Patterns of immunoglobulin G responses to egg and peanut allergens are distinct: ovalbumin-specific immunoglobulin responses are ubiquitous, but peanut-specific immunoglobulin responses are up-regulated in peanut allergy.
The clinical significance of food-specific IgG subclasses in food allergy and tolerance remains unclear. Specific IgG titres are often reported in non-standardized units, which do not allow comparisons between studies or allergens. To quantify, in absolute units, ovalbumin (OVA)- and peanut-specific IgG levels in children with peanut or egg allergy (active or resolved) and in non-allergic controls. Methods Children aged 1-15 years were recruited. Peanut allergy was diagnosed by convincing history and a 95% predictive level of specific IgE; egg allergy or resolution was confirmed by oral challenge. Serum IgG, IgG1 and IgG4 levels (microg/mL) to OVA and peanut extract were quantified by ELISA. OVA- and peanut-specific IgG was detected in all subjects. In non-allergic controls (n=18), OVA-specific IgG levels were significantly higher than peanut-specific IgG (median microg/mL IgG=15.9 vs. 2.2, IgG1=1.3 vs. 0.6, IgG4=7.9 vs. 0.7; P<0.01). There were no differences in OVA-specific IgG, IgG1 and IgG4 between egg-allergic (n=40), egg-resolved (n=22) and control (n=18) subjects. In contrast, peanut-specific IgG (median microg/mL IgG=17.0, IgG1=3.3, IgG4=5.2) were significantly higher in peanut-allergic subjects (n=59) compared with controls and with non-peanut-sensitized but egg-allergic subjects (n=26). Overall, the range of IgG4 was greater than IgG1, and IgG4 was the dominant subclass in >60% of all subjects. OVA-specific IgG levels of egg-allergic, egg-resolved or control groups are not distinguishable. Higher peanut-specific IgG levels are associated with clinical allergy, but the range of IgG titres of the allergic and control groups overlapped. Hence, OVA and peanut-specific IgG measurements do not appear to be of diagnostic value. Strong IgG responses to OVA may be a normal physiological response to a protein frequently ingested from infancy, whereas up-regulated IgG responses in peanut allergy may be indicative of a dysregulated immune response to peanut allergens.


Biochemical characterization of digestive membrane-associated alkaline phosphatase from the velvet bean caterpillar Anticarsia gemmatalis.
In Brazil, the use of transgenic plants expressing the insect-toxic Bacillus thuringiensis endotoxin has been successfully used as pest control management since 2013 in transgenic soybean lineages against pest caterpillars such as Helicoverpa armigera. These toxins, endogenously expressed by the plants or sprayed over the crops, are ingested by the insect and bind to receptors in the midgut of these animals, resulting in disruption of digestion and lower insect survival rates. Here, we identified and characterized a membrane-associated alkaline phosphatase (ALP) in the midgut of Anticarsia gemmatalis, the main soybean defoliator pest in Brazil, and data suggested that it binds to Cry1Ac toxin in vitro. Our data showed a peak of ALP activity in homogenate samples of the midgut dissected from the 4th and 5th instars larvae. The brush border membrane vesicles obtained from the midgut of these larvae were used to purify a 60 kDa ALP, as detected by in-gel activity and in vitro biochemical characterization using pharmacological inhibitors and mass spectrometry. When Cry1Ac toxin was supplied to the diet, it was efficient in decreasing larval weight gain and survival. Indeed, in vitro incubation of Cry1Ac toxin with the purified ALP resulted in a 43% decrease in ALP specific activity and enzyme-linked immunosorbent assay showed that ALP interacts with Cry1Ac toxin in vitro, thus suggesting that ALP could function as a Cry toxin ligand. This is a first report characterizing an ALP in A. gemmatalis.


Cytochrome P450 metabolism mediates low-temperature resistance in pinewood nematode.
Pinewood nematode (PWN; Bursaphelenchus xylophilus) is a devastating invasive species that is expanding into colder regions. Here, we investigated the molecular mechanisms underlying low-temperature resistance of PWN. We identified differentially expressed genes enriched under low temperature in previously published transcriptome data using the Kyoto Encyclopedia of Genes and Genomes. Quantitative real-time PCR was used to further validate the transcript level changes of three known cytochrome P450 genes under low temperature. RNA interference was used to validate the low-temperature resistance function of three cytochrome P450 genes from PWN. We report that differentially expressed genes were significantly enriched in two cytochrome P450-related pathways under low-temperature treatment. Heatmap visualization of transcript levels of cytochrome P450-related genes revealed widely different transcript patterns between PWNs treated under low and regular temperatures. Transcript levels of three cytochrome P450 genes from PWNs were elevated at low temperature, and knockdown of these genes decreased the survival rates of PWNs under low temperature. In summary, these findings suggest that cytochrome P450 metabolism plays a critical role in the low-temperature resistance mechanism of PWN.


Anticholinesterase and Antioxidative Properties of Aqueous Extract of Cola acuminata Seed In Vitro.
Background. Cola acuminata seed, a commonly used stimulant in Nigeria, has been reportedly used for the management of neurodegenerative diseases in folklore without scientific basis. This study sought to investigate the anticholinesterase and antioxidant properties of aqueous extracts from C. acuminata seed in vitro. Methodology. The aqueous extract of C. acuminata seed was prepared (w/v) and its effect on acetylcholinesterase (AChE) and butyrylcholinesterase activities, as well as some prooxidant (FeSO4, sodium nitroprusside (SNP), and quinolinic acid (QA)) induced lipid peroxidation in rat brain in vitro, was investigated. Results. The results revealed that C. acuminata seed extract inhibited AChE (IC50 = 14.6 μg/mL) and BChE (IC50 = 96.2 μg/mL) activities in a dose-dependent manner. Furthermore, incubation of rat's brain homogenates with some prooxidants caused a significant increase P < 0.05 in the brain malondialdehyde (MDA) content and inhibited MDA production dose-dependently and also exhibited further antioxidant properties as typified by their high radicals scavenging and Fe(2+) chelating abilities. Conclusion. Inhibition of AChE and BChE activities has been the primary treatment method for mild Alzheimer's disease (AD). Therefore, one possible mechanism through which the seed exerts its neuroprotective properties is by inhibiting cholinesterase activities as well as preventing oxidative-stress-induced neurodegeneration. However, this is a preliminary study with possible physiological implications.


In situ ligand reactions under hydrothermal conditions afford a novel zinc-substituted polyoxovanadate dimer.
A novel polyoxovanadate (POV), [Zn(2,2'-bpy)3]4[(ppz){{Zn(tepa)}2ZnAs8V13O41(H2O)}2][As8V14O42(0.5H2O)]2.4H2O (1, 2,2'-bpy = 2,2'-bipyridine, ppz = piperazine, tepa = tetraethylenepentamine), has been hydrothermally synthesized and structurally characterized by elemental analysis, IR spectra, thermogravimetric analysis, magnetic measurement, and single-crystal X-ray diffraction analysis. Crystal data for 1: orthorhombic, Aba2, a = 28.3414(14) A, b = 27.9995(16) A, c = 41.5819(16) A, V = 32997(3) A3, Z = 4, rho = 2.264 mg.cm-3. X-ray structure analysis shows that the structure of 1 consists of one unique zinc-substituted POV dimer and two POV monomers. Interestingly, the formation of the zinc-substituted POV dimer involves two new in situ ligand reactions under hydrothermal conditions, the intermolecular and intramolecular deamination coupling reactions of dien. Magnetization measurement revealed the presence of antiferromagnetic interaction between V(IV) ions in 1.


Comparative analysis of protein-bound ligand conformations with respect to catalyst's conformational space subsampling algorithms.
We examined the quality of Catalyst's conformational model generation algorithm via a large scale study based on the crystal structures of a sample of 510 pharmaceutically relevant protein-ligand complexes extracted from the Protein Data Bank (PDB). Our results show that the tested algorithms implemented within Catalyst are able to produce high quality conformers, which in most of the cases are well suited for in silico drug research. Catalyst-specific settings were analyzed, such as the method used for the conformational model generation (FAST vs BEST) and the maximum number of generated conformers. By setting these options for higher fitting quality, the average RMS values describing the similarity of experimental and simulated conformers were improved from an RMS of 1.06 with max. 50 FAST generated conformers to an RMS of 0.93 with max. 255 BEST generated conformers, which represents an improvement by 12%. Each method provides best fitting conformers with an RMS value<1.50 in more than 80% of all cases. We analyzed the computing time/quality ratio of various conformational model generation settings and examined ligands in high energy conformations. Furthermore, properties of the same ligands in various proteins were investigated, and the fitting qualities of experimental conformations from the PDB and the Cambridge Structural Database (CSD) were compared. One of the most important conclusions of former studies, the fact that bioactive conformers often have energy high above that of global minima, was confirmed.


[Genotoxic and ecotoxic effects of urban waste water disinfected with sodium hypochlorite or peracetic acid].
Genotoxic and ecotoxicologic effects of urban wastewater disinfected with sodium hypochlorite or peracetic acid were analyzed. The formation of genotoxic species was studied by determining clastogenic and mutagenic activity of aqueous samples and their extracts with in vivo and in vitro tests, respectively. In particular, we have applied citogenetic tests to Allium cepa roots and Tradescantia inflorescence (Allium cepa test and Tradescantia/micronuclei test) and reversion test to Salmonella typhimurium according to the microsuspension procedure (Kado test). The latter is the method of choice for the analysis of complex matrices due to its high sensitivity and specificity. The mutagenic activity of disinfected effluents was similar to the corresponding untreated wastewater both sampled in four different periods. Therefore, the disinfection process did not seem to contribute to aquatic mutagenicity in the examined range of biocide concentration. The potential toxicity of disinfected wastewater for aquatic organisms was evaluated using Daphnia magna. The acute toxicity of peracetic acid in sewage was 0.4 mg/L (24 h E(L)C50). By comparing this value with peracetic acid concentrations detected in effluents from a pilot plant it is expected that treated wastewater would show acute toxic effects on aquatic organisms. Dissociation compounds (hydrogen peroxide and acetic acid) and possible by-products of peracetic acid did not seem to contribute significantly to the toxicity of sewage treated with peracetic acid.


The Role of Classroom Contexts on Learners' Grit and Foreign Language Anxiety: Online vs. Traditional Learning Environment.
This review aimed at exploring the related investigations on the effects of online and traditional learning contexts on English as a foreign language (EFL) learners' grit and foreign language anxiety (FLA). Studies have verified the relationship between learners' grit and academic performance in online learning contexts. However, there is a need for studying the effect of face-to-face learning and face-to-screen learning on learners' grit. On the other hand, studies have shown that classroom context is a mediating variable in the relationship between grit and FLA. Furthermore, few studies have been done on the effect of traditional classroom contexts and online learning contexts on learners' FLA. Most studies showed that online learning contexts create more FLA. There are some reasons such as ambiguity of contexts, lack of feedback, lack of opportunities for communication, type of employed applications, cognitive load, technophobia, and reduction in enthusiasm which arouse learners' anxiety in an online learning environment. In the end, the pedagogical implications are expounded to promote the learners' grit and diminish anxiety for better performance. This review also provides some suggestions for further research to clarify our perspective on positive and negative emotional variables.


Nuclear genome stability in long-term cultivated callus lines of Fagopyrum tataricum (L.) Gaertn.
Long-term cultivated Fagopyrum tataricum (L.) Gaertn. (Tartary buckwheat) morphogenic and non-morphogenic callus lines are interesting systems for gaining a better understanding of the mechanisms that are responsible for the genetic stability and instability of a plant tissue culture. In this work, we used histological sections and transmission electron microscopy to identify and describe the morphology of the nuclei of all of the analysed callus lines. We demonstrated that the embryogenic callus cells had prominent round nuclei that did not contain heterochromatin clumps in contrast to the non-morphogenic callus lines, in which we found nuclei that had multiple lobes. Flow cytometry analysis revealed significant differences in the relative DNA content between the analysed calli. All of the analysed morphogenic callus lines had peaks from 2C to 8C as compared to the non-morphogenic callus lines, whose peaks did not reflect any regular DNA content and exceeded 8C and 16C for the line 6p1 and 16C and 32C for the callus line 10p2A. The results showed that non-morphogenic calli are of an aneuploid nature. The TUNEL test enabled us to visualise the nuclei that had DNA fragmentation in both the morphogenic and non-morphogenic lines. We revealed significantly higher frequencies of positively labelled nuclei in the non-morphogenic lines than in the morphogenic lines. In the case of the morphogenic lines, the highest observed frequency of TUNEL-positive nuclei was 7.7% for lines 2-3. In the non-morphogenic calli, the highest level of DNA damage (68.5%) was revealed in line 6p1. These results clearly indicate greater genome stability in the morphogenic lines.


Microstructure-Controlled Li-Rich Mn-Based Cathodes by a Gas-Solid Interface Reaction for Tackling the Continuous Activation of Li2MnO3.
Li-rich Mn-based cathodes have attracted much attention due to their high capacity stemming from anion redox above 4.5 V. However, the continuous activation of Li2MnO3 in Li-rich Mn-based materials, which correlates with O2 release and TM migration, is usually unfavorable to structural stability. Herein, based on a gas-solid interface reaction, we tackle this continuous activation phenomenon by restricting the capacity release of Li2MnO3 via NH4HCO3 treatment in the Li1.2Ni0.36Mn0.44O2 cathode. After modification, oxygen vacancies associated with the spinel phase are introduced on the surface. The 4 mol % NH4HCO3-modified material's capacity starts at 182 mAh g-1 at 1 C instead of increasing from 173 to 186 mAh g-1 for 25 cycles in the pristine material. Meanwhile, it also exhibits an excellent capacity retention of 93.24% after 200 cycles (at 1 C), with a small voltage decay rate of 1.19 mV cycle-1.


Common microbial causes of significant bacteriuria and their antibiotic resistance pattern in the Isfahan Province of Iran.
Urinary tract infections (UTIs) are considered the most common community-acquired infections worldwide, which have possible complications along with significant economic impact on national healthcare systems. The aim of this study was to identify the most common causes of significant bacteriuria and to assess their antimicrobial resistance pattern in the Isfahan province of Iran. In this cross-sectional study, 11,678 urine samples of the patients referred to Mahdieh Medical Diagnostic Centre Charity were examined over a period of 10 months (from September 2015 to June 2016). Among the cases, 6.85% were positive for bacteriuria (F/M = 11.3). Escherichia coli (62%) was the most frequently isolated bacteria, followed by Staphylococcus epidermidis (13.9%) and Staphylococcus aureus (6.8%). E. coli was more prevalent among patients with diabetes mellitus. E. coli isolates showed the highest resistance to nalidixic acid, Trimethoprim/Sulfamethoxazole and Cefixime. Our results revealed that broad-spectrum antibiotic resistance is frequent among isolated uropathogens in Isfahan, Iran.


Surveillance for waterborne disease and outbreaks associated with drinking water and water not intended for drinking--United States, 2003-2004.
Since 1971, CDC, the U.S. Environmental Protection Agency (EPA), and the Council of State and Territorial Epidemiologists have maintained a collaborative Waterborne Disease and Outbreaks Surveillance System for collecting and reporting data related to occurrences and causes of waterborne disease and outbreaks (WBDOs). This surveillance system is the primary source of data concerning the scope and effects of WBDOs in the United States. Data presented summarize 36 WBDOs that occurred during January 2003-December 2004 and nine previously unreported WBDOs that occurred during 1982-2002. The surveillance system includes data on WBDOs associated with drinking water, water not intended for drinking (excluding recreational water), and water of unknown intent. Public health departments in the states, territories, localities, and Freely Associated States (i.e., the Republic of the Marshall Islands, the Federated States of Micronesia, and the Republic of Palau, formerly parts of the U.S.-administered Trust Territory of the Pacific Islands) are primarily responsible for detecting and investigating WBDOs and voluntarily reporting them to CDC by using a standard form. During 2003-2004, a total of 36 WBDOs were reported by 19 states; 30 were associated with drinking water, three were associated with water not intended for drinking, and three were associated with water of unknown intent. The 30 drinking water-associated WBDOs caused illness among an estimated 2,760 persons and were linked to four deaths. Etiologic agents were identified in 25 (83.3%) of these WBDOs: 17 (68.0%) involved pathogens (i.e., 13 bacterial, one parasitic, one viral, one mixed bacterial/parasitic, and one mixed bacterial/parasitic/viral), and eight (32.0%) involved chemical/toxin poisonings. Gastroenteritis represented 67.7% of the illness related to drinking water-associated WBDOs; acute respiratory illness represented 25.8%, and dermatitis represented 6.5%. The classification of deficiencies contributing to WBDOs has been revised to reflect the categories of concerns associated with contamination at or in the source water, treatment facility, or distribution system (SWTD) that are under the jurisdiction of water utilities, versus those at points not under the jurisdiction of a water utility or at the point of water use (NWU/POU), which includes commercially bottled water. A total of 33 deficiencies were cited in the 30 WBDOs associated with drinking water: 17 (51.5%) NWU/POU, 14 (42.4%) SWTD, and two (6.1%) unknown. The most frequently cited NWU/POU deficiencies involved Legionella spp. in the drinking water system (n = eight [47.1%]). The most frequently cited SWTD deficiencies were associated with distribution system contamination (n = six [42.9%]). Contaminated ground water was a contributing factor in seven times as many WBDOs (n = seven) as contaminated surface water (n = one). Approximately half (51.5%) of the drinking water deficiencies occurred outside the jurisdiction of a water utility in situations not currently regulated by EPA. The majority of the WBDOs in which deficiencies were not regulated by EPA were associated with Legionella spp. or chemicals/toxins. Problems in the distribution system were the most commonly identified deficiencies under the jurisdiction of a water utility, underscoring the importance of preventing contamination after water treatment. The substantial proportion of WBDOs involving contaminated ground water provides support for the Ground Water Rule (finalized in October 2006), which specifies when corrective action is required for public ground water systems. CDC and EPA use surveillance data to identify the types of water systems, deficiencies, and etiologic agents associated with WBDOs and to evaluate the adequacy of current technologies and practices for providing safe drinking water. Surveillance data also are used to establish research priorities, which can lead to improved water-quality regulation development. The growing proportion of drinking water deficiencies that are not addressed by current EPA rules emphasizes the need to address risk factors for water contamination in the distribution system and at points not under the jurisdiction of water utilities.


A comparative review of canine and human rhabdomyosarcoma with emphasis on classification and pathogenesis.
Rhabdomyosarcomas are a diverse group of malignant mesenchymal neoplasms exhibiting variable levels of differentiation toward skeletal myocytes. Neoplastic cells may resemble relatively undifferentiated myoblasts, satellite cells, or more differentiated elongated spindle cells and multicellular myotubes. In veterinary medicine, classification into subtypes and variants is based on an outdated system derived from human pathology and is solely based on histologic characteristics. In contrast, classification of human rhabdomyosarcoma is based on histologic, immunohistochemical, and molecular diagnostic techniques, and subclassification has clinical and prognostic relevance. Relevance of tumor subtyping has not been established in veterinary medicine. Recent discoveries of components of the molecular pathogenesis and genomes of human rhabdomyosarcomas have led to new diagnostic techniques and revisions of the human classification system. The current classification system in veterinary medicine is reviewed in light of these changes. Diagnosis of rhabdomyosarcoma using histopathology, electron microscopy, and the clinical aspects of human and canine rhabdomyosarcomas is compared. The clinical features and biologic behavior of canine rhabdomyosarcomas are compared with canine soft tissue sarcomas.


Chlorination of Amino Acids: Reaction Pathways and Reaction Rates.
Chlorination of amino acids can result in the formation of organic monochloramines or organic dichloramines, depending on the chlorine to amino acid ratio (Cl:AA). After formation, organic chloramines degrade into aldehydes, nitriles and N-chloraldimines. In this paper, the formation of organic chloramines from chlorination of lysine, tyrosine and valine were investigated. Chlorination of tyrosine and lysine demonstrated that the presence of a reactive secondary group can increase the Cl:AA ratio required for the formation of N,N-dichloramines, and potentially alter the reaction pathways between chlorine and amino acids, resulting in the formation of unexpected byproducts. In a detailed investigation, we report rate constants for all reactions in the chlorination of valine, for the first time, using experimental results and modeling. At Cl:AA = 2.8, the chlorine was found to first react quickly with valine (5.4 × 104 M-1 s-1) to form N-monochlorovaline, with a slower subsequent reaction with N-monochlorovaline to form N,N-dichlorovaline (4.9 × 102 M-1 s-1), although some N-monochlorovaline degraded into isobutyraldehyde (1.0 × 10-4 s-1). The N,N-dichlorovaline then competitively degraded into isobutyronitrile (1.3 × 10-4 s-1) and N-chloroisobutyraldimine (1.2 × 10-4 s-1). In conventional drinking water disinfection, N-chloroisobutyraldimine can potentially be formed in concentrations higher than its odor threshold concentration, resulting in aesthetic challenges and an unknown health risk.


[Echocardiographic evaluation of ischemic cardiopathy].
We studied a group of patients with ischemic heart disease divided into two groups: Group I coronary insufficiency. Group II myocardial infaction. We centered the work on the following aspects: analysis of the contractility; evaluation of the movement of the ventricular wall and of the septum; movement of the mitral valve; diagnosis of ventricular dyskinesias, akinesias, and hypokinesias. The patients in group I did not show significant alterations in the values of the ejection fraction and speed of circunferential shortening. The mean values of these parimeters are significantly less than the group of patients with infarcts, and 41% of these patients have EF less than 50% and Vcf less than 0.9. We did not find a correlation between these perimeters and the localization of the infarct. The velocity of the posterior ventricular wall was disminished in both groups of patients. The amplitude of movement of the posterior wall was reduced in the group of patients with infarctions. These parimeters were more altered in the posterior infarcts than in those with anterior localization and they are more an index of the state of the posterior wall than of the ventricular contractility considered overall, contary to mitral descriptions. In 3 cases of acute infarct we found paradoxical movement of the septum, which normalized itself in one patient in 6 months. In 6 other patients with old infarct we observed localized dyskinesias of the septum and of the free wall of the left ventricle. The mitral valve appears altered in a great proportion of coronary patients the most notorious characteristics being: a decrease in the EF pendent; an increase of the F index. These findings are considered in relation with the ventricular pressures and with the degree of distensibility of the left ventricle.


Variations of circulating cardiac biomarkers during and after anthracycline-containing chemotherapy in breast cancer patients.
Over time, the chance of cure after the diagnosis of breast cancer has been increasing, as a consequence of earlier diagnosis, improved diagnostic procedures and more effective treatment options. However, oncologists are concerned by the risk of long term treatment side effects, including congestive heart failure (CHF). In this study, we evaluated innovative circulating cardiac biomarkers during and after anthracycline-based neoadjuvant chemotherapy (NAC) in breast cancer patients. Levels of cardiac-specific troponins T (cTnT), N-terminal natriuretic peptides (NT-proBNP), soluble ST2 (sST2) and 10 circulating microRNAs (miRNAs) were measured. Under chemotherapy, we observed an elevation of cTnT and NT-proBNP levels, but also the upregulation of sST2 and of 4 CHF-related miRNAs (miR-126-3p, miR-199a-3p, miR-423-5p, miR-34a-5p). The elevations of cTnT, NT-proBNP, sST2 and CHF-related miRNAs were poorly correlated, suggesting that these molecules could provide different information. Circulating miRNA and sST2 are potential biomarkers of the chemotherapy-related cardiac dysfunction (CRCD). Nevertheless, further studies and long-term follow-up are needed in order to evaluate if these new markers may help to predict CRCD and to identify the patients at risk to later develop CHF.


Impacts of Siberian biomass burning on organic aerosols over the North Pacific Ocean and the Arctic: primary and secondary organic tracers.
During the 2003 Chinese Arctic Research Expedition (CHINARE2003) from the Bohai Sea to the high Arctic (37°N-80°N), filter-based particle samples were collected and analyzed for tracers of primary and secondary organic aerosols (SOA) as well as water-soluble organic carbon (WSOC). Biomass burning (BB) tracer levoglucosan had comparatively much higher summertime average levels (476 ± 367 pg/m(3)) during our cruise due to the influence of intense forest fires then in Siberia. On the basis of 5-day back trajectories, samples with air masses passing through Siberia had organic tracers 1.3-4.4 times of those with air masses transporting only over the oceans, suggesting substantial contribution of continental emissions to organic aerosols in the marine atmosphere. SOA tracers from anthropogenic aromatics were negligible or not detected, while those from biogenic terpenenoids were ubiquitously observed with the sum of SOA tracers from isoprene (623 ± 414 pg/m(3)) 1 order of magnitude higher than that from monoterpenes (63 ± 49 pg/m(3)). 2-Methylglyceric acid as a product of isoprene oxidation under high-NOx conditions was dominant among SOA tracers, implying that these BSOA tracers were not formed over the oceans but mainly transported from the adjacent Siberia where a high-NOx environment could be induced by intense forest fires. The carbon fractions shared by biogenic SOA tracers and levoglucosan in WSOC in our ocean samples were 1-2 orders of magnitude lower than those previously reported in continental samples, BB emissions or chamber simulation samples, largely due to the chemical evolution of organic tracers during transport. As a result of the much faster decline in levels of organic tracers than that of WSOC during transport, the trace-based approach, which could well reconstruct WSOC using biogenic SOA and BB tracers for continental samples, only explained ∼4% of measured WSOC during our expedition if the same tracer-WSOC or tracer-SOC relationships were applied.


Antimicrobial activity of two antitumour agents and ribonucleotide reductase inhibitors, pyridine-2-carboxaldehyde thiosemicarbazone and the acetate form of its copper(II) chelate.
Some copper chelates have potent antitumour activity, and in some cases also the free ligands have activity in vivo. Yet, little is known about their antimicrobial properties. Copper(II) chelates of the thiosemicarbazones of a-N-heterocyclic carboxaldehydes constitute one important group of such agents, also their ligands having marked antitumour activity. Both the ligands and chelates inhibit ribonucleotide reductase. Some ligands have been or are under clinical trials as antineoplastic agents. I report here a study on the antimicrobial properties of the prototype compounds of this group, pyridine-2-carboxaldehyde thiosemicarbazone and its copper(II) chelate. They were tested against nine microbes, including bacteria (Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus lactis), yeasts (Candida albicans and Saccharomyces cerevisiae) and one mold (Aspergillus niger). Two clinical isolates of Bacillus sp. and one reference strain were also studied. Both the ligand and the chelate had marked activity. The ligand displayed considerable activity against all bacteria except for S. lactis, and its activity against E. coli and P. aeruginosa was that high that practical applications might be considued. It was highly active against A. niger and moderately active against C. albicans. The chelate was highly active against S. epidermidis and S. cerevisiae. Both compounds inhibited the clinical isolates markedly. Since some related ligands have been or are in clinical trials on humans or are entering them, their route to clinical use, also as antimicrobials, might be much more straightforward than that of substances, whose toxicity in humans is wholly unexplored.


Present and future medical applications of microbial exopolysaccharides.
Microbial exopolysaccharides (EPS) have found outstanding medical applications since the mid-20th century, with the first clinical trials on dextran solutions as plasma expanders. Other EPS entered medicine firstly as conventional pharmaceutical excipients (e.g., xanthan - as suspension stabilizer, or pullulan - in capsules and oral care products). Polysaccharides, initially obtained from plant or animal sources, became easily available for a wide range of applications, especially when they were commercially produced by microbial fermentation. Alginates are used as anti-reflux, dental impressions, or as matrix for tablets. Hyaluronic acid and derivatives are used in surgery, arthritis treatment, or wound healing. Bacterial cellulose is applied in wound dressings or scaffolds for tissue engineering. The development of drug controlled-release systems and of micro- and nanoparticulated ones, has opened a new era of medical applications for biopolymers. EPS and their derivatives are well-suited potentially non-toxic, biodegradable drug carriers. Such systems concern rating and targeting of controlled release. Their large area of applications is explained by the available manifold series of derivatives, whose useful properties can be thereby controlled. From matrix inclusion to conjugates, different systems have been designed to solubilize, and to assure stable transport in the body, target accumulation and variable rate-release of a drug substance. From controlled drug delivery, EPS potential applications expanded to vaccine adjuvants and diagnostic imaging systems. Other potential applications are related to the bioactive (immunomodulator, antitumor, antiviral) characteristics of EPS. The numerous potential applications still wait to be developed into commercial pharmaceuticals and medical devices. Based on previous and recent results in important medical-pharmaceutical domains, one can undoubtedly state that EPS medical applications have a broad future ahead.


Bladder cancer diagnosis by flow cytometry. Correlation between cell samples from biopsy and bladder irrigation fluid.
Results of flow cytometry (FCM) examinations of bladder irrigation specimens were compared with those of FCM examinations of cell suspensions from bladder biopsies of 44 urologic patients. The fluorescent dye, acridine orange (AO), was used to stain DNA and RNA differentially and abnormal urothelial cells were identified by their relative content of nucleic acids. Granulocytes and squamous cells could be distinguished from transitional cells in this procedure, and did not interfere with the analyses. Of 28 patients with papillary carcinoma, carcinoma in situ, and invasive carcinoma 27 were identified through FCM examination of irrigation cytology specimens; the one false-negative result was from a low-grade papillary carcinoma. Of 7 patients with papilloma, FCM examinations of irrigation specimens were positive in 4 and negative in 3. Results of FCM studies of biopsy specimens were in good but not complete agreement with those of irrigation specimens. In several cases, irrigation FCM disclosed tumor stemlines that were not identified in biopsy specimens. Discrepancies of this kind seemed most likely due to differences in sampling. Irrigation FCM seems to be a sensitive method for assessing multiple-site bladder tumors, and may be a useful technique for monitoring the course of conservatively managed bladder tumors.


Estimating optimal species trees from incomplete gene trees under deep coalescence.
The estimation of species trees typically involves the estimation of trees and alignments on many different genes, so that the species tree can be based on many different parts of the genome. This kind of phylogenomic approach to species tree estimation has the potential to produce more accurate species tree estimates, especially when gene trees can differ from the species tree due to processes such as incomplete lineage sorting (ILS), gene duplication and loss, and horizontal gene transfer. Because ILS (also called "deep coalescence") is a frequent problem in systematics, many methods have been developed to estimate species trees from gene trees or alignments that specifically take ILS into consideration. In this paper we consider the problem of estimating species trees from gene trees and alignments for the general case where the gene trees and alignments can be incomplete, which means that not all the genes contain sequences for all the species. We formalize optimization problems for this context and prove theoretical results for these problems. We also present the results of a simulation study evaluating existing methods for estimating species trees from incomplete gene trees. Our simulation study shows that *BEAST, a statistical method for estimating species trees from gene sequence alignments, produces by far the most accurate species trees. However, *BEAST can only be run on small datasets. The second most accurate method, MRP (a standard supertree method), can analyze very large datasets and produces very good trees, making MRP a potentially acceptable alternative to *BEAST for large datasets.


Optimization of a metastasizing human gastric cancer model in nude mice.
Our purpose was to optimize the surgical orthotopic implantation (SOI) technique to create a reproducible gastric cancer model in nude mice with stable tumor growth and metastasizing course. We performed xenotransplantation of primary human tumor specimens from patients with gastric cancer (series 1) and orthotopic transplantation of tumor specimens originating from the gastric cancer cell line 23132/87 (series 2). All specimens were transplanted using microsurgical techniques. The two series were compared with regard to tumor growth rates and kinetics, development of metastases, and induction of minimal residual disease (MRD), as determined by histology and PCR techniques. In series 1 mice, the tumor growth rate was slow; in series 2 mice, it was both fast and reproducible. Unlike animals in series 1, animals in series 2 developed metastases and MRD. In conclusion, the optimized SOI technique presented here represents a reproducible and reliably metastasizing gastric cancer model.


Variability in sperm form and function in the context of sperm competition risk in two Tupinambis lizards.
In polyandrous species, sperm morphometry and sperm velocity are under strong sexual selection. Although several hypotheses have been proposed to explain the role of sperm competition in sperm trait variation, this aspect is still poorly understood. It has been suggested that an increase in sperm competition pressure could reduce sperm size variation or produce a diversity of sperm to maximize male fertilization success. We aim at elucidating the variability of sperm morphometric traits and velocity in two Tupinambis lizards in the context of sperm competition risk. Sperm traits showed substantial variation at all levels examined: between species, among males within species, and within the ejaculate of individual males. Sperm velocity was found to be positively correlated with flagellum: midpiece ratio, with relatively longer flagella associated with faster sperm. Our results document high variability in sperm form and function in lizards.


Postnatal functional development of the dorsal and posteroventral cochlear nuclei of the cat.
The postnatal development of firing patterns and response areas was determined for single neurons in the dorsal (DCN) and posteroventral ( PVCN ) cochlear nuclei of the kitten. Extracellular, single-unit responses to pure-tone stimulation were recorded in ketamine and sodium pentobarbital anesthetized kittens between the ages of 5 and 52 days. Within the first two weeks of postnatal life threshold is high, first-spike latency is long, and maximal discharge rate is low as compared to older kittens and adult cats. Prior to the end of the second postnatal week the tone-evoked temporal discharge patterns that characterize neurons of the DCN and PVCN in the adult cat are routinely recorded. These patterns, which appear within the first 50 ms of tonal stimulation, include the so-called " primarylike ," "chopper," " pauser ," "buildup," and "onset" types and their variants. In animals younger than about 10-12 days of age, the driven activity that occurs later than about 50 ms after stimulus onset often is not sustained, but breaks up during the stimulus into bursts that are separated by intervals of about 100-150 ms. Also within the first two weeks of postnatal life, many of the response-area properties of DCN and PVCN neurons are similar to those recorded in adult cats. The excitation and inhibition found within the so-called type II/III, type IV, and type V response areas of the adult occur in this early postnatal period. We conclude that many of the cellular mechanisms that underlie the temporal firing patterns and the organization of the response areas of DCN and PVCN neurons are active in the growing, differentiating cochlear nuclei and that the emergence of these mechanisms does not depend on afferent activity generated in the cochlear and auditory nerve by the animal's acoustic environment. Furthermore, if temporal firing patterns and response-area profiles remain relatively constant over the life span of the animal, then so must the spatial and temporal relationships of the inputs that produce and maintain them as these neurons, and the circuits of which they are a part, grow in size and complexity.


Effect of cluster set warm-up configurations on sprint performance in collegiate male soccer players.
The purpose of this study was to determine if back squat cluster sets (CS) with varying inter-repetition rest periods would potentiate greater sprint performance compared with a traditional set parallel back squat in collegiate soccer players. Twelve collegiate male soccer players (age, 21.0 ± 2.0 years; height, 180.0 ± 9.0 cm; body mass, 79.0 ± 9.5 kg) performed a 20-m sprint prior to a potentiation complex and at 1, 4, 7, and 10 min postexercise on 3 separate, randomized occasions. On each occasion, the potentiation complex consisted of 1 set of 3 repetitions at 85% 1-repetition maximum (1RM) for the traditional parallel back squat. However, on 1 occasion the 3-repetition set was performed in a traditional manner (i.e., continuously), whereas on the other 2 occasions, 30s (CS30) and 60 s (CS60) of rest were allotted between each repetition. Repeated-measures ANOVA revealed greater (p = 0.022) mean barbell velocity on CS60 compared with the traditional set. However, faster (p < 0.040) 20-m sprint times were observed for CS30 (3.15 ± 0.16 s) compared with traditional (3.20 ± 0.17 s) only at 10 min postexercise. No other differences were observed. These data suggest that a single cluster set of 3 repetitions with 30-s inter-repetition rest periods at 85% 1RM acutely improves 20-m sprinting performance. Strength and conditioning professionals and their athletes might consider its inclusion during the specific warm-up to acutely improve athletic performance during the onset (≤10 min) of training or competition.


Prospects for Foamy Viral Vector Anti-HIV Gene Therapy.
Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV) infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC). Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV.


Expression of nuclear Notch3 in cervical squamous cell carcinomas and its association with adverse clinical outcomes.
The aim of this study was to clarify the functional role of Notch3 in human cervical carcinomas. Notch3 expression in cervical cancer was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. We used dual-color fluorescence in situ hybridization (FISH) to analyze DNA copy number alterations in cervical cancer. Inactivation of Notch3 and knocking down Notch3 gene were done using gamma-secretase inhibitor and Notch 3 specific SiRNA to asses Notch3 function in cervical cancer either in vivo or in vitro. Immunohistochemical analysis revealed that Notch3 was significantly overexpressed in cervical squamous cell carcinomas compared with adenocarcinomas. In contrast to normal cervical tissue and cervical intraepithelial neoplasms [CINs], squamous cell carcinomas demonstrated higher nuclear Notch3 immunoreactivity. Notch3 amplification was not found in any cervical carcinomas using FISH analysis. Notch3 nuclear expression was significantly correlated with Jagged-1, a putative Notch3 ligand, and Pbx1b, a potential Notch3 downstream target (P<0.05).Patients with cervical carcinomas positive for nuclear Notch3 expression had significantly shorter overall survival than their peers whose tumors did not express nuclear Notch3. Inactivation of Notch3 decreased cell proliferation and induced apoptosis in ME180 and SKGIIIb cell lines that overexpressed Notch3. Injection of a gamma-secretase inhibitor into ME180 cell tumors established on mice, demonstrated a reduction in tumor growth. Our findings suggest that Notch3 might play important role for the proliferation and survival of Notch3 overexpressing tumors and that inactivation of Notch3 may represent a new therapeutic avenue for cervical squamous cell carcinomas.


Factors Related to Employment Situation among Korean Cancer Survivors: Results from a Population-Based Study
Background: Due to the increased incidence and survival rate of cancer, the number of cancer survivors has been increasing. In addition, many problems have been reported regarding the employment of these survivors. Therefore, this study aims to investigate the employment situation of cancer survivors and associated factors. Methods: We analyzed data from the Korean National Health and Nutrition Examination Survey (2010-2014), which is a nationwide cross-sectional health survey, and included a total of 1,060 participants who were diagnosed with cancer. Multivariate logistic regression analysis was conducted to investigate the factors associated with the participants' employment situation. Results: The employment rate among cancer survivors was 42.0%. The variables found to be associated with being employed were male gender, younger age, higher household income level, educational level at middle school level or under, and not having activity limitations. Conclusion: These findings suggest that, in addition to cancerrelated factors, general characteristics such as gender, age, household income, and education level are important factors associated with the employment status of Korean cancer survivors.


Plantar Fasciitis or Flexor Digitorum Brevis Myositis.
As common as plantar fasciitis is, there's a lack of evidence regarding the true pathophysiologic process causing plantar fasciitis and plantar heel pain in general. This may partially explain the high variability and outcomes with current treatment of recalcitrant plantar fasciitis. Although Lemont reported myxoid degeneration of plantar fascia with histologic analysis of patients with fasciitis, muscle biopsy results were not reported. So far it appears we have not focused on the muscular component that may be present with plantar heel pain in general and in patients we diagnose with plantar fasciitis in particular. In this article we performed a retrospective analysis of biopsy results from five patients with the diagnosis of recalcitrant plantar fasciitis to determine whether this diagnosis was correct or whether other component pathologies contribute to the chronicity of symptoms or to the failure of treatment. Three of the five pathology reports included specific mention of inflammation, degeneration and atrophy of the intrinsic musculature consistent with myositis. Two of these showed lymphocytic infiltration in the muscle consistent with inflammation, with no signs of inflammation in the fascia. One showed inflammation of the fascia without signs of inflammation of the muscle. This small study introduces the idea that intrinsic myositis may contribute to, or be responsible for some cases of plantar heel pain and plantar fasciitis. This may be important in changing the way we deal with plantar heel pain in the future.


The Suture Tab Technique: Securing Implant Position in Prepectoral Breast Reconstruction.
Human acellular dermal matrix (ADM) can augment prepectoral prosthetic-based direct-to-implant breast reconstruction by providing an additional soft-tissue layer between breast implant and skin, as well as to reinforce the inframammary fold and breast pocket. Utilizing ADM in this way has helped reduce rates of implant rippling, capsular contracture, and implant extrusion. Difficulty in securing ADM-wrapped implants has caused many surgeons to improvise techniques for secure implantation. Here, we describe a simple technique for creating suture tabs within the ADM for efficient fixation of the ADM-implant construct to the chest wall.


Cobalt-Nitrogen-Doped Helical Carbonaceous Nanotubes as a Class of Efficient Electrocatalysts for the Oxygen Reduction Reaction.
The oxygen reduction reaction (ORR) is of significant importance in the development of fuel cells. Now, cobalt-nitrogen-doped chiral carbonaceous nanotubes (l/d-CCNTs-Co) are presented as efficient electrocatalysts for ORR. The chiral template, N-stearyl-l/d-glutamic acid, induces the self-assembly of well-arranged polypyrrole and the formation of ordered graphene carbon with helical structures at the molecular level after the pyrolysis process. Co was subsequently introduced through the post-synthesis method. The obtained l/d-CCNTs-Co exhibits superior ORR performance, including long-term stability and better methanol tolerance compared to achiral Co-doped carbon materials and commercial Pt/C. DFT calculations demonstrate that the charges on the twisted surface of l/d-CCNTs are widely separated; as a result the Co atoms are more exposed on the chiral CCNTs. This work gives us a new understanding of the effects of helical structures in electrocatalysis.


COX-2 chronology.
The role of selective cyclooxygenase (COX)-2 inhibitors in medical practice has become controversial since evidence emerged that their use is associated with an increased risk of myocardial infarction. Selective COX-2 inhibitors were seen as successor to non-selective non-steroidal anti-inflammatory drugs, in turn successors to aspirin. The importance of pain relief means that such drugs have always attracted attention. The fact that they work through inhibition of cyclooxygenase, are widespread, and have multiple effects also means that adverse effects that were unanticipated (even though predictable) have always emerged. In this paper I therefore present an historical perspective so that the lessons of the past may be applied to the present.


Discrete functional and mechanistic roles of chromodomain Y-like 2 (CDYL2) transcript variants in breast cancer growth and metastasis.
Rationale: Chromodomain Y-like 2 (CDYL2) is a member of the CDY gene family involved in spermatogenesis, but its role in human cancer has not been reported. Analyses of publicly available databases demonstrate that CDYL2 is abundantly expressed in breast tumors. However, whether CDYL2 is involved in breast cancer progression remains unknown. Methods: Quantitative real-time PCR and immunoblotting assays were used to determine the expression levels of CDYL2 transcript variants in breast cancer cell lines and primary breast tumors. The effect of CDYL2 transcript variants on the malignant phenotypes of breast cancer cells was examined through in vitro and in vivo assays. Immunofluorescent staining, RNA-seq, ATAC-seq, and ChIP-qPCR were used to investigate the underlying mechanisms behind the aforementioned observations. Results: Here we show that CDYL2 generated four transcript variants, named CDYL2a-CDYL2d. CDYL2a and CDYL2b were the predominant variants expressed in breast cancer cell lines and breast tumors and exerted strikingly discrete functions in breast cancer growth and metastasis. CDYL2a was upregulated in the majority of the breast cancer cell lines and tumors, and promoted breast cancer cell proliferation, colony formation in vitro, and tumorigenesis in xenografts. In contrast, CDYL2b was mainly expressed in luminal- and HER2-positive types of breast cancer cell lines and tumors, and suppressed the migratory, invasive, and metastatic potential of breast cancer cells in vitro and in vivo. Mechanistically, CDYL2a partially localized to SC35-positive nuclear speckles and promoted alternative splicing of a subset of target genes, including FIP1L1, NKTR, and ADD3 by exon skipping. Elimination of full-length FIP1L1, NKTR, and ADD3 rescued the impaired cell proliferation through CDYL2a depletion. In contrast, CDYL2b localized to heterochromatin and transcriptionally repressed several metastasis-promoting genes, including HPSE, HLA-F, and SELL. Restoration of HPSE, HLA-F, or SELL expression in CDYL2b-overexpressing cells attenuated the ability of CDYL2b to suppress breast cancer cell migration and invasion. Conclusions: Collectively, these findings establish an isoform-specific function of CDYL2 in breast cancer development and progression and highlight that pharmacological inhibition of the CDYL2a, but not the CDYL2b, isoform may be an effective strategy for breast cancer therapy.


A supercritical CO₂ extract from seabuckthorn leaves inhibits pro-inflammatory mediators via inhibition of mitogen activated protein kinase p38 and transcription factor nuclear factor-κB.
In the present study, we have demonstrated the anti-inflammatory properties of supercritical CO₂ extract of seabuckthorn leaves (SCE) on mouse alveolar macrophage cell line (MH-S), human peripheral blood mononuclear cells (hPBMCs) in-vitro and in-vivo. Treatment of MH-S cells with SCE (0.5-100 μg/ml) significantly inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production. It also inhibited the release of LPS-induced pro-inflammatory cytokines IL-6 and TNF-α, which was further confirmed by suppression of LPS induced TNF-α in hPBMCs by ELISPOT assay. In addition, western blot analysis demonstrated that SCE decreased LPS-induced inducible nitric-oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression in MH-S cells. Furthermore, SCE treatment also reduced nuclear factor-κB (NF-κB) translocation in nucleus induced by LPS in MH-S cells. To elucidate the molecular mechanism for inhibition of pro-inflammatory mediators by SCE (100 μg/ml), we further studied the effect of SCE on LPS-induced p38 mitogen-activated protein kinase (MAPK). It was observed that the phosphorylation of p38 MAPK in LPS-stimulated MH-S cells was significantly inhibited by SCE, which was further proven by suppression of LPS induced CD40 expression. The in-vivo model of AIA mice also showed a significant reduction in the inflammation of paw edema. These data collectively suggest that SCE suppressed the LPS-induced production of NO, IL-6, and TNF-α and expression of CD40, iNOS and COX-2 proteins by inhibiting NF-κB activation and phosphorylation of p38 MAPK. Hence, the SCE has potent anti-inflammatory activity and might be useful in chronic inflammatory diseases.


[It's never too late to be infected with mumps].
Mumps, although rare since the introduction of a systematic vaccination of children in 1981 in Switzerland, occurs principally in children and is uncommon in adults. Nevertheless, it should be considered in adult patients with a typical clinical presentation or with an atypical presentation suggesting the disease. The diagnosis is established based on the clinical presentation and the treatment is symptomatic.


Colon cancer screening with virtual colonoscopy: promise, polyps, politics.
Virtual colonoscopy (CT colonography) promises to become a primary method for colorectal cancer screening and return radiologists to a major role in colon cancer prevention. Results from major centers in the United States show accuracy to be comparable to conventional colonoscopy for detection of polyps of significant size--that is, greater than 10 mm--with few false-positives. The advent of virtual colonoscopy has also heightened awareness of the natural history of colonic polyps, particularly in terms of identifying an appropriate target size for detection in colorectal screening programs. Small polyps (<10 mm) are often either hyperplastic on histology or are unlikely to progress to frank cancer in the patient's lifetime and are therefore of little clinical significance for the average adult. Thus, the rationale for detecting and removing each and every colonic polyp regardless of size has come under increasing scrutiny in the context of cost-benefit analysis of various test strategies for colorectal cancer screening. Virtual colonoscopy may allow patients to obtain reliable information about the status of their colonic mucosa noninvasively and thus make a more informed decision as to whether to proceed to conventional colonoscopy for polypectomy.


Outcomes of expanded use of clinical pharmacist practitioners in addition to team-based care in a community health system intensive care unit.
Clinical and cost benefits achieved through expanded use of state-licensed clinical pharmacist practitioners (CPPs) with prescribing authority on a critical care team are reported. A retrospective pre-post analysis was conducted to evaluate patient care outcomes and cost savings during one-year periods before and after the number of CPPs on a North Carolina community health system's neurotrauma intensive care unit (NTICU) team was increased from one to three. Outcomes assessed included the number and types of medication management encounters, estimated cost savings, and the rate of preventable adverse drug events (ADEs) with expanded use of CPPs. During the two-year study period, CPPs conducted 13,386 documented medication encounters involving 2,198 patients; associated cost savings totaled an estimated $2,118,426. During the 12 months after CPP involvement on the NTICU team was increased, there was a 182% increase in encounters for therapeutic optimization (p = 0.01), with an associated 29% increase in cost savings and an improved return on investment. The CPP service expansion was also associated with a reduction in preventable ADEs, including a 75% reduction in prescribing-related ADEs (risk ratio [RR], 0.25; 95% confidence interval [CI], 0.05-1.2; p = 0.09) and a 37% reduction in higher-severity ADEs (RR, 0.63; 95% CI, 0.25-1.57; p = 0.36). With expanded CPP involvement on the NTICU team, there was a substantial increase in therapeutic optimization interventions and a clinically notable reduction in preventable ADEs, as well as an estimated 30% increase in associated cost savings.


Evaluation of two endometriosis models by transplantation of human endometrial tissue fragments and human endometrial mesenchymal cells.
The animal models of endometriosis could be a valuable alternative tool for clarifying the etiology of endometriosis. In this study two endometriosis models at the morphological and molecular levels was evaluated and compared. The human endometrial tissues were cut into small fragments then they were randomly considered for transplantation into γ irradiated mice as model A; or they were isolated and cultured up to fourth passages. 2×106 cultured stromal cells were transplanted into γ irradiated mice subcutaneously as model B. twenty days later the ectopic tissues in both models were studied morphologically by Periodic acid-Schiff and hematoxylin and eosin staining. The expression of osteopontin (OPN) and matrix metalloproteinase 2 (MMP2) genes were also assessed using real time RT-PCR. 17-β estradiol levels of mice sera were compared before and after transplantation. The endometrial like glands and stromal cells were formed in the implanted subcutaneous tissue of both endometriosis models. The gland sections per cubic millimeter, the expression of OPN and MMP2 genes and the level of 17-β estradiol were higher in model B than model A (p=0.03). Our observation demonstrated that endometrial mesenchymal stromal cells showed more efficiency to establish endometriosis model than human endometrial tissue fragments.


Metastatic bone cancer of the foot: a case report.
Metastasis to the foot is rarely presented in the literature. We describe a 56-year-old woman with nonspecific pain in the left foot, ankle, and knee for 3 months. The patient was diagnosed as having urothelial carcinoma with metastasis to the left lower extremity, including the foot. This diagnosis was reached through the combined efforts of radiologic techniques and biopsies. This case discusses the importance of paying close attention to the details of the history and physical examination, performing appropriate tests, and obtaining suitable referrals.


Rituximab: mechanism of action.
Rituximab is a mainstay in the therapy for a broad variety of B-cell malignancies. Despite its undeniable therapeutic value, we still do not fully understand the mechanisms of action responsible for rituximab's anti-tumor effects. Direct signaling, complement-mediated cytotoxicity (CMC), and antibody-dependent cellular cytotoxicity (ADCC) all appear to play a role in rituximab efficacy. In vitro, animal model and clinical data addressing each of these mechanisms of action are reviewed, as are data speaking to the complexity of interactions between these mechanisms. Taken together, these data suggest different mechanisms are likely important in different scenarios. Study of the complex mechanisms of action that contribute to the clinical efficacy of rituximab have led to novel clinical trials including novel combinations, schedules, and generation of additional antibodies designed to have even greater effect. Such studies need to be accompanied by rigorous correlative analysis if we are to understand the importance of various mechanisms of action of rituximab and use that information to improve on what is already an indispensable component of therapy.


Transbronchial biopsy guided by low-dose MDCT: a new approach for assessment of solitary pulmonary nodules.
The objective of our study was to determine whether transbronchial bronchoscopic biopsy of solitary pulmonary nodules under CT guidance using a low-dose protocol can increase diagnostic yield in patients who had undergone unsuccessful conventional bronchoscopic biopsy. We included 33 consecutive patients (25 men; mean age +/- SD, 64 +/- 9.6 years) with solitary pulmonary nodules at different sites and with a lesion-to-pleura distance of at least 2 cm who previously underwent conventional bronchoscopy that did not result in histologic diagnosis. All patients were prospectively investigated with transbronchial bronchoscopic biopsy under MDCT guidance. Examinations were performed with the patient in conscious sedation using a low-dose protocol (80 kV, 20 mAs, 5-mm collimation, 10-mm slices). The position of the tip of the biopsy device was confirmed and documented before biopsies were performed. All specimens were examined by standard histopathologic techniques. The effective radiation dose was calculated for every patient. The diagnostic yield was 24 in 33 selected patients (overall accuracy, 72.7%): 13 (54%) had primary lung cancer and 11 (46%) had benign diagnoses. The formal operative characteristics were sensitivity, 59%; specificity, 100%; positive predictive value, 100%; and negative predictive value, 55%. The final diagnoses of the remaining nine patients in whom transbronchial bronchoscopic biopsy was not diagnostic were non-small cell lung cancer (n = 3); small cell lung cancer (n = 3); and alveolar carcinoma, carcinoid tumor, and hemorrhaged bulla (n = 1 each). All nonmalignant diagnoses were confirmed by 6 months radiographic and clinical follow-up. The mean duration of the procedure was 39 +/- 15 minutes, and the average effective dose was 0.7 mSv (range, 0.5-1.1 mSv). One case of pulmonary hemorrhage (3%) occurred after the procedure. MDCT-guided transbronchial bronchoscopic biopsy is a promising and safe tool for the diagnostic pathway of solitary pulmonary nodules in previously undiagnosed patients. Image quality was sufficient with low-dose protocols, which resulted in low radiation exposure for patients and personnel.


SRC-1 localisation in lumbosacral spinal cord of male and female Wistar rats.
Nuclear receptor co-activators play an important role in enhancing transcriptional activity of steroid hormone receptors, however there is currently little information concerning their distribution within the spinal cord. In this study, the distribution of steroid receptor co-activator-1 (SRC-1) was examined with immunocytochemistry, in the lumbosacral cord of Wistar rats of both sexes. In all rats, regardless of sex, SRC-1 was predominant in neurons of the superficial laminae of the dorsal horn and within motorneurons of lamina IX. Sexually dimorphic nuclei exhibited robust SRC-1 immunoreactivity in young rats, including orchidectomised animals, but this appeared to decline in aged rats. Dorsal horn labelling appeared similarly reduced suggesting a possible age-related down-regulation of the transcription mediated by steroid receptors in some spinal neurons.


[Heat-shock protein HSP70 decreases activity of proteasomes in human neuroblastoma cells treated by amyloid-beta 1-42 with isomerized Asp7].
Experimental evidences indicate that heat-shock protein 70 (HSP70) can serve as a prospective therapeutic agent to treat Alzheimer's disease (AD). It has demonstrated a neuroprotective effect in vivo on mice models of AD. Moreover, HSP70 decreases oxidative stress in neurons induced by amyloid-β (Aβ42) and its more toxic form with isomerized Asp7 (isoAβ42). The dysfunction of Ubiquitin-proteasome system (UPS) is observed in AD. UPS is responsible for the degradation of the majority of cellular proteins and plays an important role in protecting cells from oxidative stress. Here, we have shown that the incubation of human neuroblastoma cells SK-N-SH with isoAβ42 increases the activity of intracellular proteasomes, which are the principal elements of the UPS. On the contrary, the proteasomal activity was decreased in isoAβ42-treated cells in the presence of exogenous HSP70. These results highlight the existence of an interplay between Aβ peptides, proteasomes, and HSP70.


Perioperative sublingual levodopa in Parkisnon's Disease: A useful alternative!
Timely administration of dopamine agonists is of the essence in Parkinson's disease. The perioperative period especially for abdominal surgeries under general anaesthesia poses a challenge to oral drug administration. Alternatives such as rotigotine patches and subcutaneous apomorphine administration have been described but unavailability restricts their use. Sublingual administration of tablet levodopamine as an alternative worked well in our patients and we would like to describe the same.


Numerical proof for chemostat chaos of Shilnikov's type.
A classical chemostat model is considered that models the cycling of one essential abiotic element or nutrient through a food chain of three trophic levels. The long-time behavior of the model was known to exhibit complex dynamics more than 20 years ago. It is still an open problem to prove the existence of chaos analytically. In this paper, we aim to solve the problem numerically. In our approach, we introduce an artificial singular parameter to the model and construct singular homoclinic orbits of the saddle-focus type which is known for chaos generation. From the configuration of the nullclines of the equations that generates the singular homoclinic orbits, a shooting algorithm is devised to find such Shilnikov saddle-focus homoclinic orbits numerically which in turn imply the existence of chaotic dynamics for the original chemostat model.


Paternal line multigenerational passage of altered risk assessment behavior in female but not male rat offspring of mothers fed a low protein diet.
Maternal low protein (MLP) diets in pregnancy and lactation impair offspring brain development and modify offspring behavior. We hypothesized multigenerational passage of altered behavioral outcomes as has been demonstrated following other developmental programming challenges. We investigated potential multigenerational effects of MLP in rat pregnancy and/or lactation on offspring risk assessment behavior. Founder generation mothers (F0) ate 20% casein (C) or restricted (R) 10% casein diet, providing four groups: CC, RR, CR, and RC (first letter pregnancy, second letter lactation diet) to evaluate offspring (F1) effects influenced by MLP in F0. On postnatal day (PND 250), F1 males were mated to non-colony siblings producing F2. On PND 90, F2 females (in diestrous) and F2 males were tested in the elevated plus maze (EPM) and open field. Corticosterone was measured at PND 110. Female but not male CR and RC F2 made more entries and spent more time in EPM open arms than CC females. Overall activity was unchanged as observed in male F1 fathers. There were no open field differences in F2 of either sex, indicating that multigenerational MLP effects are due to altered risk assessment, not locomotion. MLP in pregnancy reduced F1 male and F2 female corticosterone. We conclude that MLP in pregnancy and/or lactation increases the innate tendency to explore novel environments in F2 females via the paternal linage, suggesting lower levels of caution and/or higher impulsiveness to explore unknown spaces. Further studies will be necessary to identify the epigenetic modifications in the germ line through the paternal linage.


Reappraisal of Staging Laparoscopy for Patients with Pancreatic Adenocarcinoma: A Contemporary Analysis of 1001 Patients.
Recent advances in imaging and the increasing use of neoadjuvant therapy puts the contemporary utility of staging laparoscopy for patients with pancreatic adenocarcinoma (PDAC) into question. This study aimed to develop a prognostic score to optimize prevention of an unnecessary laparotomy and minimize the rate for unnecessary laparoscopy. Clinicopathologic data were evaluated for all patients undergoing surgical intervention for PDAC between 2001 and 2015, who were stratified into group 1 (2001-2008) and group 2 (2009-2014). The study identified 1001 patients eligible for analysis, 331 (33%) of whom underwent a staging laparoscopy before exploration. An unnecessary laparotomy was prevented for 44.4% of the patients in period 1 and for 24% of the patients in period 2 (p < 0.001). Male gender [odds ratio (OR), 1.8; p < 0.05], preoperative resectability (borderline resectable OR 2.1; p < 0.019; locally advanced OR 7.6; p < 0.001), CA 19-9 levels higher than 394 U/L (OR 3.1; p < 0.001), no neoadjuvant chemotherapy (OR 2.7; p = 0.012), and pancreatic body or tail lesions (OR 1.8; p = 0.063) were predictive of occult metastatic disease. The developed scoring index demonstrated a c-statistic of 0.729. The observed-to-expected ratio for the index at every score level validated the index's model. A score cutoff at 4 was able to detect 76.1% of radiographically occult metastatic disease. The rate for unnecessary laparotomy among patients with PDAC has decreased in contemporary times, but unnecessary laparotomy still occurs for 1 in 4 patients. Using our scoring system, a cutoff of 4 allows 76% of radiographically occult metastases to be predicted, thereby selecting high-risk patients for laparoscopic biopsy and potentially avoiding a non-therapeutic laparotomy.


Pro-Inflammatory Derangement of the Immuno-Interactome in Heart Failure.
Chronic heart failure (HF) is a syndrome of heterogeneous etiology associated with multiple co-morbidities. Inflammation is increasingly recognized as a key contributor to the pathophysiology of HF. Heterogeneity and lack of data on the immune mechanism(s) contributing to HF may partially underlie the failure of clinical trials targeting inflammatory mediators. We studied the Immunome in HF cohort using mass cytometry and used data-driven systems immunology approach to discover and characterize modulated immune cell subsets from peripheral blood. We showed cytotoxic and inflammatory innate lymphoid and myeloid cells were expanded in HF patients compared to healthy controls. Network analysis showed highly modular and centralized immune cell architecture in healthy control immune cell network. In contrast, the HF immune cell network showed greater inter-cellular communication and less modular structure. Furthermore, we found, as an immune mechanism specific to HF with preserved ejection fraction (HFpEF), an increase in inflammatory MAIT and CD4 T cell subsets.


Responses to dietary additions of fiber (alfalfa meal) in growing pigs housed in a cold, warm or hot thermal environment.
Five trials involving 112 individually-penned animals were conducted to determine the effects of dietary fiber additions (0 or 10% dehydrated alfalfa meal) on the rate and efficiency of growth and carcass characteristics of growing pigs housed in a cold (10 C), thermoneutral (22.5 C) or hot (35 C) thermal environment. Cold exposure (10 C) depressed efficiency of feed and energy utilization, carcass length, backfat, cold carcass dressing percentage and percentage lean cuts. Exposure to the hot environment resulted in depressed live weight gains but did not alter the efficiency of feed utilization. Dietary additions of alfalfa meal depressed daily gains by 1, 3 and 5% in pigs housed in the cold, warm and hot environments, respectively, and gain:feed ratios by 1, 7 and 10%. Ingestion of the fibrous alfalfa meal depressed cold carcass dressing percentage in the 10 and 22 C environments as compared with the basal diet. Based on these data, the nutritional value of fibrous feedstuffs (15% total dietary neutral detergent fiber or less) for growing pigs allowed to consume feed ad libitum is greater in animals housed in a moderately cold vs a warm or hot thermal environment.


Guess what? Different source-guessing strategies for old versus new information.
The probability-matching account states that learned specific episodic contingencies of item types and source dominate over general schematic expectations in source guessing. However, recent evidence from Bell et al. [(2020). Source attributions for detected new items: Persistent evidence for schematic guessing. Quarterly Journal of Experimental Psychology, 73(9), 1407-1422] suggest that this only applies to source guessing for information that is recognised as belonging to a previously encoded episode. When information was detected as being new, participants persisted in applying schematic knowledge about the sources' profession. This dissociation in source guessing for detected-old and detected-new information may have been fostered by the specific source-monitoring paradigm by Bell et al. (2020) in which sources were a group of individuals in a certain profession rather than fixed persons from that profession for whom episodic contingencies are more likely to persist also for new information. The aim of the present study was to test whether source guessing for detected-old versus detected-new information also dissociates in a more typical source-monitoring task, the doctor-lawyer paradigm, in which one individual doctor and one lawyer present profession-related information. Despite this change in paradigm, source guessing was based on the item-source contingency only for detected-old information, whereas schematic knowledge persisted for detected-new information. The present study thus adds evidence for persistent schema-based source guessing for new information.


[Periodontal diagnosis in orthodontics].
Before any orthodontic treatment can begin, it is essential that the patient's periodontium be in sound condition, capable of responding to the movement of teeth in a healthy fashion. Inspection of the dentition, palpation of tissues, and careful study of adequate X-Rays are all necessary for establishing a diagnosis, but review of the depth of gingival pockets with periodontal probes is the key procedure for avoiding blunders in treatment. After periodontal health has been validated, it is vital that orthodontists determine the patient's periodontal biotype by clinical observation and periodontal probing and assess the quality of the gingival attachments of the teeth that will be affected by the expansion forces of treatment. The ensemble of these criteria will dictate what treatment paths and forces the orthodontist will employ.


Emotion and attention interaction: a trade-off between stimuli relevance, motivation and individual differences.
Mounting evidence suggests that the neural processing of emotional stimuli is prioritized. However, whether the processing of emotional stimuli is dependent on attention remains debatable. Several studies have investigated this issue by testing the capacity of emotional distracters to divert processing resources from an attentional main task. The attentional load theory postulates that the perceptual load of the main task determines the selective processing of the distracter. Although we agree with this theory, we also suggest that other factors could be important in determining the association between the load of the main task and distracter processing, namely, (1) the relevance of the to-be ignored stimuli and (2) the engagement in the main task due to motivation. We postulate that these factors function as opposite forces to influence distracter processing. In addition, we propose that this trade-off is modulated by individual differences. In summary, we suggest that the relationship between emotion and attention is flexible rather than rigid and depends on several factors. Considering this perspective may help us to understand the divergence in the results described by several studies in this field.


Gender differences in effects of prenatal and postnatal exposure to electromagnetic field and prenatal zinc on behaviour and synaptic proteins in rats.
Humans are exposed to electromagnetic fields (EMF) from various sources throughout life. Because humans are easily impacted by environmental factors during early development, it is believed that EMF can cause structural and functional changes on the developing brain that may lead to behavioural changes. This paper investigates the impact of EMF exposure and zinc supplementation during the prenatal and postnatal periods on behavioural changes and synaptic proteins in a gender-dependent manner. Pups from four groups of pregnant rats were used: Sham, EMF (5 days/wk, 4 h/day EMF-exposure applied), Sham+Zinc (5 days/wk, 5 mg/kg/day zinc applied) and EMF+Zinc (5 days/wk, 4 h/day EMF-exposure and 5 mg/kg/day zinc applied). EMF exposure and zinc supplementation were initiated from the first day of pregnancy to the 42nd postnatal day. Zinc levels in blood, NLGN3 and SHANK3 levels in hippocampus and amygdala, and synaptic structures in amygdala were examined. Behavioural tests showed that EMF exposure had no effect on social behaviour, but adversely affected activity and exploratory behaviour, and led to increased anxiety formation. Zinc supplementation had a partially positive effect on female, but not male offspring. SHANK3 and NLGN3 proteins were significantly lower in EMF groups, however, no positive effect of zinc supplementation was found. In conclusion, EMF exposure may alter the levels of synaptic proteins in the developing brain, leading to behavioural changes in a gender-dependent manner. Evaluation of zinc supplementation at different doses could be beneficial to prevent or reduce the behavioural and structural effects of EMF.


Chromobacterium violaceum ω-transaminase variant Trp60Cys shows increased specificity for (S)-1-phenylethylamine and 4'-substituted acetophenones, and follows Swain-Lupton parameterisation.
For biocatalytic production of pharmaceutically important chiral amines the ω-transaminase enzymes have proven useful. Engineering of these enzymes has to some extent been accomplished by rational design, but mostly by directed evolution. By use of a homology model a key point mutation in Chromobacterium violaceum ω-transaminase was found upon comparison with engineered variants from homologous enzymes. The variant Trp60Cys gave increased specificity for (S)-1-phenylethylamine (29-fold) and 4'-substituted acetophenones (∼5-fold). To further study the effect of the mutation the reaction rates were Swain-Lupton parameterised. On comparison with the wild type, reactions of the variant showed increased resonance dependence; this observation together with changed pH optimum and cofactor dependence suggests an altered reaction mechanism.


Towards Personalized Federated Learning.
In parallel with the rapid adoption of artificial intelligence (AI) empowered by advances in AI research, there has been growing awareness and concerns of data privacy. Recent significant developments in the data regulation landscape have prompted a seismic shift in interest toward privacy-preserving AI. This has contributed to the popularity of Federated Learning (FL), the leading paradigm for the training of machine learning models on data silos in a privacy-preserving manner. In this survey, we explore the domain of personalized FL (PFL) to address the fundamental challenges of FL on heterogeneous data, a universal characteristic inherent in all real-world datasets. We analyze the key motivations for PFL and present a unique taxonomy of PFL techniques categorized according to the key challenges and personalization strategies in PFL. We highlight their key ideas, challenges, opportunities, and envision promising future trajectories of research toward a new PFL architectural design, realistic PFL benchmarking, and trustworthy PFL approaches.


Assisted reproductive technology in Japan: A summary report for 2016 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology.
The Japan Society of Obstetrics and Gynecology started an online cycle-based assisted reproductive technology (ART) registry system in 2007. This report presents the characteristics and treatment outcomes of ART registered for the cycles practiced during 2016. Cycle-specific information for all ART cycles implemented in participating ART facilities were collected. A descriptive analysis was conducted for the registry database of 2016. In total, 447 790 treatment cycles and 54 110 neonates (one in 18.1 neonates born in Japan) were reported in 2016. The mean patients' age was 38.1 years (SD = 4.5). Among the egg retrieval cycles, 104 575 of 251 399 (41.6%) were freeze-all cycles without fresh embryo transfers (ET), while fresh ET was performed in 64 497 cycles (58.4%). A total of 187 132 frozen-thawed ET cycles were reported, resulting in 62 432 pregnancies and 44 484 neonates born. Single ET was selected for 81.0% of fresh transfers and 82.7% of frozen cycles, resulting in singleton pregnancy/live birth rates of 97.0%/96.4% and 96.7%/96.4%, respectively. The total ART cycles and subsequent live births continued to increase in 2016. Single ET was performed more than 80%, and ET has shifted from using fresh embryos to frozen ones.


Generation of a Bactrian camel hepatitis E virus by a reverse genetics system.
Bactrian camel hepatitis E virus (HEV) is a novel HEV belonging to genotype 8 (HEV-8) in the Orthohepevirus A species of the genus Hepevirus in the family Hepeviridae. HEV-8 cross-transmits to cynomolgus monkeys and has a potential risk for zoonotic infection. Until now, neither a cell-culture system to grow the virus nor a reverse genetics system to generate the virus has been developed. To generate replication-competent HEV-8 and to establish a cell-culture system, we synthesized capped genomic HEV-8 RNAs by in vitro transcription and used them to transfect into PLC/PRF/5 cells. A HEV-8 strain, HEV-8M2, was recovered from the capped HEV-8 RNA-transfected cell-culture supernatants and subsequently passaged in the cells, demonstrating that PLC/PRF/5 cells were capable of supporting the replication of the HEV-8, and that a cell-culture system for HEV-8 was successfully established. In addition to PLC/PRF/5 cells, A549 and Caco-2 cells appeared to be competent for the replication, but HepG2 C3/A, Vero, Hela S3, HEp-2C, 293T and GL37 cells were incompetent. The HEV-8M2 strain was capable of infecting cynomolgus monkeys by an intravenous inoculation, indicating that HEV-8 was infectious and again carried a risk for zoonotic infection. In contrast, HEV-8 did not infect nude rats and BALB/c nude mice, suggesting that the reservoir of HEV-8 was limited. In addition, the replication of the HEV-8M2 strain was efficiently abrogated by ribavirin but not by favipiravir, suggesting that ribavirin is a drug candidate for therapeutic treatment of HEV-8-induced hepatitis. The infectious HEV-8 produced by a reverse genetics system would be useful to elucidate the mechanisms of HEV replication and the pathogenesis of type E hepatitis.


Variations in the mycorrhization characteristics in roots of wild-type and ABA-deficient tomato are accompanied by specific transcriptomic alterations.
Abscissic acid (ABA) determines mycorrhiza functionality and arbuscule development. In this study, we performed transcriptome analysis in response to different mycorrhization status according to the ABA content in the root to identify genes that may play a role in arbuscule functionality. Affymetrix Tomato GeneChip (approximately 10,000 probes) allowed us to detect and compare the transcriptional root profiling of tomato (Solanum lycopersicum) wild-type and ABA-deficient sitiens plants colonized by Glomus intraradices. A number of identified genes in tomato belong to a category of genes already described as "mycorrhizal core-set" in other host plants. The impairment in arbuscular mycorrhiza (AM) formation in ABA-deficient mutants was associated with upregulation of genes related to defense and cell wall modification, whereas functional mycorrhization in wild-type plants was associated with activation of genes related to isoprenoid metabolism. The oxylipin pathway was activated in tomato mycorrhizal roots at late stages of interaction, and was related to the control of fungal spread in roots, not with the establishment of the symbiosis. Induction of selected genes, representing a range of biological functions and representative of the three sets of genes specifically upregulated in the different plant phenotype, was confirmed by quantitative reverse-transcription polymerase chain reaction, and their response to phythohormone treatment was tested, showing that ethylene and jasmonic acid are key regulators of gene expression during AM development. Comparative analysis of mycorrhiza upregulated functional categories revealed significant changes in gene expression associated with the different mycorrhization status according to the ABA content in the roots.


Effect of metformin on proliferative markers in women with endometrial carcinoma: Systematic review and meta-analysis.
Endometrial carcinoma (EC) is the most common gynecologic malignancy in the USA and Western Europe. Surgery is the mainstay of both staging and treatment of EC. Fertility sparing medical therapies are often offered to young women who desire fertility. Metformin has been suggested to be an anti-cancer agent as evidenced by previous studies. It decreases Antigen Ki-67 (Ki-67) proliferation and expression which is associated with proliferative activity of malignant tumors. In this systematic review and meta-analysis, we assessed the efficacy of metformin on patients with EC. We searched PubMed, Cochrane CENTRAL, Web of Science, and SCOPUS for relevant clinical trials and excluded observational studies. The quality appraisal was evaluated according to GRADE, and we assessed the risk of bias using Cochrane's risk of bias tool. We conducted the analysis of continuous data using mean difference (MD). We included the following outcomes: Ki-67 index, glucose, insulin, P-S6, body mass index (BMI), C-peptide, Insulin-like growth factor (IGF-1), leptin, and hemoglobin. Nine studies were eligible for our meta-analysis. We found that compared to the control group, metformin is highly effective in reducing Ki-67 proliferation and expression [MD=-10.14 (-19.10, -1.17)], (p=0.03), P-S6 [MD=-1.82 (-3.17, -0.46)], (p=0.009), plasma glucose level [MD=-1.76 (-4.88, 1.37), p=0.27], and BMI [MD=-1.07 (-1.49, -0.65)], (p<0.001). We conclude that metformin administration is effective in patients with EC. It decreases Ki-67 proliferation and expression, serum glucose, and p-S6 significantly.


Impact of the Educational Boost Your Brain and Memory Program Among Senior Living Residents.
This random assignment waitlist control intervention study examined an implementation of the educational Boost Your Brain and Memory cognitive fitness intervention in 12 senior living organizations. Older adult participants ( n = 166) completed measures of brain health knowledge, use of memory techniques, physical and intellectual activity, and mindfulness, at baseline and after the intervention group's completion of the course. Changes in knowledge scores and in self-reported physical and intellectual activity increased significantly more for intervention participants than for waitlist controls at the conclusion of the course. There were no significant changes between the groups in mindfulness or use of memory techniques. This suggests that in senior living settings Boost Your Brain and Memory is effective in educating participants about brain healthy behaviors and in motivating behavioral change in the areas of physical and intellectual activity.


Regioselective Dehydration of Sugar Thioacetals under Mild Conditions.
Sugars are abundant in waste biomass, making them sustainable chiral building blocks for organic synthesis. The demand for chiral saturated heterocyclic rings for pharmaceutical applications is increasing as they provide well-defined three-dimensional frameworks that show increased metabolic resistance. A range of sugar thioacetals can be dehydrated selectively at C-2 under mild basic conditions, and the resulting ketene thioacetals can be applied to the production of useful chiral building blocks via further selective dehydration reactions.


Anatomical and radiological angiographic study of the coronary ostia in the adult human hearts and their clinical significance.
This study was carried out to investigate the morphometric parameters and variations of coronary ostia in the hearts of adult human cadavers and coronary angiographs. The hearts of 60 adult human cadavers and 400 coronary angiographs were used in this study. The root of the aorta was carefully dissected to clear aortic sinuses, coronary ostia, and sinutubular junction (STJ). Number, locations, internal diameter distance between coronary ostia and their corresponding STJ, sinus bottom, and valve commissures were investigated. The anterior aortic sinus (AAS) revealed a single ostium for right coronary artery (RCA) in 77.5% of male and 80% of female hearts. This ostium gave a common origin for RCA and third coronary artery (TCA) in 15% of male and 20% of female hearts. However, two separate ostia for RCA and TCA origin were seen in 20% of male and 15% of female hearts. Moreover, three ostia were seen in one male and one female hearts within AAS. Meanwhile, the left posterior aortic sinus showed a single ostium for left coronary artery (LCA) in 97.5% of male and 95% of female hearts and two ostia in one male and one female hearts. The ostia were commonly seen below STJ and less commonly were observed above STJ. The distance between the bottom of aortic sinus and LCA ostium was longer than that of RCA. The internal diameter of RCA ostium was significantly (P<0.05) narrower than that of LCA but with no significant sex difference. Moreover, anomalous of coronary ostia was observed in seven out 400 angiographs and in two cadaveric hearts. Knowledge the morphometric parameters and anatomical variations of coronary ostia helps the cardiac surgeons to overcome the possible difficulties that could occur during surgical and radiological coronary interventions.


Optimizing the closed suction surgical drainage system.
Closed suction drains are indicated in a wide array of postoperative settings, with many distinct drainage systems available to the surgeon. The purpose of this study was to compare the suction gradients achieved using 2 different sizes of suction reservoirs and 2 different techniques for generating negative pressure. Drainage reservoirs of 100 and 400 ml were chosen to evaluate their ability to achieve suction. Suction was established in both sizes of drains by pressing the sides of the reservoir together or by pushing the bottom of the reservoir toward the top. Negative pressures were recorded with the reservoir empty, and after every 10-ml addition of saline. Averages were graphed to illustrate the applied suction over a range of drain volumes. The 100-ml drainage system reached a peak suction of -117.6 mmHg, while the 400-ml drainage system reached only a peak suction of -71.4 mmHg. Both of the maximum suction readings were achieved using the full-squeeze technique. The bottom-pushed-in technique did not result in any sustained measurable levels of suction using either of the reservoir volumes. Smaller drain reservoirs are more successful in generating a high initial suction than larger reservoirs, especially when the volume of fluid in the drain is relatively low. In all sizes of drains, compressing the sides of the reservoir is a far better technique for establishing negative pressure than pressing the bottom of the drain up toward the top.


Reconstructing intimate violence: the structure and content of recollections of violent events.
The purpose of this article is to explore the structure and content of recollections of violent events among cohabiting partners. The authors used qualitative methodology to examine 48 in-depth interviews. Content analysis of the interviews yielded two parallel and interrelated continua: One represented the life circumstances (staying in spite of violence) impinging on the recollections; the other dealt with the content of the memories of violent events. These two interacted according to a series of structural features. Both men and women living in violent relationships described a contextual variation ranging from choosing to stay to being prevented from leaving. The memory of violence was constructed in a manner meant to achieve coherence with the appropriate context.


The effect of a priming-based training on the production of object clitic pronouns in Italian speaking children with DLD.
Children with developmental language disorders (DLD) have impaired morphosyntactic abilities despite age-appropriate nonverbal cognitive abilities and no hearing disorders or brain injury. The persistent omission of third-person object clitic pronouns (3DO clitics) has been proven to be a clinical marker of developmental language disorders (DLD) for both preschool and school-aged Italian-speaking children. According to the model of 3DO clitic derivation recently brought to attention, 3DO clitic omission is a morphosyntactic matter and, therefore, we argue that the production of 3DO clitics can be enhanced through morphosyntactic priming in children with DLD. To corroborate this hypothesis, we administered a 3DO clitic training based on a morphosyntactic priming paradigm to 23 typically developing (TD) children and 11 children with DLD. Results show that their 3DO clitic production is enhanced after the training and that these effects are persistent in time. Our results suggest that a priming-based training can concretely help children with DLD in their language development.


Lipid nanoparticle technology for therapeutic gene regulation in the liver.
Hereditary genetic disorders, cancer, and infectious diseases of the liver affect millions of people around the globe and are a major public health burden. Most contemporary treatments offer limited relief as they generally aim to alleviate disease symptoms. Targeting the root cause of diseases originating in the liver by regulating malfunctioning genes with nucleic acid-based drugs holds great promise as a therapeutic approach. However, employing nucleic acid therapeutics in vivo is challenging due to their unfavorable characteristics. Lipid nanoparticle (LNP) delivery technology is a revolutionary development that has enabled clinical translation of gene therapies. LNPs can deliver siRNA, mRNA, DNA, or gene-editing complexes, providing opportunities to treat hepatic diseases by silencing pathogenic genes, expressing therapeutic proteins, or correcting genetic defects. Here we discuss the state-of-the-art LNP technology for hepatic gene therapy including formulation design parameters, production methods, preclinical development and clinical translation.


Impact of Sociodemographic Disparities on Language Outcomes After Cochlear Implantation in a Diverse Pediatric Cohort.
We examined how sociodemographic and audiologic factors affect receptive and expressive language outcomes in children with cochlear implantation. Retrospective cohort study. A hearing loss (HL) clinic at a tertiary center. Sociodemographic variables, HL characteristics, age at implantation, and receptive language scores (Preschool Language Scale and the Clinical Evaluation of Language Fundamentals) were collected from patients with congenital HL who received their first implant by 4 years old after January 1, 2007. t Tests, linear regression, Mann-Whitney, Cohen's d, and mediation analysis were used for descriptive statistics and hypothesis testing. Among 79 patients, 42 (53%) were females, 44 (56%) under-represented minorities, and 56 (71%) had public insurance. At least 1 year after implantation, the median receptive language score was 69 (range 50-117). Females (p = .005), having private insurance (p = .00001), having a Cochlear Implant Profile score below 4 (p = .0001), and receiving their implant at or before 12 months of age (p = .0009) were significantly associated with improved receptive language outcomes. Insurance type had a significant effect on receptive language outcomes, independent from age at first implantation (total effect: coef = -13.00, p = .02; direct effect: coef = -12.26, p = .03; indirect effect: coef = -0.75, p = .47). Sociodemographic variables had large effect sizes, with the Cochlear Implant Profile score having the largest effect size (d = 1.3). Sociodemographic factors have a large impact on receptive language outcomes. Public insurance is associated with worse receptive language, not mediated by later age at implantation, suggesting that other factors primarily impact language outcomes in publicly insured children with cochlear implants.