Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE--5-a population-based study.
Cancer survival is a key measure of the effectiveness of health-care systems. EUROCARE-the largest cooperative study of population-based cancer survival in Europe-has shown persistent differences between countries for cancer survival, although in general, cancer survival is improving. Major changes in cancer diagnosis, treatment, and rehabilitation occurred in the early 2000s. EUROCARE-5 assesses their effect on cancer survival in 29 European countries. In this retrospective observational study, we analysed data from 107 cancer registries for more than 10 million patients with cancer diagnosed up to 2007 and followed up to 2008. Uniform quality control procedures were applied to all datasets. For patients diagnosed 2000-07, we calculated 5-year relative survival for 46 cancers weighted by age and country. We also calculated country-specific and age-specific survival for ten common cancers, together with survival differences between time periods (for 1999-2001, 2002-04, and 2005-07). 5-year relative survival generally increased steadily over time for all European regions. The largest increases from 1999-2001 to 2005-07 were for prostate cancer (73.4% [95% CI 72.9-73.9] vs 81.7% [81.3-82.1]), non-Hodgkin lymphoma (53.8% [53.3-54.4] vs 60.4% [60.0-60.9]), and rectal cancer (52.1% [51.6-52.6] vs 57.6% [57.1-58.1]). Survival in eastern Europe was generally low and below the European mean, particularly for cancers with good or intermediate prognosis. Survival was highest for northern, central, and southern Europe. Survival in the UK and Ireland was intermediate for rectal cancer, breast cancer, prostate cancer, skin melanoma, and non-Hodgkin lymphoma, but low for kidney, stomach, ovarian, colon, and lung cancers. Survival for lung cancer in the UK and Ireland was much lower than for other regions for all periods, although results for lung cancer in some regions (central and eastern Europe) might be affected by overestimation. Survival usually decreased with age, although to different degrees depending on region and cancer type. The major advances in cancer management that occurred up to 2007 seem to have resulted in improved survival in Europe. Likely explanations of differences in survival between countries include: differences in stage at diagnosis and accessibility to good care, different diagnostic intensity and screening approaches, and differences in cancer biology. Variations in socioeconomic, lifestyle, and general health between populations might also have a role. Further studies are needed to fully interpret these findings and how to remedy disparities. Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation, Cariplo Foundation.


Ancient individuals from the North American Northwest Coast reveal 10,000 years of regional genetic continuity.
Recent genomic studies of both ancient and modern indigenous people of the Americas have shed light on the demographic processes involved during the first peopling. The Pacific Northwest Coast proves an intriguing focus for these studies because of its association with coastal migration models and genetic ancestral patterns that are difficult to reconcile with modern DNA alone. Here, we report the low-coverage genome sequence of an ancient individual known as "Shuká Káa" ("Man Ahead of Us") recovered from the On Your Knees Cave (OYKC) in southeastern Alaska (archaeological site 49-PET-408). The human remains date to ∼10,300 calendar (cal) y B.P. We also analyze low-coverage genomes of three more recent individuals from the nearby coast of British Columbia dating from ∼6,075 to 1,750 cal y B.P. From the resulting time series of genetic data, we show that the Pacific Northwest Coast exhibits genetic continuity for at least the past 10,300 cal y B.P. We also infer that population structure existed in the late Pleistocene of North America with Shuká Káa on a different ancestral line compared with other North American individuals from the late Pleistocene or early Holocene (i.e., Anzick-1 and Kennewick Man). Despite regional shifts in mtDNA haplogroups, we conclude from individuals sampled through time that people of the northern Northwest Coast belong to an early genetic lineage that may stem from a late Pleistocene coastal migration into the Americas.


Mosaic ring 20 with no detectable deletion by FISH analysis: Characteristic seizure disorder and literature review.
Ring chromosome 20 is a rare chromosome disorder characterized by a typical seizure phenotype consisting of complex partial seizures, frequent progression to generalized tonic or tonic-clonic seizures, and nocturnal frontal lobe seizures with frequent episodes of non-convulsive status epilepticus. Development may be normal or mildly delayed, followed by cognitive and behavioral decline after seizure onset. Here, we describe a patient with a typical severe seizure phenotype and a mosaic ring chromosome 20 without loss of p or q subtelomere regions or telomeric sequences. The ring had a longer telomere length than either of the telomere ends of its homologous chromosome 20 by quantitative fluorescence in situ hybridization analysis, suggesting that it might be derived from telomere-telomere fusion. The phenotypic comparison of this patient and other chromosome 20 cases that had terminal deletions of 20qter (n = 1) and 20pter (n = 7), shows that the epilepsy phenotype and electroencephalographic abnormalities are characteristic in patients with ring chromosome 20. Several hypotheses have been proposed to address the elusive mechanisms underlying the seizure disorder in ring chromosome 20. These possibilities include haploinsufficiency of two epilepsy genes CHRNA4 and KCNQ2 located at 20qter, silencing of these genes by a telomere position effect, or microdeletions or rearrangements of genetic material during the ring formation.


Phenolic profiles and antioxidant properties of apple skin extracts.
Lipid oxidation, especially the oxidation of polyunsaturated fatty acids, is a significant issue in the food industry impacting both food quality and health of consumers. Apple skin was investigated as a source of natural antioxidants. The phenolic compound composition and antioxidant properties of 21 selected apple genotypes were evaluated. The lipid stabilizing ability of the apple skin extracts was examined using an aqueous emulsion system of methyl linolenate. The total phenolic concentrations determined by high-performance liquid chromatography tandem mass spectrometry of methanolic extracts of skins of the apple genotypes varied from 150 to 700 mg/100 g DW. The antioxidant capacity measured by Folin-Ciocalteu (16.2 to 34.1 mg GAE/100 g DW), ferric reducing antioxidant power (1.3 to 3.3 g TE/100 g DW), oxygen radical absorbance capacity (5.2 to 14.2 g TE/100 g DW), and percent inhibition of oxidation of methyl linolenate (73.8% to 97.2%) varied among the apple genotypes. The apple skin extracts, specifically the crab apple varieties such as "Dolgo," were revealed to be effective inhibitors of oxidation of polyunsaturated fatty acid in a model system and thus can be considered as a potential source of natural food antioxidants.


Mortality among US veterans with a physician-documented diagnosis of pyruvate kinase deficiency.
Real-world studies of pyruvate kinase (PK) deficiency and estimates of mortality are lacking. This retrospective observational study aimed to identify patients with PK deficiency and compare their overall survival (OS) to that of a matched cohort without PK deficiency. Patients with ≥1 diagnosis code related to PK deficiency were selected from the US Veterans Health Administration (VHA) database (01/1995-07/2019); patients with a physician-documented diagnosis were included (PK deficiency cohort; index: date of first diagnosis code related to PK deficiency). Patients in the PK deficiency cohort were matched 1:5 to patients from the general VHA population (non-PK deficiency cohort; index: random visit date during match's index year). OS from index was compared between the two cohorts. Eighteen patients in the PK deficiency cohort were matched to 90 individuals in the non-PK deficiency cohort (both cohorts: mean age 57 years, 94% males; median follow-up 6.0 and 8.0 years, respectively). At follow-up, patients in the non-PK deficiency cohort had significantly longer OS than the PK deficiency cohort (median OS: 17.1 vs. 10.9 years; hazard ratio: 2.3; p = 0.0306). During their first-year post-index, 75% and 40% of the PK deficiency cohort had laboratory-confirmed anemia and iron overload, respectively. Among patients who died, cause of death was highly heterogeneous. These results highlight the increased risk of mortality and substantial clinical burden among patients with PK deficiency. While the intrinsic characteristics of the VHA database may limit the generalizability of the results, this is the first real-world study to characterize mortality in patients with PK deficiency.


Fibromatosis of infancy and childhood. Histology, ultrastructure and clinicopathologic correlation.
Fifty-nine cases of fibromatosis in children were investigated. To our knowledge, this is the largest serie with clinicopathologic datas reported so far in German literature. The most frequent type was infantile (desmoid-type) fibromatosis. More than 50% of the tumours developed in the first five years of life. The overall male-to-female ratio was 1.36:1. The lower extremities were the most frequent site of manifestation. Vimentin could be demonstrated in the tumour cells by immunohistochemical methods. Positive staining for dipeptidylaminopeptidase (DAP) IV suggested a myofibroblastic nature of some of the neoplastic cells. These results were supported by ultrastructural examination. Two cases demonstrated the unpredictable biological behaviour of fibromatosis. It is emphasized that clinical behaviour depends on number, size, location and histologic appearance of the lesions as well as age of the patient.


Inhibition of radiation-induced lipid peroxidation by tetrahydrocurcumin: possible mechanisms by pulse radiolysis.
The antioxidant property of tetrahydrocurcumin (THC), a reduced derivative of curcumin, was examined by its ability to inhibit radiation-induced lipid peroxidation in rat liver microsomes and compared with curcumin. The lipid peroxidation caused by irradiation of N2O-purged and aerated buffered aqueous solutions was found to be inhibited by THC in a dose- and concentration-dependent manner. In order to understand the actual reaction mechanisms involved in the inhibition process, pulse radiolysis investigation of THC with radiolytically produced radicals like hydroxyl, model peroxyl radicals, and azide radicals were done and the transients were detected by kinetic spectrophotometry. The reaction of THC with hydroxyl and azide radicals gave rise to transient absorption in the region 200-400 nm with two peaks at 310 nm and 390 nm. From the spectral properties and kinetics of these radicals, a suitable mechanism is discussed to explain the antioxidant actions of THC.


A membranous nephropathy associated with adult polycystic kidney disease.
A 53-year-old woman with adult polycystic kidney disease (PKD) developed a nephrotic syndrome. Evaluation of the renal biopsy specimens showed typical findings of membranous nephropathy (MN). There are few reports of nephrotic syndrome associated with PKD and only one proved to be MN. The possible mechanism of the association of PKD with MN was evaluated. Autoantibodies against the brush border were not detected in this patient's serum by indirect immunofluorescence. Three monoclonal antibodies against the tubular brush border and epithelial cell of distal tubulus did not react with subepithelial deposits in the biopsy specimen. Therefore tubular brush border antigen which was reported to induce membranous nephropathy was not detected in the immune complexes deposited in the glomeruli. So we could not determine any direct relationship between PKD and MN. The reaction of antibodies against basement membrane components (type IV collagen, laminin, fibronectin, heparansulfate proteoglycan) with the basement membranes of the cysts was evaluated by indirect immunofluorescence. The reaction with anti-heparansulfate proteoglycan antibody was decreased compared with normal tubular basement membrane. The reactivity to anti-fibronectin antibody was remarkably increased in the cystic walls, tubules, and interstitium. Changes of tubular basement membrane antigens was observed in PKD.


Health research prioritization: global and regional perspectives.
The Eastern Mediterranean Region (EMR) confronts unprecedented health challenges, exacerbated by demographic and epidemiologic changes, triple burden of disease, increasing healthcare costs, as well as the effects of contracted emergencies, social conflicts and massive population movements. Such challenges have repercussions on health care delivery and health research systems. Research for health is essential for developing solutions that contribute to health improvements. Investment in research for health contributes to health, economic growth and equity.


Gastrointestinal bleeding. Advances in the management of gastrointestinal bleeding.
The management of patients with major gastrointestinal haemorrhage remains a significant challenge. While technological advances have certainly occurred and will continue, it is likely that greater benefit will accrue from the application of simple measures than by any of these new techniques. For example, the concentration of these patients into a single unit dealing with this condition will probably lead to a greater reduction in the overall mortality rate than the application of laser photocoagulation, electrocoagulation, or any other of the methods described above. Finally, a wider recognition of the factors that lead to a poor prognosis following surgery (which remains the final management for most patients) and how they may be prevented should produce a reduction in the mortality rate.


[Pain as a stimulator of protective and curative processes (the theory of pain)].
The work deals with the theoretical approach to problem of pain. The mechanism of the appearance of pain is considered as lack of correspondence between functional capacity of the nervous system and the presented load. The function of pain as reparator and stimulator of defensive forces of the organism in pathological processes is disclosed. The possible employment of pain as a curative factor in practical medicine is discussed.


Genetic characteristics, antimicrobial susceptibility, and virulence genes distribution of Campylobacter isolated from local dual-purpose chickens in central China.
Food-borne antibiotic-resistant Campylobacter poses a serious threat to public health. To understand the prevalence and genetic characteristics of Campylobacter in Chinese local dual-purpose (meat and eggs) chickens, the genomes of 30 Campylobacter isolates, including 13 C. jejuni and 17 C. coli from Jianghan-chickens in central China, were sequenced and tested for antibiotic susceptibility. The results showed that CC-354 and CC-828 were the dominant clonal complexes of C. jejuni and C. coli, respectively, and a phylogenetic analysis showed that three unclassified multilocus sequence types of C. coli were more closely genetically related to C. jejuni than to other C. coli in this study. Of the six antibiotics tested, the highest resistance rates were to ciprofloxacin and tetracycline (100%), followed by lincomycin (63.3%), erythromycin (30.0%), amikacin (26.7%), and cefotaxime (20.0%). The antibiotic resistance rate of C. coli was higher than that of C. jejuni. The GyrA T86I mutation and 15 acquired resistance genes were detected with whole-genome sequencing (WGS). Among those, the GyrA T86I mutation and tet(O) were most prevalent (both 96.7%), followed by the blaOXA-type gene (90.0%), ant(6)-Ia (26.7%), aac(6')-aph(3'') (23.3%), erm(B) (13.3%), and other genes (3.3%). The ciprofloxacin and tetracycline resistance phenotypes correlated strongly with the GyrA T86I mutation and tet(O)/tet(L), respectively, but for other antibiotics, the correlation between genes and resistance phenotypes were weak, indicating that there may be resistance mechanisms other than the resistance genes detected in this study. Virulence gene analysis showed that several genes related to adhesion, colonization, and invasion (including cadF, porA, ciaB, and jlpA) and cytolethal distending toxin (cdtABC) were only present in C. jejuni. Overall, this study extends our knowledge of the epidemiology and antibiotic resistance of Campylobacter in local Chinese dual-purpose chickens.


Ultrafast photodissociation dynamics of pyrazole, imidazole and their deuterated derivatives using ab initio multiple cloning.
We present results obtained using the ab initio multiple cloning (AIMC) method to simulate fully quantum dynamics for imidazole and its structural isomer pyrazole along with their selectively deuterated species. We simulate the ultrafast dissociation of the N-H/D bond for these molecules along the repulsive 1πσ* state which agrees well with previous experimental results. Our results give evidence for a two-stage dissociation of the N-H/D bond on the sub-50 fs regime for imidazole, pyrazole and their selectively deuterated species, and give evidence for the importance of the repulsive 1πσ* state along the N-H/D bond coordinate for the relaxation of both imidazole and pyrazole. The ability of these calculations to reproduce experimental results lends confidence that larger complex systems could be explored with predictive capabilities with the AIMC method. These results also confirm the ability of the AIMC method to add detailed insights into which experiments are blind.


Public Perceptions and Informational Needs Regarding Surgical Residents.
Identify what topics are of most interest to patients regarding surgical residents. Survey of general public describing a hypothetical surgery and then assessing comfort level with resident involvement in surgery, reactions to disclosure statements regarding resident involvement, and desires for additional information. This data was used to produce an amended statement about surgical residents and their involvement in a hypothetical surgery to determine the impact of increased information on participant comfort. Online survey via Mechanical Turk. Our sample was broadly representative of the United States based on race and age, but with higher education level than United States census data. Using a combination of hierarchical clustering, weighted averages, and VAS scoring, questions that were most highly valued by participants were related to what the resident will be doing in the operation and the impact of resident involvement. Participants who had a past negative experience with residents assigned higher importance to all questions, even those that may be seen as not clinically relevant. Increasing the amount of proactively provided information did not have a significant effect on comfort (p = 0.219) when compared to our baseline statement, except with those who reported past negative experience with residents (p = 0.039). These results demonstrate that the majority of potential patients want to know specific details about the residents' skills, what they will be doing in their surgery, and the impact of their participation. Surgeons should be attuned to patients with past negative experiences, who may desire more information. Additional information alone may not be sufficient to comfort some patients, and future research should consider information delivery styles and interpersonal effects on patient comfort level.


Analyses of amplified fragment length polymorphisms (AFLP) indicate rapid radiation of Diospyros species (Ebenaceae) endemic to New Caledonia.
Radiation in some plant groups has occurred on islands and due to the characteristic rapid pace of phenotypic evolution, standard molecular markers often provide insufficient variation for phylogenetic reconstruction. To resolve relationships within a clade of 21 closely related New Caledonian Diospyros species and evaluate species boundaries we analysed genome-wide DNA variation via amplified fragment length polymorphisms (AFLP). A neighbour-joining (NJ) dendrogram based on Dice distances shows all species except D. minimifolia, D. parviflora and D. vieillardii to form unique clusters of genetically similar accessions. However, there was little variation between these species clusters, resulting in unresolved species relationships and a star-like general NJ topology. Correspondingly, analyses of molecular variance showed more variation within species than between them. A Bayesian analysis with BEAST produced a similar result. Another Bayesian method, this time a clustering method, Structure, demonstrated the presence of two groups, highly congruent with those observed in a principal coordinate analysis (PCO). Molecular divergence between the two groups is low and does not correspond to any hypothesised taxonomic, ecological or geographical patterns. We hypothesise that such a pattern could have been produced by rapid and complex evolution involving a widespread progenitor for which an initial split into two groups was followed by subsequent fragmentation into many diverging populations, which was followed by range expansion of then divergent entities. Overall, this process resulted in an opportunistic pattern of phenotypic diversification. The time since divergence was probably insufficient for some species to become genetically well-differentiated, resulting in progenitor/derivative relationships being exhibited in a few cases. In other cases, our analyses may have revealed evidence for the existence of cryptic species, for which more study of morphology and ecology are now required.


Jaundice and hepatic enzyme induction during lamotrigine therapy in a bipolar II patient.
Lamotrigine is a novel mood stabiliser as well as an anti-epileptic drug that has already been used for the prevention of convulsions. Despite several known side effects, hepatic dysfunction related to the drug has not been widely reported. A few cases have been observed in neurological, especially paediatric patients, but not in psychiatric patients. We report a case of cholestatis which occurred 6 weeks after starting lamotrigine therapy and which resolved after discontinuation, during the acute phase of disease. To the best of our knowledge, this is the first case of lamotrigine associated with cholestasis reported in patients with bipolar disorder.


Novel TRKB agonists activate TRKB and downstream ERK and AKT signaling to protect Aβ-GFP SH-SY5Y cells against Aβ toxicity.
Decreased BDNF and impaired TRKB signaling contribute to neurodegeneration in Alzheimer's disease (AD). We have shown previously that coumarin derivative LM-031 enhanced CREB/BDNF/BCL2 pathway. In this study we explored if LM-031 analogs LMDS-1 to -4 may act as TRKB agonists to protect SH-SY5Y cells against Aβ toxicity. By docking computation for binding with TRKB using 7,8-DHF as a control, all four LMDS compounds displayed potential of binding to domain d5 of TRKB. In addition, all four LMDS compounds exhibited anti-aggregation and neuroprotective efficacy on SH-SY5Y cells with induced Aβ-GFP expression. Knock-down of TRKB significantly attenuated TRKB downstream signaling and the neurite outgrowth-promoting effects of these LMDS compounds. Among them, LMDS-1 and -2 were further examined for TRKB signaling. Treatment of ERK inhibitor U0126 or PI3K inhibitor wortmannin decreased p-CREB, BDNF and BCL2 in Aβ-GFP cells, implicating the neuroprotective effects are via activating TRKB downstream ERK, PI3K-AKT and CREB signaling. LMDS-1 and -2 are blood-brain barrier permeable as shown by parallel artificial membrane permeability assay. Our results demonstrate how LMDS-1 and -2 are likely to work as TRKB agonists to exert neuroprotection in Aβ cells, which may shed light on the potential application in therapeutics of AD.


FGFR1 Induces Glioblastoma Radioresistance through the PLCγ/Hif1α Pathway.
FGF2 signaling in glioblastoma induces resistance to radiotherapy, so targeting FGF2/FGFR pathways might offer a rational strategy for tumor radiosensitization. To investigate this possibility, we evaluated a specific role for FGFR1 in glioblastoma radioresistance as modeled by U87 and LN18 glioblastomas in mouse xenograft models. Silencing FGFR1 decreased radioresistance in a manner associated with radiation-induced centrosome overduplication and mitotic cell death. Inhibiting PLCγ (PLCG1), a downstream effector signaling molecule for FGFR1, was sufficient to produce similar effects, arguing that PLCγ is an essential mediator of FGFR1-induced radioresistance. FGFR1 silencing also reduced expression of HIF1α, which in addition to its roles in hypoxic responses exerts an independent effect on radioresistance. Finally, FGFR1 silencing delayed the growth of irradiated tumor xenografts, in a manner that was associated with reduced HIF1α levels but not blood vessel alterations. Taken together, our results offer a preclinical proof of concept that FGFR1 targeting can degrade radioresistance in glioblastoma, a widespread problem in this tumor, prompting clinical investigations of the use of FGFR1 inhibitors for radiosensitization. Cancer Res; 76(10); 3036-44. ©2016 AACR.


Randomized trial of perindopril, enalapril, losartan and telmisartan in overweight or obese patients with hypertension.
Obesity exacerbates hypertension and stimulates the renin-angiotensin-aldosterone system (RAAS). Full-dose RAAS inhibition could be a therapeutic option in overweight or obese patients with hypertension. This study compared four RAAS inhibitors at full therapeutic doses to determine their effect on blood pressure (BP) and cardiovascular risk factors in these patients. We conducted a 24-week, single-blind, randomized, parallel-group study in 120 overweight or obese patients (body mass index ≥27 kg/m(2)) with hypertension, aged 18-60 years. The primary endpoint was the change in mean 24-h systolic BP and diastolic BP from baseline to study end. Central BP, arterial stiffness, and metabolic and cardiac indices were also investigated. Patients were randomly allocated to perindopril 10 mg/day, enalapril 20 mg/day, losartan 100 mg/day or telmisartan 80 mg/day. Nonpharmacological interventions were also recommended. Reductions in mean 24-h systolic BP (and diastolic BP) were all significant (p < 0.05 versus baseline) for perindopril, enalapril, losartan and telmisartan: systolic BP -22, -11, -12 and -15 mmHg, respectively; (and diastolic BP -13, -6, -13 and -12 mmHg, respectively). Aortic elasticity improved with perindopril and telmisartan. Perindopril was associated with the greatest reductions in central aortic BP and leptin levels [30 % versus 2 %, 7 % and 14 % with enalapril, losartan and telmisartan, respectively (all p < 0.05 versus perindopril)]. Reductions in other BP, echocardiographic, metabolic and anthropometric parameters occurred with all treatments. Full-dose RAAS inhibition, particularly with perindopril, effectively reduces BP, improves arterial structure and regulates cardiovascular risk factors in overweight or obese patients with hypertension.


ORGM: Occlusion Relational Graphical Model for Human Pose Estimation.
Articulated human pose estimation from monocular image is a challenging problem in computer vision. Occlusion is a main challenge for human pose estimation, which is largely ignored in popular tree structured models. The tree structured model is simple and convenient for exact inference, but short in modeling the occlusion coherence especially in the case of self-occlusion. We propose an occlusion relational graphical model, which is able to model both self-occlusion and occlusion by the other objects simultaneously. The proposed model can encode the interactions between human body parts and objects, and enables it to learn occlusion coherence from data discriminatively. We evaluate our model on several public benchmarks for human pose estimation, including challenging subsets featuring significant occlusion. The experimental results show that our method is superior to the previous state-of-the-arts, and is robust to occlusion for 2D human pose estimation.


Assessing predicted age-specific breast cancer mortality rates in 27 European countries by 2020.
We assessed differences in predicted breast cancer (BC) mortality rates, across Europe, by 2020, taking into account changes in the time trends of BC mortality rates during the period 2000-2010. BC mortality data, for 27 European Union (EU) countries, were extracted from the World Health Organization mortality database. First, we compared BC mortality data between time periods 2000-2004 and 2006-2010 through standardized mortality ratios (SMRs) and carrying out a graphical assessment of the age-specific rates. Second, making use of the base period 2006-2012, we predicted BC mortality rates by 2020. Finally, making use of the SMRs and the predicted data, we identified a clustering of countries, assessing differences in the time trends between the areas defined in this clustering. The clustering approach identified two clusters of countries: the first cluster were countries where BC predicted mortality rates, in 2020, might slightly increase among women aged 69 and older compared with 2010 [Greece (SMR 1.01), Croatia (SMR 1.02), Latvia (SMR 1.15), Poland (SMR 1.14), Estonia (SMR 1.16), Bulgaria (SMR 1.13), Lithuania (SMR 1.03), Romania (SMR 1.13) and Slovakia (SMR 1.06)]. The second cluster was those countries where BC mortality rates level off or decrease in all age groups (remaining countries). However, BC mortality rates between these clusters might diminish and converge to similar figures by 2020. For the year 2020, our predictions have shown a converging pattern of BC mortality rates between European regions. Reducing disparities, in access to screening and treatment, could have a substantial effect in countries where a non-decreasing trend in age-specific BC mortality rates has been predicted.


Factors determining utility measured with the EQ-5D in patients with atrial fibrillation.
Although atrial fibrillation (AF) is associated with increased morbidity and mortality from heart failure, stroke and other thromboembolic complications, there are limited data on its health-related quality of life (HRQoL) effects. The objective was to analyse the factors determining utility in patients with all types of AF, both at baseline and after 1 year from inclusion, based on data from the Euro heart survey. HRQoL was measured with the EQ-5D questionnaire. At baseline, 5,050 patients had completed all five dimensions of the EQ-5D and 3,045 had done so after 1 year. We used Powell's censored least absolute deviations estimator for inference and ordinary least squares regressions for prediction. Regardless of time point, utility and change in utility were significantly correlated with age, gender, AF type and symptoms. At baseline, utility was also determined by domestic status, regular exercise habits, diabetic disease and comorbidities. At follow-up, additional determinants included underlying heart disease and utility at baseline, and adverse events. Utility in patients with AF and change over time are influenced by demographic and disease-specific variables. Our results can provide useful information on the effect of AF on QoL and input for economic evaluations.


Changes in neutrophil surface receptor expression, degranulation, and respiratory burst activity after moderate- and high-intensity exercise.
Intense exercise stimulates the systemic release of a variety of factors that alter neutrophil surface receptor expression and functional activity. These alterations may influence resistance to infection after intense exercise. The aim of this study was to examine the influence of exercise intensity on neutrophil receptor expression, degranulation (measured by plasma and intracellular myeloperoxidase concentrations), and respiratory burst activity. Ten well-trained male runners ran on a treadmill for 60 min at 60% [moderate-intensity exercise (MI)] and 85% maximal oxygen consumption [high-intensity exercise (HI)]. Blood was drawn immediately before and after exercise and at 1 h postexercise. Immediately after HI, the expression of the neutrophil receptor CD16 was significantly below preexercise values (P < 0.01), whereas MI significantly reduced CD35 expression below preexercise values (P < 0.05). One hour after exercise at both intensities, there was a significant decline in CD11b expression (P < 0.05) and a further decrease in CD16 expression compared with preexercise values (P < 0.01). CD16 expression was lower 1 h after HI than 1 h after MI (P < 0.01). Immediately after HI, intracellular myeloperoxidase concentration was less than preexercise values (P < 0.01), whereas plasma myeloperoxidase concentration was greater (P < 0.01), indicating that HI stimulated neutrophil degranulation. Plasma myeloperoxidase concentration was higher immediately after HI than after MI (P < 0.01). Neutrophil respiratory burst activity increased after HI (P < 0.01). In summary, both MI and HI reduced neutrophil surface receptor expression. Although CD16 expression was reduced to a greater extent after HI, this reduction did not impair neutrophil degranulation and respiratory burst activity.


[Structural reconstruction of chemo-sensitive biomembranes during the action of low molecular weight compounds using spin resonance].
Using the spin probe technique, the changes in the supramolecular structure of the central nervous system synaptic membranes and of olfactory hair membranes of Rana temporaria induced by low molecular weight organic substances of different chemical nature, were investigated. It was found that the membrane structures under study differ considerably in their sensitivity to chemical stimulation and in temporal kinetics of structural transitions. A correlation between physiological parameters of olfactory perception of the compounds used and the parameters of structural transitions in olfactory hair membranes was established. The interrelationship between the experimental data and chemoreception of odorants and mediators as well as the applicability of these preparations for membrane screening of biologically active substances are discussed.


Nursing staff-led behavioural group intervention in psychiatric in-patient care: Patient and staff experiences.
A promising intervention in mental health in-patient care is behavioural activation (BA). Interventions based on BA can be used by mental health nurses and other staff members. The aim of this study was to evaluate patients' and staff members' experiences of a nursing staff-led behavioural group intervention in mental health in-patient care. The intervention was implemented at three adult acute general mental health in-patient wards in a public hospital setting in Sweden. A self-administrated questionnaire, completed by 84 patients and 34 nurses and nurse assistants, was administered, and nonparametric data analysed using descriptive statistics. Our findings revealed that both patients and nursing staff ranked nursing care and care environment as important aspects in the recovery process. Patients and staff members reported overall positive experiences of the group sessions. Patients with higher frequencies of attendance and patients satisfied with overall care had a more positive attitude towards the intervention. A more positive experience of being a group leader was reported by staff members who had been leading groups more than ten times. The most common impeding factor during implementation, reported by staff members, was a negative attitude to change. Conducive factors were having support from a psychologist and the perception that patients were showing interest. These positive experiences reported by patients and nursing staff, combined with previous research in this field, are taking us one step further in evaluating group sessions based on BA as a meaningful nursing intervention in mental health in-patient care.


First report the role of benthic macroinvertebrates as preys for native fish in Toltén river (38° S, Araucania region Chile).
The Toltén river is located in the 137 years old Araucania region, Chile (38° S), and is characterized by low alterations through human interference due agriculture and towns in its surrounding basin, the presence of native fishes and salmonids, and by its lake effluent regime originated from Villarrica lake. The aim of the present study was to make a review of ecological role of the benthic inland water macroinvertebrates as preys for native fishes of the River Toltén, in order to understand their importance in the ecosystem of the river. The literature revealed that the main prey for native fishes are Chironomidae larvae, nevertheless there are not specific reports for Tolten river. The exposed results are similar with similar native species for Patagonia, and these native species would have prey for introduced salmonids, or these species would have prey competition with introduced salmonids in according to the literature descriptions for Argentinean and Chilean Patagonia.


A Condensed History Approach to X-Ray Dark Field Effects in Edge Illumination Phase Contrast Simulations.
X-ray dark field signals, measurable in many x-ray phase contrast imaging (XPCI) setups, stem from unresolvable microstructures in the scanned sample. This makes them ideally suited for the detection of certain pathologies, which correlate with changes in the microstructure of a sample. Simulations of x-ray dark field signals can aid in the design and optimization of XPCI setups, and the development of new reconstruction techniques. Current simulation tools, however, require explicit modelling of the sample microstructures according to their size and spatial distribution. This process is cumbersome, does not translate well between different samples, and considerably slows down simulations. In this work, a condensed history approach to modelling x-ray dark field effects is presented, under the assumption of an isotropic distribution of microstructures, and applied to edge illumination phase contrast simulations. It substantially simplifies the sample model, can be easily ported between samples, and is two orders of magnitude faster than conventional dark field simulations, while showing equivalent results.Clinical relevance- Dark field signal provides information on the microstructure distribution within the investigated sample, which can be applied in areas such as histology and lung x-ray imaging. Efficient simulation tools for this dark field signal aid in optimizing scanning setups, acquisition schemes and reconstruction techniques.


Differential utilization of expanded genetic screening tests in patients of reproductive ages from private and academic practices.
We sought to evaluate the types of genetic screening tests that are performed in women of childbearing ages in New Jersey. Data from patients who had a reproductive genetics consultation between January 1, 2012, and July 31, 2012, were stratified according to the referring providers, i.e., those from academic or private practices, and descriptive analyses performed. Unconventional genetic screening was defined as any test ordered by the referring health care provider outside the recommendations from the American Congress of Obstetricians and Gynecologists or the American College of Medical Genetics and Genomics. Overall, 30% of 371 patients referred for a genetic consultation underwent unconventional screening. As compared to patients from academic practices, the relative rate of unconventional screening was 10-fold higher among patients from private practices, resulting in a relative 34-fold increase in the estimated cost in genetic screening (P<0.01). This set of preliminary observations highlight the need for further state, nationwide, and international studies to understand the financial, personal, and societal impact that this discrepancy health care system in the use of genetic carrier screening portends.


Differential patterns of stromelysin-2 (MMP-10) and MT1-MMP (MMP-14) expression in epithelial skin cancers.
Co-expression of several members of the matrix metalloproteinase (MMP) family is characteristic of human malignant tumours. To investigate the role of stromelysin-2 (MMP-10) in growth and invasion of skin tumours, we studied cutaneous carcinomas with high metastatic capacity (squamous cell carcinomas, SCCs), only locally destructive tumours (basal cell carcinomas, BCCs) and pre-malignant lesions (Bowen's disease and actinic keratosis) using in situ hybridization. Expression of MMP-10 was compared with that of stromelysin-1 (MMP-3) and of MT1-MMP, the expression of which has been shown to correlate with tumour invasiveness. MMP-10 was expressed in 13/21 SSCs and 11/19 BCCs only in epithelial laminin-5 positive cancer cells, while premalignant lesions were entirely negative. MT1-MMP mRNA was detected in 19/21 SCCs both in epithelial cancer cells and stromal fibroblasts and in 14/18 BCCs only in fibroblasts. The level of MMP-10 was upregulated in a cutaneous SCC cell line (UT-SCC-7) by transforming growth factor-alpha and keratinocyte growth factor, and by interferon-gamma in combination with transforming growth factor-beta1 and tumour necrosis factor-alpha both in UT-SCC-7 and HaCaT cells. Our results show that MMP-10 expression does not correlate with the invasive behaviour of tumours as assessed by their histology and MT1-MMP expression, but may be induced by the wound healing and inflammatory matrix remodelling events associated with skin tumours.


Management of chronic disabling low back pain with 360 degrees fusion. Results from pain provocation test and concurrent posterior lumbar interbody fusion, posterolateral fusion, and pedicle screw instrumentation in patients with chronic disabling low back pain.
A follow-up study conducted by an independent observer was performed on the authors' first 29 consecutive patients treated with concurrent posterior lumbar interbody fusion, posterolateral fusion, and pedicle screw instrumentation, for whom at least 2 years had transpired since the operation. To evaluate the results of concurrent instrumented posterior lumbar interbody fusion and posterolateral fusion used to manage chronic disabling low back pain. Patients chosen for surgery all had a history of chronic disabling low back pain exceeding 2 years and a sick leave period in excess of 6 months (average, 3.4 years). From 1989 to 1993, 29 consecutive patients were surgically treated with fusion. The level of fusion was chosen depending on radiologic changes and results from a intradiscal injection provocation test. Bone union was verified by computed tomography scan with 1-mm-thin slices and sagittal reformation, and by a "second look" in all but three patients. All patients were evaluated subsequently by an independent observer in November 1995, 4.7 years after surgery on the average. Bone fusion was obtained in 27 of the 29 patients (93%). There was a highly significant reduction in back and leg pain measurements. Of the 29 patients, the results were excellent in 9 patients (31%), good in 6 patients (21%), fair in 6 patients (21%), and poor in 8 patients (27%). A total of 18 patients (62%) had returned to work. The authors consider posterior lumbar interbody fusion with concurrent posterolateral fusion and pedicle screw instrumentation a possible method for managing chronic disabling low back pain.


Primary intradural Ewing's sarcoma of the spine: a systematic review of the literature.
The incidence of extraosseous Ewing's sarcoma, a highly malignant mesenchymal mass, is rare in the spinal cord and its clinical outcomes unknown. To date, few cases of primary intradural extramedullary Ewing's sarcoma (PIEES) have been reported, with varying follow-up. Herein, we aimed to perform a comprehensive review of all cases published in the literature and update previously reported cases from our institution. Institutional medical records were searched for cases of PIEES of the spine managed at our institution between the years 2005 and 2018. We performed a systematic search of two electronic databases (Ovid Medline and Embase) from inception to August 2018 to obtain all published cases of primary intradural extraosseous Ewing's sarcoma (PIEES).We used our institutional medical records to update cases reported from our institution. We identified a total of 44 cases with pIEES reported in the existing literature of which 5 have been from our department. Of the 41 cases, the median age of diagnosis was 31 years. The most common presentation pattern was PIEES in the lumbar/sacral region (61%, n = 27), with a majority (59%, n = 25) presenting initially with pain. The most common modality of treatment reported was surgery (41/41, 100%), followed by adjuvant chemotherapy (31/44, 70%) and local radiation therapy (29/44, 66%). Overall, recurrence was reported in 17/36 (46%) cases, with median progression free survival (PFS) of 12 months (range, 1-72). There were 12/37 (32.4%) deaths reported, with median overall survival (OS) of 14 months (range, 1-72). Hence, we present the most updated review of all reported cases of PIEES. While surgical resection is the mainstay of treatment, tumor recurrence is a great concern given the adhesive nature of the lesion preventing complete resection. Adjuvant chemotherapy and radiotherapy should be carefully considered to prevent recurrence and improve survival outcome.


Children's gist-based false memory in working memory tasks.
False memories are well established episodic memory phenomena. Recent research in young adults has shown that semantically related associates can be falsely remembered as studied items in working memory (WM) tasks for lists of only a few items when a short 4-second interval was given between study and test. The present study reported two experiments yielding similar effects in 4- (n = 32 and 33, 18 and 14 females, respectively) and 8-year-old children (n = 33 and 34, respectively, 19 females in both). Short lists of semantically related items specifically tailored for young children were retained over a brief interval. Whether or not the interval was filled with a concurrent task that impeded or not WM maintenance, younger children were as prone to falsely recognize related distractors as their older counterparts in an immediate recognition test, and also in a delayed test. In addition, using the conjoint recognition model of the fuzzy-trace theory, we demonstrated that the retrieval of gist traces of the list themes was responsible for the occurrence of short-term false memories in 4- and 8-year-old children. Gist memory also underpinned the occurrence of false recognition in the delayed test. These findings suggest that young children are as likely to make gist-based false memories as older children in working memory tasks. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Association of Nursing Home Organizational Culture and Staff Perspectives With Variability in Advanced Dementia Care: The ADVANCE Study.
Regional, facility, and racial and ethnic variability in intensity of care provided to nursing home residents with advanced dementia is well documented but poorly understood. To assess the factors associated with facility and regional variation in the intensity of care for nursing home residents with advanced dementia. In the ADVANCE (Assessment of Disparities and Variation for Alzheimer Disease Nursing Home Care at End of Life) qualitative study, conducted from June 1, 2018, to July 31, 2021, nationwide 2016-2017 Medicare Minimum Data Set information identified 4 hospital referral regions (HRRs) with high (n = 2) and low (n = 2) intensity of care for patients with advanced dementia based on hospital transfer and tube-feeding rates. Within those HRRs, 14 facilities providing relatively high-intensity and low-intensity care were recruited. A total of 169 nursing home staff members were interviewed, including administrators, directors of nursing, nurses, certified nursing assistants, social workers, occupational therapists, speech-language pathologists, dieticians, medical clinicians, and chaplains. Data included 275 hours of observation, 169 staff interviews, and abstraction of public nursing home material (eg, websites). Framework analyses explored organizational factors and staff perceptions across HRRs and nursing homes in the following 4 domains: physical environment, care processes, decision-making processes, and implicit and explicit values. Among 169 staff members interviewed, 153 (90.5%) were women, the mean (SD) age was 47.6 (4.7) years, and 54 (32.0%) were Black. Tube-feeding rates ranged from 0% in 5 low-intensity facilities to 44.3% in 1 high-intensity facility, and hospital transfer rates ranged from 0 transfers per resident-year in 2 low-intensity facilities to 1.6 transfers per resident-year in 1 high-intensity facility. The proportion of Black residents in facilities ranged from 2.9% in 1 low-intensity facility to 71.6% in 1 high-intensity facility, and the proportion of Medicaid recipients ranged from 45.3% in 1 low-intensity facility to 81.3% in 1 high-intensity facility. Factors distinguishing facilities providing the lowest-intensity care from those providing the highest-intensity care facilities included more pleasant physical environment (eg, good repair and nonmalodorous), standardized advance care planning, greater staff engagement in shared decision-making, and staff implicit values unfavorable to tube feeding. Many staff perceptions were ubiquitous (eg, adequate staffing needs), with no distinct pattern across nursing homes or HRRs. Staff in all nursing homes expressed assumptions that proxies for Black residents were reluctant to engage in advance care planning and favored more aggressive care. Except in nursing homes providing the lowest-intensity care, many staff believed that feeding tubes prolonged life and had other clinical benefits. This study found that variability in the care of patients with advanced dementia may be reduced by addressing modifiable nursing home factors, including enhancing support for low-resource facilities, standardizing advance care planning, and educating staff about evidence-based care and shared decision-making. Given pervasive staff biases toward proxies of Black residents, achieving health equity for nursing home residents with advanced dementia must be the goal behind all efforts aimed at reducing disparities in their care.


Crystal structure of the monomeric isocitrate dehydrogenase in the presence of NADP+: insight into the cofactor recognition, catalysis, and evolution.
NADP+-dependent monomeric isocitrate dehydrogenase (IDH) from the nitrogen-fixing bacterium Azotobacter vinelandii (AvIDH) is one of members of the beta-decarboxylating dehydrogenase family and catalyzes the dehydration and decarboxylation of isocitrate to yield 2-oxoglutrate and CO2 in the Krebs cycle. We solved the crystal structure of the AvIDH in complex with cofactor NADP+ (AvIDH-NADP+ complex). The final refined model shows the closed form that has never been detected in any previously solved structures of beta-decarboxylating dehydrogenases. The structure also reveals all of the residues that interact with NADP+. The structure-based sequence alignment reveals that these residues were not conserved in any other dimeric NADP+-dependent IDHs. Therefore the NADP+ specificity of the monomeric and dimeric IDHs was independently acquired through the evolutional process. The AvIDH was known to show an exceptionally high turnover rate. The structure of the AvIDH-NADP+ complex indicates that one loop, which is not present in the Escherichia coli IDHs, reliably stabilizes the conformation of the nicotinamide mononucleotide of the bound NADP+ by forming a few hydrogen bonds, and such interactions are considered to be important for the monomeric enzyme to initiate the hydride transfer reaction immediately. Finally, the structure of the AvIDH is compared with that of other dimeric NADP-IDHs. Several structural features demonstrate that the monomeric IDHs are structurally more related to the eukaryotic dimeric IDHs than to the bacterial dimeric IDHs.


Control of pyruvate kinase activity during glycolysis and gluconeogenesis in Propionibacterium shermanii.
The concentrations of glycolytic intermediates and ATP and the activities of certain glycolytic and gluconeogenic enzymes were determined in Propionibacterium shermanii cultures grown on a fully defined medium with glucose, glycerol or lactate as energy source. On all three energy sources, enzyme activities were similar and pyruvate kinase was considerably more active than the gluconeogenic enzyme pyruvate, orthophosphate dikinase, indicating the need for regulation of pyruvate kinase activity. The intracellular concentration of glucose 6-phosphate, a specific activator of pyruvate kinase in this organism, changed markedly according to both the nature and the concentration of the growth substrate: the concentration (7-10 mM) during growth with excess glucose or glycerol was higher than that (1-2 mM) during growth with lactate or at growth-limiting concentrations of glycerol or glucose. Other glycolytic intermediates, apart from pyruvate, were present at concentrations below 2 mM. Glucose 6-phosphate overcame inhibition of pyruvate kinase activity by ATP and inorganic phosphate. With 1 mM-ATP and more than 10 mM inorganic phosphate, a change in glucose 6-phosphate concentration from 1-2 mM was sufficient to switch pyruvate kinase from a strongly inhibited to a fully active state. The results provide a plausible mechanism for the regulation of glycolysis and gluconeogenesis in P. shermanii.


[Double aortic arch associated with severe left ventricular dysfunction--a case report].
A case of a 3-month-old male infant with severe LV dysfunction and a complete double aortic arch (both arches patient) is reported. The right dominant aortic arch runs retroesophageally to the right and joins with the left smaller arch to form the descending thoracic aorta on the right side while the ligamentum arteriosum was located in its normal position (the left side). Through a left thoracotomy, the smaller left arch and the ligamentum were divided to relieve the obstruction of the trachea from compression of the vascular ring. Postoperative convalescence was good. Further follow up of this patient after 9 months showed that there was neither any respiratory failure nor any heart failure sign present, though severe LV dysfunction persisted.


[Epidemiological profile of extensively drug-resistant tuberculosis in Peru, 2013-2015Perfil epidemiológico da tuberculose extremamente resistente no Peru, 2013-2015].
Describe the clinical and epidemiological characteristics and resistance profile of cases of extensively drug-resistant tuberculosis (XDR-TB) diagnosed in Peru from 2013 to 2015. This descriptive study included patients who met the definition of XDR-TB and were reported to the national epidemiological surveillance system of Peru's Ministry of Health. It used a descriptive analysis and, to identify spatial distribution, a heat map based on kernel density estimation. It was estimated that XDR-TB cases diagnosed as new represented 7.3% of all multidrug-resistant tuberculosis (MDR-TB) cases reported during the study period; 74% of patients were aged 15 to 44 years old; and the male-female ratio was 1.7. Half of the country's departments reported at least one case of XDR-TB, and 42% of new cases had no history of resistance or previous treatment. In the other half of the departments, the majority had previous MDR and pre-XDR resistance. Among the cases, 57.7% presented resistance to 5 and 7 first- and second-line drugs and 41.6% presented resistance to 8 and 10 drugs. This study offers important details of the epidemiological profile of XDR-TB in Peru, where there has been an increase in cases of primary XDR-TB; that is, cases with no prior history of disease. Furthermore, this form of tuberculosis has spread to a greater number of departments in the country.


Look out before polypectomy in patients with diverticular disease--a case of a large, inverted diverticulum of the colon resembling a pedunculated polyp.
Diverticular disease of the colon may be responsible for abdominal symptoms requiring colonoscopy, which may reveal the presence of concomitant polyps. A polyp found during colonoscopy in patients with colonic diverticular disease may be removed by endoscopic polypectomy with electrosurgical snare, a procedure associated with an incidence of perforation of less than 0.05%. The risk of such a complication may be higher in the event of an inverted colonic diverticulum, which may be misinterpreted as a polypoid lesion at colonoscopy. To date, fewer than 20 cases of inverted colonic diverticula, diagnosed at colonoscopy or following air contrast barium enema, have been reported in the literature. The present report describes a 68-year-old woman who underwent a screening colonoscopy, which revealed a voluminous pedunculated polyp that was recognized to be an inverted giant colonic diverticulum before endoscopic polypectomy.


Relief of postoperative pain by ibuprofen: a report of two studies.
The value of ibuprofen (Motrin) as an analgesic was assessed in two consecutive studies in 425 patients with postherniorrhaphy pain. In the first study, 400 mg ibuprofen proved superior to placebo and as effective as one tablet of a compound containing 375 mg of acetylsalicylic acid, 30 mg caffeine and 8 mg codeine (ACC-8). In the second study, the analgesic effectiveness of 400 mg of ibuprofen was intermediate between that of two tablets of ACC-8 and one tablet of ACC-30 (a compound containing 375 mg ASA, 30 mg caffeine and 30 mg codeine). The side effects of all drugs were negligible. Ibuprofen should be a suitable alternative analgesic in postoperative pain of this type.


Surface-immobilized biomolecules on albumin modified porcine pericardium for preventing thrombosis and calcification.
The search for a noncalcifying tissue material to be used for valve replacement application continues to be a field of extensive investigation. A series of porcine pericardial membranes was prepared by modifying the glutaraldehyde--treated tissues with albumin and subsequently immobilizing bioactive molecules like PGE1, PGI2 or heparin via the carbodiimide functionalities. The in vitro calcification and collagenase degradation of these modified tissues were studied as a function of exposure time. Furthermore, the biocompatibility aspects of such novel interfaces were established by platelet adhesion and fibrinogen adsorption. The results reported in this article propose that the treatment with antiplatelet agents such as albumin, heparin and prostaglandins (PGE1 or PGI2) change the surface conditioning of pericardial tissues, suggesting a possible role of deposited serum components in affecting mineralization process on bioprosthesis. Therefore, it is worthy to hypothesize that besides inhibiting the accumulation of calcium in the devitalized cells, the early formation of a conditioning layer on the bioprosthesis surface may affect salt precipitations, determining the propensity of the implant to calcify. More detailed studies are needed to understand the involvement of plasma proteins and cellular components of the recipient blood in tissue-associated calcification.


Simultaneous surgical management of renal cancer with atrial thrombotic extension and severe chronic coronary artery disease: a case report.
Renal cell carcinoma accounts for 2-3% of all malignant cancers in adults and is characterized by the potential development of venous tumor thrombus. We present a rare case of a 62-year-old Caucasian man who arrived in the emergency department for monosymptomatic hematuria. Further investigation revealed a right renal cell carcinoma with 16 cm intravascular extension through the renal vein into the inferior vena cava and right atrium associated with significant coronary artery disease based on the computed tomography scan and coronary angiography. To the best of our knowledge, after an extensive literature review, only one similar case has been reported with involvement of the contralateral kidney. Therefore, there are no applicable management recommendations. After performing coronary artery bypass graft surgery, we proceeded with an open right radical nephrectomy and inferior vena cava and right atrium thrombectomy under cardiopulmonary bypass and while the patient's heart was still beating. The postoperative course went without complications, and the patient was discharged from the hospital on the 10th postoperative day. Radical nephrectomy and thrombectomy with reconstruction of the inferior vena cava combined with coronary artery bypass graft can be performed safely and effectively in selected patients with renal cell carcinoma and significant coronary artery disease. Multidisciplinary teamwork and careful patient selection are essential for optimal outcomes.


Single-Layered Hittorf's Phosphorus: A Wide-Bandgap High Mobility 2D Material.
We propose here a two-dimensional material based on a single layer of violet or Hittorf's phosphorus. Using first-principles density functional theory, we find it to be energetically very stable, comparable to other previously proposed single-layered phosphorus structures. It requires only a small energetic cost of approximately 0.04 eV/atom to be created from its bulk structure, Hittorf's phosphorus, or a binding energy of 0.3-0.4 J/m(2) per layer, suggesting the possibility of exfoliation in experiments. We find single-layered Hittorf's phosphorus to be a wide band gap semiconductor with a direct band gap of approximately 2.5 eV, and our calculations show it is expected to have a high and highly anisotropic hole mobility with an upper bound lying between 3000-7000 cm(2) V(-1) s(-1). These combined properties make single-layered Hittorf's phosphorus a very good candidate for future applications in a wide variety of technologies, in particular for high frequency electronics, and optoelectronic devices operating in the low wavelength blue color range.


Metric mechanics with nontrivial topology: Actuating irises, cylinders, and evertors.
Liquid crystal elastomers contract along their director on heating and recover on cooling, offering great potential as actuators and artificial muscles. If a flat sheet is programed with a spatially varying director pattern, then it will actuate into a curved surface, allowing the material to act as a strong machine such as a grabber or lifter. Here we study the actuation of programed annular sheets which, owing to their central hole, can sidestep constraints on area and orientation. We systematically catalog the set of developable surfaces encodable via axisymmetric director patterns and uncover several qualitatively new modes of actuation, including cylinders, irises, and everted surfaces in which the inner boundary becomes the outer boundary after actuation. We confirm our designs with a combination of experiments and numerics. Many of our actuators can reattain their initial inner or outer radius upon completing actuation, making them particularly promising, as they can avoid potentially problematic stresses in their activated state even when fixed onto a frame or pipe.


[In vitro susceptibility of the proteins of wheat-protein and bran-protein bread to attack by gastric and pancreatic proteolytic enzymes].
The hydrolysis of proteins contained in the dietetic protein-rich bread with crystalline pepsin, trypsin and chemotrypsin was studied for the first time by using an apparatus devised by A. A. Pokrovsky and I. D. Ertanov and by following procedures as proposed by them (1968). By the end of every hour of the experiment 4.31 and 4.04, 7.88 and 4.90, 9.20 and 6.00, 12.96 and 11.72,19.00 and 12.55, 21.14 and 14.00 per cent of the initial quantity of the proteins contained in these two types of bread were hydrolysed respectively. The susceptibility to the action of enzymes on the part of the study products proved much lower than the theoretical proteinic values of the wheat, rye bread (M. S. Marshak, 1971) and below the results obtained by the analogous tests with the proteolysis of the ordinary bread proteins. Inasmuch as the protein-rich bread is baked according to the 1936 formulation an inference is drawn on the expediency of enriching such bread with dairy protein, rye gluten and belip, which will rresult in a more acceptable ratio of tryptophan/lysine and should, apparently, contribute to a greater intensity of the proteins hydrolysis in case of such a bread when it reaches the stomach and the proximal segment of the small intestine.


Location of antigenic epitopes on antibody molecules.
Using X-ray crystallographic co-ordinates of immunoglobulins, surface regions accessible to a large spherical probe, comparable in size to an antibody domain, were computed. Locations of these exposed regions were compared with those of experimentally determined antigenic sites, i.e. idiotypic, allotypic and isotypic serological markers. In all cases, an excellent agreement was found. The most prominent computed epitopes correspond to convex parts of antibody surface made by reverse turn segments of the polypeptide chain. The computed epitopes occur in homologous positions in all the immunoglobulin domains, and most of the beta-sheet surfaces on the domains are poorly antigenic. The CH2 domain (Fc fragment) has many more antigenic sites than the Fab fragments (antigen-binding fragments). Variable domain epitopes (idiotypes) involve both hypervariable and framework residues, and only about 25% of the hypervariable residues are strongly antigenic. The results indicate that, in a vertebrate body, each antibody molecule may be recognized, and its concentration regulated, by at least 40 complementary anti-immunoglobulin antibodies; therefore, a possibility of an "immune network" with much higher connectivity than is generally assumed should be seriously contemplated.


The role of the pharmacy coordinating center in the DIG trial.
Large simple trials (LSTs) emerged in response to the need for large sample sizes to answer important clinical questions in which treatments have a moderate effect on clinical endpoints. Between 1991 and 1996 the National Heart, Lung, and Blood Institute and the Department of Veterans Affairs (VA) Cooperative Studies Program conducted an LST entitled "Digitalis Investigation Group (DIG): Trial to Evaluate the Effect of Digitalis on Mortality in Heart Failure." The VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center served as the DIG pharmacy coordinating center (PCC). As a direct result of involvement in the DIG trial, the PCC identified the need for an increased emphasis on computerization and automated support of clinical trials, especially LSTs.


Predicting Dementia Risk for Elderly Community Dwellers in Primary Care Services Using Subgroup-specific Prediction Models.
Early detection of individuals with a high risk of dementia is crucial for prompt intervention and clinical care. This study aims to identify high-risk groups for developing dementia by predicting the outcome of the Mini-Mental State Examination (MMSE), using historical data collected from community-based primary care services. To mitigate the effect of inter-individual variability and enhance the accuracy of the prediction, we implemented a multi-stage method powered by supervised and unsupervised machine learning methods. Firstly, we preprocessed the original data by imputing missing values and using a wrapper-based feature selection algorithm to pick significant features, resulting in ten variables out of 567 being selected for further modeling. Secondly, we optimized hierarchical clustering to partition the unlabeled data into groups by their similarities, and then applied supervised machine learning models to build subgroup-specific prediction models for the identified groups. The results demonstrate that the proposed subgroup-specific prediction models generated from the multi-stage method achieved satisfactory performance in predicting the outcome classes of dementia risk. This study highlights the potential of incorporating unsupervised and supervised learning models to predict high-risk cases of dementia early and facilitate better clinical decision-making.


Neuronal plasticity in the cingulate cortex of rats following esophageal acid exposure in early life.
The cingulate cortex has been reported to be involved in processing pain of esophageal origin. However, little is known about molecular changes and cortical activation that arise from early-life esophageal acid reflux. Excitatory neurotransmission via activation of the N-methyl-d-aspartate (NMDA) receptor and its interaction with postsynaptic density protein 95 (PSD-95) at the synapse appear to mediate neuronal development and plasticity. We investigated the effect of early-life esophageal acid exposure on NMDA receptor subunits and PSD-95 expression in the developing cingulate cortex. We assessed NMDA receptor subunits and PSD-95 protein expression in rostral cingulate cortex (rCC) tissues of rats exposed to esophageal acid or saline (control), either during postnatal day (P) 7 to 14 and/or acutely at adult stage (P60) using immunoblot and immunoprecipitation analyses. Compared with controls, acid exposure from P7 to P14 significantly increased expression of NR1, NR2A, and PSD-95, measured 6 weeks after exposure. However, acute exposure at P60 caused a transient increase in expression of NMDA receptor subunits. These molecular changes were more robust in animals exposed to acid neonatally and rechallenged, acutely, at P60. Esophageal acid exposure induced calcium calmodulin kinase II-mediated phosphorylation of the subunit NR2B at Ser1303. Esophageal acid exposure during early stages of life has long-term effects as a result of phosphorylation of the NMDA receptor and overexpression in the rCC. This molecular alteration in the rCC might mediate sensitization of patients with acid-induced esophageal disorders.


Efficacy and Acceptability of Intermittent Aerobic Exercise on Polysomnography-Measured Sleep in People With Rheumatoid Arthritis With Self-Reported Sleep Disturbance: A Randomized Controlled Trial.
This study's objective was to investigate the efficacy and acceptability of intermittent aerobic exercise training on sleep parameters, fatigue, pain, depressive symptoms, physical function, and cardiorespiratory fitness in people with rheumatoid arthritis (RA). Thirty-eight people with RA were assigned to intermittent aerobic exercise training (three sessions/week for 6 weeks; intervention group, n = 17) or usual care (control group, n = 21). The primary outcome was a change in polysomnography-assessed sleep efficiency from baseline to the end of the intervention. Secondary outcomes were sleep quality (Pittsburgh Sleep Quality Index), fatigue (Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire), depression (Center for Epidemiological Studies-Depression), and cardiorespiratory fitness (watt max test). No between-group differences were found in changes in polysomnography-assessed sleep efficiency (0.04; 95% confidence interval [CI]: -0.02 to 0.09, P = 0.17). In the intervention group, sleep efficiency was improved significantly from baseline (0.84; 95% CI: 0.80-0.88) compared with the end of the intervention (6 weeks) (0.88; 95% CI: 0.85-0.92); however, there was no significant difference in the control group. Fatigue and depression measures were significantly lower in the intervention group than in the control group. Between-group differences were overall fatigue (-16.1; 95% CI: -25.1 to -7.0, P = 0.001), physical fatigue (-5.0; 95% CI: -7.3 to -2.7, P = 0.0001), cognitive fatigue (-2.4; 95% CI: -4.2 to 0.6, P = 0.009), living with fatigue (-2.5; 95% CI: -4.5 to -0.5, P = 0.01), and depressive symptoms (-6.8; 95% CI: -12.4 to -1.1, P = 0.02). The intervention yielded no significantly better sleep efficiency compared with usual care. However, aspects of fatigue, including physical and cognitive fatigue, and depressive symptoms were significantly improved in the intervention group.


Seroprevalence and correlates of hepatitis a among HIV-negative American men who have sex with men.
Hepatitis A outbreaks are well documented among men who have sex with men (MSM). This analysis examines characteristics associated with hepatitis A virus (HAV) infection among a large group of young adult MSM from five USA cities. The Young Men's Survey was a cross-sectional prevalence study of HIV infection and related behavioural risk factors among MSM aged 15-29 years during 1994-2000. Serum specimens from HIV-negative participants were retrospectively tested for antibodies to HAV (anti-HAV). Data were stratified by ethnicity and analysed with logistic regression. Overall anti-HAV prevalence was 18.4% among the 2708 participants, and varied by ethnicity from 6.9 to 45.3% and was highest among Hispanic and Asian men (P < 0.001). Prevalence increased with age across all racial/ethnic groups. Among white men, anti-HAV positivity was associated with having 20 or more lifetime male sex partners for those aged 15-22 years (adjusted odds ratio (AOR)=2.1, 95% confidence interval (CI)=1.0-4.1) and ever having had unprotected anal sex for those aged 23-29 years (AOR=2.4, 95% CI=1.2-4.5). Factors associated with a history of HAV infection among MSM in non-outbreak settings are probably similar to those among non-MSM. MSM are still at risk for HAV infection as a result of outbreaks occurring in MSM communities. Additional studies of hepatitis A vaccination coverage are needed to determine if strategies to vaccinate MSM are adequate.


Behavioral and neural aspects of the spatial processing of conspecifics signals in the electrosensory system.
Localizing the source of a signal is often as important as deciphering the signal's message. Localization mechanisms must cope with the challenges of representing the spatial information of weak, noisy signals. Comparing these strategies across modalities and model systems allows a broader understanding of the general principles shaping spatial processing. In this review we focus on the electrosensory system of knifefish and provide an overview of our current understanding of spatial processing in this system, in particular, localization of conspecific signals. We argue that many mechanisms observed in other sensory systems, such as the visual or auditory systems, have comparable implementations in the electrosensory system. Our review therefore describes a field of research with unique opportunities to provide new insights into the principles underlying spatial processing. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Improved quality of a vitamin B12-fortified 'ready to blend' fresh-cut mix salad with chitosan.
A vitamin B12-fortified (0.25 mg L-1) chitosan (10 g L-1) coating was applied to a ready-to-blend fresh-cut salad including melon, pineapple and carrot, which was stored at 5 ℃ up to nine days. Uncoated samples were used as control while the vitamin B12 effect was compared to non-fortified chitosan-coated samples. Beverages were prepared on blending days 0, 4, 7 and 9 with subsequent storage at 5 ℃ for 0, 24 and 48 h. Physicochemical quality of fresh blended beverages was well preserved throughout storage. The chitosan coating highly reduced epiphytic microflora growth and polyphenoloxidase/peroxidase activities. No relevant variations of total phenolic contents were observed between different fresh blended beverages. However, its total antioxidant capacity reported after blending was lower as storage time of ready-to-blend samples increased. Fortified samples showed a vitamin B12 content of 8.6 µg kg-1 on processing day, ensuring 200 mL of such beverage the recommended daily intake of this vitamin. In conclusion, a ready-to-blend fruit/vegetable mix, fortified with vitamin B12, was developed with a shelf life of nine days at 5 ℃ showing the prepared beverages good quality during subsequent storage for 48 h at 5 ℃.


Single-Molecule Plasmon Sensing: Current Status and Future Prospects.
Single-molecule detection has long relied on fluorescent labeling with high quantum-yield fluorophores. Plasmon-enhanced detection circumvents the need for labeling by allowing direct optical detection of weakly emitting and completely nonfluorescent species. This review focuses on recent advances in single molecule detection using plasmonic metal nanostructures as a sensing platform, particularly using a single particle-single molecule approach. In the past decade two mechanisms for plasmon-enhanced single-molecule detection have been demonstrated: (1) by plasmonically enhancing the emission of weakly fluorescent biomolecules, or (2) by monitoring shifts of the plasmon resonance induced by single-molecule interactions. We begin with a motivation regarding the importance of single molecule detection, and advantages plasmonic detection offers. We describe both detection mechanisms and discuss challenges and potential solutions. We finalize by highlighting the exciting possibilities in analytical chemistry and medical diagnostics.


Zingerone regulates intestinal transit, attenuates behavioral and oxidative perturbations in irritable bowel disorder in rats.
Stress can lead to the manifestation of functional gastrointestinal disorders, the most prominent being irritable bowel disorder. The present study investigated the impact zingerone in ameliorating chronic water stress induced irritable bowel disorder, brain gut axis dysfunction and dysregulation of the intestinal barrier due to oxidative stress. Rats were randomly allocated to groups and subjected to chronic water stress for a period of 21 days for 1h and the fecal pellet output was measured. At the end of chronic stress, behavioral assessment for anxiety like behavior was recorded and plasma corticosterone levels were measured 60min after water stress. The colonic transit was determined, levels of oxidative and antioxidant biomarkers were measured in the colon homogenate. Myeloperoxidase activity was determined as an indirect index of neutrophil infiltration. Chronic water stress increased the rate of colonic transit, fecal output, induced behavioral changes, and decreased antioxidant levels. An increase in lipid peroxide levels, catalase and corticosterone was observed. Mast cell infiltration was evident in the stressed group. Zingerone significantly reduced colonic transit, fecal output, neutrophil infiltration, and lipid peroxide formation. The levels of catalase were not altered; however, a marginal increase in the levels of glutathione peroxidase was observed. Zingerone significantly enhanced the levels of superoxide dismutase, glutathione and decreased the levels of corticosterone. Zingerone produced marked improvement in stress induced irritable bowel disorder which could be attributed to the powerful antioxidant nature, direct effect on the intestinal smooth muscle and adaptogenic nature.


Formation Control of Multiagent Systems With Communication Noise: A Convex Analysis Approach.
Under practical environments, some certain noises may arise from the communication of agents due to electromagnetic interference, sensor error, and other disturbances, which are usually modeled by additive noise in the relative position state between an agent and its neighbors. In this article, a formation control strategy is considered for this kind of relative position state with the additive noise, where the unmeasured velocity information is estimated by an observer-based strategy. On the other hand, the considered problem is transformed into a convergence problem of infinite products of a sequence of general stochastic matrices. The general stochastic matrix means that a matrix has row sum one but its entries do not necessarily require non-negative. This article develops the convex analysis to cope with such infinite products. Then, a sufficient condition is obtained to ensure that the specified formation shape in a noisy environment can be achieved. Subsequently, an example is presented to show the effectiveness of the result.


Geographic body size variation in ectotherms: effects of seasonality on an anuran from the southern temperate forest.
Body size variation has played a central role in biogeographical research, however, most studies have aimed to describe trends rather than search for underlying mechanisms. In order to provide a more comprehensive understanding of the causes of intra-specific body size variation in ectotherms, we evaluated eight hypotheses proposed in the literature to account for geographical body size variation using the Darwin's frog (Rhinoderma darwinii), an anuran species widely distributed in the temperate forests of South America. Each of the evaluated hypotheses predicted a specific relationship between body size and environmental variables. The level of support for each of these hypotheses was assessed using an information-theoretic approach and based on data from 1015 adult frogs obtained from 14 sites across the entire distributional range of the species. There was strong evidence favouring a single model comprising temperature seasonality as the predictor variable. Larger body sizes were found in areas of greater seasonality, giving support to the "starvation resistance" hypothesis. Considering the known role of temperature on ectothermic metabolism, however, we formulated a new, non-exclusive hypothesis, termed "hibernation hypothesis": greater seasonality is expected to drive larger body size, since metabolic rate is reduced further and longer during colder, longer winters, leading to decreased energy depletion during hibernation, improved survival and increased longevity (and hence growth). Supporting this, a higher post-hibernation body condition in animals from areas of greater seasonality was found. Despite largely recognized effects of temperature on metabolic rate in ectotherms, its importance in determining body size in a gradient of seasonality has been largely overlooked so far. Based on our results, we present and discuss an alternative mechanism, the "hibernation hypothesis", underlying geographical body size variation, which can be helpful to improve our understanding of biogeographical patterns in ectotherms.


A study of the oncogenicity of adenovirus type 2 transformed rat embryo cells.
Rat embryo cells were transformed by adenovirus type 2 at different multiplicities of infection. The oncogenic potential of the resulting transformed lines varied considerably but a relationship was found to exist between transforming virus dose and oncogenicity of the resulting transformed lines. Possible reasons for the considerable variation in oncogenicity of the transformed lines are discussed, giving particular consideration to cellular antigenicity and recent molecular biology studies of adenovirus type 2 transformed cell lines.


Site and mechanism of morphine tolerance in the gastrointestinal tract.
Opioid-induced constipation is a major clinical problem. The effects of morphine, and other narcotics, on the gastrointestinal tract persist over long-term use thus limiting the clinical benefit of these excellent pain relievers. The effects of opioids in the gut, including morphine, are largely mediated by the μ-opioid receptors at the soma and nerve terminals of enteric neurons. Recent studies demonstrate that regional differences exist in both acute and chronic morphine along the gastrointestinal tract. While tolerance develops to the analgesic effects and upper gastrointestinal motility upon repeated morphine administration, tolerance does not develop in the colon with chronic opioids resulting in persistent constipation. Here, we review the mechanisms by which tolerance develops in the small but not the large intestine. The regional differences lie in the signaling and regulation of the μ-opioid receptor in the various segments of the gastrointestinal tract. The differential role of β-arrestin2 in tolerance development between central and enteric neurons defines the potential for therapeutic approaches in developing ligands with analgesic properties and minimal constipating effects.


Ornamental expression of red fluorescent protein in transgenic founders of white skirt tetra (Gymnocorymbus ternetzi).
Although the transgenic technology has been successfully used to generate fluorescent zebrafish and medaka for ornamental purposes, the practicability of the technology has not been demonstrated in other ornamental fish species. In the present study, we have tested the transgenic technology in a bona fide ornamental fish species, the white skirt tetra (Gymnocorymbus ternetzi). First, its embryonic development was briefly described. Second, we successfully introduced an rfp (red fluorescent protein) gene construct driven by a strong muscle-specific mylz2 promoter from the zebrafish into the white skirt tetra and demonstrated muscle-specific expression of the RFP reporter protein. Importantly, the vivid red fluorescent color was prominently visible in adult transgenic founders under the normal daylight, like the currently marketed red fluorescent transgenic zebrafish. Thus, our current study demonstrated the feasibility of using the well-characterized zebrafish mylz2 promoters to produce useful fluorescent ornamental fish in other fish species by the transgenic technology.


Uncertainties in Steric Sea Level Change Estimation During the Satellite Altimeter Era: Concepts and Practices.
This article presents a review of current practice in estimating steric sea level change, focussed on the treatment of uncertainty. Steric sea level change is the contribution to the change in sea level arising from the dependence of density on temperature and salinity. It is a significant component of sea level rise and a reflection of changing ocean heat content. However, tracking these steric changes still remains a significant challenge for the scientific community. We review the importance of understanding the uncertainty in estimates of steric sea level change. Relevant concepts of uncertainty are discussed and illustrated with the example of observational uncertainty propagation from a single profile of temperature and salinity measurements to steric height. We summarise and discuss the recent literature on methodologies and techniques used to estimate steric sea level in the context of the treatment of uncertainty. Our conclusions are that progress in quantifying steric sea level uncertainty will benefit from: greater clarity and transparency in published discussions of uncertainty, including exploitation of international standards for quantifying and expressing uncertainty in measurement; and the development of community "recipes" for quantifying the error covariances in observations and from sparse sampling and for estimating and propagating uncertainty across spatio-temporal scales.


Compositional equivalency of RNAi-mediated virus-resistant transgenic soybean and its nontransgenic counterpart.
RNA silencing or RNA interference (RNAi), which is triggered by double-stranded RNA (dsRNA), is an evolutionarily conserved process that is active in a wide variety of eukaryotic organisms. Engineering plants with hairpin construct in which the viral gene is arranged in inverted repeats (IR) renders plants resistant to plant virus infection. However, there is no report on whether biologically important changes occurred by the insertion of IR, which confer transgenic plants virus resistance. In the present study, the compositions of virus-resistant transgenic soybean seeds developed by insertion of three short IRs, each containing the specific, highly conserved sequences derived from one virus, were compared with those of nontransgenic counterparts by applying the principle of substantial equivalence to determine whether significant undesirable biological changes occurred by IR insertion. The results revealed that the nutrient components as well as antinutrient contents of these virus-resistant soybean lines are substantially equivalent to those of the nontransgenic counterparts, and the majority of the measured amounts of nutritional components and antinutrient contents are well within the range of values reported for other commercial soybean lines. The results imply that no biologically important changes occurred by the insertion of IRs in the RNAi-mediated virus-resistant transgenic soybeans. The results can serve as baseline information for developing RNAi-mediated transgenic soybean cultivars or other crops with broader spectrum virus resistance.


Spidroins under the Influence of Alcohol: Effect of Ethanol on Secondary Structure and Molecular Level Solvation of Silk-Like Proteins.
Future sustainable materials based on designer biomolecules require control of the solution assembly, but also interfacial interactions. Alcohol treatments of protein materials are an accessible means to this, making understanding of the process at the molecular level of seminal importance. We focus here on the influence of ethanol on spidroins, the main proteins of silk. By large-scale atomistically detailed molecular dynamics (MD) simulations and interconnected experiments, we characterize the protein aggregation, secondary structure changes, molecular level origins of them, and solvation environment changes for the proteins, as induced by ethanol as a solvation additive. The MD and circular dichoroism (CD) findings jointly show that ethanol promotes ordered structure in the protein molecules, leading to an increase of helix content and turns but also increased aggregation, as revealed by dynamic light scattering (DLS) and light microscopy. The structural changes correlate at the molecular level with increased intramolecular hydrogen bonding. The simulations reveal that polar amino acids, such as glutamine and serine, are most influenced by ethanol, whereas glycine residues are most prone to be involved in the ethanol-induced secondary structure changes. Furthermore, ethanol engages in interactions with the hydrophobic alanine-rich regions of the spidroin, significantly decreasing the hydrophobic interactions of the protein with itself and its surroundings. The protein solutes also change the microstructure of water/ethanol mixtures, essentially decreasing the level of larger local clustering. Overall, the work presents a systematic characterization of ethanol effects on a widely used, common protein type, spidroins, and generalizes the findings to other intrinsically disordered proteins by pinpointing the general features of the response. The results can aid in designing effective alcohol treatments for proteins, but also enable design and tuning of protein material properties by a relatively controllable solvation handle, the addition of ethanol.


Pathogenicity of Metarhizium anisopliae (Deuteromycetes) and permethrin to Ixodes scapularis (Acari: Ixodidae) nymphs.
Effectiveness of the entomopathogenic fungus Metarhizium anisopliae, for controlling nymphal Ixodes scapularis, was tested in laboratory and field trials. In the laboratory, M. anisopliae (Metschnikoff) Sorokin strain ESC1 was moderately pathogenic, with an LC50 of 10(7) spores/ml and induced 70% mortality at 10(9) spores/ml. In a field study, however, 10(9) spores/ml M. anisopliae did not effectively control questing I. scapularis nymphs, and significant differences were not detected in pre- and post-treatment densities. For nymphs collected and returned to the laboratory for observation, mortality was low in treatment groups, ranging from 20 to 36%. To assess whether a chemical acaricide would synergistically enhance pathogenicity of the fungus, we challenged unfed nymphal I. scapularis with combinations of M. anisopliae and permethrin, a relatively safe pyrethroid acaricide, in two separate bioassays. Significant interactions between M. anisopliae and permethrin were not observed, supporting neither synergism nor antagonism.


Predicting the timing of spikes evoked by tactile stimulation of the hand.
What does the hand tell the brain? Tactile stimulation of the hand evokes remarkably precise patterns of neural activity, suggesting that the timing of individual spikes may convey information. However, many aspects of the transformation of mechanical deformations of the skin into spike trains remain unknown. Here we describe an integrate-and-fire model that accurately predicts the timing of individual spikes evoked by arbitrary mechanical vibrations in three types of mechanoreceptive afferent fibers that innervate the hand. The model accounts for most known properties of the three fiber types, including rectification, frequency-sensitivity, and patterns of spike entrainment as a function of stimulus frequency. These results not only shed light on the mechanisms of mechanotransduction but can be used to provide realistic tactile feedback in upper-limb neuroprostheses.


Palmitate-induced down-regulation of sortilin and impaired GLUT4 trafficking in C2C12 myotubes.
Elevated saturated FFAs including palmitate (C16:0) are a primary trigger for peripheral insulin resistance characterized by impaired glucose uptake/disposal in skeletal muscle, resulting from impaired GLUT4 translocation in response to insulin. We herein demonstrate that palmitate induces down-regulation of sortilin, a sorting receptor implicated in the formation of insulin-responsive GLUT4 vesicles, via mechanisms involving PKC and TNF-α-converting enzyme, but not p38, JNK, or mitochondrial reactive oxygen species generation, leading to impaired GLUT4 trafficking in C2C12 myotubes. Intriguingly, unsaturated FFAs such as palmitoleate (C16:1) and oleate (C18:1) had no such detrimental effects, appearing instead to effectively reverse palmitate-induced impairment of insulin-responsive GLUT4 recycling along with restoration of sortilin abundance by preventing aberrant PKC activation. On the other hand, shRNA-mediated reduction of sortilin in intact C2C12 myotubes inhibited insulin-induced GLUT4 recycling without dampening Akt phosphorylation. We found that the peroxisome proliferator-activated receptor γ agonist troglitazone prevented the palmitate-induced sortilin reduction and also ameliorated insulin-responsive GLUT4 recycling without altering the palmitate-evoked insults on signaling cascades; neither highly phosphorylated PKC states nor impaired insulin-responsive Akt phosphorylation was affected. Taken together, our data provide novel insights into the pathogenesis of PKC-dependent insulin resistance with respect to insulin-responsive GLUT4 translocation, which could occur not only through defects of insulin signaling but also via a reduction of sortilin, which directly controls trafficking/sorting of GLUT4 in skeletal muscle cells. In addition, our data suggest the insulin-sensitizing action of peroxisome proliferator-activated receptor γ agonists to be at least partially mediated through the restoration of proper GLUT4 trafficking/sorting events governed by sortilin.


Mammographic density, blood telomere length and lipid peroxidation.
Extensive mammographic density is a strong risk factor for breast cancer, but may also be an indicator of biological age. In this study we examined whether mammographic density is related to blood telomere length, a potential marker of susceptibility to age-related disease. We measured mammographic density by a computer assisted method and blood telomere length using a validated PCR method. Urinary malondialdehyde (MDA), a marker of lipid peroxidation, was measured in 24 hour urine collections. In the 342 women examined telomere length was negatively correlated with age, was lower in postmenopausal compared to premenopausal women and in smokers compared to non-smokers, and was positively correlated with urinary MDA. Telomere length was not associated with percent mammographic density or dense area, before or after adjustment for risk factors and MDA. However, there was a significant interaction between telomere length and MDA in their association with mammographic density. At lower levels of MDA, mammographic density and telomere length were inversely associated; while at high levels of MDA, there was evidence of a J-shaped association between mammographic density and telomere length. Further work is need to replicate these results and to examine the association of mammographic density with age-related chronic disease and mortality.


Aspiration-assisted freeform bioprinting of prefabricated tissue spheroids in a yield-stress gel.
Bioprinting of cellular aggregates, such as tissue spheroids, to form three-dimensional (3D) complex-shaped arrangements, has posed a major challenge due to lack of robust, reproducible and practical bioprinting techniques. Here, we demonstrate 3D aspiration-assisted freeform bioprinting of tissue spheroids by precisely positioning them in self-healing yield-stress gels, enabling the self-assembly of spheroids for fabrication of tissues. The presented approach enables the traverse of spheroids directly from the cell media to the gel and freeform positioning of the spheroids on demand. We study the underlying physical mechanism of the approach to elucidate the interactions between the aspirated spheroids and the gel's yield-stress during the transfer of spheroids from cell media to the gel. We further demonstrate the application of the proposed approach in the realization of various freeform shapes and self-assembly of human mesenchymal stem cell spheroids for the construction of cartilage and bone tissues.