Frequency and determinants of missing data in clinical and prognostic variables recently added to SEER.
The objectives of the present study were to examine and quantify the frequency of missing information for the collaborative stage (CS) site-specific factors (SSF) added to the Surveillance, Epidemiology and End Results (SEER) data collection in 2004, to evaluate patient-, disease-, and registry-related factors associated with incomplete data, and to quantify time and effort required to collect information for each variable of interest. The study included 2 parts: 1) an analysis of existing nationwide SEER data; and 2) an evaluation of time and effort as reported by hospital registrars in the Metropolitan Atlanta and Rural Georgia (MARGA) SEER Registry catchment area. The first analysis examined all SSF for all types of cancers reported to the SEER Program between 2004 and 2007 from all 17 SEER registries. The data for the second analysis were limited to 5 cancer sites: breast, prostate, colon/rectum, testes, and lymphoma. Information for each cancer site was collected from 40 cancer registrars who were asked to estimate the amount of time and effort spent on abstracting each variable of interest. We analyzed 825,952 cases pertaining to 18 different cancer sites and 45 different variables. Of the 45 SSF variables examined in this study, 12 had at least 50% of cases with missing data. Conversely, a total of 21 variables were at least 80% complete. Our analysis of determinants of missing SSF data showed an improvement of reporting since 2004 for most variables. Older patients (80+ years of age) tended to have a higher proportion of missing data compared to 40- to 59-year-olds (reference category). For the specific cancers presented in this paper, patients diagnosed in non-metropolitan areas tended to have a slightly higher proportion of missing data compared to those diagnosed in metropolitan areas. We found no discernable patterns of association between probability of having missing data and patients' race, sex, or registry. According to the registrars' reports, data collection for CS SSF requires a median of 2-3 minutes with a range of 1-15 minutes. There was great variability in the perceived level of difficulty associated with finding the necessarily data. The data completeness for CS SSF ranges widely, and is largely site- and variable-specific. The main barrier to data completeness appears to be the availability of information in the medical records. Our results indicate that for a number of SSF the proportion of missing data is so high that these variables can be of little, if any, use for population-based research. The practical implications of our findings with respect to existing and future SSF need to be explored.


HIV, hepatitis B and C infection status of the blood donors in a blood bank of a tertiary health care centre of Orissa.
A record based retrospective study was conducted at the blood bank of SCB Medical College, Cuttack. All the donors who had donated blood from June to December 2005 were considered. 91.7%of the donors were males and majority belonged to 21-30 years age group. 1.98% of the donors were positive for hepatitis C, 1.13% for hepatitis B and 0.35% for HIV. For HBV infection, majority belonged to 31-40 years age group. But for HCV and HIV infection more were in the 21-30 year age group. Significantly more number of exchange donors was positive for HBV and HCV in comparison to voluntary donors in blood bank and camp. No voluntary donors from the camp were HIV positive.


α-Fetoprotein is a surrogate marker for predicting treatment failure in telaprevir-based triple combination therapy for genotype 1b chronic hepatitis C Japanese patients with the IL28B minor genotype.
Even when treated with telaprevir-based triple therapy, some patients fail to achieve a sustained virological response. This study identified factors related closely to treatment failure. A total of 146 Japanese genotype 1b chronic hepatitis C patients were enrolled in this prospective, multicenter study and received a 24-week regimen of triple therapy. The end-of-treatment response rate was significantly lower in patients with the interleukin 28B (IL28B) (rs8099917) non-TT genotype (85.2%) than in those with the TT genotype (100%, P = 0.0002). Multiple logistic regression analysis identified high α-fetoprotein levels as an independent factor related to non-end-of-treatment response in patients with the non-TT genotype. A cut-off value of 20 ng/ml was determined for a non-end-of-treatment response; sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 75.0%, 95.7%, 75.0%, 75.0%, and 92.6%, respectively. Multiple logistic regression analysis for a sustained virological response identified the IL28B TT genotype, low α-fetoprotein levels, non-responders, and a rapid virological response. The sustained virological response rate was significantly lower in patients with the non-TT genotype (59.3%) than in those with the TT genotype (96.7%, P < 0.0001). In patients with the non-TT genotype, α-fetoprotein was the most significant predictor for non-sustained virological response by univariate analysis. A cut-off value of 7.4 ng/ml α-fetoprotein was determined for non-sustained virological response; sensitivity, specificity, PPV, NPV, and accuracy were 63.6%, 87.5%, 77.8%, 77.8%, and 77.8%, respectively. For the non-TT patients, serum α-fetoprotein levels may be a surrogate marker for predicting treatment failure in telaprevir-based therapy for genotype 1b chronic hepatitis C.


Anticancer activity of new molecular hybrids combining 1,4-naphthalenedione motif with phosphonic acid moiety in hepatocellular carcinoma HepG2 cells.
Structural motifs found in naturally occurring compounds are frequently used by researchers to develop novel synthetic drug candidates. Some of these new agents are hybrid molecules which are designed through a concept of combining more than one functional element. In this report, anticancer activity of new synthetic molecular hybrids, substituted 3-diethoxyphosphorylnaphtho[2,3-b]furan-4,9-diones and 3-diethoxyphosphorylbenzo[f]indole-4,9-diones, which integrate natural 1,4-naphtalenedione scaffold, present in several anticancer agents, with pharmacophoric phosphonate moiety, were tested against hepatocellular cell line HepG2. Cytotoxicity was examined using MTT assay. Two most potent compounds, furandione 8a and benzoindoldione 12a, which reduced the number of viable HepG2 cells with the IC50 values of 4.13 µM and 5.9 µM, respectively, were selected for further research. These compounds decreased the mRNA expression levels of several genes: Bcl-2, angiogenic vascular endothelial growth factor (VEGF), c-Fos, caspase-8 and increased the expression of Bax, caspase-3 and -9, c-Jun, p21, p53, as determined by quantitative real-time PCR. The ability of these compounds to induce apoptosis and DNA damage was studied by flow cytometry. The obtained data showed that the new compounds inhibited cell viability by increasing apoptosis and decreasing angiogenesis. Compound 8a was a much stronger apoptosis inducer as compared with 12a and strongly activated the intrinsic pathway of apoptosis, associated with the loss of mitochondrial membrane potential and changes in Bax/Bcl-2 ratio. These findings show that the synthetic hybrids combining 1,4-naphthalenedione system and phosphonic acid moiety display potential to be further explored in the development of new anticancer agents.


Life-Threatening Extrarenal Manifestations in an Infant with Atypical Hemolytic Uremic Syndrome Caused by a Complement 3-Gene Mutation.
Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment caused by uncontrolled activation of the complement system. About 20% of patients show extrarenal manifestations, with central nervous system involvement being the most frequent. We described the clinical course and management of aHUS in an infant, that was caused by a complement 3 (C3) gene mutation with severe extrarenal manifestations. A 4-month-old girl visited our hospital for jaundice and petechiae. Laboratory tests revealed microangiopathic hemolytic anemia, thrombocytopenia, and hyperazotemia. She was diagnosed with aHUS with a C3 p.E1160K mutation. Daily fresh-frozen plasma (FFP) therapy was administered; however, she experienced the severe extrarenal manifestations of pulmonary hemorrhage and gastrointestinal bleeding. With aggressive treatment, supportive care, and daily FFP transfusion, the patient recovered and was discharged after 72 days of hospital stay, on a regular FFP transfusion. Four months after diagnosis, she was switched to eculizumab treatment. Twenty months have passed since then and she has been relapse-free until now. aHUS is rare but has a devastating course if not properly treated. Severe extrarenal manifestations, such as pulmonary hemorrhage and gastrointestinal bleeding, can develop in aHUS caused by a C3 mutation. In our case, long-term management with eculizumab resulted in relapse-free survival.


A formulation strategy for gamma secretase inhibitor ELND006, a BCS class II compound: development of a nanosuspension formulation with improved oral bioavailability and reduced food effects in dogs.
ELND006 is a novel gamma secretase inhibitor previously under investigation for the oral treatment of Alzheimer's disease. ELND006 shows poor solubility and has moderate to high permeability, suggesting it is a Biopharmaceutics Classification System Class II compound. The poor absolute oral bioavailability of the compound in fasted dogs (F ∼11%) is attributed to poor aqueous solubility. In addition, inhibiting amyloid precursor protein but not Notch cleavage is an important goal for gamma secretase inhibitors; therefore, significant variation in bioavailability resulting from food consumption is a potential liability for this class of compounds. The objective of the present study was to determine if an ELND006 nanocrystalline formulation would offer improved and predictable pharmacokinetics. ELND006 was formulated as a nanosuspension with a mean particle size of less than 200 nm, which was stable in particle size and crystallinity for over 1 year. In addition, ELND006 nanosuspension exhibited rapid dissolution in comparison with reference active pharmaceutical ingredient (API). The in vivo performance of the ELND006 nanosuspension was tested in fed and fasted beagle dogs and compared with a gelatin capsule containing reference API. The results show that nanosizing ELND006 profoundly improved the oral bioavailability and virtually eliminated variation resulting from food intake.


Is the scrotal testis normal in unilateral cryptorchidism?
Bilateral testicular biopsies were performed on 66 children undergoing orchiopexy for unilateral cryptorchidism and the tubular fertility index (TFI) recorded. The results in both the descended and undescended testes at various ages were compared with previously reported control data. There were no significant differences between the germ cell activity of the scrotal testis in cases with unilateral cryptorchidism and that of controls. By contrast, the mean TFI of the undescended testis was significantly less than that of control patients of all ages. In neither group was there evidence of a progressive loss of germ cell activity during childhood. It is concluded that there is little to be gained from very early orchiopexy, performed before the third year of life.


The application of regenerable sorbents for mercury capture in gas phase.
Mercury is a well-known toxic element, and flue gas streams emitted from coal-fired utilities are one of the largest anthropogenic sources of this element. This study briefly reviews the proposed technologies for reducing mercury emissions from coal combustion, focusing on an emerging process which involves the use of regenerable sorbents and especially those loaded with noble metals. Among the mercury species formed during coal combustion, elemental mercury is the most difficult to remove from the flue gases due to its low reactivity and insolubility in water. The widespread interest in using regenerable sorbents with metals is due to their ability to retain elemental mercury. With this technology, not only can efficiencies of 100 % be reached in the retention of elemental mercury but also a way to avoid the generation of new wastes loaded with mercury. This study considers the main aspects that must be taken into account when developing effective regenerable sorbents for mercury capture, with special attention to sorbents containing noble metals. The characteristics of this process are compared with those of other processes in a more advanced state of development.


ProteomIQ blue, a potent post-stain for the visualization and subsequent mass spectrometry based identification of fluorescent stained proteins on 2D-gels.
Manual spot excision for protein identification from fluorescent stained two-dimensional (2-D) gels is hard to accomplish. Here, we explore the use of ProteomIQ Blue as a post-stain method for the visualization of fluorescent stained/labeled proteins. We show that ProteomIQ Blue post-staining is almost as sensitive as staining with SYPRO Ruby or cyanine dyes alone. More than 90% of the protein spots that are stained with the fluorescent stains are still detectable with ProteomIQ Blue. In protein identification by mass spectrometry, ProteomIQ Blue post-stained spots provide high sensitivity and high protein sequence coverage of the peptide mass maps in both MALDI-TOF-MS and ESI-MS/MS analyses. In conclusion, post-staining of fluorescent stained gels with ProteomIQ Blue provides a facile and a powerful method to achieve quantitative protein analysis as well as protein identification in the same semianalytical gel without requiring sophisticated/expensive robotic equipment.


Clinical Efficacy of Percutaneous Kyphoplasty Combined with Calcitriol and Calcium in the Treatment of Traumatic Nonosteoporotic Vertebral Compression Fractures.
The present study investigated the clinical efficacy of percutaneous kyphoplasty (PKP) combined with calcitriol and calcium in the treatment of traumatic nonosteoporotic vertebral compression fractures (TNVCFs). The patients were equally divided into a control group and a treatment group by a random number table. The patients in the control group underwent PKP surgery, and the patients in the treatment group received calcitriol and calcium on the basis of PKP surgery. The visual analog scale (VAS) pain scores, Oswestry Disability Index (ODI) scores, the height of the anterior edge of the vertebral body, Cobb's angle, and the level of the bone mineral density of the two groups of TNVCF patients before surgery were recorded and compared, one and six months after surgery. Thirty-six inpatients with TNVCFs admitted to the trauma center of the First Affiliated Hospital of Soochow University from January 2019 to January 2020 were recruited. There were no significant differences in the VAS and ODI scores, the height of the anterior edge of the injured vertebral body, Cobb's angle, and bone mineral density between the two groups before surgery (P > 0.05). The VAS scores, ODI scores, the height of the anterior edge of the injured vertebral body, and Cobb's angle of the two groups of patients after surgery were significantly better than those before surgery. One and six months after surgery, the VAS and ODI scores, the height of the anterior edge of the injured vertebral body, Cobb's angle, and the bone mineral density of the patients in the treatment group improved significantly compared to those in the control group (P < 0.05). PKP combined with calcitriol and calcium medications could significantly relieve pain, alleviate the loss of compressed vertebral height and kyphosis, and improve the spinal function and the life quality of the TNVCF patients.


Hyaluronan-Cholesterol Nanogels for the Enhancement of the Ocular Delivery of Therapeutics.
The anatomy and physiology of the eye strongly limit the bioavailability of locally administered drugs. The entrapment of therapeutics into nanocarriers represents an effective strategy for the topical treatment of several ocular disorders, as they may protect the embedded molecules, enabling drug residence on the ocular surface and/or its penetration into different ocular compartments. The present work shows the activity of hyaluronan-cholesterol nanogels (NHs) as ocular permeation enhancers. Thanks to their bioadhesive properties, NHs firmly interact with the superficial corneal epithelium, without penetrating the stroma, thus modifying the transcorneal penetration of loaded therapeutics. Ex vivo transcorneal permeation experiments show that the permeation of hydrophilic drugs (i.e., tobramycin and diclofenac sodium salt), loaded in NHs, is significantly enhanced when compared to the free drug solutions. On the other side, the permeation of hydrophobic drugs (i.e., dexamethasone and piroxicam) is strongly dependent on the water solubility of the entrapped molecules. The obtained results suggest that NHs formulations can improve the ocular bioavailability of the instilled drugs by increasing their preocular retention time (hydrophobic drugs) or facilitating their permeation (hydrophilic drugs), thus opening the route for the application of HA-based NHs in the treatment of both anterior and posterior eye segment diseases.


Integration and segregation of large-scale brain networks during short-term task automatization.
The human brain is organized into large-scale functional networks that can flexibly reconfigure their connectivity patterns, supporting both rapid adaptive control and long-term learning processes. However, it has remained unclear how short-term network dynamics support the rapid transformation of instructions into fluent behaviour. Comparing fMRI data of a learning sample (N=70) with a control sample (N=67), we find that increasingly efficient task processing during short-term practice is associated with a reorganization of large-scale network interactions. Practice-related efficiency gains are facilitated by enhanced coupling between the cingulo-opercular network and the dorsal attention network. Simultaneously, short-term task automatization is accompanied by decreasing activation of the fronto-parietal network, indicating a release of high-level cognitive control, and a segregation of the default mode network from task-related networks. These findings suggest that short-term task automatization is enabled by the brain's ability to rapidly reconfigure its large-scale network organization involving complementary integration and segregation processes.


Impairment of cardiac function and energetics in experimental renal failure.
Cardiac function and energetics in experimental renal failure in the rat (5/6 nephrectomy) have been investigated by means of an isolated perfused working heart preparation and an isometric Langendorff preparation using 31P nuclear magnetic resonance (31P NMR). 4 wk after nephrectomy cardiac output of isolated hearts perfused with Krebs-Henseleit buffer was significantly lower (P < 0.0001) at all levels of preload and afterload in the renal failure groups than in the pair-fed sham operated control group. In control hearts, cardiac output increased with increases in perfusate calcium from 0.73 to 5.61 mmol/liter whereas uremic hearts failed in high calcium perfusate. Collection of 31P NMR spectra from hearts of renal failure and control animals during 30 min normoxic Langendorff perfusion showed that basal phosphocreatine was reduced by 32% to 4.7 mumol/g wet wt (P < 0.01) and the phosphocreatine to ATP ratio was reduced by 32% (P < 0.01) in uremic hearts. During low flow ischemia, there was a substantial decrease in phosphocreatine in the uremic hearts and an accompanying marked increase in release of inosine into the coronary effluent (14.9 vs 6.1 microM, P < 0.01). We conclude that cardiac function is impaired in experimental renal failure, in association with abnormal cardiac energetics and increased susceptibility to ischemic damage. Disordered myocardial calcium utilization may contribute to these derangements.


Psychophysiological, neuroendocrine and cellular immune reactions under psychological stress.
Emotional stress is often followed by increased susceptibility to infections. Natural killer (NK) cells play a major role in the immediate immune response controlling this susceptibility. In this study on 45 first-time parachutists, it is demonstrated that highly controlled psychological stress increased psychophysiological variables, enhanced the secretion of sympathetic-adrenal hormones and also led to a significant increase of NK cells and their cytotoxic activity followed by a decrease below starting values. This immunological alteration is correlated with the secretion of noradrenaline during the emotional strain. Quick mobilization of these cytotoxic effector cells is suggested as a major mechanism for the effective adaptation of the immune system to stress situations.


Green tea polyphenol epigallocatechin-3 gallate (EGCG) affects gene expression of breast cancer cells transformed by the carcinogen 7,12-dimethylbenz[a]anthracene.
Since the 1980s, the incidence of late-onset breast cancer has been increasing in the United States. Known risk factors, such as genetic modifications, have been estimated to account for approximately 5 to 10% of breast cancer cases, and these tend to be early onset. Thus, exposure to and bioaccumulation of ubiquitous environmental chemicals, such as polycyclic aromatic hydrocarbons (PAHs), have been proposed to play a role in this increased incidence. Treatment of female Sprague-Dawley rats with a single dose of the PAH 7,12-dimethylbenz[a]anthracene (DMBA) induces mammary tumors in approximately 90 to 95% of test animals. We showed previously that female rats treated with DMBA and given green tea as drinking fluid displayed significantly decreased mammary tumor burden and invasiveness and a significantly increased latency to first tumor. Here we used cDNA microarray analysis to elucidate the effects of the green tea polyphenol epigallocatechin-3 gallate (EGCG) on the gene expression profile in a DMBA-transformed breast cancer cell line. RNA was isolated, in quadruplicate, from D3-1 cells treated with 60 mug/mL EGCG for 2, 7, or 24 h and subjected to analysis. Semiquantitative RT-PCR and Northern blot analyses confirmed the changes in the expression of 12 representative genes seen in the microarray experiments. Overall, our results documented EGCG-altered expression of genes involved in nuclear and cytoplasmic transport, transformation, redox signaling, response to hypoxia, and PAHs.


Impact of SOCE Abolition by ORAI1 Knockout on the Proliferation, Adhesion, and Migration of HEK-293 Cells.
Store-operated calcium entry (SOCE) provided through channels formed by ORAI proteins is a major regulator of several cellular processes. In immune cells, it controls fundamental processes such as proliferation, cell adhesion, and migration, while in cancer, SOCE and ORAI1 gene expression are dysregulated and lead to abnormal migration and/or cell proliferation. In the present study, we used the CRISPR/Cas9 technique to delete the ORAI1 gene and to identify its role in proliferative and migrative properties of the model cell line HEK-293. We showed that ORAI1 deletion greatly reduced SOCE. Thereby, we found that this decrease and the absence of ORAI1 protein did not affect HEK-293 proliferation. In addition, we determined that ORAI1 suppression did not affect adhesive properties but had a limited impact on HEK-293 migration. Overall, we showed that ORAI1 and SOCE are largely dispensable for cellular proliferation, migration, and cellular adhesion of HEK-293 cells. Thus, despite its importance in providing Ca2+ entry in non-excitable cells, our results indicate that the lack of SOCE does not deeply impact HEK-293 cells. This finding suggests the existence of compensatory mechanism enabling the maintenance of their physiological function.


A computer-based system for urology and nephrology.
Modern technology offers new opportunities for the storage and manipulation of hospital information. A computer-based system for urology and nephrology has been designed and developed in this centre. It uses a program that allows the analysis of unrestricted non-codified texts and the operation by hospital staff who have had no more than minimal computer training. The potential of such a system is outlined and a comparison is made with other existing systems. Future prospects and potential lines of development are presented.


Double-Pass Retina Point Imaging for the Evaluation of Optical Light Scatter, Retinal Image Quality, and Staging of Keratoconus.
To measure retinal image quality using point spread function (PSF) analysis by double-pass retina point imaging in patients with keratoconus and to correlate visual quality with disease severity. Patients diagnosed as having keratoconus by clinical examination, topography, and tomography and normal eyes were included in this study. A commercially available double-pass retina point imaging instrument (OQAS 108 II AcuTarget HD; Visiometrics S.L., Terrassa, Spain) was used to collect Objective Scatter Index (OSI) values in 21 keratoconic and 22 normal eyes. Eyes were also subjected to corneal topography and tomography, and staged using the Keratoconus Severity Score (KSS) and Amsler-Krumeich (AK) scales. The OSI was increased in keratoconic eyes (5.85 ± 0.98) versus control eyes (0.83 ± 0.12; mean ± SEM), in AK stages 1 to 4, and KSS stages 3 and 4. Receiver-operator characteristic analysis obtained an area under the curve (AUC) of 0.859 when evaluating the OSI as a unimodal diagnostic indicator for any KSS stage and 0.993 for KSS stages 3 and higher. An AUC of 0.949 was obtained in comparing eyes with lower severity topographic aberrations (KSS 1 and 2) versus mild to moderate keratoconus (KSS 3 and 4). Increasing corneal steepening patterns on tomography and topography were associated with PSF broadening and increased OSI. Double-pass retina point imaging is useful in correlating retinal image quality with keratoconus severity. The OSI may represent a clinically significant parameter for staging keratoconus with a unique ability to directly evaluate quality of vision in this population. [J Refract Surg. 2016;32(11):760-765.].


Proteomics of Arabidopsis seed germination. A comparative study of wild-type and gibberellin-deficient seeds.
We examined the role of gibberellins (GAs) in germination of Arabidopsis seeds by a proteomic approach. For that purpose, we used two systems. The first system consisted of seeds of the GA-deficient ga1 mutant, and the second corresponded to wild-type seeds incubated in paclobutrazol, a specific GA biosynthesis inhibitor. With both systems, radicle protrusion was strictly dependent on exogenous GAs. The proteomic analysis indicated that GAs do not participate in many processes involved in germination sensu stricto (prior to radicle protrusion), as, for example, the initial mobilization of seed protein and lipid reserves. Out of 46 protein changes detected during germination sensu stricto (1 d of incubation on water), only one, corresponding to the cytoskeleton component alpha-2,4 tubulin, appeared to depend on the action of GAs. An increase in this protein spot was noted for the wild-type seeds but not for the ga1 seeds incubated for 1 d on water. In contrast, GAs appeared to be involved, directly or indirectly, in controlling the abundance of several proteins associated with radicle protrusion. This is the case for two isoforms of S-adenosyl-methionine (Ado-Met) synthetase, which catalyzes the formation of Ado-Met from Met and ATP. Owing to the housekeeping functions of Ado-Met, this event is presumably required for germination and seedling establishment, and might represent a major metabolic control of seedling establishment. GAs can also play a role in controlling the abundance of a beta-glucosidase, which might be involved in the embryo cell wall loosening needed for cell elongation and radicle extension.


Aberrant promoter methylation in Chinese patients with non-small cell lung cancer: patterns in primary tumors and potential diagnostic application in bronchoalevolar lavage.
This study was aimed at defining patterns of aberrant gene methylation in non-small cell lung cancer (NSCLC) in Chinese patients and its use in detecting cancer cells in bronchoalveolar lavage (BAL). The methylation-specific PCR (MSP) was used to study methylation of the p16, retinoic acid receptor-beta (RARbeta), death-associated protein (DAP) kinase, and O(6)-methylguanine-DNA-methyltransferase (MGMT) genes in 75 NSCLCs [44 adenocarcinomas and 31 squamous cell carcinomas (SCCs)] and 68 BALs from suspected lung cancers. More females had adenocarcinoma than SCC (11 of 44 versus 2 of 31, P = 0.04). Aberrant methylation in at least one gene was found in 63 of 75 (84%) NSCLCs. p16, RARbeta, DAP kinase, and MGMT methylation was similar in adenocarcinoma and SCC. However, females with NSCLC showed more frequent p16 methylation than males (12 of 13 versus 36 of 62, P = 0.02), because of more frequent p16 methylation in female adenocarcinomas (10 of 11 versus 17 of 33, P = 0.02). This sexual difference was not observed in RARbeta, DAP kinase, and MGMT. At 92%, the frequency of p16 methylation in Chinese female NSCLC is one of the highest known. For BAL, MSP and cytological analysis showed concordant and discordant results in 25 of 68 and 43 of 68 samples. Of 41 MSP+/cytology- cases, 35 were eventually shown to have malignant lung lesions, 4 were at high risk but had no evidence of lung cancer, and 2 were lost to follow-up. There were two MSP-/cytology+ cases. Frequent gene methylations were seen in Chinese NSCLC patients. More frequent p16 methylation was seen in female patients. MSP is a useful molecular adjunct for cancer cell detection in BAL samples.


Potential use of calcareous mudstones in low hydraulic conductivity earthen barriers for environmental applications.
Earthen layers play a significant role in isolating contaminants in the subsurface, controlling the migration of contaminant plumes, and as landfill liners and covers. The physical, chemical and mineralogical properties of three calcareous mudstones from the Jagüel and Roca formations in North Patagonia, Argentina, are evaluated to determine their potential for the construction of liners. These mudstones were deposited in a marine environment in the Upper Cretaceous-Paleocene. The tested specimens mainly comprise silt and clay-sized particles, and their mineralogy is dominated by a smectite/illite mixed layer (70-90% Sm) and calcite in smaller proportion. Powdered mudstone samples have little viscosity and swelling potential when suspended in water. The hydraulic conductivity of compacted mudstones and sand-mudstone mixtures is very low (around 1-3 x 10(-10) m/s) and in good agreement with the expected hydraulic behaviour of compacted earthen layers. This behaviour can be attributed to the large amount of fine particles, high specific surface and the close packing of particles as confirmed by scanning electron microscope analysis. The tested materials also show a high cation exchange capacity (50-70 cmol/kg), indicating a high contaminant retardation capability. The calcareous mudstones show satisfactory mineralogical and chemical properties as well as an adequate hydraulic behaviour, demonstrating the potential use of these materials for the construction of compacted liners for the containment of leachate or as covers in landfills. These findings confirm the potential usage of marine calcareous mudstones as a low-cost geomaterial in environmental engineering projects.


Triadimefon and triadimenol: effects on monoamine uptake and release.
Acute administration of the agricultural fungicide triadimefon produced a neurotoxic syndrome in rats characterized by increased motor activity, stereotyped behaviors, and altered monoamine metabolism. Triadimenol, a metabolite of triadimefon in mammals, plants, and soil, also increased motor activity in rodents. To test the hypothesis that triadimefon and triadimenol are indirect-acting dopamine agonists, the present studies examined their abilities to inhibit monoamine uptake, bind to the dopamine transporter, and stimulate dopamine efflux in rat brain tissue, in vitro. Both triazoles inhibited the uptake of dopamine in striatal synaptosomal preparations. Triadimefon was 100-fold less potent than GBR12909, a prototypical inhibitor of dopamine uptake (IC50 = 4.7 microM vs. 37.2 nM, respectively), and triadimenol was about three-fold less potent than triadimefon. Triadimefon also weakly inhibited the uptake of norepinephrine in cortical synaptosomes (IC50 = 22.4 microM), but neither compound blocked the uptake of serotonin in cortical synaptosomes (IC50s > 100 microM). Triadimefon and triadimenol had similar affinity for [3H]mazindol binding sites on the dopamine transporter (IC50s approximately 1-1.5 microM, only two- to threefold greater than GBR12909). Neither triadimefon nor triadimenol (0.01-100 microM) increased basal efflux of [3H]DA that had been preloaded into striatal minces in vitro. An unexpected result was that GBR12909 (10 microM) increased basal efflux of [3H]DA by 71%, suggesting that this compound has DA releasing properties. These data suggest that increased synaptic concentrations of dopamine due to inhibition of dopamine uptake may play an important role in the neurobehavioral effects of triadimefon and triadimenol.


An experimental and theoretical study of the inward particle drift in contact line deposits.
The coffee ring effect, which refers to the formation of a ring-like deposit along the periphery of a dried particle laden sessile drop, is a commonly observed phenomenon. The migration of particles from the interior to the edge of a drying drop as a result of evaporation driven flow directed outwards, is well studied. In this article, we document the inward drift of a coffee stain, which is governed by the descent of the water-air interface of the drying drop due to solvent evaporation. A combination of experimental study and model predictions is undertaken to elucidate the effect of the diameter of particles in the drying drop, the wettability of the substrate on which the drop resides, and the concentration of particles on the inward drift of the coffee stain. This work also suggests a novel method to estimate the coefficient of friction between the particles and the substrate.


Supplemental security income for the aged, blind and disabled; Medicaid eligibility determinations--Social Security Administration, HHS. Final rule.
We have revised our rules on the agreements under which we make Medicaid eligibility determinations on behalf of States for individuals who receive Supplemental Security Income (SSI) benefits. The revision provides that we may enter into an agreement with a State even though the State's Medicaid eligibility requirements differ from the requirements for SSI or for State supplementary payments, or both, in ways mandated by Federal law. We also have rewritten and reorganized our existing rules for making Medicaid eligibility determinations.


Interaction between bile salts and beta-adrenoceptor antagonists.
The interactions between beta-adrenoceptor antagonists and bile salts were investigated by microcalorimetry. Nadolol and oxprenolol interactions with dihydroxy salts could be described by a 1:1 interaction model with the thermodynamic parameters indicating that the drugs were incorporated within the bile salt aggregates. This weak interaction was primarily hydrophobic although electrostatic attraction also played a role. Atenolol and metoprolol did not interact with the dihydroxy salts. None of the compounds interacted with trihydroxy bile salts or with salts below their aggregation concentration. Phase separation resulted when propranolol and alprenolol were present in dihydroxy salt solutions above a certain concentration with the interaction being of a hydrophobic and electrostatic nature. The implications of these results on in-vivo drug absorption are discussed.


Influenza reverse genetics: dissecting immunity and pathogenesis.
Reverse genetics systems allow artificial generation of non-segmented and segmented negative-sense RNA viruses, like influenza viruses, entirely from cloned cDNA. Since the introduction of reverse genetics systems over a decade ago, the ability to generate 'designer' influenza viruses in the laboratory has advanced both basic and applied research, providing a powerful tool to investigate and characterise host-pathogen interactions and advance the development of novel therapeutic strategies. The list of applications for reverse genetics has expanded vastly in recent years. In this review, we discuss the development and implications of this technique, including the recent controversy surrounding the generation of a transmissible H5N1 influenza virus. We will focus on research involving the identification of viral protein function, development of live-attenuated influenza virus vaccines, host-pathogen interactions, immunity and the generation of recombinant influenza virus vaccine vectors for the prevention and treatment of infectious diseases and cancer.


Patterns of cytokeratin expression in human gingival epithelia.
Specimens of human gingiva were collected from teenage and adult subjects and frozen sections were stained with an extensive panel of monoclonal antibodies with defined specificities for individual cytokeratins. The results indicated different and distinctive patterns of keratin expression by the oral gingival, oral sulcular and the junctional epithelia. It was observed that epithelium with staining characteristics of sulcular epithelium extended over the gingival crest onto the oral surface of the gingiva. Junctional epithelium showed the unusual pattern of co-expression of keratins typical of the stratifying and of the simple epithelial phenotypes. The patterns of gingival keratin expression are compared with those of other mucosal epithelia. The findings are discussed in relation to mechanisms that may determine or influence the junctional epithelial phenotype.


Cyanide self-poisoning.
Four cases of cyanide self-poisoning were admitted to one hospital over a period of two years. Two of the patients died. The diagnosis in the unconscious patient may be suggested by the finding of bradycardia and the absence of cyanosis (despite inadequate ventilation). The diagnosis can be confirmed in 5 to 10 minutes by a simple test on gastric aspirate, performed by the casualty officer. Cardiac pacing was used in two patients and may have a place in the supportive management of severe cases.


Fast proton spectroscopic imaging of human brain using multiple spin-echoes.
We introduce a multi-echo multi-slice MR proton spectroscopic imaging method, which allows for a dramatic reduction of the measurement time by acquiring multiple spin-echoes within a single repetition time. In the multi-echo multi-slice experiment discussed in this paper, a threefold reduction in measurement time is obtained by sacrificing some spectral resolution. Signal-to-noise ratio and spatial resolution are preserved. Metabolite images of N-acetyl aspartate, and total choline+total creatine from multiple slices through the human brain are presented and compared with images obtained with a conventional single-echo multi-slice method.


[Diagnosis and treatment of renal cell carcinoma accompanying the cystic lesion].
Approximately 15% of cases of renal cell carcinoma (RCC) present cystic configuration on radiologic and pathologic examination. The mechanisms of cyst formation in RCC are intrinsic multilocular cystic growth (multiloculated renal cell carcinoma: MCRCC), unilocular cystic growth (cystadenocarcinoma), cystic necrosis and tumor growth from the epithelial lining of a preexisting cyst. These cystic lesions accompanying RCC are often difficult to differentiate from the multiloculated renal cyst (MLC) or other benign cystic lesions such as hemorrhagic cyst and so on. Differential diagnosis of the complicated renal cystic lesions is discussed in this review.


Explosion propagation in inert porous media.
Porous media are often used in flame arresters because of the high surface area to volume ratio that is required for flame quenching. However, if the flame is not quenched, the flow obstruction within the porous media can promote explosion escalation, which is a well-known phenomenon in obstacle-laden channels. There are many parallels between explosion propagation through porous media and obstacle-laden channels. In both cases, the obstructions play a duel role. On the one hand, the obstruction enhances explosion propagation through an early shear-driven turbulence production mechanism and then later by shock-flame interactions that occur from lead shock reflections. On the other hand, the presence of an obstruction can suppress explosion propagation through momentum and heat losses, which both impede the unburned gas flow and extract energy from the expanding combustion products. In obstacle-laden channels, there are well-defined propagation regimes that are easily distinguished by abrupt changes in velocity. In porous media, the propagation regimes are not as distinguishable. In porous media the entire flamefront is affected, and the effects of heat loss, turbulence and compressibility are smoothly blended over most of the propagation velocity range. At low subsonic propagation speeds, heat loss to the porous media dominates, whereas at higher supersonic speeds turbulence and compressibility are important. This blending of the important phenomena results in no clear transition in propagation mechanism that is characterized by an abrupt change in propagation velocity. This is especially true for propagation velocities above the speed of sound where many experiments performed with fuel-air mixtures show a smooth increase in the propagation velocity with mixture reactivity up to the theoretical detonation wave velocity.


Acute Kidney Injury and Pediatric Bone Health.
Acute kidney injury (AKI) has been associated with deleterious impacts on a variety of body systems. While AKI is often accompanied by dysregulation of mineral metabolism-including alterations in calcium, phosphate, vitamin D, parathyroid hormone, fibroblast growth factor 23, and klotho-its direct effects on the skeletal system of children and adolescents remain largely unexplored. In this review, the pathophysiology of dysregulated mineral metabolism in AKI and its potential effects on skeletal health are discussed, including data associating AKI with fracture risk.


Patients' acceptance of obesity as a chronic disease: a qualitative study in Lebanon.
This study explores patients' acceptance of obesity as a chronic disease. Cross-sectional, qualitative study using semistructured phone interviews. The study was conducted in specialty and primary care clinics from a single central tertiary hospital in Lebanon. Recruitment took place between February and March 2021. 25 adult patients with overweight or obesity were interviewed and the interviews were analysed thematically. Four themes emerged: (1) patients' knowledge and awareness of obesity are based on their own experience; (2) there is ambivalence or conditional acceptance of obesity as a chronic disease; and patients with overweight or obesity perceived (3) that the role of physicians in obesity management is related to complications and (4) that obesity management is as simple as eating less and exercising more. The study shows the studied population's ambivalence in accepting obesity as a chronic disease. Individuals with overweight or obesity considered the role of the healthcare professional in obesity conditional on morbid obesity and the presence of medical complications of obesity. Findings of this study advocate for educational campaigns about the nature of obesity as a chronic disease and the role of healthcare professionals in obesity management.


Autologous gastrointestinal reconstruction surgery for short bowel syndrome: the cornerstone for intestinal rehabilitation.
Intestinal failure (IF) evolved from being the last recognized organ failure, to become one of the most progressive fields in terms of therapeutic alternatives and results. Short bowel syndrome (SBS) is the main cause of IF in adults and children. The use of surgery allowed patients with unfavorable anatomy type and length to be wean off parenteral nutrition. We aim to evaluate its current impact on intestinal rehabilitation. Autologous gastro-intestinal reconstructive surgery (AGIRS), including bowel lengthening contributes by converting patient's anatomy to a more favorable one, improving quality of life, and modifying the natural history of the disease, allowing to recover intestinal autonomy in approximately 70% of the adults and 50% of the children's with SBS-IF. The current use of postsurgical medical rehabilitation strategies including the use of enterohormones complement the path to sufficiency, increasing the chances of success in both age group of patients. The development of AGIRS has changed the outcome of SBS-IF patients, becoming the main surgical procedure prescribed in multidisciplinary units, allowing to enhance the number of patients achieving intestinal autonomy throughout rehabilitation, leaving transplantation as the last surgical alternative.


Ketamine-induced neurotoxicity and changes in gene expression in the developing rat brain.
Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used for analgesia and anesthesia in obstetric and pediatric practice. Recent reports indicate that ketamine causes neuronal cell death in developing rodents and nonhuman primates. The present study assessed the potential dose- and time-dependent neurotoxic effects and associated changes in gene expression after ketamine administration to postnatal day 7 (PND-7) rat pups. Pups were exposed to ketamine subcutaneously at doses of 5, 10, or 20 mg/kg, in one, three or six injections respectively. Control animals received the same volume of saline at the same time points. The animals were sacrificed 6 h after the last ketamine or saline administration and brain tissues were collected for RNA isolation and histochemical examination. Six injections of 20 mg/kg ketamine significantly increased neuronal cell death in frontal cortex, while lower doses and fewer injections did not show significant effects. The ketamine induced cell death seemed to be apoptotic in nature. In situ hybridization demonstrated that NMDA receptor NR1 subunit expression was dramatically increased in the frontal cortex of ketamine treated rats. Microarray analysis revealed altered expression of apoptotic relevant genes and increased NMDA receptor gene expression in brains from ketamine treated animals. Quantitative RT-PCR confirmed the microarray results. These data suggest that repeated exposures to high doses of ketamine can cause compensatory up-regulation of NMDA receptors and subsequently trigger apoptosis in developing neurons.


Experimental evidences for a role of subinhibitory concentrations of rilopirox, nystatin and fluconazole on adherence of Candida spp. to vaginal epithelial cells.
Candidiasis is frequently localized in the mucosal epithelium which covers the vaginal and oral cavity. The pathogenicity of Candida is correlated with its ability to adhere to epithelial cells and this is the resultant of both fungal and host cell properties and their physicochemical interactions. This study was performed to investigate the ability of subinhibitory concentrations (sub-MICs) of rilopirox, a new antimycotic drug, to interfere with the adhesion of Candida albicans, Candida tropicalis and Candida glabrata to human vaginal cells, in comparison with sub-MICs of nystatin and fluconazole. The three drugs are more active on C. albicans, followed by C. tropicalis and, last, C. glabrata, on which fluconazole was inactive (MIC > 24 micrograms/ml). Rilopirox, nystatin and fluconazole have different mechanisms of action, and different molecular weights, so a comparative analysis of data was performed by means of their sub-MICs. On this basis the order of activity was nystatin [symbol: see text] rilopirox > fluconazole. These findings can be of use for optimizing also the posologic design by regarding sub-MICs which are still active in reducing the adhesiveness of Candida to cells of the vaginal mucosa.


Contributions of Counseling and Sound Generator Use in Tinnitus Retraining Therapy: Treatment Response Dynamics Assessed in a Secondary Analysis of a Randomized Trial.
Tinnitus retraining therapy (TRT) has been widely used for 30 years, but its efficacy and the component contributions from counseling and sound therapy remain controversial. The purpose of this secondary analysis from the Tinnitus Retraining Therapy Trial (TRTT) was to compare treatment response dynamics for TRT (counseling and conventional sound generators) with partial TRT (pTRT; counseling and placebo sound generators) and standard of care (SOC; a patient-centered counseling control). The TRTT randomized 151 participants with primary tinnitus (no significant hearing or sound tolerance problems) to TRT, pTRT, or SOC, each of which encouraged use of enriched environmental sound. The primary outcome, mean change in Tinnitus Questionnaire score assessed at baseline and follow-up across 18 months, was normalized for a common baseline and fitted with an exponential model. Time constants were estimated to quantify and compare the treatment response dynamics, which were evaluated for statistical significance using bootstrap analyses. The change in response to TRT took less time to achieve than that for either pTRT or SOC, as demonstrated by time for normalized Tinnitus Questionnaire scores to decline to 63% and 99% of baseline TRT values: 1.2 months (95% CI [0.2, 1.9]) and 5.7 months (95% CI [0.9, 9.0]), respectively. Corresponding SOC values were 2.7 months (95% CI [1.5, 4.1]) and 12.4 months (95% CI [6.9, 19.0]), while those for pTRT were 2.2 months (95% CI [1.2, 3.4]) and 10.1 months (95% CI [5.7, 15.9]). The differences were significant for TRT versus SOC (p = .020), borderline significant for TRT versus pTRT (p = .057), but nonsignificant for pTRT versus SOC (p = .285). The magnitude of the asymptotic treatment response did not differ significantly among groups. Sound generator use in TRT increases treatment efficiency (beyond any advantage from enriched environmental sound) without affecting treatment efficacy (determined by counseling).


Automatic quantification of microvessels using unsupervised image analysis.
An automatic method for quantification of images of microvessels by computing area proportions and number of objects is presented. The objects are segmented from the background using dynamic thresholding of the average component size histogram. To be able to count the objects, fragmented objects are connected, all objects are filled, and touching objects are separated using a watershed segmentation algorithm. The method is fully automatic and robust with respect to illumination and focus settings. A test set consisting of images grabbed with different focus and illumination for each field of view, was used to test the method, and the proposed method showed less variation than the intraoperator variation using manual threshold. Further, the method showed good correlation to manual object counting (r = 0.80) on an other test set.


Effects of estradiol on the prolactin surges and the feedback mechanisms of gonadotropins in pseudopregnant rats.
The influences of estradiol on the prolactin (PRL) surges and on the secretion of gonadotropins (LH and FSH) were investigated in the pseudopregnancy (PSP) of acutely ovariectomized rats. The four following experimental groups were prepared: 1) intact PSP as a control, 2) ovariectomy was performed on day 0 of PSP (OVX), 3) a Silastic tube containing estradiol was implanted for day 1-4 into the OVX rats (OVX-E 1-4), and 4) the Silastic tube was implanted for day 5-8 by the same manner into the OVX rats (OVX-E 5-8). In the OVX group nocturnal (N) PRL surges were observed at 0500 h on days 4, 8 and 12 examined, and increased secretions of LH and FSH were noted. In the OVX-E 1-4 group, the N PRL surge was suppressed on day 4, and the suppressed N PRL surge did not occur on day 8, after the removal of the implanted tubes. Diurnal (D) PRL surges with LH surges were observed at 1700 h on day 4 in these rats. Similarly, more remarkable results were obtained on days 8 and 12 in the OVX-E 5-8 group than in the OVX-E 1-4.(ABSTRACT TRUNCATED AT 250 WORDS)


Thrombolysis in unstable angina. Randomized double-blind trial of t-PA and placebo.
Because coronary thrombosis is important in the pathogenesis of unstable angina and correlates with in-hospital cardiac events, we hypothesized that thrombolytic therapy would decrease cardiac events. We randomized 70 patients with unstable angina to tissue-type plasminogen activator (t-PA) (0.49 MU/kg for 1 hour followed by 0.07 MU/kg per hour for 9 hours) or placebo. All patients received full doses of intravenous heparin for 96 hours and aspirin (325 mg beginning at 72 hours). The primary end points of the study were in-hospital death, myocardial infarction, and urgent revascularization. Three secondary end points were also evaluated. Myocardial perfusion was assessed with resting planar thallium scintigraphy 90 minutes after initiation of therapy. Silent ischemia was assessed with 48-hour Holter monitoring for ST shift beginning at time of initiation of drug therapy. Coronary angiography was performed at 18 +/- 6 hours and analyzed quantitatively to assess the stenosis responsible for unstable angina, the presence of intraluminal filling defects consistent with intracoronary thrombus, and stenosis morphology and severity. There was no difference in total in-hospital cardiac events between patients receiving t-PA (5% or 14%) and those receiving placebo (7% or 20%) (p = 0.83). Resting thallium defects were larger in the patients receiving t-PA than in those receiving placebo (130 +/- 118 versus 76 +/- 84 degrees, p less than 0.04), and this difference persisted when corrected for previous infarction. Although the numbers of patients with ST shift were similar, the duration of ST shift was significantly longer in the patients receiving t-PA than with placebo (20 +/- 46 versus 3 +/- 10 minutes, p less than 0.045). The frequency of intracoronary thrombi in patients with stenoses greater than 50% was significantly less in patients treated with t-PA (11 of 22, 52%) as compared with placebo (23 of 25, 92%) (p = 0.002), but there was no significant difference in minimal lesion cross-sectional area (0.49 +/- 0.42 versus 0.57 +/- 1.08 cm2, p = 0.75) or ulceration index (0.79 +/- 0.16 versus 0.77 +/- 0.15, p = 0.71) of the culprit artery. We conclude that a prolonged infusion of t-PA in unstable angina reduces intracoronary thrombi but does not significantly decrease in-hospital cardiac events. The sample size, however, does not provide sufficient power to rule out a treatment effect. Paradoxically, there appears to be an increase in ST shift and worsening of myocardial perfusion with t-PA compared with therapy with heparin alone.


The effect of tocilizumab on mortality in hospitalized patients with COVID-19: a meta-analysis of randomized controlled trials.
We aimed to perform a meta-analysis of randomized controlled trials (RCTs) to summarize the overall effect of tocilizumab on the risk of mortality among patients with coronavirus disease 2019 (COVID-19). We systematically searched PubMed, Cochrane Central Register of Controlled Trials, Google Scholar, and medRxiv (preprint repository) databases (up to 7 January 2021). Pooled effect sizes with 95% confidence interval (CI) were generated using random-effects and inverse variance heterogeneity models. The risk of bias of the included RCTs was appraised using version 2 of the Cochrane risk-of-bias tool for randomized trials. Six RCTs were included: two trials with an overall low risk of bias and four trials had some concerns regarding the overall risk of bias. Our meta-analysis did not find significant mortality benefits with the use of tocilizumab among patients with COVID-19 relative to non-use of tocilizumab (pooled hazard ratio = 0.83; 95% CI 0.66-1.05, n = 2,057). Interestingly, the estimated effect of tocilizumab on the composite endpoint of requirement for mechanical ventilation and/or all-cause mortality indicated clinical benefits, with some evidence against our model hypothesis of no significant effect at the current sample size (pooled hazard ratio = 0.62; 95% CI 0.42-0.91, n = 749). Despite no clear mortality benefits in hospitalized patients with COVID-19, tocilizumab appears to reduce the likelihood of progression to mechanical ventilation.


[Impact of climatic change on the epidemiology of diseases].
Potential climate driven changes in the epidemiology of human and animal disease are widely discussed and complex to assess. Recent spreads of exotic pathogens or vectors feed speculations; although most of these introductions are mainly linked to the increased worldwide traffic, trade of goods and transportation of animal and human, abiotic factors are known to impact on vectors and pathogens bionomics and their ability to establish in new ecosystems; altogether changes in climatic patterns and in seasonal conditions may affect disease behaviour in term of spread pattern, diffusion range, amplification and persistence in novel habitats. Invasion may result in the emergence of novel disease processes, presenting major challenges for the epidemiologists. In this paper, some of the ecological mechanisms underlying the impact of climatic change on disease transmission and disease spread are further described. Potential effects of different climatic variables on pathogens and hosts population dynamics and distributions are complex to assess and different approaches are used to describe the dynamics in ecological range and the availability of ecological niches for pathogens and vectors. However even when linkage between disease dynamics and climate change are relatively strong, there are always other factors also changing disease behaviour and these should be accounted for as well.


Genetic evidence for predominantly hydrochoric gene flow in the invasive riparian plant Impatiens glandulifera (Himalayan balsam).
Riparian systems are prone to invasion by alien plant species. The spread of invasive riparian plants may be facilitated by hydrochory, the transport of seeds by water, but while ecological studies have highlighted the possible role of upstream source populations in the establishment and persistence of stands of invasive riparian plant species, population genetic studies have as yet not fully addressed the potential role of hydrochoric dispersal in such systems. A population genetics approach based on a replicated bifurcate sampling design is used to test hypotheses consistent with patterns of unidirectional, linear gene flow expected under hydrochoric dispersal of the invasive riparian plant Impatiens glandulifera in two contrasting river systems. A significant increase in levels of genetic diversity downstream was observed, consistent with the accumulation of propagules from upstream source populations, and strong evidence was found for organization of this diversity between different tributaries, reflecting the dendritic organization of the river systems studied. These findings indicate that hydrochory, rather than anthropogenic dispersal, is primarily responsible for the spread of I. glandulifera in these river systems, and this is relevant to potential approaches to the control of invasive riparian plant species.


Do early-life insults contribute to the late-life development of Parkinson and Alzheimer diseases?
How early-life events "set the stage" for adult disease has emerged as a research focus. Historically, the epidemiology of disease risk factors has centered on adult life, with little scrutiny of early-life events. Here we review the concept that events in early life may contribute to late-life neurodegenerative disease development, with a focus on Parkinson disease (PD) and Alzheimer disease (AD). Suspect events in early life include infections, stress, poor nutrition, and environmental factors such as chemical and pesticide exposure. Adiposity appears to contribute to both PD and AD; and because early-life events contribute to the development of obesity, linkages may exist between early determinants of obesity and the subsequent development of these neurologic diseases. Many now suggest a life-course approach for determining the relative contributions of genetic and environmental factors in any chronic disease. This requires determining when during the life course that a given exposure has its greatest effect and how exposures may accumulate over the life span. The data for PD and AD suggest that a number of insults occurring early in life may lead or contribute to these diseases. More definitive knowledge of the key risk factors involved will be needed to implement intervention and preventative strategies early in life to dampen or prevent any adverse late-life outcomes.


Cerebellum and procedural learning: evidence from focal cerebellar lesions.
The aim of the present study was to investigate the influence of focal cerebellar lesions on procedural learning. Eight patients with cerebellar lesions and six control subjects were tested in a serial reaction-time task. A four-choice reaction-time task was employed in which the stimuli followed (or not) a sequence repeated 10 times, with the subjects aware (or not) of the item sequence. Learning was manifested by the reduction in response latency over the sequential blocks. Acquisition of declarative knowledge of the sequence was also tested. Reaction times displayed by patients with cerebellar lesions, even though they tended to be longer than those of control subjects in all testing conditions, significantly differed from control subjects only when the stimuli were presented in sequence. The reaction times in sequential trials were still statistically significant when simple motor response times were taken into account. Cerebellar patients were also significantly impaired in detecting and repeating the sequence. On the other hand, when the sequence was learned before testing, motor performances were significantly improved in all subjects. These data indicate that cerebellar lesions induce specific impairment in the procedural learning of a motor sequence and suggest a role of the cerebellar circuitry in detecting and recognizing event sequences.


[Influence of preoperative chemoradiotherapy on changes of epidermal growth factor receptor expression in patients treated by preoperative chemoradiotherapy for local advanced rectal carcinoma].
The aim of this retrospective study was to determine the prognostic impact of expression of epidermal growth factor receptor (EGFR) changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal adenocarcinoma. One hundred and three patients with locally advanced rectal adenocarcinoma of stage II and III were evaluated. All patients were administered the total dose of 44 -- 50.4 Gy. Concomitantly, the patients received capecitabine in the dose 825 mg/ m² in two daily oral administrations or 5- fluorouracil in the dose 200 mg/ m² in continuous infusion. Surgery was indicated at intervals of 4-8 weeks from chemoradiotherapy completion. EGFR expression in the pretreatment biopsies and in resected specimens was assessed with immunohistochemistry. All of 103 patients received radiotherapy without interruption up to the total planned dose. Downstaging was described in 64 patients. Six patients had complete pathologic remission. Recurrence occurred in 49 patients. Local recurrence was found in 22 patients, generalization of disease was reported in 27 patients. A total of 51 patients died. Increased EGFR expression was found in 26 patients. The statistically significantly shorter overall survival (p < 0.001) and disease-free survival (p < 0.001) was found in patients with increased expression of EGFR compared with patients where no increase in the expression of EGFR was observed during neoadjuvant chemoradiotherapy. The overexpression of EGFR during neoadjuvant chemoradiotherapy for locally advanced rectal adenocarcinoma is associated with significant shorter overall survival and disease-free survival.


Science, health, and cultural literacy in a rapidly changing communications landscape.
There is a gap between how many scientists communicate and how most people understand and interpret messages. This article argues that the extensive science communications literature needs to be joined by the health literacy literature and anthropological work on cultural variations in hearing and understanding messages. Rapid changes and differences in how people in the United States get information are also discussed. Better understanding of how people get and perceive messages, and how access to information and to health services affects their behavior, should be an iterative and interdisciplinary effort. Community involvement in developing communication strategies is strongly encouraged.


[Immunogenomic aspects of tumor progression].
Genomic instability is a hallmark of cancer therefore of the metastatic disease as well. High tumor mutation burden is due to deficiencies of the DNA repair systems and leads to immunosensitivity due to generation of neoantigens. However, APOBEC activation of that system, though increases mutation rate, but causes immunoresistance. Deficient antigen presentation due to HLA class I defects is another major cause of immunoresistance. The contemporary immunotherapies may exploit gene amplification of PD-L1 but if the affected chromosome is damaged IFN activation can be lost, again causing immunoresistance. Since these genetic changes can be generated continuously during tumor progression (the entire metastatic process), it would be necessary to monitor them continuously. On the other hand, since tumors are genetically and phenotypically heterogeneous, multiple sampling would be necessary to obtain a more realistic picture of biomarker expressions.


[Parosteal chondrosarcoma. A report of two cases].
Parosteal chondrosarcoma is a tumour of the soft tissues different from juxta-cortical chondrosarcoma. It is extra-periosteal, has no attachment to bone and develops primary in the soft tissues. The authors review the literature and agree that the frequency of recurrence after local excision requires treatment by amputation.


Predictors of the first between-herd animal movement for cattle born in 2002 in Ireland.
Movement of animals between farms represents a potential risk of bovine tuberculosis (BTB) and other disease transmission. The objectives of this study were to identify and quantify risk factors associated with the first between-herd movement of animals (denoted as risk move). A random sample of 1 percent of Irish calf births registered for 2002 (20,182 animals) was selected. Descriptive and survival analysis on movement over the period 2002-2005 was performed. A total of 12,119 (60%) of animals experienced a risk move over the 4-year study period. Among those that moved, 57% did so within the first 12 months of age. For animals in dairy herds, an early peak in risk move events was observed within the first 12 weeks of age; whereas in animals from suckler herds, a later risk move peak was observed between 21 and 36 weeks of age. The survival models identified a number of risk factors: two that appeared most important in predicting a risk move were gender and enterprise type. Males had a hazard ratio of 2.6 times that of females. The hazards for enterprise type, varied over time, thus a time-varying covariate (ent_type×ln(time)) was included in the Cox model. At 7 days of age, females in suckler herds were at 0.14 times the hazard of females in dairy herds for risk move, and over time, the hazards converged, equalised by day 140, and then diverged, so that by 4 years of age, females in suckler herds were at 4.64 times the hazard of females in dairy herds. Herds with a history of selling animals in previous years maintained that record during the study period with increased hazard of risk move. Enterprise type interacted with gender so that relative to females, males from dairy herds were at greater hazard of risk move than males from suckler herds. Hazard of risk move was also a function of ln (herd area), so that each doubling of farm area was accompanied by a 30.6% decrease in the hazards. The main conclusion was that risk of movement related disease transmission also depends on the purpose of the movement whether for breeding or for beef finishing. While males were at greater hazard of movement than females, they would have a shorter lifespan, thus limiting the opportunity for further transmission post-movement.


Perfectionism Group Treatment for Eating Disorders in an Inpatient, Partial Hospitalization, and Outpatient Setting.
Perfectionism is elevated in individuals with eating disorders and is posited to be a risk factor, maintaining factor, and treatment barrier. However, there has been little literature testing the feasibility and effectiveness of perfectionism interventions in individuals specifically with eating disorders in an open group format. In the current study, we tested the feasibility of (a) a short cognitive behavioural therapy for perfectionism intervention delivered in an inpatient, partial hospitalization, and outpatient for eating disorders setting (combined N = 28; inpatient n = 15; partial hospital n = 9; outpatient n = 4), as well as (b) a training for disseminating the treatment in these settings (N = 9). Overall, we found that it was feasible to implement a perfectionism group in each treatment setting, with both an open and closed group format. This research adds additional support for the implementation of perfectionism group treatment for eating disorders and provides information on the feasibility of implementing such interventions across multiple settings. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.


Acoustic resonance laser calorimetry for measurements of low optical absorption.
A novel method of acoustic resonance laser calorimetry (ARLC) for the determination of low optical absorption coefficients of crystals and glasses is introduced. It is based on measurements of the kinetics of the equivalent temperature of the sample irradiated by the pulse laser radiation. The equivalent temperature of the sample is directly obtained by measuring the frequency changes of its temperature-calibrated acoustic resonances excited by the laser radiation with a corresponding pulse repetition rate. In contrast to the conventional resonant photoacoustic spectroscopy, where the resonance is used for the enhancement of the registered signal, in ARLC, the laser-excited acoustic resonance of the sample acts as a high-sensitivity temperature probe for measurements of its heating kinetics. The ARLC approach was verified by measuring the optical absorption coefficient of the potassium dihydrogen phosphate crystal (α=4.2⋅10-2cm-1) at 1064 nm wavelength.


The longer/sicker dilemma.
Our aging population is likely to experience more severe illnesses and longer hospital stays as they develop chronic illnesses. For discharge planners working with the "longer/sicker" patient, post-hospital followup and psychosocial assessment become primary considerations to meet the needs of the chronically ill.


Experimental Analysis of Mechanical Anisotropy of Selected Roofing Felts.
In this work, four representatives of roofing felts are under consideration. Special attention is paid to the mechanical behaviour under the tensile load of the samples. The results of strength tests for the entire range of material work, from the first load to sample breaking, are shown with respect to a specific direction of sample cutting. Moreover, a unique study of the microstructure obtained with the scanning electron microscope and chemical composition determined by energy dispersive spectroscopy of the tested materials is presented. The significant mechanical material anisotropy is reported and moreover argued by microstructure characteristics. In perspective, the outcomes can give comprehensive knowledge on optimal usage of roofing felt and proper mathematical modelling.


The early complications of inferior turbinectomy.
A retrospective study has assessed the early complications occurring in 90 patients who underwent inferior turbinectomy during a 3-year period. The operation was complicated by haemorrhage, adhesions, crusting, infection and septal perforation in a proportion of cases, the overall incidence being 20 per cent, and that of significant reactionary or secondary haemorrhage was 9 per cent. Attention has been directed towards possible aetiological factors and measures proposed that may minimise the occurrence of complications.


Ganoderma lucidum inspired silver nanoparticles and its biomedical applications with special reference to drug resistant Escherichia coli isolates from CAUTI.
In the search for alternative therapy for infections and other ailments, metallic nanoparticles, mainly silver nanoparticles (AgNPs) synthesized through bioengineered sources are extensively explored. Fungal bioactive compounds and their nanoparticles were reported with the potential biomedical application. A medicinal mushroom Ganoderma lucidum was reported as a repository of rich medicinal properties. In the current study, silver nanoparticles were synthesized using the extracts of G. lucidum and its antimicrobial activity was tested against drug-resistant Escherichia coli isolated from the catheter used for urinary tract infection (CAUTI). The GC-MS study of G. lucidum extracts showed the presence of ethyl acetoacetate ethylene acetal with the highest area percentage of 72.2% and retention time (RT 5873). Pyridine-3-ol is the second primary compound with a peak height of 6.44% and a retention time of 2.143. The third compound is l,4-Dioxane-2,3-diol, with an area of 8.09% and RT 5450. Butylated Hydroxy Toluene [BHT] is the fourth major compound with an area of 3.32%, and 9-Cedranone constitutes the fifth position in occupying the area percentage [1.88] and height 1.56%. Pyrrole is the sixth primary compound registering an area size of 0.96% and height 2.06%. The AgNPs synthesized using G. lucidum extract were in size range 23 and 58 nm as per SEM analysis and within the range wavelength 0.556-0.796 nm as per UV-Vis spectral study. FTIR Spectroscopy and X-ray diffraction analysis (XRD) were made to characterize the formed nanoparticles. The AgNPs synthesized effectively inhibited the growth of E. coli isolated from catheter-associated urinary tract infection and showed resistance to many drugs. The antioxidant potential of the synthesized nanoparticles assessed using DPPH radical scavenging activity, EC50 (µg/ml), and ARP data showed that the prepared nanoparticles were more potent in free radical scavenging activity than the standard quercetin. The cytotoxicity effect of Ag-NPs on breast cancer cell line- MDA-MB-231 confirmed its anticancer potential. The half-maximal inhibitory concentration (IC50) of Ag-NPs to inhibit 50% of the tumor was 9.2 g/mL. The synthesized GL-AgNPs was exhibited a multifocal biomedical potential.


Seasonal maturation of Glypthelmins vitellinophilum (Trematoda: Digenea) in Lysapsus limellus (Anura: Pseudidae) from an Argentinian subtropical permanent pond.
From December 1995 to November 2000, the seasonal maturation of Glypthelmins vitellinophilum Dobbin, 1958, in its definitive host, the frog Lysapsus limellus Cope, 1862, was studied in a subtropical permanent pond in northeastern Argentina. The objectives of this study were: 1) to determine the infrapopulation dynamics of the parasite, analyzing the seasonal maturation cycle throughout the years; and 2) to examine the relationship between the intensity of trematode infection in different developmental stages (recruitment, growth and maturation) and the host's body length. Of a total of 1,400 frogs examined over 60 months (5 years), 38% were found to be infected with G. vitellinophilum, and the intensity of infection was 1-15 trematodes per frog. Specimens of G. vitellinophilum were present in L. limellus throughout the years, but did not show a pronounced seasonal maturation cycle. Possible reasons for these findings are discussed with reference to climatic fluctuations and biotic factors. The infective period of the parasite (stage I) occurred in summer, autumn and spring, coinciding with the time each frog cohort appeared. These infections were found principally in small body sizes (classes 1 and 2) of L. limellus. Juvenile and nongravid specimens of worms (stage II and III) were found in frogs of different body sizes throughout the period of investigation. Gravid specimens of the parasite (stage IV) were generally recorded in autumn, winter and spring, mainly in the bodies of larger frogs. The body length of Trematodes in stages I and IV was significantly and positively correlated with that of the frogs.


Newborn screening policy in the United Kingdom & the United States: two different communities of practice.
Newborn screening is a rapidly developing area driven by both technological advances and public pressure. If they are not yet, all nurses working with mothers and children will soon be involved with implementing newborn-screening programs, and it is therefore important that they appreciate both the benefits and potential harms of such programs. In the United Kingdom, policy regarding the implementation of newborn-screening programs is developed at national level, and consideration of the introduction of new tests is subject to a formalized evaluation framework. In the United States, by contrast, each state develops its own screening program. Knowledge of developments in newborn screening in different countries that have diverse types of healthcare systems helps to inform nurses about the totality of healthcare for newborns, and assists them in becoming more knowledgeable about how international standards differ from those in the United States.


The shallow shell approach to Pogorelov's problem and the breakdown of 'mirror buckling'.
We present a detailed asymptotic analysis of the point indentation of an unpressurized, spherical elastic shell. Previous analyses of this classic problem have assumed that for sufficiently large indentation depths, such a shell deforms by 'mirror buckling'-a portion of the shell inverts to become a spherical cap with equal but opposite curvature to the undeformed shell. The energy of deformation is then localized in a ridge in which the deformed and undeformed portions of the shell join together, commonly referred to as Pogorelov's ridge. Rather than using an energy formulation, we revisit this problem from the point of view of the shallow shell equations and perform an asymptotic analysis that exploits the largeness of the indentation depth. This reveals first that the stress profile associated with mirror buckling is singular as the indenter is approached. This consequence of point indentation means that mirror buckling must be modified to incorporate the shell's bending stiffness close to the indenter and gives rise to an intricate asymptotic structure with seven different spatial regions. This is in contrast with the three regions (mirror-buckled, ridge and undeformed) that are usually assumed and yields new insight into the large compressive hoop stress that ultimately causes the secondary buckling of the shell.


Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis.
Neonatal necrotizing enterocolitis (NEC) is a major cause of morbidity in preterm infants. We hypothesize that the intestinal injury in this disease is a consequence of synergy among three of the major risk factors for NEC: prematurity, enteral feeding, and bacterial colonization. Together these factors result in an exaggerated inflammatory response, leading to ischemic bowel necrosis. Human milk may decrease the incidence of NEC by decreasing pathogenic bacterial colonization, promoting growth of nonpathogenic flora, promoting maturation of the intestinal barrier, and ameliorating the proinflammatory response.


[The Prevalence of Metallo-β-Lactamases and Efflux-Mediated Mechanisms in Carbapenem Nonsusceptible Nosocomial Pseudomonas aeruginosa Isolated in Moscow in 2012-2015].
Pseudomonas aeruginosa, the major nosocomial opportunistic pathogen, is an important cause of infectious morbidity and mortality among immunocompromised patients. To establish the role of metallo-β-lactamases (MBL) and efflux-mediated mechanisms in confer- ring carbapenem resistance in nosocomial isolates of P. aeruginosa. We analyzed carbapenem nonsusceptible nosocomial P. aeruginosa isolates obtained from pediatric and adult patients at three hospitals in Moscow in 2012-2015. Carbapenem susceptibility was assessed using the E-test. In addition, minimal inhibitory concentrations (MICs) of meropenem were tested by the broth microdilution method. The presence of MBL was determined using the ED TA-mediated suppression test. Efflux-dependent resistance was measured using an assay based on MIC modification by an ionophore carbonyl cyanide 3-chlorophenyl hydrazine (CCCP). A total of 54 carbapenem nonsusceptible P. aeruginosa isolates was examined. The presence of an MBL was detected in 37 (69%) isolates, 29 (54%) isolates had efflux-mediated resistance. In 10 (19%) isolates neither MBL nor efflux activity was found. Five out of 6 isolates (83%) with highly active efflux were MBL-positive. Among isolates with low efflux activity, 74% (17/23) possessed MBL, whereas in isolates with no efflux the rate of MBL-positivity was 60% (15/25). The prevalence of MBL- and efflux-mediated carbapenem resistance in nosocomial P. aeruginosa is high. Moreover, our results reveal that several resistance mechanisms may combine at the isolate level. These data may contribute to the development of novel strategies in combating carbapenem resistance.


College Students' Reasons for Using JUULs.
To identify reasons that college students use JUUL and explore associations between reasons for using JUUL and social and behavioral (tobacco use) factors. On-line, cross-sectional survey. Large southwestern university in the US. Undergraduate students (n = 605) who owned JUUL and used it weekly. The study measured age of JUUL initiation, JUUL dependence, and use of other e-cigarettes and other tobacco products. Participants described reasons for JUUL use as brief open-ended responses. Responses were categorized by 2 researchers using an inductive procedure. Logistic regressions examined associations between demographics and use frequency and categorized reasons for using JUUL. Four reasons for using JUUL emerged: self-help (48.4%), social (30.4%), experience (42.8%), and substance use/addiction (42.3%). Daily JUUL users were 1.66 (95% CI: 1.05-2.63) times as likely to use JUUL for self-help than those who used JUUL 1-3 days/week. Those who had never tried a cigarette were twice (OR = 2.08; 95% CI: 1.22-3.54) as likely as cigarette-first users to use JUUL for social reasons. Males (OR = 1.87; 95% CI: 1.32-2.65) had higher odds of using JUUL for the experience than females, and JUUL and other e-cigarettes users were 4.37 (95% CI: 1.83-10.45) times as likely as JUUL-only users to use JUUL due to substance use/addiction. JUUL users report unique reasons for use (e.g., addiction) not previously reported for older models of e-cigarette devices.


The Role of the Neutrophil to Lymphocyte Ratio for Survival Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone.
The purpose of this study was to examine the prognostic capability of baseline neutrophil-to-lymphocyte-ratio (NLR) and NLR-change under Abiraterone in metastatic castration-resistant prostate cancer patients. The impact of baseline NLR and change after eight weeks of treatment on progression-free survival (PFS) and overall survival (OS) was analyzed using Kaplan-Meier-estimates and Cox-regression. 79 men with baseline NLR <5 and 17 with NLR >5 were analyzed. In baseline analysis of PFS NLR >5 was associated with non-significantly shorter median PFS (five versus 10 months) (HR: 1.6 (95%CI:0.9-2.8); p = 0.11). After multivariate adjustment (MVA), ECOG > 0-1, baseline LDH>upper limit of normal (UNL) and presence of visceral metastases were independent prognosticators. For OS, NLR >5 was associated with shorter survival (seven versus 19 months) (HR: 2.3 (95%CI:1.3-4.0); p < 0.01). In MVA, ECOG > 0-1 and baseline LDH > UNL remained independent prognosticators. After 8 weeks of Abiraterone NLR-change to <5 prognosticated worse PFS (five versus 12 months) (HR: 4.1 (95%CI:1.1-15.8); p = 0.04). MVA showed a trend towards worse PFS for NLR-change to <5 (p = 0.11). NLR-change to <5 led to non-significant shorter median OS (seven versus 16 months) (HR: 2.3 (95%CI:0.7-7.1); p = 0.15). MVA showed non-significant difference for OS. We concluded baseline NLR <5 is associated with improved survival. In contrast, in patients with baseline NLR >5, NLR-change to <5 after eight weeks of Abiraterone was associated with worse survival and should be interpreted carefully.


Silica Nanochannel Array Film Supported by ß-Cyclodextrin-Functionalized Graphene Modified Gold Film Electrode for Sensitive and Direct Electroanalysis of Acetaminophen.
Convenient and sensitive detection of active analytes in complex matrix is crucial in biological, medical, and environmental analysis. Silica nanochannel array film (SNF) equipped electrochemical sensors have shown excellent anti-fouling performance in direct analysis of complex samples. In this work, we demonstrated an electrochemical sensor with anti-fouling performance for highly sensitive detection of acetaminophen (APAP) based on SNF supported by ß-cyclodextrin-graphene (CDG) nanocomposite modified Au film electrode (AuF). Because of their rich surface hydroxyls and 2D lamellar structure, CDG on AuF can serve as the nanoadhesive for compact binding SNF, which can be grown by electrochemical assisted self-assembly method in a few seconds. Attributable to the electrocatalytic property of graphene and the synergistic enrichment from both CD and SNF nanochannels towards analyte, the SNF/CDG/AuF sensor demonstrates sensitive detection of acetaminophen ranged from 0.2 to 50 μM with an ultralow limit-of-detection of 14 nM. Taking advantage of the anti-fouling ability of SNF, the sensor is able to realize accurate and convenient analysis of APAP in commercially available paracetamol tablets.


P2X7 Receptor Induces Pyroptotic Inflammation and Cartilage Degradation in Osteoarthritis via NF-κB/NLRP3 Crosstalk.
Osteoarthritis (OA) is an urgent public health problem; however, the underlying causal mechanisms remain unclear, especially in terms of inflammatory mediators in cartilage degradation and chondrocyte imbalance. P2X7 receptor (P2X7R) is a critical inflammation switch, but few studies have examined its function and mechanisms in OA-like pyroptotic inflammation of chondrocytes. In this study, Sprague-Dawley rats were injected in the knee with monosodium iodoacetate (MIA) to induce OA, followed by multiple intra-articular injections with P2X7R antagonist A740003, P2X7R agonist BzATP, NF-κB inhibitor Bay 11-7082, and NLRP3 inhibitor CY-09. Primary rat chondrocytes were harvested and treated similarly. We assessed cell viability, damage, and death via cell viability assay, lactate dehydrogenase (LDH) release, and flow cytometry. Concentrations of adenosine triphosphate (ATP) and interleukin- (IL-) 1β in cell culture supernatant and joint cavity lavage fluid were analyzed by enzyme-linked immunosorbent assay. Changes in expression levels of P2X7 and inflammation-related indicators were analyzed by immunofluorescence, quantitative reverse-transcription polymerase chain reaction, and western blotting. Cell morphology changes and pyroptosis were observed using transmission electron microscopy. Histology, immunohistochemistry, and microcomputed tomography were used to analyze damage to bone and cartilage tissues and assess the severity of OA. Similar to MIA, BzATP reduced cell viability and collagen II expression in a dose-dependent manner. Conversely, A740003 ameliorated MIA-induced cartilage degradation and OA-like pyroptotic inflammation by rescuing P2X7, MMP13, NF-κB p65, NLRP3, caspase-1 (TUNEL-positive and active), and IL-1β upregulation. Additionally, A740003 reduced the caspase-1/propidium iodide double-positive rate, LDH concentration, and reactive oxygen species production. These effects also occurred via coincubation with Bay 11-7082 and CY-09. In conclusion, activated P2X7 promoted extracellular matrix degradation and pyroptotic inflammation in OA chondrocytes through NF-κB/NLRP3 crosstalk, thus, aggravating the symptoms of OA. The study findings suggest P2X7 as a potential target for inflammation treatment, providing new avenues for OA research and therapy.


Primary Care Provider Perceptions of Pharmacist Services in an Urban, Safety Net Health System.
While pharmacists have provided services in a multidisciplinary, primary care setting for decades, few publications have yet to evaluate providers' impressions of- these services. An anonymous 14-item survey distributed to nonresident primary care providers aimed to identify clinical pharmacist services that are most and least helpful to primary care providers, identify barriers to pharmacy services, and develop recommendations to improve pharmacy services in primary care. The most important pharmacist contribution identified by providers is medication management, whereas the least important contributions are case conference, panel management, quality improvement, and transition of care. The primary reasons for referrals to pharmacists included inadequately controlled chronic diseases, poor or questionable adherence, longer visits for more in-depth discussion, and complex regimen requiring frequent monitoring or titration. Providers favored pharmacists working in direct patient care versus indirect patient care activities. Although many providers perceived no barriers to pharmacist service access, pharmacists' presence and visibility were 2 barriers identified. Most providers preferred comprehensive to disease-specific medication management.


[Hederagenin inhibits proliferation and promotes apoptosis of cervical cancer CaSki cells by blocking STAT3 pathway].
Objective To investigate the effect of hederagenin on the activity and apoptosis of cervical cancer cells and its mechanism. Methods Cervical cancer CaSki cells were cultured and treated with 0, 10, 20, 40, 80 μg/mL hederagenin. Cell viability was determined by MTT assay. The 50% inhibitory concentration (IC50) was determined to be about 40 μg/mL. The cervical cancer cells were treated with 40 μg/mL hederagenin. The apoptosis of cervical cancer cells was measured by flow cytometry, and the levels of cleaved caspase-3 (c-caspase-3), c-caspase-9, and STAT3 and p-STAT3 proteins were determined by Western blot analysis. STAT3 signaling pathway inhibitor AG490 and hederagenin were used to treat cervical cancer cells, and then the activity and apoptotic level of cervical cancer cells were detected by the above methods. Results Compared with the control cells, the proliferation activity of the cervical cancer cells treated with 40 μg/mL hederagenin decreased, the apoptotic level increased, the levels of c-caspase-3 and c-caspase-9 increased, and the level of p-STAT3 protein decreased. Compared with the cells treated with hederagenin, the activity of cervical cancer cells treated with AG490 and hederagenin decreased further, the apoptotic rate increased, and the protein levels of c-caspase-3 and c-caspase-9 increased. Conclusion Hederagenin inhibits the proliferation and promotes the apoptosis of cervical cancer cells, which is related to the inhibition of STAT3 signaling pathway.


Femtosecond study of Cu(H(2)O) dynamics.
The short-time nuclear dynamics of Cu(H(2)O) is investigated using femtosecond photodetachment-photoionization spectroscopy and time-dependent quantum wave packet calculations. The Cu(H(2)O) dynamics is initiated in the electronic ground state of the complex by electron photodetachment from the Cu(-)(H(2)O) complex, where hydrogen atoms are oriented toward Cu. Several time-resolved resonant multiphoton ionization schemes are used to probe the ensuing reorientation and dissociation. Immediately following photodetachment, the neutral complex is far from its minimum energy geometry and possesses an internal energy comparable to the Cu-H(2)O dissociation energy and undergoes both large-amplitude H(2)O motion and dissociation. Dissociation is observed to occur on three distinct time scales: 0.6, 8, and 100 ps. These results are compared to the results of time-dependent J=0 wave packet calculations, propagating the initial anion vibrational wave functions on the ground-state potential of the neutral complex. An excellent agreement is obtained between the experimental results and the ionization signals derived from the calculated probability amplitudes. Related experiments and calculations are carried out on the Cu(D(2)O) complex, with results very similar to those of Cu(H(2)O).


Systemic mastocytosis associated with myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis: Report of three cases.
The association of systemic mastocytosis with another hematologic neoplasia of myeloid or lymphoid origin is recognized as an advanced subvariant of mastocytosis. Here, we report the association of indolent or smoldering systemic mastocytosis with three cases of myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis, a recently recognized disease characterized by SF3B1 mutations. The hierarchical pattern of KIT, SF3B1, JAK2, and additional mutations was studied in whole and fractionated subpopulations of peripheral blood cells and whole bone marrow. In two cases, we could demonstrate a multilineage D816V KIT mutation, involving all myeloid lineages in one patient and also the lymphoid series in the other. Two patients displaying both SF3B1 and V617F JAK2 mutations had a very poor prognosis. Another patient bearing SF3B1, but not V617F JAK2 mutation, had a favorable response to erythropoietin treatment and long survival.


Air Corridors: Concept, Design, Simulation, and Rules of Engagement.
Air corridors are an integral part of the advanced air mobility infrastructure. They are the virtual highways in the sky for the transportation of people and cargo in a controlled airspace at an altitude of around 1000 ft. to 2000 ft. above ground level. These corridors will be utilized by (unmanned) air taxis, which will be deployed in rural and metropolitan regions to carry passengers and freight, as well as air ambulances, which will be deployed to offer first responder services such as 911 emergencies. This paper presents fundamental insights into the design of air corridors with high operational efficiency as well as zero collisions. It begins with the definitions of air cube, skylane or track, intersection, vertiport, gate, and air corridor. Then a multi-layered air corridor model is proposed. Traffic at intersections is analyzed in detail with examples of vehicles turning in different directions. The concept of capacity of an air corridor is introduced along with the nature of distribution of locations of vehicles in the air corridor and collision probability inside the corridor are discussed. Finally, results of traffic flow simulations are presented.


Impact of the Great East Japan Earthquake and tsunami on health, medical care and public health systems in Iwate Prefecture, Japan, 2011.
The Great East Japan Earthquake was one of the largest earthquakes ever recorded in global history. The damage was spread over a wide area, with the worst-hit areas being Iwate, Miyagi and Fukushima prefectures. In this paper we report on the damage and the impact of the damage to describe the health consequences among disaster victims in Iwate Prefecture. In Iwate Prefecture the tsunami claimed 4659 lives, with 1633 people missing. In addition to electricity, water and gas being cut off following the disaster, communication functions were paralysed and there was a lack of gasoline. Medical and public health teams from Iwate Prefecture and around the country, including many different specialists, engaged in a variety of public health activities mainly at evacuation centres, including medical and mental health care and activities to prevent infectious diseases. Given the many fatalities, there were relatively few patients who required medical treatment for major injuries. However, there were significant medical needs in the subacute and chronic phases of care in evacuation centres, with great demand for medical treatment and public health assistance, measures to counteract infection and mental health care. By referring to past experiences of national and international large-scale disasters, it was possible to respond effectively to the health-related challenges. However, there are still challenges concerning how to share information and coordinate overall activities among multiple public health response teams. Further examination will be required to ensure better preparedness in response to future disasters.