1), 37% of predicted) were recruited for the study. The patients were randomized into four groups: eight patients were assigned to receive specific expiratory muscle training (SEMT); eight patients received specific inspiratory muscle training (SIMT); eight patients received SEMT and SIMT (ie, the SEMT + SIMT group); and eight patients who were assigned to a control group received training with very low load. All patients trained daily, six times a week, with each session consisting of one half hour of training, for 3 months. Spirometry, respiratory muscle strength and endurance, 6-min walk test distance, the perception of dyspnea, and the Mahler baseline dyspnea index (BDI) were measured before and following training. Training caused a statistically significant specific increase in the expiratory muscle strength and endurance (in the SEMT and SEMT + SIMT groups) and in the inspiratory muscle strength and endurance (in the SIMT and SEMT + SIMT groups). There was significant increase in the distance walked in 6 min in the SEMT, SIMT, and SEMT + SIMT groups. However, the increase in the SIMT and SEMT + SIMT groups was significantly greater than that in the SEMT group. There was a statistically significant increase in the BDI, and a decrease in the mean Borg score during breathing against resistance in the SIMT and SEMT + SIMT groups, with no changes in the SEMT and control groups. The inspiratory and expiratory muscles can be specifically trained with improvement of both muscle strength and endurance. The improvement in the inspiratory muscle performance is associated with an increase in the 6-min walk test distance and the sensation of dyspnea. There is no additional benefit gained by combining SIMT with SEMT, compared to using SIMT alone.


Estimating individualized treatment rules in longitudinal studies with covariate-driven observation times.
The sequential treatment decisions made by physicians to treat chronic diseases are formalized in the statistical literature as dynamic treatment regimes. To date, methods for dynamic treatment regimes have been developed under the assumption that observation times, that is, treatment and outcome monitoring times, are determined by study investigators. That assumption is often not satisfied in electronic health records data in which the outcome, the observation times, and the treatment mechanism are associated with patients' characteristics. The treatment and observation processes can lead to spurious associations between the treatment of interest and the outcome to be optimized under the dynamic treatment regime if not adequately considered in the analysis. We address these associations by incorporating two inverse weights that are functions of a patient's covariates into dynamic weighted ordinary least squares to develop optimal single stage dynamic treatment regimes, known as individualized treatment rules. We show empirically that our methodology yields consistent, multiply robust estimators. In a cohort of new users of antidepressant drugs from the United Kingdom's Clinical Practice Research Datalink, the proposed method is used to develop an optimal treatment rule that chooses between two antidepressants to optimize a utility function related to the change in body mass index.


Regional distribution of imipramine, desipramine and specific [3H]desipramine binding sites in the rat brain after acute and chronic treatment with imipramine.
Regional distribution of imipramine, desipramine and specific [3H]desipramine binding sites in the rat brain after acute and chronic treatment of rats with imipramine has been investigated. Both substances were distributed unevenly within rat brain after single and prolonged administration of imipramine. This was partly connected with the regional cerebral blood flow, lipid content in the regions and lipophilicity of the substances investigated. It was also found that the number of specific [3H]desipramine binding sites was different in the various brain areas, and that prolonged administration of imipramine led to a decrease of their number in some of those regions. No correlation was found between the regional cerebral distribution of desipramine and the regional density of specific [3H]desipramine binding sites.


Impaired function of macrophage Fc gamma receptors and bacterial infection in alcoholic cirrhosis.
Bacterial infection is a frequent and often fatal complication in patients with cirrhosis. Macrophages play an important part in the host defense against infection because their Fc gamma receptors recognize antibody-coated bacteria. We prospectively studied macrophage Fc gamma-receptor function in vivo and in vitro in 49 patients with alcoholic cirrhosis, 10 alcoholics without cirrhosis, and 20 normal volunteers. The clearance of IgG-sensitized autologous red cells was decreased in 37 of the 49 patients with cirrhosis but in none of the subjects without cirrhosis. In the 49 patients clearance was inhibited by a mean (+/- SE) of 47 +/- 3 percent at 1 hour and 53 +/- 3 percent at 1 1/2 hours, as compared with the clearance in the normal controls (P < 0.001). The impairment of macrophage Fc gamma-receptor-dependent clearance correlated with the degree of liver insufficiency but not with age, sex, nutritional status, HLA haplotype, or the presence of circulating immune complexes. The clearance of unsensitized and heat-altered autologous erythrocytes was normal. In vitro recognition of IgG-sensitized red cells by monocytes from the patients was not significantly decreased. During a two-year follow-up period, 11 patients had severe bacterial infections, and in 4 they were fatal. The mean clearance of IgG-sensitized red cells in these 11 patients (half-time, 126.2 +/- 22 hours) was significantly impaired, as compared with that in the 38 patients without severe infection (half-time, 32.2 +/- 18 hours, P < 0.001). The function of macrophage Fc gamma receptors is impaired in patients with alcoholic cirrhosis, and this impairment probably contributes to the high incidence of bacterial infections among such patients.


A COMPARISON OF GENETIC AND PHENOTYPIC CORRELATIONS.
Genetic variances and correlations lie at the center of quantitative evolutionary theory. They are often difficult to estimate, however, due to the large samples of related individuals that are required. I investigated the relationship of genetic- and phenotypic-correlation magnitudes and patterns in 41 pairs of matrices drawn from the literature in order to determine their degree of similarity and whether phenotypic parameters could be used in place of their genetic counterparts in situations where genetic variances and correlations cannot be precisely estimated. The analysis indicates that squared genetic correlations were on average much higher than squared phenotypic correlations and that genetic and phenotypic correlations had only broadly similar patterns. These results could be due either to biological causes or to imprecision of genetic-correlation estimates due to sampling error. When only those studies based on the largest sample sizes (effective sample size of 40 or more) were included, squared genetic-correlation estimates were only slightly greater than their phenotypic counterparts and the patterns of correlation were strikingly similar. Thus, much of the dissimilarity between phenotypic- and genetic-correlation estimates seems to be due to imprecise estimates of genetic correlations. Phenotypic correlations are likely to be fair estimates of their genetic counterparts in many situations. These further results also indicate that genetic and environmental causes of phenotypic variation tend to act on growth and development in a similar manner.


Molecular imaging contrast media for visualization of liver function.
Diagnosis of liver disease has improved because of progress in imaging technology. Among the imaging methods, magnetic resonance imaging (MRI) has the advantage of a lack of radiation exposure, but the basis of the method (imaging of hydrogen atoms in water molecules) makes it hard to detect changes in tissue or the location of the diseased tissue in the liver. The aims of this study are to develop new contrast media for visualization of functional changes in the liver and to check the effectiveness of the media. We developed a new molecular imaging contrast media that targets the asialoglycoprotein receptor (ASGP-R), a membrane protein that is specific to hepatocytes. We first checked the contrast media diameter and the cytotoxicity. Next, we examined the interaction of the media with ASGP-R through observation of fluorescein isothiocyanate (FITC)-labeled molecular imaging contrast media bound to normal hepatocellular ASGP-R using confocal laser scanning microscopy. Finally, we used MRI to observe hepatocyte interactions with the molecular imaging contrast media. The contrast media forms a nanoparticle of about 30 nm diameter in aqueous solution and the cytotoxicity is low. In vitro, the media has high specificity for ASGP-R in normal rat hepatocyte RLN-8 cells and this interaction was blocked by lactose (which has a similar molecular structure to that of galactose) and by an anti-ASGP-R antibody. The contrast media markedly enhanced T1-weighted images in MRI of normal rat hepatocytes compared to the signal strength for rat liver cancer cells. We have shown that our new contrast media for molecular imaging of hepatocytes by MRI is effective in vitro.


Evidence for social phobia and other psychiatric disorders in adults who were growth hormone deficient during childhood.
We assessed the psychiatric status of 21 growth hormone deficient (GHD) adults who had been treated with growth hormone (GH) for short stature during childhood. Eight individuals (38%) were found to have undiagnosed social phobia. On a psychometric battery, the scores of GHD subjects with social phobia corresponded closely to those of a matched group of psychiatric patients with social phobia. Because these psychiatric symptoms have deleterious effects on quality of life, social function, and productivity, the physician should be alert to obtain psychiatric assessment of patients with GHD.


Distinct molecular patterns of TDP-43 pathology in Alzheimer's disease: relationship with clinical phenotypes.
The co-existence of multiple pathologies and proteins is a common feature in the brains of cognitively impaired elderly individuals. Transactive response DNA-binding protein (TDP-43) has been discovered to accumulate in limbic brain regions of a portion of late-onset Alzheimer's disease (AD) patients, in addition to amyloid-β and τ protein. However, it is not yet known whether the TDP-43 species in the AD brain differ in their composition, when compared among different AD cases and to frontotemporal lobar degeneration cases with TDP-43 inclusions (FTLD-TDP). Furthermore, it is not known whether TDP-43 pathology in AD is related to symptoms of the frontotemporal dementia (FTD) spectrum. In this study, we investigated the molecular pattern of TDP-43 lesions with five different antibodies against different phosphorylated (pTDP-43) and non-phosphorylated TDP-43 epitopes. We analyzed a cohort of 97 autopsy cases, including brains from 20 non-demented individuals, 16 cognitively normal pathologically-defined preclinical AD (p-preAD), 51 neuropathologically-confirmed AD cases and 10 FTLD-TDP cases as positive controls. We observed distinct neuropathological patterns of TDP-43 among AD cases. In 11 neuropathologically-confirmed AD cases we found dystrophic neurites (DNs), neuronal cytoplasmic inclusions (NCIs) and/or neurofibrillary tangle (NFT)-like lesions not only positive for pTDP-43409/410, but also for pTDP-43 phosphorylated at serines 403/404 (pTDP-43403/404) and non-phosphorylated, full-length TDP-43, as seen with antibodies against C-terminal TDP-43 and N-terminal TDP-43. These cases were referred to as ADTDP + FL because full-length TDP-43 was presumably present in the aggregates. FTLD-TDP cases showed a similar molecular TDP-43 pattern. A second pattern, which was not seen in FTLD-TDP, was observed in most of p-preAD, as well as 30 neuropathologically-confirmed AD cases, which mainly exhibited NFTs and NCIs stained with antibodies against TDP-43 phosphorylated at serines 409/410 (pTDP-43409, pTDP-43409/410). Because only phosphorylated C-terminal species of TDP-43 could be detected in the lesions we designated these AD cases as ADTDP + CTF. Ten AD cases did not contain any TDP-43 pathology and were referred to as ADTDP-. The different TDP-43 patterns were associated with clinically typical AD symptoms in 80% of ADTDP + CTF cases, 63,6% of ADTDP + FL and 100% of the ADTDP- cases. On the other hand, clinical symptoms characteristic for FTD were observed in 36,4% of ADTDP + FL, in 16,6% of the ADTDP + CTF, and in none of the ADTDP- cases. Our findings provide evidence that TDP-43 aggregates occurring in AD cases vary in their composition, suggesting the distinction of different molecular patterns of TDP-43 pathology ranging from ADTDP- to ADTDP + CTF and ADTDP + FL with possible impact on their clinical picture, i.e. a higher chance for FTD-like symptoms in ADTDP + FL cases.


Chroma-dependence of CIEDE2000 acceptability thresholds for dentistry.
Determine visual 50:50% color difference acceptability thresholds (AT) for regions of the dental color space with varying chromaticity. A 40-observer panel belonging to two different groups (dentists and laypersons) evaluated 144 dental resin composites pairs (divided in three different sets of 48 pairs according to chroma value: Low Chroma (LC), Medium Chroma (MC) and High Chroma (HC) placed 40 cm away and inside of a viewing cabinet (D65 Standard light source; diffuse/0° geometry). A Takagi-Sugeno-Kang (TSK) fuzzy approximation was used for fitting the data points and calculate the 50:50% acceptability thresholds in CIEDE2000. A paired t-test was used to evaluate the statistical significance between thresholds differences and Bonferroni correction was applied. The CIEDE2000 50:50% AT were ∆E00 = 2.84, ∆E00 = 2.31 and ∆E00 = 1.80 for LC, MC and HC sets of sample pairs, respectively. The 50:50% AT values were statistically significant between the different sets of sample pairs, as well as the 50:50% AT values obtained for different observer groups. 50:50% CIEDE2000 acceptability thresholds for dentistry are significantly different depending on the chromaticity of the samples. Observers show higher acceptability for more achromatic samples (low chroma value) than for more chromatic samples. The difference in the AT for distinct regions of the dental color space can assist professionals as a quality control tool to assess clinical performance and interpret visual and instrumental findings in clinical dentistry, dental research, and subsequent standardization processes.


Progressive Learning of 3D Reconstruction Network From 2D GAN Data.
This paper presents a method to reconstruct high-quality textured 3D models from single images. Current methods rely on datasets with expensive annotations; multi-view images and their camera parameters. Our method relies on GAN generated multi-view image datasets which have a negligible annotation cost. However, they are not strictly multi-view consistent and sometimes GANs output distorted images. This results in degraded reconstruction qualities. In this work, to overcome these limitations of generated datasets, we have two main contributions which lead us to achieve state-of-the-art results on challenging objects: 1) A robust multi-stage learning scheme that gradually relies more on the models own predictions when calculating losses, 2) A novel adversarial learning pipeline with online pseudo-ground truth generations to achieve fine details. Our work provides a bridge from 2D supervisions of GAN models to 3D reconstruction models and removes the expensive annotation efforts. We show significant improvements over previous methods whether they were trained on GAN generated multi-view images or on real images with expensive annotations. Please visit our web-page for 3D visuals: https://research.nvidia.com/labs/adlr/progressive-3d-learning.


Negotiating conservation and competition: national parks and 'victory-over-communism' diplomacy in South Korea.
Focusing on South Korean biologists and their efforts to establish national parks in the 1960s and 1970s, I illuminate the ways in which they negotiated their relationship with the ecological diplomacy of the International Union for Conservation of Nature (IUCN) and the anti-communist and developmentalist diplomacy of the South Korean government. To justify their activities, these South Korean biologists emphasized the importance of nature conservation activities in the competition for international recognition and economic development with their northern counterparts. The national-park initiative was thus subsumed into the politics of this legitimacy competition between the two Koreas, or what I call 'victory-over-communism' diplomacy. The IUCN's influence over South Korea was limited to the extent that both the government and scientists recognized the diplomatic merit they could gain in the context of their Cold War competition and developmentalism. It is also shown how, during the short detente period of the two Koreas, South Korean biologists used victory-over-communism diplomacy to renew their government's attention to their activities. This Korean episode contributes to the wider perspective of decentralizing the Cold War history of environmental diplomacy in the free-world bloc by illustrating the importance of its entanglement with the Cold War politics surrounding Asian developmentalism.


Analysis of human and organizational factors that influence mining accidents based on Bayesian network.
Purpose. The present study aimed to analyze human and organizational factors involved in mining accidents and determine the relationships among these factors. Materials and methods. In this study, the human factors analysis and classification system (HFACS) was combined with Bayesian network (BN) in order to analyze contributing factors in mining accidents. The BN was constructed based on the hierarchical structure of HFACS. The required data were collected from a total of 295 cases of Iranian mining accidents and analyzed using HFACS. Afterward, prior probability of contributing factors was computed using the expectation-maximization algorithm. Sensitivity analysis was applied to determine which contributing factor had a higher influence on unsafe acts to select the best intervention strategy. Results. The analyses showed that skill-based errors, routine violations, environmental factors and planned inappropriate operation had higher relative importance in the accidents. Moreover, sensitivity analysis revealed that environmental factors, failed to correct known problem and personnel factors had a higher influence on unsafe acts. Conclusion. The results of the present study could provide guidance to help safety and health management by adopting proper intervention strategies to reduce mining accidents.


Fournier gangrene: diagnosis with scrotal US.
Skin thickening and subcutaneous air were detected at ultrasound (US) of the scrotum in a patient with normal-appearing testicles and signs and symptoms suggestive of an acute inflammatory process, such as epidydimitis or orchitis. The patient was found to have Fournier gangrene. In more advanced cases, US can demonstrate that this skin thickening and subcutaneous air extends posteriorly to include the perineum and buttocks. Because of the high mortality of this mixed anaerobic and aerobic infection, it is important to recognize Fournier gangrene early so that the correct surgical and medical treatment can be promptly instituted. To the authors' knowledge, this is the first description of the US characteristics of Fournier gangrene.


Design, characterization, and in vitro cellular inhibition and uptake of optimized genistein-loaded NLC for the prevention of posterior capsular opacification using response surface methodology.
This study was to design an innovative nanostructured lipid carrier (NLC) for drug delivery of genistein applied after cataract surgery for the prevention of posterior capsular opacification. NLC loaded with genistein (GEN-NLC) was produced with Compritol 888 ATO, Gelucire 44/14 and Miglyol 812N, stabilized by Solutol(®) HS15 by melt emulsification method. A 2(4) central composite design of 4 independent variables was performed for optimization. Effects of drug concentration, Gelucire 44/14 concentration in total solid lipid, liquid lipid concentration, and surfactant concentration on the mean particle size, polydispersity index, zeta potential and encapsulation efficiency were investigated. Analysis of variance (ANOVA) statistical test was used to assess the optimization. The optimized GEN-NLC showed a homogeneous particle size of 90.16 nm (with PI=0.33) of negatively charged surface (-25.08 mv) and high encapsulation efficiency (91.14%). Particle morphology assessed by TEM revealed a spherical shape. DSC analyses confirmed that GEN was mostly entrapped in amorphous state. In vitro release experiments indicated a prolonged and controlled genistein release for 72 h. In vitro growth inhibition assay showed an effective growth inhibition of GEN-NLCs on human lens epithelial cells (HLECs). Preliminary cellular uptake test proved a enhanced penetration of genistein into HLECs when delivered in NLC.


[Localized pigmented vellonodular sunovitis, cause of knee hemarthrosis].
The pigmented vellonodular sinovitis (PVNS) is benign neoplasm with synovial proliferation and hemosiderin deposit, characterized by large compromising joints, especially the knee. At present, two variants of clinics, the diffuse form (PVNSD) and the localized (PVNSL) are described. Arthroscopic synovectomy and radiosynoviorthesis (RSO) is the treatment that has shown the best functional results. Nuclear magnetic resonance is an appropriate method for conducting the diagnosis of PVNSL.


Sustainable biosolids--welcomed practice through community partnership and the consequential economic benefits.
Technically, most people agree that conserving soil organic matter and completing nutrient cycles by applying animal manures, treated organic wastes and biosolids to land is the most sustainable option in the majority of situations. It is also generally the least expensive. There has been a huge amount of research into the hazards, and this has concluded that the risks can be managed to acceptable levels. But there has been insufficient attention to communicating this knowledge, as so often in the scientific and technological arena. Perception is reality. Nowadays compliance with regulations (whilst essential) is not enough; public and stakeholder attitudes can be of decisive importance. Sometimes policy-makers speculate what public attitudes might be without really asking them. This paper will describe an initiative to create a partnership open to anybody with an interest in the use of organic materials on land to develop consensus on good practice and to share knowledge. It summarises an attitude survey of more than 140 organisations, which was then debated at a workshop in July 2002. The conclusion from this study was that all parties considered a partnership is essential to share knowledge, build mutual trust and agree practices that are welcomed by all in the food chain. The paper will describe the steps to establishing a partnership organisation, its aims and objectives, the work to date and the plans for the future. The Environment Agency considers this very important and has largely funded the work to date. The consequences of failing to establish welcomed practices would be loss of the facility to use organic resources on land.


Role of external ventriculostomy in the management of fever after hemispherectomy.
Fever is a common occurrence after cerebral hemispherectomy in children and prolongs the hospital stay. The authors determined whether an external ventriculostomy might reduce the incidence of fever following a hemispherectomy. The postoperative courses of 27 patients who had undergone cerebral hemispherectomy for intractable seizures were retrospectively analyzed. Thirteen children underwent an external ventriculostomy, and only 1 had an elevated axillary body temperature of > or = 39 degrees C during the postoperative period. Among 14 patients who did not undergo an external ventriculostomy, 7 had a posthemispherectomy fever of > or = 39 degrees C. Patients who underwent an external ventriculostomy had a lower risk of postoperative fever compared with those who did not undergo the procedure (8 vs 50%, respectively; p = 0.03, Fisher exact test). None of the patients had an infection accounting for the cause of the fever. The hospital stay for patients who had undergone postoperative external ventriculostomy was significantly shorter than for those who had not (7.2 +/- 2 vs 11.3 +/- 5 days, respectively; p = 0.01, Student t-test). The use of external ventriculostomy following hemispherectomy for intractable epilepsy in children reduces the incidence of postoperative fever due to infection.


Gelsolin Promotes Cancer Progression by Regulating Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma and Correlates with a Poor Prognosis.
Gelsolin (GSN), a cytoskeletal protein, is frequently overexpressed in different cancers and promotes cell motility. The biological function of GSN in hepatocellular carcinoma (HCC) and its mechanism remain unclear. The expression of GSN was assessed in a cohort of 188 HCC patients. The effects of GSN on the migration and invasion of tumour cells were examined. Then, the role of GSN in tumour growth in vivo was determined by using a cancer metastasis assay. The possible mechanism by which GSN promotes HCC progression was explored. As a result, GSN was overexpressed in HCC tissues. High GSN expression was significantly correlated with late Edmondson grade, encapsulation, and multiple tumours. Patients with high GSN expression had worse overall survival (OS) and disease-free survival (DFS) than those with low GSN expression. GSN expression was identified as an independent risk factor in both OS (hazard risk (HR) = 1.620, 95% confidence interval (CI) = 1.105-2.373, P < 0.001) and DFS (HR = 1.744, 95% CI = 1.205-2.523, P=0.003). Moreover, GSN knockdown significantly inhibited the migration and invasion of HCC tumour cells, while GSN overexpression attenuated these effects by regulating epithelial-mesenchymal transition (EMT) In conclusion, GSN promotes cancer progression and is associated with a poor prognosis in HCC patients. GSN promotes HCC progression by regulating EMT.


Drug interaction between valproic acid and carbapenems in patients with epileptic seizures.
Valproic acid (VPA) is a widely used antiepileptic drug (AED). When carbapenems are concomitantly used with VPA, the serum levels of VPA may decrease and aggravate seizures. The aim of this study was to evaluate the risk factors associated with decreased serum VPA levels and clinical outcome in patients being treated with a combination of carbapenems and VPA. Fifty-four adult patients who were treated with VPA for epileptic seizures concomitant with carbapenems for the treatment of infections were evaluated in this study. Serum VPA levels were measured before and during combination therapy with VPA and carbapenems, and the change in serum VPA levels was calculated. The risk factors related to the decrease in serum VPA levels and clinical outcomes were evaluated. Our results show that VPA concentrations were reduced to subtherapeutic levels after the introduction of carbapenems. The reduction in VPA concentrations was found within 24 hours of the start of treatment with carbapenems. VPA levels continuously declined while the combination of treatments was used, which aggravated epileptic seizures in 48% of the patients. Renal disease and enzyme-inducing AEDs were risk factors that contributed to the severity of reduced serum VPA levels during combined treatment with carbapenems. This study suggests that clinicians need to be aware of the reduction of VPA concentrations to subtherapeutic levels and the aggravation of seizures while patients are treated with a combination of carbapenems and VPA.


The Effect of Cervical Paravertebral Extensor Degeneration on Sagittal Alignment and Functional Status of Cervical Spine in Patients With Cervical Spondylotic Myelopathy.
This was a cross-sectional study. The objective of this study was to assess cervical paravertebral extensor degeneration in patients with cervical spondylotic myelopathy (CSM) and its impact on the sagittal parameters and functional status of the cervical spine. Paravertebral extensor degeneration is well-studied in CSM; however, the effect of extensor degeneration on the sagittal balance and functional status of the cervical spine is unclear. We enrolled 52 CSM patients (CSM group) and 52 age-matched and sex-matched healthy adults (control group). The C2-C7 and C0-C2 Cobb angles (CAs), C7 slope, T1 slope, cervical arc cord distance, cervical tilt (CERT), cranial tilt (CRAT), and C2-C7 sagittal vertical axis (SVA) were measured. The cross-sectional areas of the deep extensors (DEA), superficial extensors (SEA), and cervical vertebral body (VBA) of C4-C7 were measured. DEA/VBA and SEA/VBA were used to quantify the extensor volume. We analyzed the fatty infiltration ratio of the deep (DFIR) and superficial extensors (SFIR). The Visual Analog Scale, Neck Disability Index, and modified Japanese Orthopaedic Association Scale scores of the CSM group were calculated. The DEA/VBA was significantly lower and the DFIR and SFIR were significantly higher in the CSM group. The C4 DEA/VBA correlated with the C2-C7 SVA, C2-C7 CA, CERT, and the Neck Disability Index and modified Japanese Orthopaedic Association Scale scores (r=-0.608, 0.291, 0.335,-0.649, and 0.409, respectively). The DEA/VBA of C5 correlated with the cervical arc cord distance and CRAT (r=-0.350 and -0.356, respectively). The C4 DFIR correlated with the C2-C7 SVA, C2-C7 CA, and the Visual Analog Scale (r=0.286, -0.297, and 0.429, respectively). The SFIR of C7 correlated with the T1 slope and C7 slope (r=0.368 and 0.319, respectively). Paravertebral extensor degeneration negatively impacts the sagittal sequence and functional status of the cervical spine in CSM patients. Our study provides an insight into understanding the significance of cervical muscular degeneration in CSM patients. Level III.


Effects of Preseason Training on the Sleep Characteristics of Professional Rugby League Players.
To investigate the influence of daily and exponentially weighted moving training loads on subsequent nighttime sleep. Sleep of 14 professional rugby league athletes competing in the National Rugby League was recorded using wristwatch actigraphy. Physical demands were quantified using GPS technology, including total distance, high-speed distance, acceleration/deceleration load (SumAccDec; AU), and session rating of perceived exertion (AU). Linear mixed models determined effects of acute (daily) and subacute (3- and 7-d) exponentially weighted moving averages (EWMA) on sleep. Higher daily SumAccDec was associated with increased sleep efficiency (effect-size correlation; ES = 0.15; ±0.09) and sleep duration (ES = 0.12; ±0.09). Greater 3-d EWMA SumAccDec was associated with increased sleep efficiency (ES = 0.14; ±0.09) and an earlier bedtime (ES = 0.14; ±0.09). An increase in 7-d EWMA SumAccDec was associated with heightened sleep efficiency (ES = 0.15; ±0.09) and earlier bedtimes (ES = 0.15; ±0.09). The direction of the associations between training loads and sleep varied, but the strongest relationships showed that higher training loads increased various measures of sleep. Practitioners should be aware of the increased requirement for sleep during intensified training periods, using this information in the planning and implementation of training and individualized recovery modalities.