Prevalence of HIV and malaria: a cross-sectional study on Bioko Island, Equatorial Guinea.
Malaria and HIV are two of the most severe public health problems in Africa. However, epidemiological data on Bioko Island is scarce. To investigate the prevalence of malaria and HIV infections and assess association of malaria and HIV infections and possible confounding factors, we performed a cross-sectional survey of people of malaria-endemic Bioko Island, Equatorial Guinea. A cross-sectional study of 1 526 subjects was carried out to determine the prevalence of malaria and HIV infection in Malabo region hospital on Bioko Island. Questionnaires were administered and venous blood samples were drawn for malaria parasites and HIV detection. The prevalence of participants infected with malaria and HIV in this area were 13.8% and 6.6% respectively. The average prevalence of co-infection for malaria and HIV was 0.92%. HIV-infection was significantly associated with the age and gender. Malaria infections were significantly associated with the age. This study showed that the prevalence of HIV and malaria on Bioko Island was higher than expected, although the co-infection prevalence of malaria and HIV was low. The results also indicated that malaria and HIV infections lead to more public health risk to youngsters and women.


The nucleotide sequences recognized by endonucleases AvaI and AvaII from Anabaena variabilis.
Determination of the 5'-terminal sequences flanking all the individual cleavage sites for endonuclease AvaI in bacteriophage-lambda DNA has shown that this enzyme recognizes the hexanucleotide sequences: (Formula: see text), This sequence is cut as shown by the arrows to give single-stranded 5'-tetranucleotide protrusions (cohesive ends). Endonucleases SmaI, XhoI and XmaI recognize different symmetrical subsets of this sequence and provide independent evidence for the occurrence of these subsets at particular endonuclease-AvaI cleavage sites in the bacteriophage-lambda genome. Further evidence for this structure came from the demonstration that DNA fragments generated by endonuclease AvaI can be ligated to form a discrete set of larger molecules and from nearest-neighbor analysis which showed that cytosine residues occurred at the 3'-side of cleavage points. The observation that endonuclease AvaII recognized a subset of the sites recognized by AsuI [Hughes, Bruce & Murray (1979) Biochem. J. 185, 59-63[ led to the deduction that AvaII recognize the pentanucleotide sequence: (Formula: see text), and breaks internucleotide bonds at the positions indicated by the arrows.


Transformer Based Cross-Subject Mental Workload Classification Using FNIRS for Real-World Application.
Mental state monitoring is a hot topic especially in neurorehabilitation, skill training, etc, for which the functional near-infrared spectroscopy (fNIRS) has been suggested to be used, and fewer detection channels and cross-subject performance are usually required for real-world application. To this goal, we propose a transformer-based method for cross-subject mental workload classification using fewer channels of fNIRS. Firstly, the input fNIRS signals in a window are divided into patches in the temporal order and transformed into embeddings, to which a classification token and learnable position embeddings are added. Then, a transformer encoder is used to learn the long-range dependencies among the embeddings, of which the output classification token is sent to a multilayer perceptron (MLP) head. Mental workload classification results can be represented by the outputs of the MLP head. Finally, comparison experiments were conducted on the open-access fNIRS2MW dataset. The results show that, the proposed method can outperform previous methods in cross-subject classification accuracy, and relatively efficient computation can be obtained.


Divergent motifs but overlapping binding repertoires of six HLA-DQ molecules frequently expressed in the worldwide human population.
Knowledge of the binding repertoires and specificities of HLA-DQ molecules is somewhat limited and contradictory, partly because of the scarcity of reports addressing some of the most common molecules and possibly because of the diversity of the techniques used. In this paper, we report the development of high-throughput binding assays for the six most common DQ molecules in the general worldwide population. Using comprehensive panels of single substitution analogs of specific ligands, we derived detailed binding motifs for DQA1*0501/DQB1*0301, DQA1*0401/DQB1*0402, and DQA1*0101/DQB1*0501 and more detailed motifs for DQA1*0501/DQB1*0201, DQA1*0301/DQB1*0302, and DQA1*0102/DQB1*0602, previously characterized on the basis of sets of eluted ligands and/or limited sets of substituted peptides. In contrast to what has previously been observed for DR and DP molecules, DQ motifs were generally less clearly defined in terms of chemical specificity and, strikingly, had little overlap with each other. However, testing a panel of peptides spanning a set of Phleum pratense Ags, and panels of known DQ epitopes, revealed a surprisingly significant and substantial overlap in the repertoire of peptides bound by these DQ molecules. Although the mechanism underlying these apparently contradictory findings is not clear, it likely reflects the peculiar mode of interaction between DQ (and not DR or DP) molecules and their peptide ligands. Because the DQ molecules studied are found in >85% of the general human population, these findings have important implications for epitope identification studies and monitoring of DQ-restricted immune responses.


Clues to the presence of pathogenic fungi in certain environments.
The presence of various pathogenic fungi in rather unsuspected hosts and environments has always attracted the attention of the scientific community. Reports on the putative role of animals in fungal infections of humans bear important consequences on public health as well as on the understanding of fungal ecology. Fungi are ubiquitous in nature and their great capacity for adaptation allows them to survive and indeed, to thrive, in plants, trees and other natural substrata. Nonetheless, we are just beginning to learn the significance that these diverse fungal habitats have on the increasing number of immunosuppressed individuals. The accidental or permanent presence of fungi in animals, plants, soils and watercourses should not be taken too lightly because they constitute the source where potential pathogens will be contracted. If those fungal habitats that carry the largest risks of exposure could be defined, if seasonal variations in the production of infectious propagules could be determined, and if their mode of transmission were to be assessed, it would be possible to develop protective measures in order to avoid human infection. Additionally, unsuspected avenues for the exploration of fungal survival strategies would be opened, thus enhancing our capacity to react properly to their advancing limits. This paper explores several ecological connections between human pathogenic fungi and certain animals, trees, waterways and degraded organic materials. The occurrence of such connections in highly endemic areas will hopefully furnish more precise clues to fungal habitats and allow the design of control programs aimed at avoiding human infection.


Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate.
Elevated plasma homocyst(e)ine levels are an independent risk factor for vascular disease. In a case-control study, the authors studied the associations of fasting plasma homocyst(e)ine and vitamins, which are important cofactors in homocysteine metabolism, with the risk of myocardial infarction. The cases were 130 Boston area patients hospitalized with a first myocardial infarction and 118 population controls, less than 76 years of age, enrolled in 1982 and 1983. Dietary intakes of vitamins B6, B12, and folate were estimated from a food frequency questionnaire. After adjusting for sex and age, the authors found that the geometric mean plasma homocyst(e)ine level was 11% higher in cases compared with controls (p = 0.006). There was no clear excess of cases with extremely elevated levels. The age- and sex-adjusted odds ratio for each 3-mumol/liter (approximately 1 standard deviation) increase in plasma homocyst(e)ine was 1.35 (95% confidence interval 1.05-1.75; p trend = 0/007). After further control for several risk factors, the odds ratio was not affected, but the confidence interval was wider and the p value for trend was less significant. Dietary and plasma levels of vitamin B6 and folate were lower in cases than in controls, and these vitamins were inversely associated with the risk of myocardial infarction, independently of other potential risk factors. Vitamin B12 showed no clear association with myocardial infarction, although methylmalonic acid levels were significantly higher in cases. Comparing the mean levels of several homocysteine metabolites among cases and controls, the authors found that impairment of remethylation of homocyst(e)ine (dependent of folate and vitamin B12 rather than on vitamin B6-dependent transsulfuration) was the predominant cause of high homocyst(e)ine levels in cases. Accordingly, plasma folate and, to a lesser extent, plasma vitamin B12, but not vitamin B6, correlated inversely with plasma homocyst(e)ine, even for concentrations at the high end of normal values. These data provide further evidence that plasma homocyst(e)ine is an independent risk factor for myocardial infarction. In this population, folate was the most important determinant of plasma homocyst(e)ine, even in subjects with apparently adequate nutritional status of this vitamin.


TLR9-Mediated Conditioning of Liver Environment Is Essential for Successful Intrahepatic Immunotherapy and Effective Memory Recall.
Immune defense against hepatotropic viruses such as hepatitis B (HBV) and hepatitis C (HCV) poses a major challenge for therapeutic approaches. Intrahepatic cytotoxic CD8 T cells that are crucial for an immune response against these viruses often become exhausted resulting in chronic infection. We elucidated the T cell response upon therapeutic vaccination in inducible transgenic mouse models in which variable percentages of antigen-expressing hepatocytes can be adjusted, providing mosaic antigen distribution and reflecting the varying viral antigen loads observed in patients. Vaccination-induced endogenous CD8 T cells could eliminate low antigen loads in liver but were functionally impaired if confronted with elevated antigen loads. Strikingly, only by conditioning the liver environment with TLR9 ligand prior and early after peripheral vaccination, successful immunization against high intrahepatic antigen density with its elimination was achieved. Moreover, TLR9 immunomodulation was also indispensable for functional memory recall after high frequency antigen challenge. Together, the results indicate that TLR9-mediated conditioning of liver environment during therapeutic vaccination or antigen reoccurrence is crucial for an efficacious intrahepatic T cell response.


Validation of the CoVID-TE model as a tool to predict thrombosis, bleeding, and mortality in the oncology patient with Sars-Cov-2 infection: a study by the SEOM cancer and thrombosis group.
The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation. Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan-Meier method was also used to compare mortality by stratification. 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0-2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9-7.9), 4.5% (95% CI 2.3-8.6), and 52.5% (95% CI 45.2-59.7), respectively. For the high-risk group it was 6% (95% CI 2.6-13.2), 9.6% (95% CI 5.0-17.9), and 58.0% (95% CI 45.3-66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84-16.46), while in the high-risk group it was 3.68 months (95% CI 0.0-7.79). The differences detected were not statistically significant (p = 0.375). The data from our series does not validate of the CoVID-TE as a model to predict thrombosis, hemorrhage, or mortality in cancer patients with Sars-Cov-2 infection.


Multiple cone visual pigments and the potential for trichromatic colour vision in two species of elasmobranch.
Elasmobranchs (sharks, skates and rays) are the modern descendents of the first jawed vertebrates and, as apex predators, often occupy the highest trophic levels of aquatic (predominantly marine) ecosystems. However, despite their crucial role in the structure of marine communities, their importance both to commercial and to recreational fisheries, and the inherent interest in their role in vertebrate evolution, very little is known about their visual capabilities, especially with regard to whether or not they have the potential for colour vision. Using microspectrophotometry, we show that the retinae of the giant shovelnose ray (Rhinobatos typus) and the eastern shovelnose ray (Aptychotrema rostrata) contain three spectrally distinct cone visual pigments with wavelengths of maximum absorbance (lambdamax) at 477, 502 and 561 nm and at 459, 492 and 553 nm, respectively. The retinae of R. typus and A. rostrata also contain a single type of rod visual pigment with lambdamax at 504 and 498 nm, respectively. R. typus, living in the same estuarine waters as A. rostrata, were found to have identical visual pigments to R. typus inhabiting coral reef flats, despite a considerable difference in habitat spectral radiance. This is the first time that multiple cone visual pigments have been measured directly in an elasmobranch. The finding raises the possibility that some species are able to discriminate colour--a visual ability traditionally thought to be lacking in this vertebrate class--and it is evident that the visual ecology of elasmobranchs is far more complex than once thought.


Prognostic factors in the initial response to therapy by patients with advanced breast cancer.
Identification of important prognostic factors with respect to the patient's initial response to therapy was made from a set of 25 covariates available on 281 patients with advanced breast cancer. Since the patients studied were all participants in a randomized clinical trial that involved three different treatment regimens (repeated weekly treatment of a combination of cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone; intermittent treatment of the same preceding five drugs given in 5-day courses every 4 weeks; or treatment every 3 weeks with adriamycin as a single agent), the effect of these treatments on the selection of important covariates was assessed. Although some evidence indicated that the set of important covariates differed by treatment, the differences were not strong enough to be of practical importance. Non-Caucasian patients did poorly on all regimens with a response rate of only 31% compared to 62% for Caucasian patients. The covariates of major prognostic importance for Caucasians were: disease-free interval, liver involvement, and performance status. Ambulatory patients with long disease-free intervals and no liver involvement had the best prognosis. After adjustments were made for these three covariates, the remaining covariates (such as menopausal status, bone involvement, number of metastatic sites, and duration of metastatic disease) were not significantly related to response. As reported earlier, the treatment effect was significant, even after adjustments were made for the important covariates.


Enhanced CO2 reduction and valuable C2+ chemical production by a CdS-photosynthetic hybrid system.
Semi-artificial photosynthesis is an emerging technique in recent years. Here, we presented an inorganic-biological hybrid system composed of photosynthetic Rhodopseudomonas palustris and CdS nanoparticles coated on the bacterial surface. Under visible light irradiation, the CO2 reduction and valuable C2+ chemical production of R. palustris could be promoted by the photo-induced electrons from the CdS NPs. The increased energy-rich NADPH cofactor promoted the generation of the Calvin cycle intermediate, glyceraldehyde-3-phosphate. As a result, the production of solid biomass, carotenoids and poly-β-hydroxybutyrate (PHB) was increased to 148%, 122% and 147%, respectively. The photosynthetic efficiency (PE) of CdS-R. palustris was elevated from the original 4.31% to 5.98%. The surface loaded NP amount and the material-cell interface both played important roles in the efficient electron generation and transduction. The CdS-R. palustris hybrid system also exhibited a survival advantage over its natural counterparts under the autotrophic conditions. Under a practical solar/dark cycle, the produced biomass, carotenoid and PHB from the hybrid system also reach 139%, 117% and 135%, respectively. The CdS-photosynthetic hybrid system represents a powerful and expandable platform for advanced CO2 reduction and solar-to-chemical (S2C) conversion.


A national survey of prisoners on antiretroviral therapy in Malawi: access to treatment and outcomes on therapy.
Malawi is making good progress scaling up antiretroviral therapy (ART), but we do not know the levels of access of high-risk, disadvantaged groups such as prisoners. The aim of this study was to measure access and treatment outcomes of prisoners on ART at the national level. A retrospective cohort study was conducted examining patient follow-up records from all 103 public sector ART clinics in Malawi, and observations were censored on 31 December, 2006. By 31 December, 2006, a total of 81,821 patients had been started on ART. Of these, 103 (0.13%) were prisoners. At ART initiation, 93% of prisoners were in World Health Organization (WHO) clinical stage 3 or 4 while 7% started in stage 1 or 2 with a CD4-lymphocyte count of < or =250/mm3. Treatment outcomes by the end of December 2006 were as follows: 66 (64%) alive and on ART at their registration facility; 9 (9%) dead; 8 (8%) lost to follow-up; and 20 (19%) transferred out to another facility. The probability of being alive and on ART at 6 and 12 months was 82.5% and 77.7%. In spite of the rapid scale-up of ART, only a small number of HIV-positive prisoners had accessed ART by the end of 2006. Treatment outcomes were good. Initiatives are now needed to improve access to HIV testing and ART in Malawi's prisons.


[Ganglioneuroblastoma of the orbit].
Ganglioneuroblastoma a transitional tumor of sympathetic origin has not yet been described as involving orbit. It is characterized by a mixture of cells ranging from primitive neuroblast to well differentiated ganglion cells within a neurofibromatous tissue. The prognosis is uncertain, as the tumor may either undergo maturation into a ganglioneuroma or may metastasize widely and rapidly as in neuroblastoma. We may postulate a relationship between ganglioneuroblastoma and Recklinghausen's neurofibromatosis in view of the development of the tumor in conjunction with the phacomatosis.


The circadian Clock mutation increases exploratory activity and escape-seeking behavior.
Disturbances of circadian rhythms are associated with many types of mood disorders; however, it is unknown whether a dysfunctional circadian pacemaker can be the primary cause of altered emotional behavior. To test this hypothesis, male and female mice carrying a mutation of the circadian gene, Clock, were compared to wild-type mice in an array of behavioral tests used to measure exploratory activity, anxiety, and behavioral despair. Female Clock mutant mice exhibited significantly greater activity and rearing in an open field and a greater number of total arm entries in the elevated plus maze. In addition, female Clock mutant mice spent significantly more time swimming in the forced swim test than wild-type mice on both days of a 2-day test. Male Clock mutant mice also exhibited increased exploration of the open field and increased swimming in the forced swim test; however, behavioral changes were less robust in Clock mutant males compared to Clock mutant females. These changes in behavior were not dependent on the expression of a lengthened free-running period but were more or less striking depending on the testing conditions. These data indicate that the Clock mutation leads to increased exploratory behavior and increased escape-seeking behavior, and, conversely, does not result in increased anxiety or depressive-like behavior. These results suggest that the Clock gene is involved in regulating behavioral arousal, and that Clock may interact with sex hormones to produce these behavioral changes.


Interrelationship between erythropoietin and erythropoiesis: insights from renal transplantation.
In successful renal transplant recipients, transient and modest increases in endogenous erythropoietin (Epo) reverse anemia, whereas in dialysis patients, sustained administration of large doses of exogenous Epo is required for the correction of uremic anemia. Moreover, in transplant recipients, serum Epo returns to normal as the hematocrit level increases to greater than 32%. Thereafter, the hematocrit continues to increase to normal levels, while serum Epo remains in the normal range. Thus, the restoration of renal function may improve the erythropoietic response to Epo, and/or erythropoiesis in transplant patients may be stimulated by factors other than, or in addition to, Epo. In early posttransplant patients who develop erythrocytosis, serum Epo levels are often elevated, while in long-term transplant recipients, erythrocytotic patients (with normal serum ferritin) have normal serum Epo levels. On the other hand, in long-term transplant recipients with low serum ferritin, circulating Epo levels are elevated, even in patients with no overt anemia. This suggests a possible interaction between body iron store status and the synthesis of Epo.


Genome-wide diversity and differentiation in New World populations of the human malaria parasite Plasmodium vivax.
The Americas were the last continent colonized by humans carrying malaria parasites. Plasmodium falciparum from the New World shows very little genetic diversity and greater linkage disequilibrium, compared with its African counterparts, and is clearly subdivided into local, highly divergent populations. However, limited available data have revealed extensive genetic diversity in American populations of another major human malaria parasite, P. vivax. We used an improved sample preparation strategy and next-generation sequencing to characterize 9 high-quality P. vivax genome sequences from northwestern Brazil. These new data were compared with publicly available sequences from recently sampled clinical P. vivax isolates from Brazil (BRA, total n = 11 sequences), Peru (PER, n = 23), Colombia (COL, n = 31), and Mexico (MEX, n = 19). We found that New World populations of P. vivax are as diverse (nucleotide diversity π between 5.2 × 10-4 and 6.2 × 10-4) as P. vivax populations from Southeast Asia, where malaria transmission is substantially more intense. They display several non-synonymous nucleotide substitutions (some of them previously undescribed) in genes known or suspected to be involved in antimalarial drug resistance, such as dhfr, dhps, mdr1, mrp1, and mrp-2, but not in the chloroquine resistance transporter ortholog (crt-o) gene. Moreover, P. vivax in the Americas is much less geographically substructured than local P. falciparum populations, with relatively little between-population genome-wide differentiation (pairwise FST values ranging between 0.025 and 0.092). Finally, P. vivax populations show a rapid decline in linkage disequilibrium with increasing distance between pairs of polymorphic sites, consistent with very frequent outcrossing. We hypothesize that the high diversity of present-day P. vivax lineages in the Americas originated from successive migratory waves and subsequent admixture between parasite lineages from geographically diverse sites. Further genome-wide analyses are required to test the demographic scenario suggested by our data.


Tisp40, a spermatid specific bZip transcription factor, functions by binding to the unfolded protein response element via the Rip pathway.
TISP40, a mouse spermatid-specific gene, encodes a CREB/CREM family transcription factor that is predominantly expressed during spermiogenesis. We report here that TISP40 generates two types of proteins, Tisp40alpha and Tisp40beta, both of which contain a transmembrane domain and localize to the endoplasmic reticulum (ER). In contrast, mutant proteins lacking the transmembrane domain (Tisp40alpha/betaDeltaTM) primarily localize to the nucleus. Endoglycosidase H treatment shows that the C-terminus of Tisp40alpha/beta is glycosylated. Protease experiments demonstrate that Tisp40alpha/beta are Type II transmembrane proteins that are released into the nucleus by a two-step cleavage mechanism called 'regulated intramembrane proteolysis' (Rip). Unlike previously published observations, Tisp40alpha does not bind to the NF-kappaB site; instead, it specifically binds to the unfolded protein response element (UPRE). Luciferase assays reveal that Tisp40betaDeltaTM activates transcription through UPRE. Northern blot analysis shows that Tisp40alpha/betaDeltaTM proteins up-regulate EDEM (ER degradation of enhancing alpha-manosidase-like protein) mRNA. These observations unveil a novel event in mouse spermiogenesis and show that the final stage of transcriptional regulation is controlled by the Rip pathway.


In-hospital resource utilization during multiple casualty incidents.
To suggest guidelines for hospital organization during terror-related multiple casualty incidents (MCIs) based on the experience of 6 level I trauma centers. Most terror-related MCIs are bombings. The sporadic nature of these events complicates in-hospital preparation. Data were collected at all level I Trauma centers during/after MCIs for the Israel National Trauma registry. Patients were included if they were admitted or died in hospital following injury in suicide bombings (October 1, 2000 to June 30, 2003), which fulfilled Ministry of Health suggested criteria for MCIs (number of admissions, severity of injury). Included were 325 casualties from 32 events, 34% of which had an Injury Severity Score >16. A third of the admissions arrived within 10 minutes and 65% within 30 minutes. Forty percent of the patients underwent CT scans directly from the ED. Operative procedures were performed on 60% of patients and 36% were transferred directly from the ED to the OR. Initiation of surgical procedures peaked at 1 to 1.5 hours, mainly multidisciplinary abdominal, thoracic, and vascular surgery. Orthopedic and plastic surgery predominated later. A third of the patients were admitted to ICUs, often (31%) directly from the ED. High staffing demands for ED, OR, and ICU overlap. Anesthesiologists, general, thoracic, and vascular surgeons are in immediate demand. ICU admissions occur simultaneously with ongoing patient arrival to the ED. Most patients operated within the first 2 hours require multidisciplinary surgical teams. Demand for orthopedic and plastic surgery and anesthesiology services continues for >24 hours.


The phylogenomic landscape of extended-spectrum β-lactamase producing Citrobacter species isolated from surface water.
Citrobacter species are Gram-negative opportunistic pathogens commonly reported in nosocomial-acquired infections. This study characterised four Citrobacter species that were isolated from surface water in the North West Province, South Africa. Phenotypic antimicrobial susceptibility profiles of the isolates demonstrated their ability to produce the extended-spectrum β-lactamase (ESBL). Whole genomes were sequenced to profile antibiotic resistance and virulence genes, as well as mobile genetic elements. In silico taxonomic identification was conducted by using multi-locus sequence typing and average nucleotide identity. A pangenome was used to determine the phylogenomic landscape of the Citrobacter species by using 109 publicly available genomes. The strains S21 and S23 were identified as C. braakii, while strains S24 and S25 were C. murliniae and C. portucalensis, respectively. Comparative genomics and sequenced genomes of the ESBL-producing isolates consisted of n = 91; 83% Citrobacter species in which bla-CMY-101 (n = 19; 32,2%) and bla-CMY-59 (n = 12; 38,7%) were prevalent in C. braakii, and C. portucalensis strains, respectively. Macrolide (acrAB-TolC, and mdtG) and aminoglycoside (acrD) efflux pumps genes were identified in the four sequenced Citrobacter spp. isolates. The quinolone resistance gene, qnrB13, was exclusive to the C. portucalensis S25 strain. In silico analysis detected plasmid replicon types IncHI1A, IncP, and Col(VCM04) in C. murliniae S24 and C. portucalensis S25, respectively. These potentially facilitate the T4SS secretion system in Citrobacter species. In this study, the C. braakii genomes could be distinguished from C. murliniae and C. portucalensis on the basis of gene encoding for cell surface localisation of the CPS (vexC) and identification of genes involved in capsule polymer synthesis (tviB and tviE). A cluster for the salmochelin siderophore system (iro-BCDEN) was found in C. murliniae S24. This is important when it comes to the pathogenicity pathway that confers an advantage in colonisation. The emerging and genomic landscapes of these ESBL-producing Citrobacter species are of significant concern due to their dissemination potential in freshwater systems. The presence of these ESBL and multidrug-resistant (MDR) pathogens in aquatic environments is of One Health importance, since they potentially impact the clinical domain, that is, in terms of human health and the agricultural domain, that is, in terms of animal health and food production as well as the environmental domain.


Microfluidic-enabled bottom-up hydrogels from annealable naturally-derived protein microbeads.
Naturally-derived proteins, such as collagen, elastin, fibroin, and gelatin (denatured collagen) hold a remarkable promise for tissue engineering and regenerative medicine. Gelatin methacryloyl (GelMA), synthesized from the methacryloyl modification of gelatin, mimicking the structure of extracellular matrix, has widely been used as a universal multi-responsive scaffold for a broad spectrum of applications, spanning from cell therapy to bioprinting and organoid development. Despite the widespread applications of GelMA, coupled stiffness and porosity has inhibited its applications in 3D cellular engineering wherein a stiff scaffold with large pores is demanded (e.g., at concentrations >10 wt%). Taking advantage of the orthogonal thermo-chemical responsivity of GelMA, we have developed microfluidic-assisted annealable GelMA beads, that are first stabilized by temperature-mediated physical crosslinking, flowed to form a scaffold structure, and then chemically annealed using light to fabricate novel bead-based 3D GelMA scaffolds with high mechanical resilience. We show how beaded GelMA (B-GelMA) provides a self-standing microporous environment with an orthogonal void fraction and stiffness, promoting cell adhesion, proliferation, and rapid 3D seeding at a high polymer concentration (∼20 wt%) that would otherwise be impossible for bulk GelMA. B-GelMA, decorated with methacryloyl and arginylglycylaspartic acid (RGD) peptide motifs, does not require additional functionalization for annealing and cell adhesion, providing a versatile biorthogonal platform with orthogonal stiffness and porosity for a myriad of biomedical applications. This technology provides a universal method to convert polymeric materials with orthogonal physico-chemical responsivity to modular platforms, opening a new horizon for converting bulk hydrogels to beaded hydrogels (B-hydrogels) with decoupled porosity and stiffness.


Reconstructing Genotypes in Private Genomic Databases from Genetic Risk Scores.
Some organizations such as 23andMe and the UK Biobank have large genomic databases that they re-use for multiple different genome-wide association studies. Even research studies that compile smaller genomic databases often utilize these databases to investigate many related traits. It is common for the study to report a genetic risk score (GRS) model for each trait within the publication. Here, we show that under some circumstances, these GRS models can be used to recover the genetic variants of individuals in these genomic databases-a reconstruction attack. In particular, if two GRS models are trained by using a largely overlapping set of participants, it is often possible to determine the genotype for each of the individuals who were used to train one GRS model, but not the other. We demonstrate this theoretically and experimentally by analyzing the Cornell Dog Genome database. The accuracy of our reconstruction attack depends on how accurately we can estimate the rate of co-occurrence of pairs of single nucleotide polymorphisms within the private database, so if this aggregate information is ever released, it would drastically reduce the security of a private genomic database. Caution should be applied when using the same database for multiple analysis, especially when a small number of individuals are included or excluded from one part of the study.


Mimicking the membrane-mediated conformation of dynorphin A-(1-13)-peptide: circular dichroism and nuclear magnetic resonance studies in methanolic solution.
The structural requirements for the binding of dynorphin to the kappa-opioid receptor are of profound clinical interest in the search for a powerful nonaddictive analgesic. These requirements are thought to be met by the membrane-mediated conformation of the opioid peptide dynorphin A-(1-13)-peptide, Tyr1-Gly2-Gly3-Phe4-Leu5-Arg6-Arg7-Ile8-Arg9-Pro10- Lys11-Leu12-Lys13. Schwyzer has proposed an essentially alpha-helical membrane-mediated conformation of the 13 amino acid peptide [Schwyzer, R. (1986) Biochemistry 25, 4281-4286]. In the present study, circular dichroism (CD) studies on dynorphin A-(1-13)-peptide bound to an anionic phospholipid signified negligible helical content of the peptide. CD studies also demonstrated that the aqueous-membraneous interphase may be mimicked by methanol. The 500- and 620-MHz 1H nuclear magnetic resonance (NMR) spectra of dynorphin A-(1-13)-peptide in methanolic solution were sequence-specifically assigned with the aid of correlated spectroscopy (COSY), double-quantum filtered phase-sensitive COSY (DQF-COSY), relayed COSY (RELAY), and nuclear Overhauser enhancement spectroscopy (NOESY). 2-D CAMELSPIN/ROESY experiments indicated that at least the part of the molecule from Arg7 to Arg9 was in an extended or beta-strand conformation, which agreed with deuterium-exchange and temperature-dependence studies of the amide protons and analysis of the vicinal spin-spin coupling constants 3JHN alpha. The results clearly demonstrated the absence of extensive alpha-helix formation. chi 1 rotamer analysis of the 3J alpha beta demonstrated no preferred side-chain conformations.


Measurement of quality of life VI. Quality-adjusted life years (QALY) is an unfortunate use of the quality-of-life concept.
The QALY (quality-adjusted life years) attempts to incorporate the dimension of quality of life into the evaluation by adjusting life years by a quality factor. In practice, this is based on discussing with people the progression of a number of hypothetical illnesses and their ensuing side effects. From this information, the person assesses how each state of health described compares with a theoretical maximum state of health. For example, 1 day with a certain condition might the equivalent of living only 0.5 days in good health. We believe that QALY value only represents a superficial impression of a person's quality of life. In short, the QALY does not express what it means for a person to live a life at reduced quality. We believe that if the patients were optimally informed and allowed to decide for themselves, they would more often reject high-tech expensive biomedical treatments that only serve to prolong life and do not increase its quality. The problem of priorities may then turn out to be far more simple and also more ethical: the focus will be on the quality of life, not on QALY, and the question of the meaning of life and death will achieve greater openness and respect.


Root growth restraint can be an acclimatory response to low pH and is associated with reduced cell mortality: a possible role of class III peroxidases and NADPH oxidases.
Low pH (<5.0) can significantly decrease root growth but whether this is a direct effect of H(+) or an active plant response is examined here. Tomato (Solanum lycopersicum cv Micro-Tom) roots were exposed directly or gradually to low pH through step-wise changes in pH over periods ranging from 4 to 24 h. Roots exposed gradually to pH 4.5 grew even less than those exposed directly, indicating a plant-coordinated response. Direct exposure to pH 4.0 suppressed root growth and caused high cell mortality, in contrast to roots exposed gradually, in which growth remained inhibited but cell viability was maintained. Total class III peroxidase activity increased significantly in all low pH treatments, but was not correlated with the observed differential responses. Use of the enzyme inhibitors salicylhydroxamic acid (SHAM) or diphenyleneiodonium chloride (DPI) suggest that peroxidase and, to a lesser extent, NADPH oxidase were required to prevent or reduce injury in all low pH treatments. However, a role for other enzymes, such as the alternative oxidase is also possible. The results with SHAM, but not DPI, were confirmed in tobacco BY-2 cells. Our results indicate that root growth inhibition from low pH can be part of an active plant response, and suggest that peroxidases may have a critical early role in reducing loss of cell viability and in the observed root growth constraint.


Characteristics of symptomatic reflux episodes on Acid suppressive therapy.
Persistent symptoms on acid suppressive therapy are due to either acid or nonacid gastroesophageal reflux (GER) episodes or are not related to reflux. To compare physical and chemical characteristics of GER episodes associated with symptoms in patients on acid suppressive therapy. Patients with persistent symptoms on acid suppressive therapy underwent combined impedance-pH monitoring. Reflux episodes were classified as acid if nadir pH was <4.0, and nonacid if it remained at >/=4.0, separated into liquid-only or mixed (liquid-gas), and considered to reach the proximal esophagus if liquid was present 15 cm above the lower esophageal sphincter (LES). Reflux episodes were considered symptomatic if patients recorded a symptom within 5 min after the reflux episode. Risk factors of symptomatic reflux episodes were identified using multivariable generalized estimating equations (GEEs). One hundred twenty patients (85 women, median age 54 yr, range 18-85 yr) recorded 3,547 reflux episodes (84.3% nonacid, 50.6% mixed), of which 468 (13.2%) were symptomatic. Based on multivariable GEE analysis with episode-level symptom status (symptomatic vs nonsymptomatic) as the outcome variable, reflux episode acidity was not significantly associated with symptoms (P= 0.40). Mixed reflux episodes were significantly associated with symptoms relative to liquid-only episodes (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.19-1.87, P= 0.0005), as were reflux episodes reaching the proximal esophagus compared with those reaching the distal esophagus only (OR 1.28, 95% CI 1.06-1.55, P= 0.012). The majority of reflux episodes on acid suppressive therapy are asymptomatic. Reflux episodes extending proximally and having a mixed (liquid-gas) composition are significantly associated with symptoms, irrespective of whether pH is acid (<4) or nonacid (>/=4).


Prioritizing climate change adaptation needs for food security in 2030.
Investments aimed at improving agricultural adaptation to climate change inevitably favor some crops and regions over others. An analysis of climate risks for crops in 12 food-insecure regions was conducted to identify adaptation priorities, based on statistical crop models and climate projections for 2030 from 20 general circulation models. Results indicate South Asia and Southern Africa as two regions that, without sufficient adaptation measures, will likely suffer negative impacts on several crops that are important to large food-insecure human populations. We also find that uncertainties vary widely by crop, and therefore priorities will depend on the risk attitudes of investment institutions.


[Role of alpha- and beta-adrenoreceptors of the jejunum and ileum in displays of their contractile reactions].
Acute experiments were performed on isolated segments of the cat small intestine vessels. The contractile activity of the jejunum and ileum was estimated by the maximal isometric tension. Blocking of the alpha-adrenoreceptors with phentolamine induced a reinforcement of the contractile reactions, whereas blocking of the beta-adrenoreceptors with propranolol led to inhibition of both jejunum and ileum contractile responses either to exogenous acetylcholine or electrical stimulation of vagal efferent fibers. The subthreshold activation of alpha-adrenoreceptors with noradrenaline induced mostly inhibition, whereas activation of beta-adrenoreceptors with isopropylnoradrenaline caused a potentiation of the contractile response to exogenous acetylcholine. The data obtained suggest existence of excitatory beta-adrenoreceptors with a presynaptic localization in the jejunum and ileum.


A functional-structural model of elongation of the grass leaf and its relationships with the phyllochron.
The emergence of a regular phyllochron from the dynamic processes of leaf initiation, leaf elongation and whorl construction suggests causal relationships between leaf elongation and leaf emergence. This paper presents a hypothesis as to how the ontogeny of the growth zone of leaves is triggered by emergence events, and implements it in a dynamic model of leaf elongation. Two different experiments, presenting two contrasted cases of relationships between leaf emergence and kinetics of leaf elongation, were analysed and interpreted with the model in terms of the functioning of the growth zone. Analysis of elongation kinetics revealed that the hypothesis allows for several contrasted elongation patterns that were observed, and for a regular phyllochron emerging from the variable dynamic of elongation. The model was able to simulate these patterns, and helped to identify the mechanisms underlying the key points of the analysis. The hypothesis is not demonstrated, but its coherence and robustness are established, which should inform a renewal of the modelling of leaf elongation in architectural models.


Assessment of Patient Knowledge, Awareness, and Adherence in Heart Failure in a Real-Life Setting: Insights from Data Acquired in Pharmacies.
Patient knowledge is crucial for managing and/or monitoring patients with heart failure (HF). However, "real-life" evidence of knowledge level and awareness in HF is yet to be explored. We assessed unselected HF patients' knowledge and awareness in a pharmacy setting. One hundred eight HF patients (mean age [SD], 70 (12) years, 61% men) were studied in pharmacies in the north-east region of France in 2019. All patients were interviewed by their pharmacist to quantify their knowledge in HF, self-assessment of symptoms of congestion, as well as their adherence to HF treatment and guideline-recommended lifestyle. Overall, 40% of patients had not consulted their cardiologist in the past 6 months, and 89% never underwent an HF education program. Regarding HF knowledge, nearly half were unsure whether they had HF (43.5%). Only half of the patients knew how to self-assess HF symptoms (57.4%), while a quarter (25%) were unsure of the purpose of HF medications. In patients with HF assessed in their pharmacies, a majority lacked fundamental knowledge regarding HF, such as self-assessment of congestion, possibly due to a minimal proportion of patients undergoing an HF education program. These results suggest that interventions led by pharmacies may help improve HF education coverage in patients who may have poor access to specialized care.


Survival of Microencapsulated Probiotic Bacteria after Processing and during Storage: A Review.
The use of live probiotic bacteria as food supplement has become popular. Capability of probiotic bacteria to be kept at room temperature becomes necessary for customer's convenience and manufacturer's cost reduction. Hence, production of dried form of probiotic bacteria is important. Two common drying methods commonly used for microencapsulation are freeze drying and spray drying. In spite of their benefits, both methods have adverse effects on cell membrane integrity and protein structures resulting in decrease in bacterial viability. Microencapsulation of probiotic bacteria has been a promising technology to ensure bacterial stability during the drying process and to preserve their viability during storage without significantly losing their functional properties such acid tolerance, bile tolerance, surface hydrophobicity, and enzyme activities. Storage at room temperatures instead of freezing or low temperature storage is preferable for minimizing costs of handling, transportation, and storage. Concepts of water activity and glass transition become important in terms of determination of bacterial survival during the storage. The effectiveness of microencapsulation is also affected by microcapsule materials. Carbohydrate- and protein-based microencapsulants and their combination are discussed in terms of their protecting effect on probiotic bacteria during dehydration, during exposure to harsh gastrointestinal transit and small intestine transit and during storage.


Big Five Personality Characteristics and Adherence to Clinic-Based Rehabilitation Activities after ACL Surgery: A Prospective Analysis.
A prospective, longitudinal study was conducted to examine Big Five personality characteristics as predictors of adherence to clinic-based rehabilitation activities following anterior cruciate ligament (ACL) reconstruction surgery. Participants (72 men, 36 women) completed a questionnaire assessing Big Five personality dimensions prior to surgery. For the first 7 weeks after surgery, participants' rehabilitation session attendance was recorded and rehabilitation professionals rated participants' adherence during rehabilitation sessions.. Results of multiple regression analyses indicated that the 5 personality factors explained 11 percent of the variance in attendance and 17 percent of the variance in adherence ratings, that agreeableness was a significant positive predictor of attendance, and that conscientiousness and openness to experience were significant positive predictors of adherence ratings. As a potential contributor to adherence, personality warrants consideration when implementing rehabilitation programs after ACL surgery.


A study of job turnover among clinical laboratory personnel.
A study of job turnover in clinical laboratories in the Minneapolis-St. Paul area was conducted in the years 1970, 1975, and 1980. Annual turnover rates for all laboratory personnel were 20%, 19% and 15% respectively. The groups with the lowest turnover were cytotechnologists, histologic technicians and clinical laboratory scientists (medical technologists). The highest turnover occurred among clinical laboratory technicians and "others," primarily supportive personnel such as phlebotomists, assistants, and aides.


A Placebo-Controlled Trial of Riboflavin for Enhancement of Ultramarathon Recovery.
Riboflavin is known to protect tissue from oxidative damage but, to our knowledge, has not been explored as a means to control exercise-related muscle soreness. This study investigated whether acute ingestion of riboflavin reduces muscle pain and soreness during and after completion of a 161-km ultramarathon and improves functional recovery after the event. In this double-blind, placebo-controlled trial, participants of the 2016 161-km Western States Endurance Run were assigned to receive a riboflavin or placebo capsule shortly before the race start and when reaching 90 km. Capsules contained either 100 mg of riboflavin or 95 mg of maltodextrin and 5 mg of 10% ß-carotene. Subjects provided muscle pain and soreness ratings before, during, and immediately after the race and for the 10 subsequent days. Subjects also completed 400-m runs at maximum speed on days 3, 5, and 10 after the race. For the 32 (18 in the riboflavin group, 14 in the placebo group) race finishers completing the study, muscle pain and soreness ratings during and immediately after the race were found to be significantly lower (p = .043) for the riboflavin group. Analysis of the 400-m run times also showed significantly faster (p < .05) times for the riboflavin group than the placebo group at post-race days 3 and 5. Both groups showed that muscle pain and soreness had returned to pre-race levels by 5 days after the race and that 400-m run times had returned to pre-race performance levels by 10 days after the race. This preliminary work suggests that riboflavin supplementation before and during prolonged running might reduce muscle pain and soreness during and at the completion of the exercise and may enhance early functional recovery after the exercise.


Harnessing the effects of endurance exercise to optimize cognitive health: Fundamental insights from Dr. Mark P. Mattson.
Dr. Mark Mattson has had a highly productive and impactful tenure as a neuroscientist at the Intramural Research Program of the National Institute on Aging. He has made notable contributions to understanding the mechanisms by which energetic stress, imparted by behaviors such as physical activity and periods of fasting, promotes rejuvenation and resilience within brain regions critical for learning and memory. In honor of Dr. Mattson's work, this manuscript will highlight the fascinating mechanisms by which endurance exercise training conveys beneficial effects upon the structure and function of the nervous system; that is, by mediating the synthesis and secretion of factors that directly support brain homeostasis, including brain-derived neurotrophic factor, FNDC5/irisin, ketone bodies, growth factors, cathepsin B, serotonin, and 4-hydroxynonenal. The molecular and cellular effects of these factors are discussed herein. In the face of population aging and an overwhelming surge in the prevalence of Alzheimer's disease and related disorders, Dr. Mattson's work as a champion and role model for physically active lifestyles is more important than ever.


Intraoperative stenting for brachiocephalic and carotid artery stenosis.
Endovascular stenting is an alternative treatment for brachiocephalic artery stenosis, replacing standard surgical approaches such as carotid endarterectomy. However, a percutaneous approach may be difficult because various conditions such as severe arteriosclerosis of iliac or femoral arteries and aortic disease. We report our experience with intraoperative stenting for these lesions, presenting indications, strategy, and results. Seven patients underwent intraoperative stent placement via an open cervical approach. The sites of lesions included 1 innominate artery, 1 common carotid artery, and 5 cervical carotid arteries. Stenting was performed with a sheath introducer placed through a surgically exposed common carotid artery via a small skin incision or common carotid artery exposed for simultaneously performed carotid endarterectomy. Distal protection was used in 6 patients with an endovascular protective balloon or external clamping with forceps. Sufficient dilation of stenosis was obtained in all cases. No complications such as transient ischemic attack, cerebral infarction, and hyperperfusion were encountered. Wound hematoma was not experienced despite perioperative antiplatelet therapy and heparinization during the procedure. Angiographic follow-up over 1 year showed no restenosis in 5 available patients. Intraoperative stenting may be an excellent alternative for patients in whom both direct surgical approach and standard percutaneous endovascular approach are not possible.


Plant and Microbial Responses to Repeated Cu(OH)2 Nanopesticide Exposures Under Different Fertilization Levels in an Agro-Ecosystem.
The environmental fate and potential impacts of nanopesticides on agroecosystems under realistic agricultural conditions are poorly understood. As a result, the benefits and risks of these novel formulations compared to the conventional products are currently unclear. Here, we examined the effects of repeated realistic exposures of the Cu(OH)2 nanopesticide, Kocide 3000, on simulated agricultural pastureland in an outdoor mesocosm experiment over 1 year. The Kocide applications were performed alongside three different mineral fertilization levels (Ambient, Low, and High) to assess the environmental impacts of this nanopesticide under low-input or conventional farming scenarios. The effects of Kocide over time were monitored on forage biomass, plant mineral nutrient content, plant-associated non-target microorganisms (i.e., N-fixing bacteria or mycorrhizal fungi) and six soil microbial enzyme activities. We observed that three sequential Kocide applications had no negative effects on forage biomass, root mycorrhizal colonization or soil nitrogen fixation rates. In the Low and High fertilization treatments, we observed a significant increase in aboveground plant biomass after the second Kocide exposure (+14% and +27%, respectively). Soil microbial enzyme activities were significantly reduced in the short-term after the first exposure (day 15) in the Ambient (-28% to -82%) and Low fertilization (-25% to -47%) but not in the High fertilization treatment. However, 2 months later, enzyme activities were similar across treatments and were either unresponsive or responded positively to subsequent Kocide additions. There appeared to be some long-term effects of Kocide exposure, as 6 months after the last Kocide exposure (day 365), both beta-glucosidase (-57% in Ambient and -40% in High fertilization) and phosphatase activities (-47% in Ambient fertilization) were significantly reduced in the mesocosms exposed to the nanopesticide. These results suggest that when used in conventional farming with high fertilization rates, Kocide applications did not lead to marked adverse effects on forage biomass production and key plant-microorganism interactions over a growing season. However, in the context of low-input organic farming for which this nanopesticide is approved, Kocide applications may have some unintended detrimental effects on microbially mediated soil processes involved in carbon and phosphorus cycling.


Apoptosis in relation to neuronal loss in experimental Creutzfeldt-Jakob disease in mice.
Apoptosis constitutes a genetically determined process to eliminate superfluous or damaged cells in tissues. Deficiencies in apoptosis regulation are involved in different pathologies including prion diseases. Some experimental studies show that neuronal loss--one of the hallmarks of prion diseases may be accomplished by apoptosis. We evaluated twenty five mice infected experimentally with the Fujisaki strains of CJD and sacrified sequentially in one week intervals. Apoptotic cells in various brain regions were detected by in situ end labelling (TUNEL) and electron microscopy in comparison with neuronal cell loss. The number of labelled cells per brain was very low--from a few labelled cells 6 weeks after inoculation to a maximum of 14 in the terminal stage. The number of neurones counted in 8 selected areas were considerably lower in terminally sick animals (20 and 21 week of incubation period) than in control mice. The mean value of loss of neuronal cells was 32%. The greatest loss (55%) of neurones was noted in the septal nuclei of the paraterminal body and the least lost (16%) in the hypothalamus. Compared to the extensive neuronal loss (30-50%), the number of apoptotic cells detected by in situ end labelling seems to be very low, and the process of neuronal death become more intensive during the progression of the disease.


The Complexity of Immigrant Generations: Implications for Assessing the Socioeconomic Integration of Hispanics and Asians.
Because of data limitations, virtually all studies of the later-generation descendants of immigrants rely on subjective measures of ethnic self-identification rather than arguably more objective measures based on the countries of birth of the respondent and his ancestors. In this context, biases can arise from "ethnic attrition" (e.g., U.S.-born individuals who do not self-identify as Hispanic despite having ancestors who were immigrants from a Spanish-speaking country). Analyzing 2003-2013 data from the Current Population Survey (CPS), this study shows that such ethnic attrition is sizeable and selective for the second- and third-generation populations of key Hispanic and Asian national origin groups. In addition, the results indicate that ethnic attrition generates measurement biases that vary across groups in direction as well as magnitude, and that correcting for these biases is likely to raise the socioeconomic standing of the U.S.-born descendants of Hispanic immigrants relative to their Asian counterparts.


Antigenic diversity of lipooligosaccharides of nontypable Haemophilus influenzae.
The lipooligosaccharides (LOS) of nontypable Haemophilus influenzae are an antigenically heterogeneous group of macromolecules. Immunodiffusion and enzyme-linked immunosorbent assay inhibition studies with phenol-water-extracted LOS and absorbed antisera specific for the oligosaccharide portion of the LOS identified six LOS strain-specific antigens. To facilitate screening large numbers of strains to search for LOS antigenic heterogeneity, a system utilizing proteinase K whole cell digests in Western blots was developed. Seventy-two nontypable H. influenzae LOS extracts were analyzed in this Western blot assay. Thirty-seven of these extracts could be segregated into 10 antigenically distinct LOS groups based on immunologic recognition by one or more of the rabbit antisera. Thirty-five of the strains did not contain these LOS antigens. These results demonstrate that antigenic differences exist among the LOS of nontypable H. influenzae strains, and this heterogeneity has the potential to be used to establish an LOS-based serogrouping system.


Allergic contact dermatitis in psoriasis patients: typical, delayed, and non-interacting.
Psoriasis is characterized by an apoptosis-resistant and metabolic active epidermis, while a hallmark for allergic contact dermatitis (ACD) is T cell-induced keratinocyte apoptosis. Here, we induced ACD reactions in psoriasis patients sensitized to nickel (n = 14) to investigate underlying mechanisms of psoriasis and ACD simultaneously. All patients developed a clinically and histologically typical dermatitis upon nickel challenge even in close proximity to pre-existing psoriasis plaques. However, the ACD reaction was delayed as compared to non-psoriatic patients, with a maximum intensity after 7 days. Whole genome expression analysis revealed alterations in numerous pathways related to metabolism and proliferation in non-involved skin of psoriasis patients as compared to non-psoriatic individuals, indicating that even in clinically non-involved skin of psoriasis patients molecular events opposing contact dermatitis may occur. Immunohistochemical comparison of ACD reactions as well as in vitro secretion analysis of lesional T cells showed a higher Th17 and neutrophilic migration as well as epidermal proliferation in psoriasis, while ACD reactions were dominated by cytotoxic CD8+ T cells and a Th2 signature. Based on these findings, we hypothesized an ACD reaction directly on top of a pre-existing psoriasis plaque might influence the clinical course of psoriasis. We observed a strong clinical inflammation with a mixed psoriasis and eczema phenotype in histology. Surprisingly, the initial psoriasis plaque was unaltered after self-limitation of the ACD reaction. We conclude that sensitized psoriasis patients develop a typical, but delayed ACD reaction which might be relevant for patch test evaluation in clinical practice. Psoriasis and ACD are driven by distinct and independent immune mechanisms.


Acute Orbital Apex Syndrome Caused by Idiopathic Sclerosing Orbital Inflammation.
Idiopathic sclerosing orbital inflammation (ISOI) is a distinct entity among other orbital diseases. It is characterized by marked fibrosis and inflammatory cell infiltration that can damage orbital structures. Clinical manifestations were variable, including ocular and periocular redness, proptosis, and pain. Ocular motor restrictions and optic nerve dysfunction might occur in severe cases. We herein report a patient of ISOI who presented with total ophthalmoplegia and acute vision loss. His symptoms were relieved mainly as his vision improved to 20/25 after receiving corticosteroid and immunosuppressant therapies. Therefore, ISOI should be one of the deferential diagnoses when we encounter cases with acute orbital apex syndrome. With prompt evaluation and in-time treatment, a favorable outcome is possible.


Intraocular concentration and pharmacokinetics of triamcinolone acetonide after a single intravitreal injection.
To describe the pharmacokinetics occurring after the direct injection of triamcinolone acetonide into the vitreous humor of humans. Interventional case series. Five patients who received a single 4-mg intravitreal injection of triamcinolone acetonide. An aqueous humor sample was obtained from 5 eyes via an anterior chamber paracentesis at days 1, 3, 10, 17, and 31 after injection. At each visit, visual acuity and intraocular pressure were measured and indirect ophthalmoscopy was performed. A fluorescein angiogram was carried out at day 10. Concentrations were determined using high performance liquid chromatography; pharmacokinetic analysis was carried out using PK Analyst, an iterative, nonlinear, weighted, least-squares regression program. Intraocular concentrations of triamcinolone were measured and population pharmacokinetic parameters were calculated. Pharmacokinetic data followed a two-compartment model. Peak aqueous humor concentrations ranged from 2151 to 7202 ng/ml, half-lives from 76 to 635 hours, and the integral of the area under the concentration-time curve (AUC(0-t)) from 231 to 1911 ng/h per milliliter. After a single intravitreal injection of triamcinolone, the mean elimination half-life was 18.6 days in nonvitrectomized patients. The half-life in a patient who had undergone a vitrectomy was shorter at 3.2 days. There was considerable intrasubject variation among peak concentration, AUC(0-t) values, and elimination half-lives. After intravitreal injection, measurable concentrations of triamcinolone would be expected to last for approximately 3 months (93 +/- 28 days) in the absence of a vitrectomy. Because triamcinolone pharmacokinetics were characterized only in elderly patients with macular edema, the results cannot be extrapolated to other patient populations.


Effect of free carriers on pump-to-signal noise transfer in silicon Raman amplifiers.
We study noise transfer from pump to signal in silicon Raman amplifiers, with particular emphasis on the regimes of strong cumulative free-carrier absorption and heavy pump depletion. We calculate the relative intensity noise (RIN) transfers in copumped and counterpumped amplifiers and provide intuitive explanations for RIN peculiarities. We show that noise transfer at low frequencies may be suppressed by carefully choosing the pump intensity, effective free-carrier lifetime, or amplifier length, but only at the expense of a rise in noise at high frequencies.


Topoisomerase I interactive drugs in children with cancer.
Topotecan, irinotecan, and 9-aminocamptothecin (9-AC) are analogs of the plant alkaloid 20(S)-camptothecin (CMT), the prototypical DNA topoisomerase I interactive agent. These agents interact with the topoisomerase I-DNA complex and prevent resealing topoisomerase I-mediated DNA single-strand breaks. This eventual leads to double-strand DNA breaks and apoptosis or cell death. Topotecan, irinotecan, and 9-AC have shown significant activity in mice bearing pediatric solid tumor xenografts; the greatest antitumor responses were found with protracted continuous schedules. Preclinical data also suggest that maintenance of an exposure-duration threshold (EDT) may be required to achieve optimal cytotoxicity. Pediatric Phase I trials have evaluated the toxicity and safety to camptothecin analogs in children with relapsed solid tumors and relapsed acute leukemia. The primary dose-limiting toxicity (DLT) for the CMT analogs in children has been myelosuppression, except for mucositis observed with the 120-hr continuous topotecan infusion schedule. Pharmacodynamic relationships with these analogs have been reported between systemic exposure, and myelosuppression and mucositis. Although not a primary objective of the early Phase I studies, antitumor responses have been reported. In this review, the pharmacokinetic and pharmacodynamics of the CMT analogs studied in children are summarized, and future studies of these agents are discussed.


Nutrient adequacy of low fat intakes for children: the Bogalusa Heart Study.
Nutritional adequacy is important when diets and dietary alterations are recommended for children. Concern is expressed that low fat intakes may have deleterious effects on growth and development and may be deficient in total calories and essential nutrients. In a study of the effect of variation in percent fat in the diet, a sample of 871 ten-year-olds was stratified according to four different fat intakes: less than 30% of total kilocalories (kcal), 30% to 35% kcal, 35% to 40% kcal, and greater than 40% kcal. The race/sex distribution was similar within each fat intake group. Fourteen percent of the sample had fat intakes less than 30% of total calories. The amount of calories from breakfast, dinner, and snacks was higher in the children with fat intakes greater than 40% of total calories than those with lower fat intakes. The energy intake of all race/sex groups fell within the recommended range. The low fat intake group was eating 25% less calories than the high fat intake group (1800 kcal vs 2400 kcal). The percentage of calories from carbohydrate, specifically sugar, was greater in the low fat intake group compared with the high fat intake group. Percentage of calories from protein was approximately 13% for all groups. Fiber and starch were the same across all fat intakes.(ABSTRACT TRUNCATED AT 250 WORDS)


Pathologic factors affecting postsplenectomy survival in dogs.
The apparently high prevalence of splenomegaly in dogs, along with the surgical accessibility of the spleen, results in a relatively large number of splenectomies in dogs in clinical veterinary practice. Splenic nodular lesions are widely considered to be indicative of hemangiosarcoma and thus a disease that is ultimately fatal. This study correlates the results of complete pathologic evaluation and classification of 500 spleens obtained by splenectomy with survival information for each dog. Among the spleens examined, 257 of 500 (51.4%) were classified nonneoplastic and 241 (48.2%) were neoplastic; 2 (0.4%) were unclassified. Miscellaneous non-nodular splenomegaly accounted for 46 of 257 (18%) of the nonneoplastic lesions; nodular splenomegaly accounted for 206 of 257 (79%) of nonneoplastic splenic lesions and was composed of lymphoid hyperplastic nodules and associated hematomas, hyperplastic lymphoid nodules alone, or hematomas with no apparent underlying cause. Nodular neoplastic diseases of the spleen were divided among benign tumors (11.5%) and a variety of primary sarcomas. Hemangiosarcoma made up 51% of splenic malignancies but accounted for less than 25% of the spleens evaluated. Survival of dogs with hematomas associated with nonneoplastic conditions of the spleen was markedly different from that in dogs with hemangiosarcoma-associated hematomas, even though most could not be effectively differentiated on gross inspection. Two month postoperative survival was 83% for dogs with nonneoplastic-related hematomas, whereas only 31% of dogs with hemangiosarcoma, with or without associated hematomas, were alive after 2 months. Twelve-month survival times were 64% and 7%, respectively. An overall postsplenectomy survival rate of 52% was based on the number of dogs surviving for a minimum of 6 months postoperatively.


Randomized Trial of Motivational Interviewing to Prevent Early Childhood Caries in Public Housing.
Caries experience among preschool-age children has remained relatively unchanged for the past 2 decades, despite recently documented decreases in untreated decay. In a community-based cluster-randomized controlled trial, a motivational interviewing (MI) intervention administered to primary caregivers was hypothesized to reduce caries increment over 2 y as compared with controls, among children aged 0 to 5 y at baseline living in public housing. Public housing residents, who served as interventionists, were trained in MI with a focus on early childhood caries prevention. All 26 eligible public housing developments were randomized to either control (quarterly clinical examinations, fluoride varnish applications, toothbrush/toothpaste, and educational brochures) or intervention (same procedures as control plus MI counseling). Quarterly MI sessions were delivered in English or Spanish over 2 y, audio recorded, and assessed for treatment fidelity. The primary outcome was the increment in dmfs (decayed, missing, and filled tooth surfaces) as assessed by clinical examination at baseline, 12 mo, and 24 mo. Secondary outcomes included caregiver oral health knowledge and child oral health behaviors (child toothbrushing and sugar-sweetened beverage intake). Baseline characteristics were compared between groups and adjusted for housing-site clusters. Longitudinal outcomes were analyzed with mixed models. A total of 1,065 children (49% female, 55% non-White, 61% Hispanic, 89% below poverty level, n = 686 control) and their caregivers were enrolled. During 2 y of follow-up, the mean dmfs increment increased in both groups; however, there were no statistically significant group differences at 24 mo or group × time interactions. The mean increase in intervention caregivers' knowledge was significantly greater than that of control, F(2, 1,593) = 3.48, P = 0.0310, but there were no significant intervention effects on caregiver-reported child sugar-sweetened beverage intake or child toothbrushing. MI counseling plus intensive caries prevention activities resulted in knowledge increases but did not improve oral health behaviors or caries increment (ClinicalTrials.gov NCT01205971). When viewed in light of the findings from the companion Pine Ridge study and other recent MI studies, the results of this study suggest that when the complex disease of early childhood caries is addressed in high-risk populations, MI is not effective, and alternative approaches are warranted.


Multi-Omics Approach Reveals Prebiotic and Potential Antioxidant Effects of Essential Oils from the Mediterranean Diet on Cardiometabolic Disorder Using Humanized Gnotobiotic Mice.
Essential oils sourced from herbs commonly used in the Mediterranean diet have demonstrated advantageous attributes as nutraceuticals and prebiotics within a model of severe cardiometabolic disorder. The primary objective of this study was to assess the influences exerted by essential oils derived from thyme (Thymus vulgaris) and oregano (Origanum vulgare) via a comprehensive multi-omics approach within a gnotobiotic murine model featuring colonic microbiota acquired from patients diagnosed with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM). Our findings demonstrated prebiotic and potential antioxidant effects elicited by these essential oils. We observed a substantial increase in the relative abundance of the Lactobacillus genus in the gut microbiota, accompanied by higher levels of short-chain fatty acids and a reduction in trimethylamine N-oxide levels and protein oxidation in the plasma. Moreover, functional enrichment analysis of the cardiac tissue proteome unveiled an over-representation of pathways related to mitochondrial function, oxidative stress, and cardiac contraction. These findings provide compelling evidence of the prebiotic and antioxidant actions of thyme- and oregano-derived essential oils, which extend to cardiac function. These results encourage further investigation into the promising utility of essential oils derived from herbs commonly used in the Mediterranean diet as potential nutraceutical interventions for mitigating chronic diseases linked to CAD and T2DM.


Lipids and atherosclerosis.
More than 50 years ago the observation was made that the prevalence of atherosclerosis is unusually low among some of the world's populations. Shortly thereafter came the suggestion that this circumstance is due to the low fat content of their diets and the low cholesterol concentration in their blood. Efforts to apply this thinking for the benefit of human health have taken various turns. The first approach was to recommend a low-fat diet. It was thought that the type of fat in the diet was immaterial and that the dietary cholesterol content made no difference either. Later, it was shown that excellent falls in blood cholesterol could be obtained with high-fat diets if most of the fat was polyunsaturated. Dietary cholesterol was found to play a role, but it must be held at exceptionally low levels before its importance becomes evident. Recently, we have become fearful of excessively high intakes of polyunsaturated fats because no population has consumed such a diet over a long period of time and because of suggestive experimental and epidemiological evidence that the incidence of some forms of cancer may be increased. A low-fat, low-cholesterol diet is the preferred prescription for hyperlipidemia.


Using cloud-based mobile technology for assessment of competencies among medical students.
Valid, direct observation of medical student competency in clinical settings remains challenging and limits the opportunity to promote performance-based student advancement. The rationale for direct observation is to ascertain that students have acquired the core clinical competencies needed to care for patients. Too often student observation results in highly variable evaluations which are skewed by factors other than the student's actual performance. Among the barriers to effective direct observation and assessment include the lack of effective tools and strategies for assuring that transparent standards are used for judging clinical competency in authentic clinical settings. We developed a web-based content management system under the name, Just in Time Medicine (JIT), to address many of these issues. The goals of JIT were fourfold: First, to create a self-service interface allowing faculty with average computing skills to author customizable content and criterion-based assessment tools displayable on internet enabled devices, including mobile devices; second, to create an assessment and feedback tool capable of capturing learner progress related to hundreds of clinical skills; third, to enable easy access and utilization of these tools by faculty for learner assessment in authentic clinical settings as a means of just in time faculty development; fourth, to create a permanent record of the trainees' observed skills useful for both learner and program evaluation. From July 2010 through October 2012, we implemented a JIT enabled clinical evaluation exercise (CEX) among 367 third year internal medicine students. Observers (attending physicians and residents) performed CEX assessments using JIT to guide and document their observations, record their time observing and providing feedback to the students, and their overall satisfaction. Inter-rater reliability and validity were assessed with 17 observers who viewed six videotaped student-patient encounters and by measuring the correlation between student CEX scores and their scores on subsequent standardized-patient OSCE exams. A total of 3567 CEXs were completed by 516 observers. The average number of evaluations per student was 9.7 (±1.8 SD) and the average number of CEXs completed per observer was 6.9 (±15.8 SD). Observers spent less than 10 min on 43-50% of the CEXs and 68.6% on feedback sessions. A majority of observers (92%) reported satisfaction with the CEX. Inter-rater reliability was measured at 0.69 among all observers viewing the videotapes and these ratings adequately discriminated competent from non-competent performance. The measured CEX grades correlated with subsequent student performance on an end-of-year OSCE. We conclude that the use of JIT is feasible in capturing discrete clinical performance data with a high degree of user satisfaction. Our embedded checklists had adequate inter-rater reliability and concurrent and predictive validity.


P-Doped NiCo2S4 nanotubes as battery-type electrodes for high-performance asymmetric supercapacitors.
NiCo2S4 is a promising electrode material for supercapacitors, due to its rich redox reactions and intrinsically high conductivity. Unfortunately, in most cases, NiCo2S4-based electrodes often suffer from low specific capacitance, low rate capability and fast capacitance fading. Herein, we have rationally designed P-doped NiCo2S4 nanotube arrays to improve the electrochemical performance through a phosphidation reaction. Characterization results demonstrate that the P element is successfully doped into NiCo2S4 nanotube arrays. Electrochemical results demonstrate that P-doped NiCo2S4 nanotube arrays exhibit better electrochemical performance than pristine NiCo2S4, e.g. higher specific capacitance (8.03 F cm-2 at 2 mA cm-2), good cycling stability (87.5% capacitance retention after 5000 cycles), and lower charge transfer resistance. More importantly, we also assemble an asymmetric supercapacitor using P-doped NiCo2S4 nanotube arrays and activated carbon on carbon cloth, which delivers a maximum energy density of 42.1 W h kg-1 at a power density of 750 W kg-1. These results demonstrate that the as-fabricated P-doped NiCo2S4 nanotube arrays on carbon cloth show great potential as a battery-type electrode for high-performance supercapacitors.


The basic reproductive ratio of Barbour's two-host schistosomiasis model with seasonal fluctuations.
Motivated by the first mathematical model for schistosomiasis proposed by Macdonald and Barbour's classical schistosomiasis model tracking the dynamics of infected human population and infected snail hosts in a community, in our previous study, we incorporated seasonal fluctuations into Barbour's model, but ignored the effect of bovine reservoir host in the transmission of schistosomiasis. Inspired by the findings from our previous work, the model was further improved by integrating two definitive hosts (human and bovine) and seasonal fluctuations, so as to understand the transmission dynamics of schistosomiasis japonica and evaluate the ongoing control measures in Liaonan village, Xingzi County, Jiangxi Province. The basic reproductive ratio R 0 and its computation formulae were derived by using the operator theory in functional analysis and the monodromy matrix theory. The mathematical methods for global dynamics of periodic systems were used in order to show that R 0 serves as a threshold value that determines whether there was disease outbreak or not. The parameter fitting and the ratio calculation were performed with surveillance data obtained from the village of Liaonan using numerical simulation. Sensitivity analysis was carried out in order to understand the impact of R 0 on seasonal fluctuations and snail host control. The modified basic reproductive ratios were compared with known results to illustrate the infection risk. The Barbour's two-host model with seasonal fluctuations was proposed. The implicit expression of R 0 for the model was given by the spectral radius of next infection operator. The R 0 s for the model ranged between 1.030 and 1.097 from 2003 to 2010 in the village of Liaonan, Xingzi County, China, with 1.097 recorded as the maximum value in 2005 but declined dramatically afterwards. In addition, we proved that the disease goes into extinction when R 0 is less than one and persists when R 0 is greater than one. Comparisons of the different improved models were also made. Based on the mechanism and characteristics of schistosomiasis transmission, Barbour's model was improved by considering seasonality. The implicit formula of R 0 for the model and its calculation were given. Theoretical results showed that R 0 gave a sharp threshold that determines whether the disease dies out or not. Simulations concluded that: (i) ignoring seasonality would overestimate the transmission risk of schistosomiasis, and (ii) mollusiciding is an effective control measure to curtail schistosomiasis transmission in Xingzi County when the removal rate of infected snails is small.


Time resolved in situ X-ray diffraction study of crystallisation processes of large pore nanoporous aluminophosphate materials.
Time resolved high-resolution X-ray powder diffraction was utilized to obtain detailed changes in the crystal structure parameters during the hydrothermal crystallization process of the nanoporous aluminophosphate AlPO-5 (AFI) structure. This in situ study offered not only the influence of metal ions on the onset of crystallization and estimation of the activation energy of the process, but also allowed us to determine in detail the changes in lattice parameters during this process. More importantly the time-resolved study clearly showed the lattice expansion in the divalent metal ions substituted system right from the on-set of crystallization process, compared to the one without any dopant ions, which suggest that an amorphous or poorly crystalline network is formed prior to crystallization that contains the large divalent ions (compared to Al(iii), the substituting element), which is in agreement with the combined XAS/XRD study reported earlier. A mechanism based on this and the earlier study is suggested.


The diabetes-linked transcription factor Pax4 is expressed in human pancreatic islets and is activated by mitogens and GLP-1.
We previously demonstrated that the transcription factor Pax4 is important for beta-cell replication and survival in rat islets. Herein, we investigate Pax4 expression in islets of non-diabetic and diabetic donors, its regulation by mitogens, glucose and the incretin GLP-1 and evaluate its effect on human islet proliferation. Pax4 expression was increased in islets derived from Type 2 diabetic donors correlating with hyperglycaemia. In vitro studies on non diabetic islets demonstrated that glucose, betacellulin, activin A, GLP-1 and insulin increased Pax4 mRNA levels. Glucose-induced Pax4 expression was abolished by the inhibitors LY294002, PD98050 or H89. Surprisingly, increases in Pax4 expression did not prompt a surge in human islet cell replication. Furthermore, expression of the proliferation marker gene Id2 remained unaltered. Adenoviral-mediated expression of human Pax4 resulted in a small increase in Bcl-xL expression while Id2 transcript levels and cell replication were unchanged in human islets. In contrast, overexpression of mouse Pax4 induced human islet cell proliferation. Treatment of islets with 5-Aza-2'-deoxycytidine induced Pax4 without stimulating Bcl-xL and Id2 expression. Human Pax4 DNA binding activity was found to be lower than that of the mouse homologue. Thus, human pax4 gene expression is epigenetically regulated and induced by physiological stimuli through the concerted action of multiple signalling pathways. However, it is unable to initiate the transcriptional replication program likely due to post-translational modifications of the protein. The latter highlights fundamental differences between human and rodent islet physiology and emphasizes the importance of validating results obtained with animal models in human tissues.


Detection and incidence of Escherichia coli on storage pen surfaces of fishing trawlers.
Six methods for the detection and enumeration of Escherichia coli on the storage pen surfaces of commercial fishing trawlers and in harbor wash water were evaluated. E. coli was found consistently present in Boston harbor water used for washing vessel holds and was detected either in small numbers or not at all on storage pen surfaces. Violet Red Bile Agar as a primary enumeration medium was found ineffective for detection of coliforms because of the nonselective development of large numbers of other gram-negative organisms. The use of E. coli broth at 44.5 C for primary most-probable-number determinations, followed by confirmation of E. coli on Levine Eosine Methylene Blue Agar, appears to offer numerous advantages over more conventional methods of detecting E. coli for survey studies of the fishing industry, where coliform-like organisms result in many false-positive presumptives with other methods.


Shoulder imbalance treated with scapuloplasty surgery in scoliosis patients: a clinical retrospective study.
To discuss the clinical efficacy and safety of scapuloplasty treating the shoulder imbalance in scoliosis patients. A retrospective analysis was made on 21 patients who underwent scoliosis corrective surgery combined with scapuloplasty from September 2013 to March 2015. The average follow-up was 31.4 ± 5.3 months (24-42 months). The shoulder vertical difference (SVD), adjusted Constant-Murley score, range of shoulder motion function, Cavendish grade, and the overall satisfaction were compared among the pre-surgery, post-surgery, and the final follow-up periods. The shoulder vertical difference (SVD) significantly decreased at the time of post-surgery and the final follow-up, comparing the score of the pre-surgery. The SVD of all patients were decreased from preoperatively 3.2 ± 1.1 cm to 0.4 ± 0.3 cm, with the Cavendish grade improved to grade 1 at the final follow-up. The adjusted Constant-Murley score and range of shoulder motion function showed no significant difference during the three time periods (p > 0.05). And no severe complications had occurred over 2 years follow-up. The scapuloplasty surgery shows to be an effective and safety procedure to improve the shoulder imbalance, cosmetic appearance, and the overall satisfaction in scoliosis patients without impairing the shoulder function, which can be widely applied in clinic.


Downregulation of cytochrome c oxidase 1 induced radioresistance in esophageal squamous cell carcinoma.
Comprehensive gene screening with transposons is a novel procedure for the systematic identification of resistant genes. The present study aimed to use this technique to identify candidate radioresistant genes in esophageal squamous cell carcinoma. A transposon is a base sequence that can translocate to another location in the genome at random. By inserting the cytomegalovirus promotor as a transcriptional activator in the transposon, the following gene in the new location becomes overexpressed and the gene located at the transposon insertion site is downregulated. Consequently, various transposon-tagged cells, which have differentially overexpressed or downregulated genes using the transposon method can be obtained. Following the irradiation of transposon-tagged cells, candidate radioresistant genes can be selected in order to detect the location of the transposon in the cells that have survived. A total of 11 genes were detected as candidate radioresistant genes. Cytochrome c oxidase 1 (MT-CO1), an enzyme involved in apoptosis through the activation of the caspase cascade, was one of the candidate genes identified. The relative expression level of MT-CO1 was 0.12 in MT-CO1-downregulated cells which was significantly lower compared with the expression level in parent TE4 cells (P<0.001). The survival rate was 28.7% in MT-CO1-downregulated cells and 10.5% in parent TE4 cells 9 days following 5-Gy irradiation. The activity of cytochrome c and caspase-3 following irradiation was significantly lower in the MT-CO1-downregulated radioresistant cells compared with in TE4 cells. In conclusion, the novel gene screening technique demonstrated to be useful for detecting candidate radioresistant genes in esophageal squamous cell carcinoma. The results of the present study revealed that the downregulation of MT-CO1 induced radioresistance occurs by inhibiting the activation of the caspase cascade in radioresistant esophageal cancer cells.


Matrix effect of sodium compounds on the determination of metal ions in aqueous solutions by underwater laser-induced breakdown spectroscopy.
A significant portion of the carbon sequestration research being performed in the United States involves the risk assessment of injecting large quantities of carbon dioxide into deep saline aquifers. Leakage of CO2 has the potential to affect the quality of groundwater supplies in case contaminants migrate through underlying conduits. New remote sensing and near-surface monitoring technologies are needed to ensure that injection, abandoned, and monitoring wells are structurally sound, and that CO2 remains within the geologic storage reservoir. In this paper, we propose underwater laser-induced breakdown spectroscopy (underwater LIBS) as an analytical method for monitoring naturally occurring elements that can act as tracers to detect a CO2 leak from storage sites. Laboratory-scale experiments were conducted to measure Sr2+, Ca2+, K(+), and Li(+) in bulk solutions to ascertain the analytical performance of underwater LIBS. We compared the effect of NaCl, Na2CO3, and Na2SO4 on the analytes calibration curves to determine underwater LIBS' ability to analyze samples of sodium compounds. In all cases, the calibration curves showed a good linearity within 2 orders of magnitude. The limit of detections (LODs) obtained for K(+) (30±1 ppb) and Li(+) (60±2 ppb) were in ppb range, while higher LODs were observed for Ca(2+) (0.94±0.14 ppm) and Sr(2+) (2.89±0.11 ppm). Evaluation of the calibration curves for the analytes in mixed solutions showed dependence of the lines' intensity with the sodium compounds. The intensities increased respectively in the presence of dissolved NaCl and Na2SO4, whereas the intensities slightly decreased in the presence of Na2CO3. Finally, the capabilities of underwater LIBS to detect certain elements in the ppb or in the low ppm range make it particularly appealing for in situ monitoring of a CO2 leak.


Protective preparation: a process central to family caregivers of persons with mild cognitive impairment.
ABSTRACTBackground:To develop a theoretical model explaining the longitudinal changes in the caregiving process for family caregivers of persons with mild cognitive impairment (MCI) in Taiwan. A longitudinal, grounded theory approach using in-depth face-to-face interviews and an open-ended interview guide. We conducted 42 interviews over a two-year period; each participant was interviewed at least once every six months. All participants were interviewed in their home. The participants total of 13 family caregivers of persons with MCI. One core theme emerged: "protective preparation." This reflected the family caregiving process of preparation for a further decline in cognitive function, and protection from the impact of low self-esteem, accidents, and symptoms of comorbidities for the family member with MCI. Protective preparation contained three components: ambivalent normalization, vigilant preparation, and protective management. Interventions to help family caregivers manage the changes in persons with MCI can reduce caregiver burden. Our findings could provide a knowledge base for use by healthcare providers to develop and implement strategies to reduce caregiver burden for family caregivers of persons with MCI.


From gestation to weaning: Combining robust design and multi-event models unveils cost of lactation in a large herbivore.
The cost of current reproduction on survival or future reproduction is one of the most studied trade-offs governing resource distribution between fitness components. Results have often been clouded, however, by the existence of individual heterogeneity, with high-quality individuals able to allocate energy to several functions simultaneously, at no apparent cost. Surprisingly, it has also rarely been assessed within a breeding season by breaking down the various reproductive efforts of females from gestation to weaning, even though resource availability and energy requirements vary greatly. We filled this gap by using an intensively monitored population of Pyrenean chamois and by expanding a new methodological approach integrating robust design in a multi-event framework. We distinguished females that gave birth or not, and among reproducing females whether they lost their kid or successfully raised it until weaning. We estimated spring and summer juvenile survival, investigated whether gestation, lactation or weaning incurred costs on the next reproductive occasion, and assessed how individual heterogeneity influenced the detection of such costs. Contrary to expectations if trade-offs occur, we found a positive relationship between gestation and adult survival suggesting that non-breeding females are in poor condition. Costs of reproduction were expressed through negative relationships between lactation and both subsequent breeding probability and spring juvenile survival. Such costs could be detected only once individual heterogeneity (assessed as two groups contrasting good vs. poor breeders) and time variations in juvenile survival were accounted for. Early lactation decreased the probability of future reproduction, providing quantitative evidence of the fitness cost of this period recognized as the most energetically demanding in female mammals and critical for neonatal survival. The new approach employed made it possible to estimate two components of kid survival that are often considered practically unavailable in free-ranging populations, and also revealed that reproductive costs appeared only when contrasting the different stages of reproductive effort. From an evolutionary perspective, our findings stressed the importance of the temporal resolution at which reproductive cost is studied, and also provided insights on the reproductive period during which internal and external factors would be expected to have the greatest fitness impact.


Expression of O6-methylguanine-DNA methyltransferase in six human medulloblastoma cell lines.
Six well characterized human medulloblastoma cell lines (D283 Med, Daoy, D341 Med, D384 Med, D425 Med, and D458 Med) were examined for the expression of O6-methylguanine-DNA methyltransferase (MGMT) by activity and Western and Northern blot analysis. High levels of MGMT activity were present in D283 Med, Daoy, D341 Med, and D384 Med (1.36, 0.80, 1.68, and 1.62 pmol/mg of protein, respectively), but negligible MGMT activity was detected in D425 Med and D458 Med (0.06 and 0.05 pmol/mg of protein, respectively), which were derived separately at different times from the same patient. The presence of MGMT protein and its transcript was demonstrated in D283 Med, Daoy, D341 Med, and D384 Med, but both the protein and the mRNA were undetectable in D425 Med and D458 Med. Nevertheless, all six cell lines contained an apparently unaltered MGMT gene, as determined by Southern blot analysis. The absence of MGMT activity in D425 Med and D458 Med is likely due to the absence of the protein, resulting from a lack of transcription of the MGMT gene. The varying levels of expression of MGMT in medulloblastoma cells found in this study should provide a molecular basis for drug design and selection in chemotherapy of this tumor.


Variable Adjustment Methods for Hemihamate Autograft Arthroplasty in Proximal Interphalangeal Joint Fracture/Dislocations: A Surgical Technique Revisited and Case Series.
Proximal interphalangeal joint fracture/dislocations, even after surgical correction, often lead to long-term complications including posttraumatic arthritis, prolonged joint stiffness, and chronic joint instability. A wide range of surgical techniques has been devised to resolve this issue, but none has been promising enough. Despite this circumstance, arthroplasty using a hemihamate autograft of size and contour that match the middle phalangeal base has progressed into one of more acceptable methods that provide both articular congruency and osseous stability. In this article, we introduce various types of proximal interphalangeal joint fracture/dislocations and individualized surgical approach using hemihamate autograft and lag screw and/or hook plate as fixation methods.