A hormonal role for endogenous opiate alkaloids: vascular tissues.
The distribution of morphine-containing cells in the central nervous system, adrenal gland, and its presence in blood may serve to demonstrate that this signal molecule can act as a hormone besides its role in cell-to-cell signaling within the brain. This speculative review is the result of a literature evaluation with an emphasis on studies from our laboratory. Opioid peptides and opiate alkaloids have been found to influence cardiac and vascular function. They have also been reported to promote ischemic preconditioning protection in the heart. Given the presence of morphine and the novel mu(3) opiate receptor on vascular endothelial cells, including cardiac and vascular endothelial cells in the median eminence, it would appear that endogenous opiate alkaloids are involved in modulating cardiac function, possible at the hormonal level. This peripheral target tissue, via nitric oxide coupling to mu opiate receptors, may serve to down regulate the excitability of this tissue given the heart's high performance state as compared to that of the saphenous vein, a passive resistance conduit. With this in mind, morphine and other endogenous opiate alkaloids may function as a hormone.


Resonance in quantum dot fluorescence in a photonic bandgap liquid crystal host.
Microcavity resonance is demonstrated in nanocrystal quantum dot fluorescence in a one-dimensional (1D) chiral photonic bandgap cholesteric-liquid crystal host under cw excitation. The resonance demonstrates coupling between quantum dot fluorescence and the cholesteric microcavity. Observed at a band edge of a photonic stop band, this resonance has circular polarization due to microcavity chirality with 4.9 times intensity enhancement in comparison with polarization of the opposite handedness. The circular-polarization dissymmetry factor g(e) of this resonance is ~1.3. We also demonstrate photon antibunching of a single quantum dot in a similar glassy cholesteric microcavity. These results are important in cholesteric-laser research, in which so far only dyes were used, as well as for room-temperature single-photon source applications.


Asiatic acid protects against hepatic ischemia/reperfusion injury by inactivation of Kupffer cells via PPARγ/NLRP3 inflammasome signaling pathway.
Hepatic ischemia/reperfusion (I/R) contributes to major complications in clinical practice affecting perioperative morbidity and mortality. Recent evidence suggests the key role of nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammaosme activation on the pathogenesis of I/R injury. Asiatic acid (AA) is a pentacyclic triterpene derivative presented with versatile activities, including antioxidant, anti-inflammation and hepatoprotective effects. This study was designed to determine whether AA had potential hepatoprotective benefits against hepatic I/R injury, as well as to unveil the underlying mechanisms involved in the putative effects. Mice subjected to warm hepatic I/R, and Kupffer cells (KCs) or RAW264.7 cells challenged with lipopolysaccharide (LPS)/H2O2, were pretreated with AA. Administration of AA significantly attenuated hepatic histopathological damage, global inflammatory level, apoptotic signaling level, as well as NLRP3 inflammasome activation. These effects were correlated with increased expression of peroxisome proliferator-activated receptor gamma (PPARγ). Conversely, pharmacological inhibition of PPARγ by GW9662 abolished the protective effects of AA on hepatic I/R injury and in turn aggravated NLRP3 inflammasome activation. Activation of NLRP3 inflammasome was most significant in nonparenchymal cells (NPCs). Depletion of KCs by gadolinium chloride (GdCl3) further attenuated the detrimental effects of GW9662 on hepatic I/R as well as NLRP3 activation. In vitro, AA concentration-dependently inhibited LPS/H2O2-induced NLRP3 inflammaosome activation in KCs and RAW264.7 cells. Either GW9662 or genetic knockdown of PPARγ abolished the AA-mediated inactivation of NLRP3 inflammasome. Mechanistically, AA attenuated I/R or LPS/H2O2-induced ROS production and phosphorylation level of JNK, p38 MAPK and IκBα but not ERK, a mechanism dependent on PPARγ. Finally, AA blocked the deleterious effects of LPS/H2O2-induced macrophage activation on hepatocyte viability in vitro, and improved survival in a lethal hepatic I/R injury model in vivo. Collectively, these data suggest that AA is effective in mitigating hepatic I/R injury through attenuation of KCs activation via PPARγ/NLRP3 inflammasome signaling pathway.


Coco Peat as Agricultural Waste Sorbent for Sustainable Diesel-Filter System.
Oil spill incidents are hazardous and have prolonged damage to the marine environment. Management and spill clean-up procedures are practical and rapid, with several shortcomings. Coco peat (CP) and coco fibre (CF) are refined from coconut waste, and their abundance makes them desirable for diesel spillage treatment. Using a filter-based system, the selectivity of coco peat sorbent was tested using CP, CF and peat-fibre mix (CPM). CP exhibited maximal diesel sorption capacity with minimal seawater uptake, thus being selected for further optimisation analysis. The heat treatment considerably improved the sorption capacity and efficiency of diesel absorbed by CP, as supported by FTIR and VPSEM-EDX analysis. Conventional one-factor-at-a-time (OFAT) examined the performance of diesel sorption by CP under varying parameters, namely temperature, time of heating, packing density and diesel concentration. The significant factors were statistically evaluated using response surface methodology (RSM) via Plackett-Burman design (PB) and central composite design (CCD). Three significant (p < 0.05) factors (time, packing density and diesel concentration) were identified by PB and further analysed for interactions among the parameters. CCD predicted efficiency of diesel absorbed at 59.92% (71.90 mL) (initial diesel concentration of 30% v/v) and the experimental model validated the design with 59.17% (71.00 mL) diesel sorbed at the optimised conditions of 14.1 min of heating (200 °C) with packing density of 0.08 g/cm3 and 30% (v/v) of diesel concentration. The performance of CP in RSM (59.17%) was better than that in OFAT (58.33%). The discoveries imply that natural sorbent materials such as CP in oil spill clean-up operations can be advantageous and environmentally feasible. This study also demonstrated the diesel-filter system as a pilot study for the prospective up-scale application of oil spills.


Complement and innate immune evasion strategies of the human pathogenic fungus Candida albicans.
Candida albicans is a medically important fungus that can cause a wide range of diseases ranging from superficial infections to disseminated disease, which manifests primarily in immuno-compromised individuals. Despite the currently applied anti-fungal therapies, both mortality and morbidity caused by this human pathogenic fungus are still unacceptably high. Therefore new prophylactic and therapeutic strategies are urgently needed to prevent fungal infection. In order to define new targets for combating fungal disease, there is a need to understand the immune evasion strategies of C. albicans in detail. In this review, we summarize different sophisticated immune evasion strategies that are utilized by C. albicans. The description of the molecular mechanisms used for immune evasion does on one hand help to understand the infection process, and on the other hand provides valuable information to define new strategies and diagnostic approaches to fight and interfere with Candida infections.


A common LPA null allele associates with lower lipoprotein(a) levels and coronary artery disease risk.
Increased levels of lipoprotein(a) are a highly heritable risk factor for coronary artery disease (CAD). The genetic determinants of lipoprotein(a) levels are mainly because of genetic variation in the apolipoprotein(a) gene (LPA). We have tested the association of a relatively common null allele of LPA with lipoprotein(a) levels and CAD risk in a large case-control cohort. We have also examined how null allele genotyping complements apolipoprotein(a) isoform typing to refine the relationship between LPA isoform size and circulating lipoprotein(a) levels. The LPA null allele (rs41272114) was genotyped in the PROCARDIS (Precocious Coronary Artery Disease) case-control cohort (4073 CAD cases and 4225 controls). Lipoprotein(a) levels were measured in 909 CAD cases and 922 controls; apolipoprotein(a) isoform size was estimated using sodium dodecyl sulfate-agarose gel electrophoresis and a high-throughput quantitative polymerase chain reaction-based method. Null carriers are common (null allele frequency, 3%) and have significantly lower circulating lipoprotein(a) levels (P=2.1×10(-10)) and reduced CAD risk (odds ratio, 0.79 [0.66-0.97]; P=0.023) compared with noncarriers. An additive allelic model of apolipoprotein(a) isoform size, refined by null allele genotype and quantitative polymerase chain reaction values, showed a sigmoid relationship with lipoprotein(a) levels, with baseline levels for longer isoform alleles and progressively higher levels of lipoprotein(a) for shorter isoform alleles. The LPA null allele (rs41272114) is associated with decreased circulating lipoprotein(a) levels and decreased CAD risk. Incorporating rs41272114 refined apolipoprotein(a) isoform size typing obtained by immunoblotting and quantitative polymerase chain reaction. A joint genomic and isoform analysis revealed details of the relationship between apolipoprotein(a) isoform size and circulating lipoprotein(a) level consistent with a threshold effect on lipoprotein secretion.


The relationship between knowledge of recent HbA1c values and diabetes care understanding and self-management.
Knowledge of one's actual and target health outcomes (such as HbA(1c) values) is hypothesized to be a prerequisite for effective patient involvement in managing chronic diseases such as diabetes. We examined 1) the frequency and correlates of knowing one's most recent HbA(1c) test result and 2) whether knowing one's HbA(1c) value is associated with a more accurate assessment of diabetes control and better diabetes self-care understanding, self-efficacy, and behaviors related to glycemic control. We conducted a cross-sectional survey of a sample of 686 U.S. adults with type 2 diabetes in five health systems who had HbA(1c) checked in the previous 6 months. Independent variables included patient characteristics, health care provider communication, and health system type. We examined bivariate and multivariate associations between each variable and the respondents' knowledge of their last HbA(1c) values and assessed whether knowledge of HbA(1c) was associated with key diabetes care attitudes and behaviors. Of the respondents, 66% reported that they did not know their last HbA(1c) value and only 25% accurately reported that value. In multivariate analyses, more years of formal education and high evaluations of provider thoroughness of communication were independently associated with HbA(1c) knowledge. Respondents who knew their last HbA(1c) value had higher odds of accurately assessing their diabetes control (adjusted odds ratio 1.59, 95% CI 1.05-2.42) and better reported understanding of their diabetes care (P < 0.001). HbA(1c) knowledge was not associated with respondents' diabetes care self-efficacy or reported self-management behaviors. Respondents who knew their HbA(1c) values reported better diabetes care understanding and assessment of their glycemic control than those who did not. Knowledge of one's HbA(1c) level alone, however, was not sufficient to translate increased understanding of diabetes care into the increased confidence and motivation necessary to improve patients' diabetes self-management. Strategies to provide information to patients must be combined with other behavioral strategies to motivate and help patients effectively manage their diabetes.


Copulatory behaviour and the process of intromission in Anastrepha ludens (Diptera: Tephritidae).
Complex genitalia occur in many arthropods and in some species extreme female morphologies lead to serious mechanical difficulties for males. Tephritid flies offer examples of such complex genitalia. Because of their economic importance and the extensive use of sterile male releases for tephritid control in Texas and Mexico, studies have been done on various aspects of their basic reproductive biology, but the process of intromission has received little attention. The distiphallus of the male of Anastrepha ludens is complex. One membranous sac on the distiphallus is capable of rhythmic cycles of inflation and deflation. Inflations of the sac near the base of the distiphallus probably help propel the aedeagus deeper into the female along with stiffening of the basiphallus and may drive the genital rod (which does not transfer sperm) into the ventral receptacle. We were unable to establish an association between some of the behaviours displayed by males during mating and intromission process.


Blocking the metabolism of starch breakdown products in Arabidopsis leaves triggers chloroplast degradation.
In most plants, a large fraction of photo-assimilated carbon is stored in the chloroplasts during the day as starch and remobilized during the subsequent night to support metabolism. Mutations blocking either starch synthesis or starch breakdown in Arabidopsis thaliana reduce plant growth. Maltose is the major product of starch breakdown exported from the chloroplast at night. The maltose excess 1 mutant (mex1), which lacks the chloroplast envelope maltose transporter, accumulates high levels of maltose and starch in chloroplasts and develops a distinctive but previously unexplained chlorotic phenotype as leaves mature. The introduction of additional mutations that prevent starch synthesis, or that block maltose production from starch, also prevent chlorosis of mex1. In contrast, introduction of mutations in disproportionating enzyme (DPE1) results in the accumulation of maltotriose in addition to maltose, and greatly increases chlorosis. These data suggest a link between maltose accumulation and chloroplast homeostasis. Microscopic analyses show that the mesophyll cells in chlorotic mex1 leaves have fewer than half the number of chloroplasts than wild-type cells. Transmission electron microscopy reveals autophagy-like chloroplast degradation in both mex1 and the dpe1/mex1 double mutant. Microarray analyses reveal substantial reprogramming of metabolic and cellular processes, suggesting that organellar protein turnover is increased in mex1, though leaf senescence and senescence-related chlorophyll catabolism are not induced. We propose that the accumulation of maltose and malto-oligosaccharides causes chloroplast dysfunction, which may by signaled via a form of retrograde signaling and trigger chloroplast degradation.


Dynamics of extended-spectrum beta-lactamase-producing Enterobacterales colonization in long-term carriers following travel abroad.
Travel to tropical regions is associated with high risk of acquiring extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) that are typically cleared in less than 3 months following return. The conditions leading to persistent carriage that exceeds 3 months in some travellers require investigation. Whole-genome sequencing (Illumina MiSeq) was performed on the 82 ESBL-E isolates detected upon return and 1, 2, 3, 6 and 12 months later from the stools of 11 long-term (>3 months) ESBL-E carriers following travel abroad. One to five different ESBL Escherichia coli strains were detected per traveller upon return, and this diminished to one after 3 months. Long-term carriage was due to the presence of the same ESBL E. coli strain, for more than 3 months, in 9 out of 11 travellers, belonging to epidemic sequence type complexes (STc 10, 14, 38, 69, 131 and 648). The mean carriage duration of strains belonging to phylogroups B2/D/F, associated with extra-intestinal virulence, was higher than that for commensal-associated A/B1/E phylogroups (3.5 vs 0.5 months, P=0.021). Genes encoding iron capture systems (fyuA, irp), toxins (senB, sat), adhesins (flu, daaF, afa/nfaE, pap, ecpA) and colicin (cjrA) were more often present in persistent strains than in transient ones. Single-nucleotide polymorphism (SNP) analysis in persistent strains showed a maximum divergence of eight SNPs over 12 months without signs of adaptation. Genomic plasticity was observed during the follow-up with the loss or gain of mobile genetic elements such as plasmids, integrons and/or transposons that may contain resistance genes at different points in the follow-up. Long-term colonization of ESBL-E following travel is primarily due to the acquisition of E. coli strains belonging to epidemic clones and harbouring 'virulence genes', allowing good adaptation to the intestinal microbiota.


Median Nerve Cavernous Hemangioma.
Hemangiomas of the median nerve are extremely rare; only 12 cases have been reported in the literature. We discuss a patient who presented with paresthesia and pain along the distribution of the left median nerve secondary to a cavernoma of the proximal part of the nerve as suspected on MRI scan. Total removal of the mass was achieved with immediate relief of the symptoms and no neurologic deficit. We conclude that despite being quite rare, the diagnosis of occult vascular lesions of peripheral nerves such as the median nerve, should be considered, especially when other common pathologies are excluded.


Socio-demographic and sexual practices associated with HIV infection in Kenyan injection and non-injection drug users.
Substance use is increasingly becoming prevalent on the African continent, fueling the spread of HIV infection. Although socio-demographic factors influence substance consumption and risk of HIV infection, the association of these factors with HIV infection is poorly understood among substance users on the African continent. The objective of the study was to assess socio-demographic and sexual practices that are associated with HIV infection among injection drug users (IDUs), non-IDUs, and non-drug users (DUs) at an urban setting of coastal Kenya. A cross-sectional descriptive study was conducted among 451 adults comprising HIV-infected and -uninfected IDUs (n = 157 and 39); non-IDUs (n = 17 and 48); and non-DUs (n = 55 and 135); respectively at coastal, Kenya. Respondent driven sampling, snowball and makeshift methods were used to enroll IDUs and non-IDUs. Convenience and purposive sampling were used to enroll non-DUs from the hospital's voluntary HIV testing unit. Participant assisted questionnaire was used in collecting socio-demographic data and sexual practices. Binary logistic regression analysis indicated that higher likelihood of HIV infection was associated with sex for police protection (OR, 9.526; 95% CI, 1.156-78.528; P = 0.036) and history of sexually transmitted infection (OR, 5.117; 95% CI, 1.924-13.485; P = 0.001) in IDUs; divorced, separated or widowed marital status (OR, 6.315; 95% CI, 1.334-29.898; P = 0.020) in non-IDUs; and unemployment (OR, 2.724; 95% CI, 1.049-7.070; P = 0.040) in non-drug users. However, never married (single) marital status (OR, 0.140; 95% CI, 0.030-0.649; P = 0.012) was associated with lower odds for HIV infection in non-drug users. Altogether, these results suggest that socio-demographic and sexual risk factors for HIV transmission differ with drug use status, suggesting targeted preventive measures for drug users.


Integration of gadolinium in nanostructure for contrast enhanced-magnetic resonance imaging.
Magnetic resonance imaging (MRI) is a routinely used imaging technique in medical diagnostics, which is further enhanced with the use of contrast agents (CAs). The most commonly used CAs are gadolinium-based contrast agents (GBCAs), in which gadolinium (Gd) is chelated with organic chelating agents (linear or cyclic). However, the use of GBCA is related to toxic side effect due to the release of free Gd3+ ions from the chelating agents. The repeated use of GBCAs has led to Gd deposition in various major organs including bone, brain, and kidneys. As a result, the use of GBCA has been linked to the development of nephrogenic systemic fibrosis (NSF). Due to the GBCA associated toxicities, some clinically approved GBCAs have been limited or revoked recently. Therefore, there is an urgent need for the development of new strategies to chelate and stabilize Gd3+ ions for contrast enhancement, safety profile, and selective imaging of a pathological site. Toward this endeavor, GBCAs have been engineered using different nanoparticulate systems to improve their stability, biocompatibility, and pharmacokinetics. Throughout this review, some of the important strategies for engineering small molecular Gd3+ chelates into a nanoconstruct is discussed. We focus on the development of GBCAs as liposomes, mesoporous silica nanoparticles (MSNs), polymeric nanocarriers, and plasmonic nanoparticles-based design strategies to improve safety and contrast enhancement for contrast enhanced-magnetic resonance imaging (Ce-MRI). We also discuss the in-vitro/in-vivo properties of strategically designed nanoscale MRI CAs, its potentials, and limitations. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Diagnostic Tools > Diagnostic Nanodevices Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.


Cost-effectiveness analysis alongside clinical trials II-An ISPOR Good Research Practices Task Force report.
Clinical trials evaluating medicines, medical devices, and procedures now commonly assess the economic value of these interventions. The growing number of prospective clinical/economic trials reflects both widespread interest in economic information for new technologies and the regulatory and reimbursement requirements of many countries that now consider evidence of economic value along with clinical efficacy. As decision makers increasingly demand evidence of economic value for health care interventions, conducting high-quality economic analyses alongside clinical studies is desirable because they broaden the scope of information available on a particular intervention, and can efficiently provide timely information with high internal and, when designed and analyzed properly, reasonable external validity. In 2005, ISPOR published the Good Research Practices for Cost-Effectiveness Analysis Alongside Clinical Trials: The ISPOR RCT-CEA Task Force report. ISPOR initiated an update of the report in 2014 to include the methodological developments over the last 9 years. This report provides updated recommendations reflecting advances in several areas related to trial design, selecting data elements, database design and management, analysis, and reporting of results. Task force members note that trials should be designed to evaluate effectiveness (rather than efficacy) when possible, should include clinical outcome measures, and should obtain health resource use and health state utilities directly from study subjects. Collection of economic data should be fully integrated into the study. An incremental analysis should be conducted with an intention-to-treat approach, complemented by relevant subgroup analyses. Uncertainty should be characterized. Articles should adhere to established standards for reporting results of cost-effectiveness analyses. Economic studies alongside trials are complementary to other evaluations (e.g., modeling studies) as information for decision makers who consider evidence of economic value along with clinical efficacy when making resource allocation decisions.


Effect of thoracic radiotherapy on mortality in limited small cell lung cancer. A meta-analysis of 13 randomized trials among 2,140 patients.
This meta-analysis was designed to evaluate the hypothesis that thoracic radiotherapy contributes to a moderate increase in overall survival in limited small-cell lung cancer. We collected individual data on all patients enrolled before December 1988 in randomized trials comparing chemotherapy alone with chemotherapy combined with thoracic radiotherapy. The study included 13 trials and 2140 patients with limited disease. A total of 433 patient with extensive disease were excluded. Overall, 1862 of 2103 patients who could be evaluated died; the median follow-up period for the surviving patients was 43 months. The relative risk of death in the combined therapy group as compared with the chemotherapy group was 0.86 (95 percent confidence interval, 0.78 to 0.94; P = 0.001), corresponding to a 14 percent reduction in the mortality rate. The benefit in terms of overall survival at three years (+/- SD) was 5.4 +/- 1.4 percent. Indirect comparison of early with late radiotherapy and of sequential with non-sequential radiotherapy did not reveal any optimal time for treatment. There was a trend toward a larger reduction in mortality among younger patients. In conclusion, thoracic radiotherapy moderately improves overall survival in patients with limited small-cell lung cancer who are treated with combination chemotherapy.


Ultrasonographic characteristics and cystoscopic correlates of bladder wall invasion by endophytic cervical cancer.
To present the ultrasonographic findings and explore cystoscopic correlates of endophytic cervical cancer invading the bladder wall. We retrospectively reviewed the imaging files in 19 cases of cervical cancer, comprising six cases of endophytic lesions invading the bladder wall (study group) and 13 cases of endo- or exophytic, clinical stage IB1 lesions without bladder wall invasion (controls). Bladder wall infiltration or invasion was confirmed by cystoscopic biopsy or surgical findings or both. All 19 patients had undergone transvaginal ultrasound examination to evaluate the cervix and lower urinary tract. The main measures included tumor volume of the primary cervical neoplasm, tumor protuberance, mobility of the cervix over the lower bladder wall, continuity of the endopelvic fascia and echogenicity and morphological texture of the bladder wall and its thickness. A tumor protuberance emerging from the cervicocorporeal junction and invading the bladder in the supratrigonal area was seen in the study group but not in the controls. Disruption of the endopelvic fascia, a thickened bladder wall, changes in the bladder mucosa and interruption of the entire bladder wall were ultrasonographic characteristics demonstrating the sequential stages of bladder wall invasion. The morphological changes in the bladder wall on ultrasound examination were categorized into four stages. Based on the morphological classification, two of the six patients in the study group belonged to stage I, one to stage II, one to stage III and two to stage IV of bladder wall invasion. In cervical cancer, transvaginal ultrasonography helps to explore sequential changes seen in bladder wall invasion, information that is not as readily available from cystoscopic examination.


In vivo measurement of lead in bone using x-ray fluorescence.
The factors affecting the accuracy and minimum detectable concentration of in vivo tibia lead measurement are discussed, and it is demonstrated that the use of a 109Cd source in a backscatter geometry and using the 88 keV coherently scattered photon for normalisation optimizes both criteria. The measurement is shown to be independent of variations in source-sample distance, thickness of overlying tissue and tibia size and shape. Applying the same technique in vitro to samples of human tibia and metatarsals, it is shown that the results are not significantly different (p approximately equal to 0.9) from atomic absorption spectrometry results from another laboratory. The results of Monte Carlo dose distribution calculations are presented and compared with measurements using thermoluminescent dosemeters: the mean absorbed dose to a 20 cm leg section is less than 0.1 mGy (10 mrad) and the maximum absorbed skin dose is 0.45 mGy (45 mrad). For this dose the minimum detectable lead concentration is 10 micrograms g-1. Finally, the technique has been applied to groups of normals and occupationally exposed workers, and the means have been shown to be significantly different, namely 10 and 31 micrograms g-1 respectively. In the normal subjects tibia lead correlated strongly with age (r = 0.63, p less than 0.001).


Stereotype accommodation concerning older people.
From a cultural learning perspective, immigrants can integrate novel stereotypes learned in host countries into pre-existing stereotypes. Research has not previously addressed this possibility in relation to stereotypes specifically about older people. This cross-sectional study examines whether cultural differences concerning stereotypes about older people, duration of stay in the host culture and cultural orientation affect stereotype accommodation amongst immigrants from 40 host countries. In two multinational, country-representative datasets-the European Social Survey (ESS) and the World Value Survey (WVS)-stereotype accommodation is measured along dimensions of warmth and competence and operationalised as absolute differences between the meta-beliefs of immigrants and the corresponding average meta-beliefs of the general population in host countries and countries of origin. Complex regressions that corrected beta-coefficients at the individual level for country effects show that more meaningful cross-cultural differences in the stereotype about the social warmth of older people predicted that immigrants' meta-beliefs were less similar to the origin culture than the host culture. This finding is a first step towards understanding the effect that moving from one culture to another has on the stereotypes about old age held by immigrants, and, potentially, how this will impact their own well-being when they become old.


Hydration Marker Diagnostic Accuracy to Identify Mild Intracellular and Extracellular Dehydration.
Identifying mild dehydration (≤2% of body mass) is important to prevent the negative effects of more severe dehydration on human health and performance. It is unknown whether a single hydration marker can identify both mild intracellular dehydration (ID) and extracellular dehydration (ED) with adequate diagnostic accuracy (≥0.7 receiver-operating characteristic-area under the curve [ROC-AUC]). Thus, in 15 young healthy men, the authors determined the diagnostic accuracy of 15 hydration markers after three randomized 48-hr trials; euhydration (water 36 ml·kg-1·day-1), ID caused by exercise and 48 hr of fluid restriction (water 2 ml·kg-1·day-1), and ED caused by a 4-hr diuretic-induced diuresis begun at 44 hr (Furosemide 0.65 mg/kg). Body mass was maintained on euhydration, and dehydration was mild on ID and ED (1.9% [0.5%] and 2.0% [0.3%] of body mass, respectively). Urine color, urine specific gravity, plasma osmolality, saliva flow rate, saliva osmolality, heart rate variability, and dry mouth identified ID (ROC-AUC; range 0.70-0.99), and postural heart rate change identified ED (ROC-AUC 0.82). Thirst 0-9 scale (ROC-AUC 0.97 and 0.78 for ID and ED) and urine osmolality (ROC-AUC 0.99 and 0.81 for ID and ED) identified both dehydration types. However, only the thirst 0-9 scale had a common dehydration threshold (≥4; sensitivity and specificity of 100%; 87% and 71%, 87% for ID and ED). In conclusion, using a common dehydration threshold ≥4, the thirst 0-9 scale identified mild intracellular and ED with adequate diagnostic accuracy. In young healthy adults', thirst 0-9 scale is a valid and practical dehydration screening tool.


Phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic head and neck cancer: an eastern cooperative oncology group trial.
We hypothesized that the addition of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, to docetaxel would enhance therapeutic efficacy in squamous cell carcinoma of the head and neck (SCCHN). Patients with recurrent or metastatic SCCHN with Eastern Cooperative Oncology Group (ECOG) performance status of 2, or patients with ECOG performance status of 0 to 2 but were previously treated with chemotherapy, were randomly assigned to receive weekly docetaxel plus either placebo (arm A) or gefitinib 250 mg/d, orally (arm B) until disease progression. At the time of progression, patients in the placebo arm could receive single-agent gefitinib. EGFR, c-MET, and KRAS mutations and polymorphisms in drug metabolizing enzymes and transporters were evaluated by pyrosequencing. Two hundred seventy patients were enrolled before the study was closed early at interim analysis (arm A, n = 136; arm B, n = 134). Median overall survival was 6.0 months in arm A versus 7.3 months in arm B (hazard ratio, 0.93; 95% CI, 0.72 to 1.21; P = .60). An unplanned subset analysis showed that gefitinib improved survival in patients younger than 65 years (median 7.6 v 5.2 months; P = .04). Also, there was a trend for improved survival in patients with c-MET wild-type (5.7 v 3.6 months; P = .09) regardless of treatment. Grade 3/4 toxicities were comparable between the two arms except that grade 3/4 diarrhea was more common with docetaxel/gefitinib. Of 18 eligible patients who received gefitinib after disease progression in arm A, one patient had a partial response. The addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN.


Development of Benzimidazole Derivatives as Novel Anti-platelet Drugs.
Benzimidazoles are privileged biomolecules which form an integral part of vitamin B12 and have been attracting numerous researchers all over the world to assess their potential therapeutic significance. The comparative in vitro antiplatelet activity of newly synthesized benzimidazole derivatives, M3BIM, C2BIM, and L2BIM in thrombin, adenosine diphosphate (ADP) and epinephrineinduced washed human platelets was investigated. Reversed-phase silica gel column chromatography, Aggregometry, Flow cytometry and Immunoblotting were used in this study. M3BIM exhibited a concentration (25-100 µM) dependent inhibitory effect on platelet aggregation induced by thrombin (0.01 U/mL) in washed human platelets and by epinephrine (10 µM) only at a maximum concentration of 500 µM in platelet-rich plasma (PRP); however, C2BIM and L2BIM had no response even at 500 µM against thrombin and 1mM against epinephrine-induced platelet aggregation. Moreover, all these three compounds were not inhibited platelet aggregation induced by ADP (20 µM). Additionally, these compounds showed no effects in thrombin-induced P-selectin expression and αIIbβ3 activation, as evidenced by flow cytometry and clot reaction assays, respectively. Besides, M3BIM (100 µM) significantly abolished thrombin-induced Akt and mitogen-activated protein kinases (MAPKs) phosphorylation; whereas 200 µM C2BIM and L2BIM were not effective on these proteins. This study affords confirmation for the inhibitory effect of M3BIM in a low dose thrombin and epinephrine-induced platelet aggregation in vitro compared to other imidazole derivatives, C2BIM and L2BIM. These outcomes may recommend that M3BIM can be appraised as a prospective benzeimidazole compound for the treatment of thrombin -induced platelet defect and its related diseases.


Hempseed Peptides Exert Hypocholesterolemic Effects with a Statin-Like Mechanism.
This study had the objective of preparing a hempseed protein hydrolysate and investigating its hypocholesterolemic properties. The hydrolysate was prepared treating a total protein extract with pepsin. Nano HPLC-ESI-MS/MS analysis permitted identifying in total 90 peptides belonging to 33 proteins. In the range 0.1-1.0 mg/mL, it inhibited the catalytic activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) in a dose-dependent manner. HepG2 cells were treated with 0.25, 0.5, and 1.0 mg/mL of the hydrolysate. Immunoblotting detection showed increments in the protein levels of regulatory element binding proteins 2 (SREBP2), low-density lipoprotein receptor (LDLR), and HMGCoAR. However, the parallel activation of the phospho-5'-adenosine monophosphate-activated protein kinase (AMPK) pathway, produced an inactivation of HMGCoAR by phosphorylation. The functional ability of HepG2 cells to uptake extracellular LDL was raised by 50.5 ± 2.7%, 221.5 ± 1.6%, and 109 ± 3.5%, respectively, versus the control at 0.25, 0.5, and 1.0 mg/mL concentrations. Finally, also a raise of the protein level of proprotein convertase subtilisin/kexintype 9 was observed. All of these data suggest that the mechanism of action has some similarity with that of statins.


Impact of whole body positron emission tomography on initial staging and therapy in patients with squamous cell carcinoma of the oral cavity.
The aim of this study is to evaluate the additional clinical information provided by whole body positron emission tomography (PET) with fluorodeoxyglucose (FDG) for initial staging of patients with squamous cell carcinoma (SCC) of the oral cavity. PET scans from the head to the pelvic floor of 34 consecutive patients (22 male, 12 female; mean age 71 years) with histologically confirmed SCC of the oral cavity were retrospectively evaluated. Clinical information including CT of the head and neck and chest X-Ray or chest CT was compared with information on nodal involvement and distant metastases or secondary tumours obtained with PET. The primary tumour was identified with PET in 33 of 34 patients (97%). In 27 Patients (81%) the clinical N-stage was confirmed with PET. In two Patients (6%) additional pathologic loco-regional lymph nodes were found. In five patients more lymph nodes were identified with CT. Distant lesions were seen with PET imaging in bone, lung, mediastinum, liver and colon. In three patients (6%) distant metastases were correctly identified. In another four patients (12%) a secondary cancer was detected. One false positive finding was described with PET. In five of 34 patients (15%) the additional findings as revealed with PET lead to a change of treatment. Whole body PET provides relevant additional information to a standard clinical staging procedure in patients with oral cavity SCC. The detection of distant metastases and secondary primary tumours can have a great impact on patient management.


Cutaneous Melanoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.


The rights of nursing home patients: possibilities and limitations of federal regulation.
Using as their point of departure the proposed nursing home standards recently published by the U.S. Department of Health and Human Services, the authors discuss the dilemma of regulating for human rights. Provisions considered for inclusion in the regulations are discussed in light of positions taken by regulators, providers and consumers. By highlighting the trade-offs involved, the authors point out the limitations of regulation in this emotion-laden area. Former Secretary Patricia Roberts Harris approved a final version of human rights provisions on her last day in office. However, in his first official act, her successor withdrew that approval.


Reduced bone stress as predicted by composite beam theory correlates with cortical bone loss following cemented total hip arthroplasty.
Clinical and experimental evidence suggest that periprosthetic bone loss following total hip arthroplasty is caused in part by stress-shielding. Changes in bone stress in the proximal femur following implantation can be estimated with use of composite beam theory. We hypothesized that the degree of stress-shielding predicted by beam theory correlates with the magnitude of bone loss following cemented total hip arthroplasty. We analyzed cross sections from the proximal femur of 13 patients who had undergone unilateral cemented total hip arthroplasty. A matching implant was inserted contralaterally, and the cross-sectional properties of the implant and bone and the bone density were determined. Bone loss was calculated on the basis of differences between contralateral (control) and ipsilateral (remodeled) sections and correlated to several beam-theory parameters calculated from the control sections: implant rigidity, bone rigidity, ratio of implant to bone rigidity, and predicted decrease in bone stress. All parameters except implant rigidity were significantly correlated with bone loss (p < 0.05). Parameters that included implant and bone properties were more strongly correlated with bone loss than were those based on bone properties alone. The predicted decrease in bone stress explained 50-60% of the variance in bone loss. The data also indicated that patients were not likely to lose substantial amounts of bone unless the reduction in bone stress exceeded a threshold value. Although limited by a small and heterogeneous sample, these results indicate that beam-theory predictions correlate with the degree of femoral resorption and should be investigated further as a means to identify patients at high risk for bone loss.


Central auditory processing. Are the emotional perceptions of those listening to classical music inherent in the composition or acquired by the listeners?
There is seemingly some inherent component in selected musical compositions that elicits specific emotional perceptions, feelings, and physical conduct. The purpose of the study was to determine if the emotional perceptions of those listening to classical music are inherent in the composition or acquired by the listeners. Fifteen kindergarten students, aged 5 years, from three different sociocultural groups, were evaluated. They were exposed to portions of five purposefully selected classical compositions and asked to describe their emotions when listening to these musical pieces. All were instrumental compositions without human voices or spoken language. In addition, they were played to an audience of an age at which they were capable of describing their perceptions and supposedly had no significant previous experience of classical music. Regardless of their sociocultural background, the children in the three groups consistently identified similar emotions (e.g. fear, happiness, sadness), feelings (e.g. love), and mental images (e.g. giants or dangerous animals walking) when listening to specific compositions. In addition, the musical compositions generated physical conducts that were reflected by the children's corporal expressions. Although the sensations were similar, the way of expressing them differed according to their background.


Photosynthetic water oxidation: binding and activation of substrate waters for O-O bond formation.
Photosynthetic water oxidation occurs at the oxygen-evolving complex (OEC) of Photosystem II (PSII). The OEC, which contains a Mn4CaO5 inorganic cluster ligated by oxides, waters and amino-acid residues, cycles through five redox intermediates known as S(i) states (i = 0-4). The electronic and structural properties of the transient S4 intermediate that forms the O-O bond are not well understood. In order to gain insight into how water is activated for O-O bond formation in the S4 intermediate, we have performed a detailed analysis of S-state dependent substrate water binding kinetics taking into consideration data from Mn coordination complexes. This analysis supports a model in which the substrate waters are both bound as terminal ligands and react via a water-nucleophile attack mechanism.


A mechanism of leading-edge protrusion in the absence of Arp2/3 complex.
Cells employ protrusive leading edges to navigate and promote their migration in diverse physiological environments. Classical models of leading-edge protrusion rely on a treadmilling dendritic actin network that undergoes continuous assembly nucleated by the Arp2/3 complex, forming ruffling lamellipodia. Recent work demonstrated, however, that, in the absence of the Arp2/3 complex, fibroblast cells adopt a leading edge with filopodia-like protrusions (FLPs) and maintain an ability to move, albeit with altered responses to different environmental signals. We show that formin-family actin nucleators are required for the extension of FLPs but are insufficient to produce a continuous leading edge in fibroblasts lacking Arp2/3 complex. Myosin II is concentrated in arc-like regions of the leading edge in between FLPs, and its activity is required for coordinated advancement of these regions with formin-generated FLPs. We propose that actomyosin contraction acting against membrane tension advances the web of arcs between FLPs. Predictions of this model are verified experimentally. The dependence of myosin II in leading-edge advancement helps explain the previously reported defect in directional movement in the Arpc3-null fibroblasts. We provide further evidence that this defect is cell autonomous during chemotaxis.


Qualitative approaches in occupational therapy research.
Development of research in occupational therapy requires a continuous critical discussion concerning methodological approaches. In this paper the authors wish to contribute to such a discussion by introducing the formal data-structure analysis approach (FDSA) as a method for understanding people's experiences. A review of selected publications from occupational therapy journals between 2003 and 2005 illustrated that qualitative articles within occupational therapy publications were mainly descriptive in nature. This finding raises questions about how to develop new knowledge that contributes to occupational therapy. In this paper the authors suggest that it is possible to apply the FDSA approach not only when describing and categorizing qualitative phenomena, but also when aiming to reach an in-depth understanding of issues related to human meaning-making; for example, how we understand engagement in occupations or living with a disability. Examples of the application of the FDSA approach are included and discussed.


Applying Multiple Data Collection Tools to Quantify Human Papillomavirus Vaccine Communication on Twitter.
Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. There are several vaccines that protect against strains of HPV most associated with cervical and other cancers. Thus, HPV vaccination has become an important component of adolescent preventive health care. As media evolves, more information about HPV vaccination is shifting to social media platforms such as Twitter. Health information consumed on social media may be especially influential for segments of society such as younger populations, as well as ethnic and racial minorities. The objectives of our study were to quantify HPV vaccine communication on Twitter, and to develop a novel methodology to improve the collection and analysis of Twitter data. We collected Twitter data using 10 keywords related to HPV vaccination from August 1, 2014 to July 31, 2015. Prospective data collection used the Twitter Search API and retrospective data collection used Twitter Firehose. Using a codebook to characterize tweet sentiment and content, we coded a subsample of tweets by hand to develop classification models to code the entire sample using machine learning procedures. We also documented the words in the 140-character tweet text most associated with each keyword. We used chi-square tests, analysis of variance, and nonparametric equality of medians to test for significant differences in tweet characteristic by sentiment. A total of 193,379 English-language tweets were collected, classified, and analyzed. Associated words varied with each keyword, with more positive and preventive words associated with "HPV vaccine" and more negative words associated with name-brand vaccines. Positive sentiment was the largest type of sentiment in the sample, with 75,393 positive tweets (38.99% of the sample), followed by negative sentiment with 48,940 tweets (25.31% of the sample). Positive and neutral tweets constituted the largest percentage of tweets mentioning prevention or protection (20,425/75,393, 27.09% and 6477/25,110, 25.79%, respectively), compared with only 11.5% of negative tweets (5647/48,940; P<.001). Nearly one-half (22,726/48,940, 46.44%) of negative tweets mentioned side effects, compared with only 17.14% (12,921/75,393) of positive tweets and 15.08% of neutral tweets (3787/25,110; P<.001). Examining social media to detect health trends, as well as to communicate important health information, is a growing area of research in public health. Understanding the content and implications of conversations that form around HPV vaccination on social media can aid health organizations and health-focused Twitter users in creating a meaningful exchange of ideas and in having a significant impact on vaccine uptake. This area of research is inherently interdisciplinary, and this study supports this movement by applying public health, health communication, and data science approaches to extend methodologies across fields.


[Morpho-functional characteristics of reflux gastritis in patients after cholecystectomy and without cholecystectomy].
The aim of this study was to evaluate some biochemical and histopathological aspects in a group of patients with a view to identifying any differences depending on whether the pathology was associated with previous cholecystectomy or idiopathic. The study involved 23 patients (8 post-cholecystectomy cases and 15 ulcer-free dyspeptic patients) with the diagnosis of duodenogastric reflux gastritis confirmed by endoscopic histopathological evaluation. The following parameters were considered: 1) pH and bile salt concentration in gastric juice; 2) histological classification of antral biopsies (Niemela's criteria); 3) dyspeptic symptoms (dyspepsia, pyrosis and epigastric pain, sense of repletion, foul-tasting mouth) graded on a scale from 0 to 4. All parameters were considered in relation to whether or not Helicobacter Pylori was found in the histological specimens. No significant differences were found between the two groups for pH and bile salt values or for Helicobacter Pylori positivity. No relationship was observed between the Helicobacter Pylori and either the severity of the histological picture, the features of the biochemical parameters or the severity of the clinical symptoms. Such findings confirm the common pathophysiological pattern of reflux gastritis regardless of any permanent biliary tract alterations and the low importance of Helicobacter Pylori infection in determining this syndrome.


Coupling of Ca(2+) microdomains to spatially and temporally distinct cellular responses by the tyrosine kinase Syk.
Communication between the cell surface and the nucleus is essential for regulated gene expression. In neurons, Ca(2+)-dependent gene transcription is sensitive to local Ca(2+) entry. In immune cells, excitation-transcription coupling is thought to involve global Ca(2+) signals. Here, we show that in mast cells, Ca(2+) microdomains from store-operated Ca(2+) release-activated Ca(2+) channels activate expression of the transcription factor c-fos. Local Ca(2+) entry is sensed by the tyrosine kinase Syk, which signals to the nucleus through the transcription factor STAT5. Ca(2+) microdomains also promote secretion of proinflammatory messengers, which, like gene expression, requires Syk. Syk therefore couples Ca(2+) microdomains to the activation of two spatially and temporally distinct cellular responses, revealing the versatility of local Ca(2+) signals in driving cell activation.


The water footprint of sweeteners and bio-ethanol.
An increasing demand for food together with a growing demand for energy crops result in an increasing demand for and competition over water. Sugar cane, sugar beet and maize are not only essential food crops, but also important feedstock for bio-ethanol. Crop growth requires water, a scarce resource. This study aims to assess the green, blue and grey water footprint (WF) of sweeteners and bio-ethanol from sugar cane, sugar beet and maize in the main producing countries. The WFs of sweeteners and bio-ethanol are mainly determined by the crop type that is used as a source and by agricultural practise and agro-climatic conditions; process water footprints are relatively small. The weighted global average WF of sugar cane is 209 m(3)/tonne; for sugar beet this is 133 m(3)/tonne and for maize 1222 m(3)/tonne. Large regional differences in WFs indicate that WFs of crops for sweeteners and bio-ethanol can be improved. It is more favourable to use maize as a feedstock for sweeteners or bio-ethanol than sugar beet or sugar cane. The WF of sugar cane contributes to water stress in the Indus and Ganges basins. In the Ukraine, the large grey WF of sugar beet contributes to water pollution. In some western European countries, blue WFs of sugar beet and maize need a large amount of available blue water for agriculture. The allocation of the limited global water resources to bio-energy on a large scale will be at the cost of water allocation to food and nature.


Effect of ritodrine on labor after premature rupture of the membranes.
The effect on labor of administering ritodrine after a premature rupture of the membranes (PROM) was studied in a double-blind trial in 30 patients. The patients were selected according to the following criteria: 28 to 36 weeks' gestation, only 1 fetus, cervix dilated 4 cm or less, and absence of pyrexia or other signs of uterine infection. Fourteen patients received ritodrine and 16 received a placebo. The 2 groups were statistically comparable. None of the patients receiving ritodrine delivered within 24 hours. The difference between the 2 groups was statistically significant with respect to the number of patients delivered within 24 hours (P less than 0.05). However, after 24 hours, there was no difference between the groups as regards the length of pregnancy. The infections registered in the mothers of infants were few and easily controlled. The incidence of idiopathic respiratory distress syndrome (IRDS) was low in the study and allows no conclusions concerning the benefit of prolonging the pregnancy for more than 24 hours after PROM.


Developing a portable natural language processing based phenotyping system.
This paper presents a portable phenotyping system that is capable of integrating both rule-based and statistical machine learning based approaches. Our system utilizes UMLS to extract clinically relevant features from the unstructured text and then facilitates portability across different institutions and data systems by incorporating OHDSI's OMOP Common Data Model (CDM) to standardize necessary data elements. Our system can also store the key components of rule-based systems (e.g., regular expression matches) in the format of OMOP CDM, thus enabling the reuse, adaptation and extension of many existing rule-based clinical NLP systems. We experimented with our system on the corpus from i2b2's Obesity Challenge as a pilot study. Our system facilitates portable phenotyping of obesity and its 15 comorbidities based on the unstructured patient discharge summaries, while achieving a performance that often ranked among the top 10 of the challenge participants. Our system of standardization enables a consistent application of numerous rule-based and machine learning based classification techniques downstream across disparate datasets which may originate across different institutions and data systems.


Regional changes of cortical mean diffusivities with aging after correction of partial volume effects.
Accurately measuring the cortical mean diffusivity (MD) derived from diffusion tensor imaging (DTI) at the comprehensive lobe, gyral and voxel level of young, elderly healthy brains and those with Alzheimer's disease (AD) may provide insights on heterogeneous cortical microstructural changes caused by aging and AD. Due to partial volume effects (PVE), the measurement of cortical MD is overestimated with contamination of cerebrospinal fluid (CSF). The bias is especially severe for aging and AD brains because of significant cortical thinning of these brains. In this study, we aimed to quantitatively characterize the unbiased regional cortical MD changes due to aging and AD and delineate the effects of cortical thinning of elderly healthy and AD groups on MD measurements. DTI and T1-weighted images of 14 young, 15 elderly healthy subjects and 17 AD patients were acquired. With the parcellated cortical gyri and lobes from T1 weighted image transformed to DTI, regional cortical MD of all subjects before and after PVE correction were measured. CSF contamination model was used to correct bias of MD caused by PVE. Compared to cortical MD of young group, significant increases of corrected MD for elderly healthy and AD groups were found only in frontal and limbic regions, respectively, while there were significant increases of uncorrected MD all over the cortex. Uncorrected MD are significantly higher in limbic and temporal gyri in AD group, compared to those in elderly healthy group but higher MD only remained in limbic gyri after PVE correction. Cortical thickness was also measured for all groups. The correlation slopes between cortical MD and thickness for elderly healthy and AD groups were significantly decreased after PVE correction compared to before correction while no significant change of correlation slope was detected for young group. It suggests that the cortical thinning in elderly healthy and AD groups is a significant contributor to the bias of uncorrected cortical MD measurement. The established comprehensive unbiased cortical MD profiles of young, elderly healthy subjects and AD patients at the lobe, gyral and voxel level may serve as clinical references for cortical microstructure.


Profiling of gene duplication patterns of sequenced teleost genomes: evidence for rapid lineage-specific genome expansion mediated by recent tandem duplications.
Gene duplication has had a major impact on genome evolution. Localized (or tandem) duplication resulting from unequal crossing over and whole genome duplication are believed to be the two dominant mechanisms contributing to vertebrate genome evolution. While much scrutiny has been directed toward discerning patterns indicative of whole-genome duplication events in teleost species, less attention has been paid to the continuous nature of gene duplications and their impact on the size, gene content, functional diversity, and overall architecture of teleost genomes. Here, using a Markov clustering algorithm directed approach we catalogue and analyze patterns of gene duplication in the four model teleost species with chromosomal coordinates: zebrafish, medaka, stickleback, and Tetraodon. Our analyses based on set size, duplication type, synonymous substitution rate (Ks), and gene ontology emphasize shared and lineage-specific patterns of genome evolution via gene duplication. Most strikingly, our analyses highlight the extraordinary duplication and retention rate of recent duplicates in zebrafish and their likely role in the structural and functional expansion of the zebrafish genome. We find that the zebrafish genome is remarkable in its large number of duplicated genes, small duplicate set size, biased Ks distribution toward minimal mutational divergence, and proportion of tandem and intra-chromosomal duplicates when compared with the other teleost model genomes. The observed gene duplication patterns have played significant roles in shaping the architecture of teleost genomes and appear to have contributed to the recent functional diversification and divergence of important physiological processes in zebrafish. We have analyzed gene duplication patterns and duplication types among the available teleost genomes and found that a large number of genes were tandemly and intrachromosomally duplicated, suggesting their origin of independent and continuous duplication. This is particularly true for the zebrafish genome. Further analysis of the duplicated gene sets indicated that a significant portion of duplicated genes in the zebrafish genome were of recent, lineage-specific duplication events. Most strikingly, a subset of duplicated genes is enriched among the recently duplicated genes involved in immune or sensory response pathways. Such findings demonstrated the significance of continuous gene duplication as well as that of whole genome duplication in the course of genome evolution.


Extension traction treatment for patients with discogenic lumbosacral radiculopathy: a randomized controlled trial.
To investigate the effects of lumbar extension traction in patients with unilateral lumbosacral radiculopathy due to L5-S1 disc herniation. A randomized controlled study with six-month follow-up. University research laboratory. Sixty-four patients with confirmed unilateral lumbosacral radiculopathy due to L5-S1 disc herniation and a lumbar lordotic angle less than 39°, randomly assigned to traction or control group. The control group (n = 32) received hot packs and interferential therapy, whereas the traction group (n = 32) received lumbar extension traction in addition to hot packs and interferential therapy. Absolute rotatory angle, back and leg pain rating scale, Oswestry Disability Index, Modified Schober test, H-reflex (latency and amplitude) and intervertebral movements were measured for all patients three times (before treatment, after 10 weeks of treatment and at six-month follow-up). There was a significant difference between the traction group and the control group adjusted to baseline values at 10 weeks post treatment with respect to: absolute rotatory angle (P < 0.001), Oswestry Disability Index (P = 0.002), back and leg pain (P = 0.009, P = 0.005), Modified Schober test (P = 0.002), latency and amplitude of H-reflex (P = 0.01, P < 0.001), intervertebral movements (P < 0.05). At six-month follow-up there were statistically significant differences between the study and control groups for all the previous variables (P < 0.05). The traction group receiving lumbar extension traction in addition to hot packs and interferential therapy had better effects than the control group with regard to pain, disability, H-reflex parameters and segmental intervertebral movements.


Characterisation of advanced glycation endproducts in saliva from patients with diabetes mellitus.
Patients with diabetes mellitus are prone to develop increased advanced glycation endproducts causing local complications and increased overall morbidity and mortality. Nuclear magnetic resonance spectra were determined in saliva of 52 consecutive patients with diabetes mellitus and 47 age-matched healthy control subjects. Resonance spectra showed specific peaks at 2.3, 7.3, and 8.4 ppm in saliva from patients with diabetes mellitus. These peaks could be generated by incubation of saliva from healthy control subjects with hypochloric acid in vitro, indicating the presence of advanced glycation endproducts. The presence of advanced glycation endproducts in patients with diabetes mellitus was associated with approximal plaque index, indicating increased periodontal damage. The study indicates that increased advanced glycation endproducts are involved in the pathogenesis of diabetic complications.


Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway.
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a complex condition. Causal factors are not established, although underlying psychological or immunological susceptibility has been proposed. We studied primary care diagnoses for children with CFS/ME, with children with another hospital diagnosis (type 1 diabetes mellitus [T1DM]) and the general child population as comparison groups. All Norwegian children born 1992-2012 constituted the study sample. Children with CFS/ME (n = 1670) or T1DM (n = 4937) were identified in the Norwegian Patient Register (NPR) (2008-2014). Children without either diagnosis constituted the general child population comparison group (n = 1337508). We obtained information on primary care diagnoses from the Norwegian Directorate of Health. For each primary care diagnosis, the proportion and 99 % confidence interval (CI) within the three groups was calculated, adjusted for sex and age by direct standardization. Children with CFS/ME were more often registered with a primary care diagnosis of weakness/general tiredness (89.9 % [99 % CI 88.0 to 91.8 %]) than children in either comparison group (T1DM: 14.5 % [99 % CI: 13.1 to 16.0 %], general child population: 11.1 % [99 % CI: 11.0 to 11.2 %]). Also, depressive disorder and anxiety disorder were more common in the CFS/ME group, as were migraine, muscle pain, and infections. In the 2 year period prior to the diagnoses, infectious mononucleosis was registered for 11.1 % (99 % CI 9.1 to 13.1 %) of children with CFS/ME and for 0.5 % (99 % CI (0.2 to 0.8 %) of children with T1DM. Of children with CFS/ME, 74.6 % (1292/1670) were registered with a prior primary care diagnosis of weakness / general tiredness. The time span from the first primary care diagnosis of weakness / general tiredness to the specialist health care diagnosis of CFS/ME was 1 year or longer for 47.8 %. This large nationwide registry linkage study confirms that the clinical picture in CFS/ME is complex. Children with CFS/ME were frequently diagnosed with infections, supporting the hypothesis that infections may be involved in the causal pathway. The long time span often observed from the first diagnosis of weakness / general tiredness to the diagnosis of CFS/ME might indicate that the treatment of these patients is sometimes not optimal.


Genome-wide search for miRNA-target interactions in Arabidopsis thaliana with an integrated approach.
MiRNA are about 22nt long small noncoding RNAs that post transcriptionally regulate gene expression in animals, plants and protozoa. Confident identification of MiRNA-Target Interactions (MTI) is vital to understand their function. Currently, several integrated computational programs and databases are available for animal miRNAs, the mechanisms of which are significantly different from plant miRNAs. Here we present an integrated MTI prediction and analysis toolkit (imiRTP) for Arabidopsis thaliana. It features two important functions: (i) combination of several effective plant miRNA target prediction methods provides a sufficiently large MTI candidate set, and (ii) different filters allow for an efficient selection of potential targets. The modularity of imiRTP enables the prediction of high quality targets on genome-wide scale. Moreover, predicted MTIs can be presented in various ways, which allows for browsing through the putative target sites as well as conducting simple and advanced analyses. Results show that imiRTP could always find high quality candidates compared with single method by choosing appropriate filter and parameter. And we also reveal that a portion of plant miRNA could bind target genes out of coding region. Based on our results, imiRTP could facilitate the further study of Arabidopsis miRNAs in real use. All materials of imiRTP are freely available under a GNU license at (http://admis.fudan.edu.cn/projects/imiRTP.htm).


Distinct Frontoparietal Networks Underlying Attentional Effort and Cognitive Control.
We investigated the brain activity patterns associated with stabilizing performance during challenges to attention. Our findings revealed distinct patterns of frontoparietal activity and functional connectivity associated with increased attentional effort versus preserved performance during challenged attention. Participants performed a visual signal detection task with and without presentation of a perceptual-attention challenge (changing background). The challenge condition increased activation in frontoparietal regions including right mid-dorsal/dorsolateral PFC (RPFC), approximating Brodmann's area 9, and superior parietal cortex. We found that greater behavioral impact of the challenge condition was correlated with greater RPFC activation, suggesting that increased engagement of cognitive control regions is not always sufficient to maintain high levels of performance. Functional connectivity between RPFC and ACC increased during the challenge condition and was also associated with performance declines, suggesting that the level of synchronized engagement of these regions reflects individual differences in attentional effort. Pretask, resting-state RPFC-ACC connectivity did not predict subsequent performance, suggesting that RPFC-ACC connectivity increased dynamically during task performance in response to performance decrement and error feedback. In contrast, functional connectivity between RPFC and superior parietal cortex not only during the task but also during pretask rest was associated with preserved performance in the challenge condition. Together, these data suggest that resting frontoparietal connectivity predicts performance on attention tasks that rely on those same cognitive control networks and that, under challenging conditions, other control regions dynamically couple with this network to initiate the engagement of cognitive control.


Tertiary treatment of Berlin WWTP effluents with ferrate (Fe(VI)).
New and higher standards in the EU water framework directive necessitate advanced treatment of secondary effluents for reduction of trace organic compounds (TrOCs) and nutrients before the discharge into receiving surface waters. Due to its dual function as oxidant and coagulant, ferrate is considered as a promising alternative for tertiary treatment. The oxidation of selected TrOCs and simultaneous flocculation of phosphates by ferrate was tested in batch experiments with secondary effluent from Berlin Ruhleben. The concentrations of carbamazepine (CBZ) and diclofenac were reduced by >90% with ferrate dosages of 6 mg/L as Fe. CBZ was transformed to 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one, which is known as the major product from the reaction of CBZ with ozone. In contrast to ozonation, no further transformation of this product was observed. The concentration of ibuprofen was not reduced by ferrate treatment. For efficient removal of 60-100 μg/L phosphate-P to values <20 μg/L, ferrate dosages of 3-4 mg/L as Fe were sufficient.


pH-sensitive hydrogel based on a novel photocross-linkable copolymer.
A pH sensitive hydrogel has been prepared by a UV irradiation technique. Starting polymer was the PHM (poly hydroxyethylaspartamide methacrylated) obtained from polyaspartamide (PHEA) partially derivatized with methacrylic anhydride (MA). This new copolymer has been further derivatized with succinic anhydride (SA) to obtain PHM-SA that has been cross-linked by UV irradiation to form a pH sensitive hydrogel. The network, recovered after washing as a powder, has been been characterized by FT-IR spectrophotometry and particle size distribution analysis. Moreover, to have information about water affinity of the prepared sample, swelling measurements have been carried out in aqueous media mimicking biological fluids. The possibility to employ the prepared hydrogel as a pH-sensitive drug delivery system (DDS) has been investigated. In particular, ibuprofen ((S)(+)4-isobutyl-alpha-methylphenyl-acetic acid), chosen as a model drug, has been entrapped into the PHM-SA hydrogel, and in vitro release studies have showed that its release rate depends on different swelling of the network as a function of the environmental pH.


Retrograde transport of transmissible mink encephalopathy within descending motor tracts.
The spread of the abnormal conformation of the prion protein, PrP(Sc), within the spinal cord is central to the pathogenesis of transmissible prion diseases, but the mechanism of transport has not been determined. For this report, the route of transport of the HY strain of transmissible mink encephalopathy (TME), a prion disease of mink, in the central nervous system following unilateral inoculation into the sciatic nerves of Syrian hamsters was investigated. PrP(Sc) was detected at 3 weeks postinfection in the lumbar spinal cord and ascended to the brain at a rate of approximately 3.3 mm per day. At 6 weeks postinfection, PrP(Sc) was detected in the lateral vestibular nucleus and the interposed nucleus of the cerebellum ipsilateral to the site of sciatic nerve inoculation and in the red nucleus contralateral to HY TME inoculation. At 9 weeks postinfection, PrP(Sc) was detected in the contralateral hind limb motor cortex and reticular thalamic nucleus. These patterns of PrP(Sc) brain deposition at various times postinfection were consistent with that of HY TME spread from the sciatic nerve to the lumbar spinal cord followed by transsynaptic spread and retrograde transport to the brain and brain stem along descending spinal tracts (i.e., lateral vestibulospinal, rubrospinal, and corticospinal). The absence of PrP(Sc) from the spleen suggested that the lymphoreticular system does not play a role in neuroinvasion following sciatic nerve infection. The rapid disease onset following sciatic nerve infection demonstrated that HY TME can spread by retrograde transport along specific descending motor pathways of the spinal cord and, as a result, can initially target brain regions that control vestibular and motor functions. The early clinical symptoms of HY TME infection such as head tremor and ataxia were consistent with neuronal damage to these brain areas.


Experimental comparison of six population-based algorithms for continuous black box optimization.
Six population-based methods for real-valued black box optimization are thoroughly compared in this article. One of them, Nelder-Mead simplex search, is rather old, but still a popular technique of direct search. The remaining five (POEMS, G3PCX, Cauchy EDA, BIPOP-CMA-ES, and CMA-ES) are more recent and came from the evolutionary computation community. The recently proposed comparing continuous optimizers (COCO) methodology was adopted as the basis for the comparison. The results show that BIPOP-CMA-ES reaches the highest success rates and is often also quite fast. The results of the remaining algorithms are mixed, but Cauchy EDA and POEMS are usually slow.


Measurement of the distribution of ventilation-perfusion ratios in the human lung with proton MRI: comparison with the multiple inert-gas elimination technique.
We have developed a novel functional proton magnetic resonance imaging (MRI) technique to measure regional ventilation-perfusion (V̇A/Q̇) ratio in the lung. We conducted a comparison study of this technique in healthy subjects (n = 7, age = 42 ± 16 yr, Forced expiratory volume in 1 s = 94% predicted), by comparing data measured using MRI to that obtained from the multiple inert gas elimination technique (MIGET). Regional ventilation measured in a sagittal lung slice using Specific Ventilation Imaging was combined with proton density measured using a fast gradient-echo sequence to calculate regional alveolar ventilation, registered with perfusion images acquired using arterial spin labeling, and divided on a voxel-by-voxel basis to obtain regional V̇A/Q̇ ratio. LogSDV̇ and LogSDQ̇, measures of heterogeneity derived from the standard deviation (log scale) of the ventilation and perfusion vs. V̇A/Q̇ ratio histograms respectively, were calculated. On a separate day, subjects underwent study with MIGET and LogSDV̇ and LogSDQ̇ were calculated from MIGET data using the 50-compartment model. MIGET LogSDV̇ and LogSDQ̇ were normal in all subjects. LogSDQ̇ was highly correlated between MRI and MIGET (R = 0.89, P = 0.007); the intercept was not significantly different from zero (-0.062, P = 0.65) and the slope did not significantly differ from identity (1.29, P = 0.34). MIGET and MRI measures of LogSDV̇ were well correlated (R = 0.83, P = 0.02); the intercept differed from zero (0.20, P = 0.04) and the slope deviated from the line of identity (0.52, P = 0.01). We conclude that in normal subjects, there is a reasonable agreement between MIGET measures of heterogeneity and those from proton MRI measured in a single slice of lung.NEW & NOTEWORTHY We report a comparison of a new proton MRI technique to measure regional V̇A/Q̇ ratio against the multiple inert gas elimination technique (MIGET). The study reports good relationships between measures of heterogeneity derived from MIGET and those derived from MRI. Although currently limited to a single slice acquisition, these data suggest that single sagittal slice measures of V̇A/Q̇ ratio provide an adequate means to assess heterogeneity in the normal lung.


Survival after surgery and stereotactic radiosurgery for patients with multiple intracranial metastases: results of a single-center retrospective study.
Patients with systemic cancer and a single brain metastasis who undergo treatment with resection plus radiotherapy live longer and have a better quality of life than those treated with radiotherapy alone. Historically, whole-brain radiotherapy (WBRT) has been the mainstay of radiation therapy; however, it is associated with significant delayed neurocognitive sequelae. In this study, the authors looked at survival in patients with single and multiple intracranial metastases who had undergone surgery and adjuvant stereotactic radiosurgery (SRS) to the tumor bed and synchronous lesions. The authors retrospectively reviewed the records from an 8-year period at a single institution for consecutive patients with brain metastases treated via complete resection of dominant lesions and adjuvant radiosurgery. The cohort was analyzed for time to local progression, synchronous lesion progression, new intracranial lesion development, systemic progression, and overall survival. The Kaplan-Meier method (stratified by age, sex, tumor histology, and number of intracranial lesions prior to surgery) was used to calculate both progression-free and overall survival. A Cox proportional-hazards regression model was also fitted with the number of intracranial lesions as the predictor and survival as the outcome controlling for disease severity, age, sex, and primary histology. The median overall follow-up among the 150-person cohort eligible for analysis was 17 months. Patients had an average age of 46.2 years (range 16-82 years), and 62.7% were female. The mean (± standard deviation) number of intracranial lesions per patient was 2.5 ± 2.3. The mean time between surgery and stereotactic radiosurgery (SRS) was 3.2 ± 4.1 weeks. Primary cancers included lung cancer (43.3%), breast cancer (21.3%), melanoma (10.0%), renal cell carcinoma (6.7%), and colon cancer (6.7%). The average number of isocenters per treated lesion was 7.6 ± 6.6, and the average treatment dose was 17.8 ± 2.8 Gy. One-year survival for patients in this cohort was 52%, and the 1-year local control rate was 77%. The median (±standard error) overall survival was 13.2 ± 1.9 months. There was no difference in survival between patients with a single lesion and those with multiple lesions (p = 0.319) after controlling for age, sex, and histology of primary tumor. Patients with primary breast histology had the greatest overall median survival (22.9 ± 6.2 months); patients with colorectal cancer had the shortest overall median survival (5.3 ± 1.8 months). The most common cause of death in this series was systemic progression (79%). These results confirm that 1-year survival for patients with multiple intracranial metastases treated with resection followed by SRS to both the tumor bed and synchronous lesions is similar to established outcomes for patients with a single intracranial metastasis.


Multicontrast nonlinear optical microscopy with a compact and rapid pulse shaper.
Homodyne detection can dramatically enhance measurement sensitivity for weak signals. In nonlinear optical microscopy it can make accessible a range of novel, intrinsic, contrast like nonlinear absorption and nonlinear phase contrast. Here a compact and rapid pulse shaper is developed, implemented, and demonstrated for homodyne detection in nonlinear microscopy with high-repetition rate mode-locked femtosecond lasers. With this method we generate two-photon absorption (TPA) and self-phase modulation images of gold nanostars in biological samples. Simultaneous imaging of two-photon luminescence and TPA also enables us to produce two-photon quantum yield images.


Regional fisheries management: COVID-19 calendars and decision making.
In 2020 the management of transboundary fisheries was severely impacted by the global COVID-19 pandemic. Most annual meetings of regional fisheries and marine management organizations were held virtually, postponed, or cancelled. Even though most organizations managed to meet virtually in 2020, many important decisions were postponed to 2021. Consequently, regional secretariats and delegations face a difficult calendar with substantial agendas and complex decision-making challenges. This commentary provides a brief overview of the virtual meeting processes that have been implemented by regional organisations in response to COVID-19 and provides a calendar of their plans for 2021.


A comparative study of reliability of self report of tobacco use among patients with bipolar and somatoform disorders.
To compare the use and reliability of self-reported tobacco use (both smoked and smokeless) among patients with bipolar disorder and somatoform disorders. The study was conducted at psychiatry out-patient department of a tertiary care hospital. A total of 50 consecutive patients were recruited. The subjects were asked about the use of tobacco products (smoked as well as smokeless) over the past one week. Those reporting affirmatively in response to the question were assessed using Fagerstrom Test for Nicotine Dependence (FTND) scales. Quantitative urinary cotinine levels were assessed using Enzyme-linked immunosorbent assay (ELISA). Calculation of Cohen's kappa using cross tabulation revealed discordance between the self-reported use of smoked as well as smokeless tobacco products in both the groups. Analysis using the lower cut off of 50 ng/ ml also revealed discordance between the self-reported tobacco use (smoked as well as smokeless) for both the groups. The reliability of self-report is questionable among both these groups for smoking as well as smokeless tobacco products.


Association between migraine and asthma: matched case-control study.
Earlier studies have suggested a link between asthma and severe headache, and also between migraine and wheezing illness. Recent analysis have also shown an increase of asthma among cases with a prior history of migraine but without a history of hay fever, allergic rhinitis or eczema. To examine whether there is an association between migraine and asthma in the United Kingdom. Matched case-control study using the General Practice Research Database (GPRD). Practices in the United Kingdom providing data on 5,110,619 patients to the GPRD. The subjects were the patients with one or more diagnoses of migraine plus treatment for migraine. Each case was matched by general practice, sex, and age, with one control who had never been given a diagnosis of migraine. Case and control groups were compared for prevalence of asthma, chronic obstructive pulmonary disease, respiratory symptoms treated with inhalers or hay fever. Investigations were carried out to determine whether the association between migraine and asthma was stronger among patients with hayfever or those without hayfever, and whether patients with migraine had an increased prescription of other (non-migraine and non-asthma) medications. Among 64 678 case-control pairs, the relative risk of asthma in patients with migraine was 1.59 (95% CI = 1.54 to 1.65) among definite cases, and 0.75 (95% CI = 0.67 to 0.83) among those whose selection as case included beta-blocker prophylaxis. Among definite migraine cases, relative risks of chronic obstructive pulmonary disease, respiratory symptoms, eczema, and hay fever (pollinosis), were all raised (at 1.22, 1.85, 1.55, and 1.67, respectively). The association between migraine and asthma was stronger in patients without a diagnosis of hay fever, than in those with hayfever (relative risk = 1.32 and 1.19, respectively). The relative risk of prescription for a range of non-migraine, non-asthma medications was raised, the exception being anti-diabetic medication. This large case-control study provides evidence for an association between migraine and asthma. Frequent attendance at a general practice surgery may confound this association. However, if the association is real, its elucidation may help the understanding of disease mechanisms shared by migraine and asthma.


Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box interface and the molecular basis for SOCS-dependent EGFR degradation.
Tyrosine kinase signaling is tightly controlled by negative feedback inhibitors including suppressors of cytokine signaling (SOCS). SOCS assemble as SH2 domain substrate recognition modules in ElonginB/C-cullin ubiquitin ligases. In accordance, SOCS4 reduces STAT3 signaling from EGFR through increased receptor degradation. Variable C-termini in SOCS4-SOCS7 exclude these family members from a SOCS2-type domain arrangement in which a strictly conserved C terminus determines domain packing. The structure of the SOCS4-ElonginC-ElonginB complex reveals a distinct SOCS structural class. The N-terminal ESS helix functionally replaces the CIS/SOCS1-SOCS3 family C terminus in a distinct SH2-SOCS box interface that facilitates further interdomain packing between the extended N- and C-terminal regions characteristic for this subfamily. Using peptide arrays and calorimetry the STAT3 site in EGFR (pY(1092)) was identified as a high affinity SOCS4 substrate (K(D) = 0.5 microM) revealing a mechanism for EGFR degradation. SOCS4 also bound JAK2 and KIT with low micromolar affinity, whereas SOCS2 was specific for GH-receptor.


Similarity-Based Fusion of MEG and fMRI Reveals Spatio-Temporal Dynamics in Human Cortex During Visual Object Recognition.
Every human cognitive function, such as visual object recognition, is realized in a complex spatio-temporal activity pattern in the brain. Current brain imaging techniques in isolation cannot resolve the brain's spatio-temporal dynamics, because they provide either high spatial or temporal resolution but not both. To overcome this limitation, we developed an integration approach that uses representational similarities to combine measurements of magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) to yield a spatially and temporally integrated characterization of neuronal activation. Applying this approach to 2 independent MEG-fMRI data sets, we observed that neural activity first emerged in the occipital pole at 50-80 ms, before spreading rapidly and progressively in the anterior direction along the ventral and dorsal visual streams. Further region-of-interest analyses established that dorsal and ventral regions showed MEG-fMRI correspondence in representations later than early visual cortex. Together, these results provide a novel and comprehensive, spatio-temporally resolved view of the rapid neural dynamics during the first few hundred milliseconds of object vision. They further demonstrate the feasibility of spatially unbiased representational similarity-based fusion of MEG and fMRI, promising new insights into how the brain computes complex cognitive functions.


Fetal tachycardia: intrauterine and postnatal course.
Eighteen consecutive cases of fetal tachycardia referred to the department of Pediatric Cardiology, Uppsala University, were studied retrospectively. All cases were detected at a routine visit at an antenatal clinic. None of the cases had a structural heart disease. Fetal supraventricular tachycardia was found in 8 cases and atrial flutter in 10 cases. In 7 cases, hydrops and heart failure were diagnosed. Antenatal treatment with digoxin, alone or in combination with other antiarrhythmic drugs, was needed in 15 cases. In 10 cases an obvious effect of the therapy was observed. No intrauterine deaths occurred. One infant died postnatally. At birth, 4 infants were in need of neonatal intensive care when delivered. Antiarrhythmic treatment was started in 13 cases postnatally. Late relapse of tachycardia was reported in 3 children. In 1 of these cases the prenatal tachycardia had resolved spontaneously and the infant was not treated antenatally nor during the neonatal period. Although fetal tachycardia is a serious condition, antenatal treatment in combination with careful monitoring and induction of delivery in cases with deteriorating fetal condition result in a satisfactory outcome for the majority of infants. However, there is a risk of late recurrence.


Halwaxiids and the early evolution of the lophotrochozoans.
Halkieriids and wiwaxiids are cosmopolitan sclerite-bearing metazoans from the Lower and Middle Cambrian. Although they have similar scleritomes, their phylogenetic position is contested. A new scleritomous fossil from the Burgess Shale has the prominent anterior shell of the halkieriids but also bears wiwaxiid-like sclerites. This new fossil defines the monophyletic halwaxiids and indicates that they have a key place in early lophotrochozoan history.


Correlations between COVID-19 and burden of dementia: An ecological study and review of literature.
Current evidence on the association between COVID-19 and dementia is sparse. This study aims to investigate the associations between COVID-19 caseload and the burden of dementia. We gathered data regarding burden of dementia (disability-adjusted life years [DALYs] per 100,000), life expectancy, and healthy life expectancy (HALE) from the Global Burden of Disease (GBD) 2017 study. We obtained COVID-19 data from Our World in Data database. We analyzed the association of COVID-19 cases and deaths with the burden of dementia using Spearman's rank correlation coefficient. Globally, we found significant positive (p < .001) correlations between life expectancy (r = 0.60), HALE (r = 0.58), and dementia DALYs (r = 0.46) with COVID-19 caseloads. Likewise, we found similar correlations between life expectancy (r = 0.60), HALE (r = 0.58) and dementia DALYs (r = 0.54) with COVID-19 mortality. Health policymakers should clarify a targeted model of disease surveillance in order to reduce the dual burden of dementia and COVID-19.


Chronic fatigue syndrome.
The chronic fatigue syndrome is an illness of unknown etiology characterized by severe fatigue, myalgias, lymphadenopathy, arthralgias, chills, fevers, and postexertional malaise. Recognizing chronic fatigue syndrome is primarily a method of exclusion with no definitive diagnostic test or physical findings. As research continues to delve into the many possible etiologic agents for chronic fatigue syndrome-infectious, immunologic, neurologic, or psychiatric alone or in combination- the answer remains elusive. What is known is that chronic fatigue syndrome is a heterogeneous disorder very possibly involving an interaction of biological systems. Therefore, chronic fatigue syndrome may describe a large subset of patients, each exhibiting unique symptoms and serologic profiles dependent on the nature of the onset of illness and the genetic profile of individual patients.


A glycosaminoglycan mimetic peptide nanofiber gel as an osteoinductive scaffold.
Biomineralization of the extracellular matrix (ECM) plays a crucial role in bone formation. Functional and structural biomimetic native bone ECM components can therefore be used to change the fate of stem cells and induce bone regeneration and mineralization. Glycosaminoglycan (GAG) mimetic peptide nanofibers can interact with several growth factors. These nanostructures are capable of enhancing the osteogenic activity and mineral deposition of osteoblastic cells, which is indicative of their potential application in bone tissue regeneration. In this study, we investigated the potential of GAG-mimetic peptide nanofibers to promote the osteogenic differentiation of rat mesenchymal stem cells (rMSCs) in vitro and enhance the bone regeneration and biomineralization process in vivo in a rabbit tibial bone defect model. Alkaline phosphatase (ALP) activity and Alizarin red staining results suggested that osteogenic differentiation is enhanced when rMSCs are cultured on GAG-mimetic peptide nanofibers. Moreover, osteogenic marker genes were shown to be upregulated in the presence of the peptide nanofiber system. Histological and micro-computed tomography (Micro-CT) observations of regenerated bone defects in rabbit tibia bone also suggested that the injection of a GAG-mimetic nanofiber gel supports cortical bone deposition by enhancing the secretion of an inorganic mineral matrix. The volume of the repaired cortical bone was higher in GAG-PA gel injected animals. The overall results indicate that GAG-mimetic peptide nanofibers can be utilized effectively as a new bioactive platform for bone regeneration.


Internet addiction and sleep quality among Vietnamese youths.
Internet addiction has been a major behavioral disorder over the past decade. Prior meta-analytic review has demonstrated the association between Internet addiction and psychiatric disorders, as well as sleep related disorders. There remains a paucity of literature about Internet addiction and sleep related disorders in low and middle income countries like Vietnam. It is the aim of this exploratory study to determine the association. An online cross-sectional study was conducted between August through to October 2015. Respondent drive sampling technique was utilized in the recruitment of participants. The short form version of the Young's Internet addiction test was administered and sleep related disorders was ascertained by means of a self-report questionnaire. Chi-squared, t-test and ANOVA were used to determine whether there were any significant differences amongst the variables considered. Multivariate logistic regressions were also used in the analysis, in order to identify factors associated with Internet addiction. 21.2% Of the participants were diagnosed with Internet addiction. 26.7% of those with Internet addiction also reported that they have had sleep related difficulties. 77.2% of these participants were receptive towards seeking medical treatment. Our current study also highlighted that being single and those who were using tobacco products were not at heightened risk of developing associated sleep related issues. Our current study is largely a cross-sectional exploratory study that has shown that there is a significant prevalence of both Internet addiction and sleep related disorders amongst Vietnamese youth.


HMGA1 and HMGA2 rearrangements in mass-forming endometriosis.
Endometriosis is a common gynecologic disorder characterized by ectopic endometrium associated with pelvic pain and infertility. The pathogenesis of endometriosis is unclear, and several genetic, endocrine, immune, and environmental agents have been studied as putative causative factors. However, consistent somatic genetic alterations have not been identified. Rarely, endometriosis presents as a mass lesion with an infiltrative pattern reminiscent of malignancy. We describe cytogenetic and molecular cytogenetic findings of mass-forming endometriosis. The index case of pulmonary endometriosis underwent conventional and molecular cytogenetics analysis. In addition, 16 cases of mass-forming endometriosis, 11 cases of usual endometriosis, and six endometriomas were investigated by fluorescence in situ hybridization (FISH) for HMGA1 and HMGA2 loci, performed on paraffin-embedded thin tissue sections with custom-designed probes. The index patient had an endometriotic lung nodule, with a 46,XX, t(5;6)(q13;p21) karyotype and HMGA1 rearrangement by FISH. A second patient had decidualized endometriosis forming a large abdominal mass and HMGA1 rearrangement by FISH. Of the 15 other cases of mass-forming endometriosis, one had HMGA1 rearrangement and two had HMGA2 rearrangement. The rearrangements were found in the stromal component exclusively. None of the usual endometriosis cases or endometriomas had HMGA1 or HMGA2 rearrangements. In conclusion, mass-forming endometriosis is an uncommon subset of endometriosis that harbors HMGA1 or HMGA2 rearrangements in up to 29% of cases. The present findings support the concept that endometriosis is clonal and that rearrangement of HMGA genes likely contributes to its pathogenesis.


The enhanced representation of surface texture consequent on the loss of sight.
The unitisation effect in probed feature-recall was exploited to reveal changes in the representation of objects consequent on the loss of sight. Blind and sighted adults were given verbal descriptions of simple objects and later recalled the colour and surface texture of each object. While the blind and sighted were equally capable of recalling an object's colour, the blind were more capable than the sighted at recalling its surface texture. The superior recall of surface texture by the blind emerged very gradually as an increasing percentage of their lifetime was spent without sight. It is concluded that features salient for the haptic sense are increasingly likely to be incorporated in the blind person's representation of objects.