Affinity purification and some molecular properties of human liver alkaline phosphatase.
Alkaline phosphatase from human liver was purified to homogeneity. The purification procedure included solubilization with butanol, fractionation with acetone, and chromatography on concanavalin A-Sepharose, DEAE-cellulose, Sephadex G-200 and DEAE-Sephadex. Purity was established by standard and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The isoelectric point of the protein was determined to be 4.0. Sephadex-gel filtration gave a mol.wt. of 146000, although a higher value was obtained in the presence of 100mM-NaC1. The subunit mol.wt. 76700, was determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Neuraminidase treatment resulted in two enzyme-activity bands on isoelectric-focused gels with isoelectric points of 6.6 and 6.8. The desialylated enzyme gave only one protein band on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis with a subunit molecular weight indistinguishable from that of the non-neuraminidase-treated protein. The desialylated enzyme was more readily denatured by sodium dodecyl sulphate in the presence of mercaptoethanol than was the native enzyme.


Exploring the clinical information system implementation readiness activities to support nursing in hospital settings.
The implementation of clinical information systems can have a profound impact on nurses and their productivity. Poorly implemented systems can lead to unintended consequences that may have a negative impact on clinical processes and patient outcomes. Executives must have adequate knowledge to address nurses' concerns related to implementation. This study explored the clinical information system implementation readiness activities adopted by chief nurse executivesin hospital settings. A descriptive qualitative design was used, including interviews with six chief nurse executives, held from December 2003 through March 2004. The constant comparative method was used to analyze the interviews to extract readiness activity themes and compare these to the literature. The synthesized themes showed that the executives were knowledgeable about and engaged in several key areas, but not all, of the implementation readiness process. The majority of responses were classified into the thematic areas of champion support, staff preparation for change, training, organizational alignment, planning, and vendor support. The theme of a lack of vendor support was not identified in previous studies but was clear in the responses of the chief nurse executives interviewed.


Nutrition (Micronutrients) in Child Growth and Development: A Systematic Review on Current Evidence, Recommendations and Opportunities for Further Research.
An important aspect of malnutrition is deficiency of different micronutrients during pregnancy or early childhood. We systematically reviewed the role of nutrition in child growth (weight or height gain) and development. A comprehensive literature search was done on PubMed/Cochrane Library browsing through 38,795 abstracts until December 31, 2016 to select systematic reviews/meta-analyses and individual randomized controlled trials (RCTs) of micronutrient supplementation. Micronutrients studied included iron, iodine, folate, zinc, calcium, magnesium, selenium, vitamin D, vitamin A, vitamin B complex, and multiple micronutrients. We summarize evidence with details and results of RCTs, highlight strengths/weaknesses, and critically interpret findings. Effects of breastfeeding-promotion, food-supplementation (complementary and school feeding), conditional-cash-transfers, and integrated nutrition/psychosocial interventions are discussed. Based on this evidence we make policy and programmatic recommendations for supplementation to mothers and children at high-risk of deficiency.


A mathematical model of calcium and phosphorus metabolism in two forms of hyperparathyroidism.
Parathyroid hormone (PTH) plays a critical role in calcium and phosphorus metabolism. Interestingly, in two forms of hyperparathyroidism (excessive amount of PTH in the serum), the metabolic disturbances in patients with chronic kidney disease (CKD) significantly differ from those with primary hyperparathyroidism (PHP). Since an intuitive understanding of these PTH-linked regulatory mechanisms are hardly possible, we developed a mathematical model using clinical data (1586 CKD and 40 PHP patients). The model was composed of a set of ordinary differential equations, in which the regulatory mechanism of PTH together with other key factors such as 1,25-Dihydroxyvitamin D (1,25(OH)₂D) and calcium was described in the tissues including bone, the kidney, the serum, and the parathyroid glands. In this model, an increase in PTH was induced by its autonomous production in PHP, while PTH in CKD was elevated by a decrease in feedback inhibition of 1,25(OH)₂D in the serum, as well as an increase in stimulation by phosphorus in the serum. The model-based analysis revealed characteristic differences in the outcomes of hyperparathyroidism in CKD and PHP. The calcium exchange in bone, for instance, was predicted significantly higher in PHP than CKD. Furthermore, we evaluated the observed and predicted responses to the administration of calcimimetics, a recently developed synthetic drug that modulated efficacy of calcium-sensing receptors. The results herein support the notion that the described model would enable us to pose testable hypotheses about the actions of PTH, providing a quantitative analytical tool for evaluating treatment strategies of PHP and CKD.


Position-Related Differences in Selected Morphological Body Characteristics of Top-Level Female Handball Players.
The study aimed to establish the main morphological characteristics of Slovenian junior and senior female national handball team players. Morphological characteristics of various player subgroups (goalkeepers, wings, back players and pivots) were also determined so as to establish whether they had distinct profiles. The subjects were 87 handball players who were members of the Slovenian junior and senior female national teams in the period from 2003 to 2009. A standardised anthropometric protocol was used to assess the subjects' morphological characteristics. The measurements included 23 different anthropometric measures. First, basic statistical characteristics of anthropometric measures were obtained for all subjects together and then for each group separately. Somatotypes were determined using Heath-Carter's method. Endomorphic, mesomorphic and ectomorphic components were calculated by computer on the basis of formulas. In order to determine differences in the body composition and anthropometric data of the subjects playing in different positions, a one-way analysis of variance was employed. The results show that, on average, the wings differed the most from the other player groups in terms of their morphological body characteristics. The wings differed most prominently from the other player groups in terms of their morphological body parameters as they were significantly smaller and had a statistically significantly lower body mass than the other groups. In terms of transversal measures of the skeleton and the circumferences, the wings significantly differed mainly from the pivots and goalkeepers and less from the backs. The goalkeepers were the tallest, with high values of body mass and low values of transversal measures compared to P. Their skin folds were the most pronounced among all the groups on average and their share of subcutaneous fat in total body mass was the highest. Consequently, their endomorphic component of the somatotype was pronounced. Players in the Pivot position were significantly taller than the Wplayers but were not significantly different from G and B. They had high values of body mass which were significantly higher than that of W but did not differ significantly from the body mass values of B and G. The average values of their circumferences were the highest among all the player groups and the same is true for transversal measures of the skeleton. It is very interesting that, compared to the players in other playing positions, they achieved low values of subcutaneous fat. Their values of the somatotype revealed an endo-mesomorphic somatotype, with a pronounced mesomorphic component. Back players were tall and had the lowest share of subcutaneous fat of all the player groups. Significant differences were established mainly in terms of the structure of the lower extremities. The values of the somato-type characteristics were very balanced between all three components. The results of our study confirm that groups of handball players occupying different positions differed amongst themselves in terms of many measurements. This is a result of the specific requirements of handball play which are to be met by particular players. The tallest players should thus be oriented to back player positions. As regards pivots, the coaches must, besides body height, consider robustness. For goal-keepers, body height is very important; however, the robustness criteria are slightly lower. For wings, body height is not a decisive factor and smaller players can also occupy this position. Both of the above (also taking other criteria into account) facilitate coaches' decisions when orienting players into their playing positions.


A Brain Computer Interface Neuromodulatory Device for Stroke Rehabilitation: Iterative User-Centered Design Approach.
Rehabilitation technologies for people with stroke are rapidly evolving. These technologies have the potential to support higher volumes of rehabilitation to improve outcomes for people with stroke. Despite growing evidence of their efficacy, there is a lack of uptake and sustained use in stroke rehabilitation and a call for user-centered design approaches during technology design and development. This study focuses on a novel rehabilitation technology called exciteBCI, a complex neuromodulatory wearable technology in the prototype stage that augments locomotor rehabilitation for people with stroke. The exciteBCI consists of a brain computer interface, a muscle electrical stimulator, and a mobile app. This study presents the evaluation phase of an iterative user-centered design approach supported by a qualitative descriptive methodology that sought to (1) explore users' perspectives and experiences of exciteBCI and how well it fits with rehabilitation, and (2) facilitate modifications to exciteBCI design features. The iterative usability evaluation of exciteBCI was conducted in 2 phases. Phase 1 consisted of 3 sprint cycles consisting of single usability sessions with people with stroke (n=4) and physiotherapists (n=4). During their interactions with exciteBCI, participants used a "think-aloud" approach, followed by a semistructured interview. At the end of each sprint cycle, device requirements were gathered and the device was modified in preparation for the next cycle. Phase 2 focused on a "near-live" approach in which 2 people with stroke and 1 physiotherapist participated in a 3-week program of rehabilitation augmented by exciteBCI (n=3). Participants completed a semistructured interview at the end of the program. Data were analyzed from both phases using conventional content analysis. Overall, participants perceived and experienced exciteBCI positively, while providing guidance for iterative changes. Five interrelated themes were identified from the data: (1) "This is rehab" illustrated that participants viewed exciteBCI as having a good fit with rehabilitation practice; (2) "Getting the most out of rehab" highlighted that exciteBCI was perceived as a means to enhance rehabilitation through increased engagement and challenge; (3) "It is a tool not a therapist," revealed views that the technology could either enhance or disrupt the therapeutic relationship; and (4) "Weighing up the benefits versus the burden" and (5) "Don't make me look different" emphasized important design considerations related to device set-up, use, and social acceptability. This study offers several important findings that can inform the design and implementation of rehabilitation technologies. These include (1) the design of rehabilitation technology should support the therapeutic relationship between the patient and therapist, (2) social acceptability is a design priority in rehabilitation technology but its importance varies depending on the use context, and (3) there is value in using design research methods that support understanding usability in the context of sustained use.


The complex impact of risk and protective factors on suicide mortality: a study of the Ukrainian general population.
This study assesses the complex impact of risk and protective factors on suicide mortality in the Ukrainian general population. Data on suicide rates and socioeconomic and medical factors were obtained from the Ukrainian State Statistical Office, WHO, and the European Social Survey. Structural equation modeling was used for data analysis. Religion and education were negatively associated with suicide. The relationship between drug addiction/alcoholism and suicide was positive. The association between urbanization and suicide mortality was negative. The relationship between gross regional product (GRP) and female suicide was slightly negative. Religiosity was the protective factor most strongly linked with suicide mortality followed by urbanization. The harmful role of drug addiction and alcoholism was confirmed. The role of education and GRP is controversial. No striking gender differences were found.


[Replication and integration of the fragments of the new chains of the DNA of infusoria Tetrahymena pyriformis GL].
The size of the double-stranded molecules of DNA of the macronucleus of an infusoria Tetrahymena pyriformis GL in the G-1 period of the cell cycle is not less than 400 . 10(6) d. This was shown by alkaline and neutral isokinetic sucrose gradient centrifugation. At the S-period newly synthesized daughter strands of the DNA exist as the fragments of 10-30 . 10(6) daltons for a certain time (about 30 min). The sizes of the primer chains are not decreased. Thus, during the process of replication the primer chains are not fragmented, but the new ones are covalently bound. The synthesis of the new chains in the form of fragments and their subsequent assembly takes place during the S-period of Tetrahymena lasting for about 80 min. It is suggested that the found fragments correspond to the replicative units.


Multifunctional surfaces with discrete functionalized regions for biological applications.
In this paper we describe a method for creating multifunctional glass surfaces presenting discrete patches of different proteins on an inert PEG-functionalized background. Microcontact printing is used to stamp the substrate with octadecyltrichlorosilane to define the active regions. The substrate is then back-filled with PEG-silane {[[2-methoxypoly(ethyleneoxy)]propyl]trimethoxysilane} to define passive regions. A microfluidics device is subsequently affixed to the substrate to deliver proteins to the active regions, with as many channels as there are proteins to be patterned. Examples of trifunctional surfaces are given which present three terminating functional groups, i.e., protein 1, protein 2, and PEG. These surfaces should be broadly useful in biological studies, as patch size is well established to influence cell viability, growth, and differentiation. Three examples of cellular interactions with the surfaces are demonstrated, including the capture of cells from a single cell suspension, the selective sorting of cells from a mixed suspension, and the adhesion of cells to ligand micropatches at critical shear stresses. Within these examples, we demonstrate that the patterned immobilized proteins are active, as they retain their ability to interact with either antibodies in solution or receptors presented by cells. When appropriate (e.g., for E-selectin), proteins are patterned in their physiological orientations using a sandwich immobilization technique, which is readily accommodated within our method. The protein surface densities are highly reproducible in the patches, as supported by fluorescence intensity measurements. Potential applications include biosensors based on the interaction of cells or of marker proteins with protein patches, fundamental studies of cell adhesion as a function of patch size and shear stress, and studies of cell differentiation as a function of surface cues.


Involving practice nurse and other assistant clinical staff members in the management of low back pain: A qualitative interview study from Danish general practice.
Involving practice nurse and other assistant clinical staff members in providing information and education to patients with low back pain at follow-up appointments may release more time and improve care in general practice. However, this requires a shift in the division of tasks, and general practitioners' barriers and facilitators for this are currently unknown. The objectives were to explore general practitioners' experiences and perceptions of including assistant clinical staff members in the management of low back pain. This is a semi-structured interview study in Danish general practice. General practitioners with a variation in demographics and experience with task-delegation to clinical staff were recruited for in-depth interviews. We used a phenomenological approach to guide the data collection and the analysis in order to gain insight into the subjective experiences of the general practitioners and to understand the phenomenon of 'delegating tasks to practice staff' from the perspective of the general practitioners' lifeworld. Analysis was conducted using an inductive descriptive method. The sample size was guided by information power. We conducted five interviews with general practitioners. All general practitioners had experience with task delegation, but there was a variation in which tasks the general practitioners delegated and to which types of clinical staff members. The following themes were derived from the analysis: general practice organisation, delegating to clinical staff members, doctor-patient relationship, exercise instruction, clinical pathway for patients and external support. General practitioners consider patients with low back pain to be a heterogeneous group with a variety of treatment needs and a patient group without any predetermined content or frequency of consultations; this can be a barrier for delegating these patients to clinical staff members.


The effect of combined treatment methods on survival and toxicity in patients with pancreatic cancer.
In Lithuania, there were 476 new pancreatic cancer cases in 2005. Based on international scientific literature and the results of our retrospective studies, a prospective study has been designed. The aim of study was a prospective evaluation of the impact of two concomitant chemoradiation methods on the survival and the time to disease progression in patients diagnosed with resectable and unresectable pancreatic cancer and prospective evaluation of the safety of two concomitant chemoradiation methods for the treatment of resectable and unresectable pancreatic cancer. MATERIAL AND METHODS. During the period of 2000-2005 at the Clinic of Oncology, Kaunas University of Medicine Hospital, we performed a prospective randomized study to analyze two concomitant chemoradiation treatment methods. The patients were stratified according to the resectability of the tumor: with resectable tumor (stage I-IVA) and with unresectable tumor (stage III-IVA). Treatment for each group of patients was selected randomly choosing concomitant chemoradiation treatment: radiation therapy and 5-fluorouracil or radiation therapy and gemcitabine. Criteria of the efficacy of the treatment methods were median survival, time to disease progression, and treatment safety (qualitative and quantitative analysis). RESULTS AND CONCLUSIONS. The treatment methods - radiotherapy and 5-fluorouracil or radiotherapy and gemcitabine - were equally effective when assessing the survival and time to disease progression in patients diagnosed with pancreatic cancer. Treatment of patients diagnosed with pancreatic cancer with radiotherapy and 5-fluorouracil was a safer approach than treatment with radiotherapy and gemcitabine, which induced more severe toxic adverse effects.


A Novel Hypothetical Approach to Explain the Mechanisms of Pathogenicity of Rheumatic Arthritis.
The autoimmune disorder rheumatoid arthritis (RA) is a relapsing and chronic inflammatory disease that affects the synovial cells, cartilage, bone, and muscle. It is characterised by the accumulation of huge numbers of polymorphonuclear neutrophils (PMNs) and macrophages in the synovia. Auto-antibodies are deposited in the joint via the activity of highly cationic histones released from neutrophil extracellular traps (NETs) in a phenomenon termed NETosis. The cationic histones function as opsonic agents that bind to negatively charged domains in autoantibodies and complement compounds via strong electrostatic forces, facilitating their deposition and endocytosis by synovial cells. However, eventually the main cause of tissue damage is the plethora of toxic pro-inflammatory substances released by activated neutrophils recruited by cytokines. Tissue damage in RA can also be accompanied by infections which, upon bacteriolysis, release cell-wall components that are toxic to tissues. Some amelioration of the damaged cells and tissues in RA may be achieved by the use of highly anionic heparins, which can neutralize cationic histone activity, provided that these polyanions are co-administrated with anti-inflammatory drugs such as steroids, colchicine, or methotrexate, low molecular weight antioxidants, proteinase inhibitors, and phospholipase A2 inhibitors.


Creating an evidence-based dentistry culture at Baylor College of Dentistry: the winds of change.
In the early years of the new millennium, the National Institute of Dental and Craniofacial Research of the National Institutes of Health began funding Oral Health Research Education Grants using the R25 mechanism to promote the application of basic and clinical research findings to clinical training and to encourage students to pursue careers in oral health research. This report describes the impact of an R25 grant awarded to the Texas A&M Health Science Center's Baylor College of Dentistry (BCD) on its curriculum and faculty development efforts. At BCD, the R25 grant supports a multipronged initiative that employs clinical research as a vehicle for acquainting both students and faculty with the tools of evidence-based dentistry (EBD). New coursework and experiences in all four years of the curriculum plus a variety of faculty development offerings are being used to achieve this goal. Progress on these fronts is reflected in a nascent EBD culture characterized by increasing participation and buy-in by students and faculty. The production of a new generation of dental graduates equipped with the EBD skill set as well as a growing nucleus of faculty members who can model the importance of evidence-based practice is of paramount importance for the future of dentistry.


"They paged me what?": A transplant infectious disease guide to donor calls.
Donor-derived infections in solid organ transplantation can be prevented by risk stratification of donors based on available information, and inquiries surrounding possible or diagnosed infection are common questions posed to transplant infectious disease subspecialists. This article outlines the five key steps in addressing a donor call from a transplant team in a systematic approach, focusing on donor and recipient-specific factors, transmissibility and treatment of possible infections, and the likelihood of a patient's future organ offers and mortality remaining on the waitlist. These principles are then applied to five donor call cases, in which we review the key takeaway points and supporting literature. These cases can be used as a resource for teaching with trainees.


Identification of Mycobacterium kansasii by using a DNA probe (AccuProbe) and molecular techniques.
The newly formulated Mycobacterium kansasii AccuProbe was evaluated, and the results obtained with the new version were compared to the results obtained with the old version of this test by using 116 M. kansasii strains, 1 Mycobacterium gastri strain, and 19 strains of several mycobacterial species. The sensitivity of this new formulation was 97.4% and the specificity was 100%. Still, three M. kansasii strains were missed by this probe. To evaluate the variability within the species, genetic analyses of the hsp65 gene, the spacer sequence between the 16S and 23S rRNA genes, and the 16S rRNA gene of several M. kansasii AccuProbe-positive strains as well as all AccuProbe-negative strains were performed. Genetic analyses of the one M. gastri strain from the comparative assay and of two further M. gastri strains were included because of the identity of the 16S rRNA gene in M. gastri to that in M. kansasii. The data confirmed the genetic heterogeneity of M. kansasii. Furthermore, a subspecies with an unpublished hsp65 restriction pattern and spacer sequence was described. The genetic data indicate that all M. kansasii strains missed by the AccuProbe test belong to one subspecies, the newly described subspecies VI, as determined by the hsp65 restriction pattern and the spacer sequence. Since the M. kansasii strains that are missed are rare and all M. gastri strains are correctly negative, the new formulated AccuProbe provides a useful tool for the identification of M. kansasii.


Measures of reliability in sports medicine and science.
Reliability refers to the reproducibility of values of a test, assay or other measurement in repeated trials on the same individuals. Better reliability implies better precision of single measurements and better tracking of changes in measurements in research or practical settings. The main measures of reliability are within-subject random variation, systematic change in the mean, and retest correlation. A simple, adaptable form of within-subject variation is the typical (standard) error of measurement: the standard deviation of an individual's repeated measurements. For many measurements in sports medicine and science, the typical error is best expressed as a coefficient of variation (percentage of the mean). A biased, more limited form of within-subject variation is the limits of agreement: the 95% likely range of change of an individual's measurements between 2 trials. Systematic changes in the mean of a measure between consecutive trials represent such effects as learning, motivation or fatigue; these changes need to be eliminated from estimates of within-subject variation. Retest correlation is difficult to interpret, mainly because its value is sensitive to the heterogeneity of the sample of participants. Uses of reliability include decision-making when monitoring individuals, comparison of tests or equipment, estimation of sample size in experiments and estimation of the magnitude of individual differences in the response to a treatment. Reasonable precision for estimates of reliability requires approximately 50 study participants and at least 3 trials. Studies aimed at assessing variation in reliability between tests or equipment require complex designs and analyses that researchers seldom perform correctly. A wider understanding of reliability and adoption of the typical error as the standard measure of reliability would improve the assessment of tests and equipment in our disciplines.


Evaluation of post-contrast myocardial t1 in duchenne muscular dystrophy using cardiac magnetic resonance imaging.
The objective of the study was to perform a retrospective pilot study to evaluate the potential of myocardial T1 in assessment of Duchenne muscular dystrophy (DMD) cardiomyopathy. Early identification of DMD cardiac disease, particularly myocardial fibrosis, would allow earlier therapy, potentially improving outcomes. Shortened myocardial T1 measured by cardiac MRI (CMR) is a measure of cardiac fibrosis that may be detected before late gadolinium enhancement (LGE). We hypothesized that the post-contrast T1 obtained from the Look-Locker sequences (T1LL), an easily obtainable surrogate of myocardial T1, would be abnormally shortened in DMD compared with controls. T1LL measurement was performed on 21 DMD subjects and 11 controls; to account for individual variations in gadolinium distribution, myocardial T1LL was divided by blood pool T1LL, deriving T1LL ratios. DMD subjects had shorter mean T1LL ratio than controls (1.42 vs 1.72, p < 0.001). Subset analyses in DMD subjects with normal LVEF and without LGE also demonstrated significantly shorter T1LL ratio (-0.28, p < 0.001 and -0.25, p = 0.028). Post-contrast T1LL ratio is abnormally shortened in DMD compared with controls, even in DMD patients with otherwise normal CMRs. The application of more aggressive therapy for those with shorter T1LL may favorably alter morbidity and improve mortality associated with DMD cardiomyopathy. These data suggest that further prospective evaluation of myocardial T1 will be of benefit to patients with DMD.


A review of quantitative structure-activity relationship methods for the prediction of atmospheric oxidation of organic chemicals.
Organic compounds are chemically transformed in the troposphere by reaction with photochemically generated oxidants that include hydroxyl radicals, nitrate radicals, and ozone. The reaction rates are a measure of atmospheric persistence and are necessary for developing environmental exposure assessments. Since relatively few experimentally measured rate constants are available, environmental risk/exposure assessors must estimate degradation rates. Rates can be predicted through use of quantitative structure-activity relationships (QSARs). QSAR methods are described for estimating reaction rates with hydroxyl radicals, nitrate radicals, and ozone. QSAR accuracy and limitations are also discussed.


Salmonella testing of pooled pre-enrichment broth cultures for screening multiple food samples.
A method has been described for testing multiple food samples for Salmonella without loss in sensitivity. The method pools multiple pre-enrichment broth cultures into single enrichment broths. The subsequent stages of the Salmonella analysis are not altered. The method was found applicable to several dry food materials including nonfat dry milk, dried egg albumin, cocoa, cottonseed flour, wheat flour, and shredded coconut. As many as 25 pre-enrichment broth cultures were pooled without apparent loss in the sensitivity of Salmonella detection as compared to individual sample analysis. The procedure offers a simple, yet effective, way to increase sample capacity in the Salmonella testing of foods, particularly where a large proportion of samples ordinarily is negative. It also permits small portions of pre-enrichment broth cultures to be retained for subsequent individual analysis if positive tests are found. Salmonella testing of pooled pre-enrichment broths provides increased consumer protection for a given amount of analytical effort as compared to individual sample analysis.


Ceramide glycanase activities in human cancer cells.
Ceramide glycanase (CGase) activities have been detected in different human tumor cells (colon, carcinoma Colo-205; neuroblastoma, IMR-32; breast cancer lines, SKBr3 and MCF7). However, the level of enzymatic activity is lower in these cells compared to that present in other mammalian tissues reported before (Basu, M., Kelly, P., Girzadas, M. A., Li, Z., and Basu, S. Methods Enzymol. (in press)). The majority of CGase activity was found in the 100,000 g soluble supernatant fraction isolated from all these cell lines and tissues. Using the soluble enzyme, the requirement for optimum CGase activity was found to be consistent with previous observations found for rat and rabbit tissues (Basu, M., Dastgheib, S., Girzadas, M. A., O'Donnell, P. H., Westervelt, C. W., Li, Z., Inokuchi, J. I., and Basu, S. (1998) Acta Pol. Biochim. 42:327). The CGase activities from both Colo-205 and IMR-32 cells are optimum at a protein to detergent ratio of one. All the mammalian CGases, including human cancer cells, show an optimum pH between 5.5 and 5.8 in sodium acetate buffer. The CGase activities from cancer cells are found to be cation-independent; however, mercury, zinc, and copper ions seem to inhibit the enzyme activity substantially in both tumor cells lines. The mercury ion inhibition of CGase activities from all different sources indicates a possible structural homology in the CGase proteins. Radiolabeled substrates, labeled at the sphingosine double bond or at the 3-position of sphingosine without modifying double bond of sphingosine were used in this investigation. Both were active substrates with all enzyme preparations isolated from different cancer cells (apparent Km, 500 microM for nLcOse5[3H-DT]Cer and 350 microM for GgOse4[sph-3-3H]Cer with Colo-205 enzyme). Structural analogues of ceramide and sphingosine (L-PPMP. L-PDMP, alkylamines, and Tamoxifen) inhibited cancer cell CGase activities in vitro.


Has the generalized deficit become the generalized criticism?
The "generalized cognitive deficit problem" refers to a situation in which a generalized deficit gives the false appearance of a specific deficit due to the psychometric properties of tests, and it is an important methodological consideration in schizophrenia research. However, it also generates considerable confusion and is often used indiscriminately as a scientific criticism, even in situations to which it does not apply. Further, the generalized deficit problem creates few concerns in interpretation for many central questions in contemporary schizophrenia research. The research literature has shifted away from the traditional goal of identifying generalized vs differential deficits, and the field now demonstrates (1) increased recognition that a generalized deficit, broadly defined, probably does not exist in schizophrenia, (2) increased emphasis on explaining both shared and unique variance across measures to understand the mechanisms through which cognition relates to external variables (eg, functional outcome), and (3) increased use of neuroscientific methods to explore cognition in schizophrenia in which the structure and richness of data can be used to minimize misinterpretation of the sort that can occur when using only behavioral measures. Clearly, consideration of the generalized deficit still remains essential in certain experimental contexts, but criticisms based on this concern are unwarranted in many other situations in schizophrenia research. This commentary is intended to help clarify the distinctions between these 2 situations so that concerns will be expressed in a more selective, less reflexive, manner.


Location of CD39+ T cell subpopulations within tumors predict differential outcomes in non-small cell lung cancer.
An improved mechanistic understanding of immunosuppressive pathways in non-small cell lung cancer (NSCLC) is important to develop novel diagnostic and therapeutic approaches. Here, we investigate the prognostic significance of the ectonucleotidases CD39 and CD73 in NSCLC. The expression and localization of CD39, CD73 and CD103 was digitally quantified in a cohort of 162 early treatment naïve NSCLC patients using multiplex-immunofluorescence and related to patient outcome. Expression among different cell-populations was assessed via flow cytometry. Targeted RNA-Seq was performed on CD4+ and CD8+ T cells from digested NSCLC tumor tissue and single-cell RNA-Seq data was analyzed to investigate the functional significance of CD39+ T cell populations. We demonstrate that flow cytometry of early untreated NSCLC patients shows an upregulation of CD39 expression in the tumor tissue among natural killer (NK) cells, fibroblasts and T cells. CD73 expression is mainly found among fibroblasts and Epcam+cells in the tumor tissue. Multiplex Immunofluorescence in a cohort of 162 early untreated NSCLC patients demonstrates that CD39 expression is mainly localized in the tumor stroma while CD73 expression is equally distributed between tumor nest and stroma, and high expression of CD39 and CD73 in the tumor stroma is associated with poor recurrence-free survival (RFS) at 5 years. Additionally, we find that CD8+T cells located in the tumor nest express CD103 and the density of CD39+CD103+CD8+ T cells in the tumor nest predicts improved RFS at 5 years. Targeted RNA-Seq shows that the tumor microenvironment of NSCLC upregulates regulatory pathways in CD4+ T cells and exhaustion in CD8+ T cells, and analysis of a single cell RNA sequencing dataset shows that CD39+CD4+ cells are enriched in Treg signature gene-sets, and CD39+CD103+ cytotoxic T lymphocyte show gene signatures indicative of an exhausted cytotoxic phenotype with upregulated expression of CXCL13. Knowledge of patterns of distribution and location are required to understand the prognostic impact of CD39+ T cell populations in NSCLC. This study provides an improved understanding of spatial and functional characteristics of CD39+ T cells and their significance to patient outcome.


Complications of cryosurgery.
We describe 70 patients who underwent cryosurgery to the lids during a two-year period. Of the 58 receiving adequate follow-up, approximately one fourth had complications thought to be directly caused by cryosurgery. These include visual loss, lid notching, corneal ulcer, acceleration of symblepharon formation, xerosis, cellulitis, activation of herpes zoster, skin depigmentation, and severe soft-tissue reaction. In addition, 9% of the lids showed possible induction of trichiasis in areas adjacent to treatment. More than two thirds of patients with conjunctival shrinkage or grafted or irradiated lids had adverse effects, with one case of permanent visual loss. Misdirected lashes were successfully eliminated with a single double freeze-thaw technique in 90% of lids treated. Cryosurgery for aberrant lashes and some benign lid lesions is the most effective method of therapy presently available, but one must be aware of its potential complications. It has a low complication rate in "normal" lids, but should be used with caution in patients with conjunctival shrinkage or in those with grafted and/or irradiated lids.


Polypoid Malignant Melanoma with Spontaneous Decapitation Showing Favorable Prognosis: A Case Report.
Regression of malignant melanoma (MM) is a commonly observed phenomenon, which refers to disappearance or loss of all or part of MM. It can be identified both clinically and histologically, and high probability of histological regression of MM (10-58%) has been reported. However, the decapitation of skin tumor has rarely been described in the English literature, and decapitation in MM has not been reported. Here, we report the case of polypoid MM with spontaneous decapitation. An 81-year-old Japanese woman was referred to our hospital due to a polypoid nodule on her cheek. She was diagnosed with MM at stage IIC (T4bN0M0) by histological examinations. Three weeks after the biopsy, the nodule decapitated spontaneously without bleeding, and an ulcer developed on the base of the polypoid nodule. The histological examination of the additionally resected ulcerative lesion under the nodule revealed infiltration of T cells mainly composed of CD8⁺ natural killer T cells. No recurrence or metastasis has been observed for 4 years. This is the first case report of polypoid MM with spontaneous decapitation, which may be attributed to natural killer T cells. Moreover, this case shows favorable prognosis, while it is said that the regression in thick MM does not have prognostic advantage and polypoid topography has been reported to be related to extremely poor prognosis. Further investigations are needed to evaluate the prognostic advantage of decapitation in MM and other skin tumors.


A complex interplay of tandem- and whole-genome duplication drives expansion of the L-type lectin receptor kinase gene family in the brassicaceae.
The comparative analysis of plant gene families in a phylogenetic framework has greatly accelerated due to advances in next generation sequencing. In this study, we provide an evolutionary analysis of the L-type lectin receptor kinase and L-type lectin domain proteins (L-type LecRKs and LLPs) that are considered as components in plant immunity, in the plant family Brassicaceae and related outgroups. We combine several lines of evidence provided by sequence homology, HMM-driven protein domain annotation, phylogenetic analysis, and gene synteny for large-scale identification of L-type LecRK and LLP genes within nine core-eudicot genomes. We show that both polyploidy and local duplication events (tandem duplication and gene transposition duplication) have played a major role in L-type LecRK and LLP gene family expansion in the Brassicaceae. We also find significant differences in rates of molecular evolution based on the mode of duplication. Additionally, we show that LLPs share a common evolutionary origin with L-type LecRKs and provide a consistent gene family nomenclature. Finally, we demonstrate that the largest and most diverse L-type LecRK clades are lineage-specific. Our evolutionary analyses of these plant immune components provide a framework to support future plant resistance breeding.


Call combination patterns in Icelandic killer whales (Orcinus orca).
Acoustic sequences have been described in a range of species and in varying complexity. Cetaceans are known to produce complex song displays but these are generally limited to mysticetes; little is known about call combinations in odontocetes. Here we investigate call combinations produced by killer whales (Orcinus orca), a highly social and vocal species. Using acoustic recordings from 22 multisensor tags, we use a first order Markov model to show that transitions between call types or subtypes were significantly different from random, with repetitions and specific call combinations occurring more often than expected by chance. The mixed call combinations were composed of two or three calls and were part of three call combination clusters. Call combinations were recorded over several years, from different individuals, and several social clusters. The most common call combination cluster consisted of six call (sub-)types. Although different combinations were generated, there were clear rules regarding which were the first and last call types produced, and combinations were highly stereotyped. Two of the three call combination clusters were produced outside of feeding contexts, but their function remains unclear and further research is required to determine possible functions and whether these combinations could be behaviour- or group-specific.


Vaccination, immunity, and the changing impact of COVID-19 on infant health.
In utero exposure to COVID-19 infection may lead to large intergenerational health effects. The impact of infection exposure has likely evolved since the onset of the pandemic as new variants emerge, immunity from prior infection increases, vaccines become available, and vaccine hesitancy persists, such that when infection is experienced is as important as whether it is experienced. We examine the changing impact of COVID-19 infection on preterm birth and the moderating role of vaccination. We offer the first plausibly causal estimate of the impact of maternal COVID-19 infection by using population data with no selectivity, universal information on maternal COVID-19 infection, and linked sibling data. We then assess change in this impact from 2020 to 2023 and evaluate the protective role of COVID-19 vaccination on infant health. We find a substantial adverse effect of prenatal COVID-19 infection on the probability of preterm birth. The impact was large during the first 2 y of the pandemic but had fully disappeared by 2022. The harmful impact of COVID-19 infection disappeared almost a year earlier in zip codes with high vaccination rates, suggesting that vaccines might have prevented thousands of preterm births. The findings highlight the need to monitor the changing consequences of emerging infectious diseases over time and the importance of mitigation strategies to reduce the burden of infection on vulnerable populations.


Residency perception survey among neurosurgery residents in lower-middle-income countries: grassroots evaluation of neurosurgery education.
The evolution of the neurosurgical specialty in lower-middle-income countries is uniformly a narrative of continuous struggle for recognition and resource allocation. Therefore, it is not surprising that neurosurgical education and residency training in these countries is relatively nascent. Dr. Harvey Cushing in 1901 declared that he would specialize in neurosurgery and gave his greatest contribution to the advancement of neurosurgical education by laying the foundations of a structured residency training program. Similar efforts in lower-middle-income countries have been impeded by economic instability and the lack of well-established medical education paradigms. The authors sought to evaluate the residency programs in these nations by conducting a survey among the biggest stakeholders in these educational programs: the neurosurgical residents. A questionnaire addressing various aspects of the residency program from a resident's perspective was prepared with Google Forms and circulated among neurosurgery residents through social media and email groups. Where applicable, a 5-point Likert scale was used to grade the responses to the questions. Responses were collected from May to October 2019 and analyzed using descriptive statistics. Complete anonymity of the respondents was ensured to keep the responses unbiased. A total of 195 responses were received, with 189 of them from lower-middle-income countries (LMICs). The majority of these were from India (75%), followed by Brazil and Pakistan. An abiding concern among residents was lack of work hour regulations, inadequate exposure to emerging subspecialties, and the need for better hands-on training (> 60% each). Of the training institutions represented, 89% were offering more than 500 major neurosurgical surgeries per year, and 40% of the respondents never got exposure to any subspecialty. The popularity of electronic learning resources was discernible and most residents seemed to be satisfied with the existent system of evaluation. Significant differences (p < 0.05) among responses from India compared with those from other countries were found in terms of work hour regulations and subspecialty exposure. It is prudent that concerned authorities in LMICs recognize and address the deficiencies perceived by neurosurgery residents in their training programs. A determined effort in this direction would be endorsed and assisted by a host of international neurosurgical societies when it is felt that domestic resources may not be adequate. Quality control and close scrutiny of training programs should ensure that the interests of neurosurgical trainees are best served.


Hearing loss and its impact on residents in long term care facilities: Asystematic review of literature.
The prevalence of age-related hearing loss is high among older adults. Growing longevity and the older profile of aged care residents is likely to result in an increasing incidence of hearing loss among this cohort. This review reports on the findings of a systematic search of the academic databases CINAHL, Medline, PsychInfo and Scopus undertaken to investigate the hearing experiences of residents of aged care facilities. Twenty-two studies met the inclusion criteria. Our analysis revealed clear barriers and facilitators to optimal hearing experiences and indicated the importance of the physical and social environment for effective communication. Under-detection of hearing loss and underuse of hearing aids were prevalent. The findings highlight the importance of addressing these issues for this cohort's quality of life. Future trends that may impact on training needs are considered and recommendations are made.


Physiology of the Neonatal Gastrointestinal System Relevant to the Disposition of Orally Administered Medications.
A thorough knowledge of the newborn (age, birth to 1 month postpartum) infant's gastrointestinal tract (GIT) is critical to the evaluation of the absorption, distribution, metabolism, and excretion (ADME) of orally administered drugs in this population. Developmental changes in the GIT during the newborn period are important for nutrient uptake as well as the disposition of orally administered medications. Some aspects of gastrointestinal function do not mature until driven by increased dietary complexity and nutritional demands later in the postnatal period. The functionalities present at birth, and subsequent maturation, can also impact the ADME parameters of orally administered compounds. This review will examine some specific contributors to the ADME processes in human neonates, as well as what is currently understood about the drivers for their maturation. Key species differences will be highlighted, with a focus on laboratory animals used in juvenile toxicity studies. Because of the gaps and inconsistencies in our knowledge, we will also highlight areas where additional study is warranted to better inform the appropriate use of medicines specifically intended for neonates.


An outbreak of salmonellosis associated with duck prosciutto at a Northern Territory restaurant.
In June 2015, an outbreak of salmonellosis occurred among people who had eaten at a restaurant in Darwin, Northern Territory over 2 consecutive nights. We conducted a retrospective cohort study of diners who ate at the restaurant on 19 and 20 June 2015. Diners were telephoned and a questionnaire recorded symptoms and menu items consumed. An outbreak case was defined as anyone with laboratory confirmed Salmonella Typhimurium PT9 (STm9) or a clinically compatible illness after eating at the restaurant. Environmental health officers inspected the premises and collected food samples. We contacted 79/83 of the cohort (response rate 95%); 21 were cases (attack rate 27%), and 9 had laboratory confirmed STm9 infection. The most commonly reported symptoms were diarrhoea (100%), abdominal pain (95%), fever (95%) and nausea (95%). Fifteen people sought medical attention and 7 presented to hospital. The outbreak was most likely caused by consumption of duck prosciutto, which was consumed by all cases (OR 18.6, CI 3.0-∞, P < 0.01) and was prepared on site. Salmonella was not detected in any food samples but a standard plate count of 2 x 107 colony forming units per gram on samples of duck prosciutto demonstrated bacterial contamination. The restaurant used inappropriate methodology for curing the duck prosciutto. Restaurants should consider purchasing pre-made cured meats, or if preparing them on site, ensure that they adhere to safe methods of production.


Phenotype and function of nasal dendritic cells.
Intranasal (i.n.) vaccination generates immunity across local, regional, and distant sites. However, nasal dendritic cells (DCs), pivotal for the induction of i.n. vaccine-induced immune responses, have not been studied in detail. Here, by using a variety of parameters, we define nasal DCs in mice and humans. Distinct subsets of "classical" DCs, dependent on the transcription factor zbtb46 were identified in the murine nose. The murine nasal DCs were Fms-related tyrosine 3 kinase ligand responsive and displayed unique phenotypic and functional characteristics, including the ability to present antigen, induce an allogeneic T-cell response, and migrate in response to lipopolysaccharide or live bacterial pathogens. Importantly, in a cohort of human volunteers, BDCA-1(+) DCs were observed to be the dominant nasal DC population at steady state. During chronic inflammation, the frequency of both BDCA-1(+) and BDCA-3(hi) DCs was reduced in the nasal tissue, associating the loss of these immune sentinels with chronic nasal inflammation. The present study is the first detailed description of the phenotypic, ontogenetic, and functional properties of nasal DCs, and will inform the design of preventative immunization strategies as well as therapeutic modalities against chronic rhinosinusitis.


Combining Time-of-Flight Secondary Ion Mass Spectrometry Imaging Mass Spectrometry and CARS Microspectroscopy Reveals Lipid Patterns Reminiscent of Gene Expression Patterns in the Wing Imaginal Disc of Drosophila melanogaster.
Using label-free ToF-SIMS imaging mass spectrometry, we generated a map of small molecules differentially expressed in the Drosophila wing imaginal disc. The distributions of these moieties were in line with gene expression patterns observed during wing imaginal disc development. Combining ToF-SIMS imaging and coherent anti-Stokes Raman spectroscopy (CARS) microspectroscopy allowed us to locally identify acylglycerols as the main constituents of the pattern differentiating the future body wall tissue from the wing blade tissue. The findings presented herein clearly demonstrate that lipid localization patterns are strongly correlated with a developmental gene expression. From this correlation, we hypothesize that lipids play a so far unrecognized role in organ development.


Burden of diabetes in Australia: life expectancy and disability-free life expectancy in adults with diabetes.
The aim of this work was to estimate the life expectancy (LE) and disability-free life expectancy (DFLE) for adults with and without diabetes. The Chiang method and the adapted Sullivan method were used to estimate LE and DFLE by age and sex. Mortality data in 2011 were available from the National Diabetes Services Scheme for diabetes and from standard national mortality datasets for the general population. Data on prevalence of disability and severe or profound core activity limitation were derived from the 2012 Australian Survey of Disability, Ageing and Carers (SDAC). The definitions of disability used in the SDAC followed the International Classification of Functioning, Disability and Health. Data on diabetes prevalence were derived from the Australian Diabetes, Obesity and Lifestyle study. The estimated LE and DFLE (with 95% uncertainty interval [UI]) at age 50 years were 30.2 (30.0, 30.4) and 12.7 (11.5, 13.7) years, respectively, for men with diabetes, and the estimates were 33.9 (33.6, 34.1) and 13.1 (12.3, 13.9) years, respectively, for women with diabetes. The estimated loss of LE associated with diabetes at age 50 years was 3.2 (3.0, 3.4) years for men and 3.1 (2.9, 3.4) years for women, as compared with their counterparts without diabetes. The corresponding estimated loss of DFLE was 8.2 (6.7, 9.7) years for men and 9.1 (7.9, 10.4) years for women. Women with diabetes spent a greater number of absolute years and a greater proportion of their life with disability as compared with men with diabetes and women without diabetes. The gains in LE and DFLE across the whole population at age 50 years after hypothetically eliminating diagnosed diabetes were 0.6 (0.5, 0.6) years and 1.8 (1.0, 2.8) years. In adults, diabetes results in a modest reduction in LE and a substantial reduction in DFLE. Efforts to identify the specific causes of disability and effective interventions are needed.


SEVERE COLONIC BLEEDING.
Patients requiring emergency operation for severe acute colonic hemorrhage usually arrive in the operating room inadequately studied and the point of bleeding not known. A well planned procedure for making an operative diagnosis is lacking. The fact that diverticular disease is the most common cause of massive colonic bleeding, dominates the surgical management of this problem. A critical interpretation of the color and the consistency of the stools must be made by the surgeon. Since the bleeding lesion is usually otherwise clinically silent, the character of the stools may be the only indication of the level of bleeding and the rate and the amount of the blood loss. A proctoscopic examination, followed by an emergency barium enema study if possible, is always done before subjecting a patient to laparotomy. The indications for emergency operation include acute exsanguinating hemorrhage, less severe but persistent colonic bleeding and recurrent colonic bleeding. The steps for the operative diagnosis and the surgical procedure utilized for a specific situation are discussed.


[Biosynthesis and metabolism of histamine in the central nervous system of Carcinus maenas].
The central nervous system of Carcinus maenas synthesizes radioactive histamine when incubated in the presence of [14C] histidine and pyridoxal-5' phosphate. This biosynthesis increases linearly as a function of the amount of enzyme and the incubation time. It is not effected by heart, muscle or hepatopancreas extracts nor by haemolymph. Thus histamine appears to be synthesized mainly in the nervous system. The latter is also the seat of carcinine (beta-alanylhistamine) biosynthesis. Since carcinine seems to be a product of histamine neutralization, histamine metabolism should take place in its entirety in the nervous system. Thus histamine appears to be implicated in the neuronal activity of Carcinus. Different areas of the crustacean central nervous system: brain, eyestalks and thoracic ganglionic mass biosynthesize and metabolize histamine. Thus they all could contain sites of action for histamine. The nervous systems of two other Decapodes, Cancer and Astacus also effect histamine biosynthesis but don't metabolize it into carcinine.


A Prospective, Postmarket, Compassionate Clinical Evaluation of a Novel Acellular Fish-skin Graft Which Contains Omega-3 Fatty Acids for the Closure of Hard-to-heal Lower Extremity Chronic Ulcers.
A novel piscine acellular fish-skin graft product has 510k clearance on the US market. This product (Omega3, Kerecis, Isafjordur, Iceland) is to be used similarly to extracellular matrices (ECMs) on the market (eg, bovine and porcine) except that it contains fats, including omega-3 polyunsaturated fatty acids that have been associated with anti-inflammatory properties in many studies. While many current ECMs are effective on open wounds, studies have largely excluded application to hard-to-heal ulcers. To test this product in a real-world environment, the authors chose to look specifically at hard-to-heal ulcers based on previously defined wound and patient factors. The primary objective was to assess the percentage of wound closure area from baseline after 5 weekly fish-skin graft applications in 18 patients with at least 1 "hard-to-heal" criteria. Patients underwent application of the fish skin for 5 sequential weeks, followed by 3 weeks of standard of care. Wound area, skin assessments, and pain were assessed weekly. A 40% decrease in wound surface area (P < 0.05) and a 48% decrease in wound depth was seen with 5 weekly applications of the fish-skin graft and secondary dressing (P < 0.05). Complete closure was seen in 3 of 18 patients by the end of the study phase. This fish-skin product appears to provide promise as an effective wound closing adjunctive ECM. This is true when used in this compassionate setting, where many other products fail. This study lacks a control arm and an aggressive application schedule, but the investigators believe it represents real-world practice.


Discrimination of primer 3'-nucleotide mismatch by taq DNA polymerase during polymerase chain reaction.
We investigated the effect of primer-template mismatch on the efficiency of polymerase chain reaction. For primers with T, C, or G as the 3' nucleotide, Thermus aquaticus (Taq) DNA polymerase was highly specific for template complementarity to this base, but was somewhat less constrained opposite the penultimate nucleotide. In contrast, primers with a 3'-terminal A were less efficiently amplified regardless of the corresponding nucleotide on the template strand. Thus, allele-specific PCR with Taq polymerase offers the greatest template discrimination (40- to 100-fold) against mismatch to a primer's 3'-terminal T, G, or C, but not A. Nucleotides at the penultimate position are responsible for roughly one-fifth as much mismatch discrimination (8- to 20-fold), and amplification efficiency is reduced when T and especially A occupy this primer position. We thus have defined conditions which allow robust discrimination for PCR-mediated analysis of single-nucleotide polymorphisms (SNPs), and for reduction in complexity of anchor-ligation PCR products.


Chaotic mixing in cross-channel micromixers.
In this article we concentrate on a particular micromixer that exploits chaotic trajectories to achieve mixing. The micromixer we consider here is a cross-channel intersection, in which a main stream is perturbed by an oscillatory flow, driven by an external source. Depending on the amplitude and frequency of the oscillatory flow, one obtains wavy and chaotic regimes, reminiscent of a tendril-whorl mapping. The chaotic states, in which material lines are stretched and folded, favour mixing. A spatiotemporal resonance phenomenon, in which the material-line deformation is transient, is shown. An experiment using soft lithography and integrated valves, in which the resonant states are revealed, is described. From a practical viewpoint, the cross-channel micromixer offers a variety of regimes, which can be exploited to mix fluids or separate particles of different sizes. In the context of microsystems, it can be viewed as a 'smart' elementary system.


Inferior head resection of the pancreas for intraductal papillary mucinous tumors.
Patients with intraductal papillary mucinous tumor have a favorable prognosis after surgical treatment. When this neoplasm is located in the head of the pancreas, resection has conventionally required pancreatoduodenectomy. Although pancreatoduodenectomy can now be performed with a low mortality rate, morbidity still occurs frequently. Between November 1982 and January 1999, 38 intraductal papillary mucinous tumors of the pancreas were resected at the Chiba University Hospital. Seven patients (18%) underwent inferior head resection of the pancreas. In this preliminary study, the operative technique is presented, and its efficacy in improvement of quality of life is evaluated. Patients with intraductal papillary mucinous tumor underwent resection with no perioperative mortality. After discharge from hospital, 6 patients who underwent inferior head resection were still alive without recurrent disease after a median follow-up of 3 years. However, 1 patient developed peritoneal dissemination and died 18 months after inferior head resection. Patients had regained 98% of preoperative weight 1 year after inferior head resection. N-benzoyl-L-tyrosyl-p-amino-benzoic acid (BT-PABA) excretion test showed the same value before (73%) and after (73%) inferior head resection (n = 7). Pancreatic fistulas occurred more frequently after inferior head resection (38%), but the incidence of major complications was similar between inferior head resection and other types of pancreatic head resection. Pancreatic function was well preserved, and patients regained 98% of preoperative weight after inferior head resection of the pancreas. The authors concluded that the limited involvement of intraductal papillary mucinous tumors enables the surgeons to perform inferior head resection of the pancreas.


An adaptive geometry regulation strategy for 3D graphene materials: towards advanced hybrid photocatalysts.
Three-dimensional graphene (3DG) is promising for constructing monolithic photocatalysts for solar energy conversion. However, the structure-associated light-shielding effect and the intricate porous architecture of 3DG result in intrinsic limitations in light penetration and mass transfer over 3DG supported hybrids, which restricts their photocatalytic efficiency. Here, taking 3DG-organic hybrids as examples, we report a geometry regulation strategy to minimize such structural restrictions, which not only favors the interaction between light and the photoactive component, but also facilitates reactant adsorption over the 3DG-organic hybrids, thereby cooperatively boosting their photoactivity. Such an adaptive geometry regulation strategy is expected to guide the rational utilization of 3DG to construct high-performance hybrids for photoredox catalysis.


Mental health of Urban Mothers (MUM) study: a multicentre randomised controlled trial, study protocol.
Mental health disorders are common during pregnancy and the postnatal period and can have serious adverse effects on women and their children. The consequences for global mental health due to COVID-19 are likely to be significant and may have a long-term impact on the global burden of disease. Besides physical vulnerability, pregnant women are at increased risk of mental health problems such as anxiety, depression and post-traumatic stress disorder due to the consequences of social distancing. It can result in altered healthcare routines, less support from the family and friends, and in some cases, partners not being allowed to be present during prenatal visits, labour and delivery. Higher than expected, rates of perinatal anxiety and depression have been already reported during the pandemic. Pregnant women may also feel insecure and worried about the effects of COVID-19 on their unborn child if they get infected during pregnancy. Today, young urban women are used to using internet services frequently and efficiently. Therefore, providing mental health support to pregnant women via internet may be effective in ameliorating their anxiety/depression, reducing the risk of serious mental health disorders, and lead to improved maternal and perinatal outcomes. Our aim is to explore the effectiveness of a web-based psychosocial peer-to-peer support intervention in reducing the risk and severity of perinatal mental health disorders and preventing adverse pregnancy outcomes among pregnant women living in metropolitan urban settings. We plan to conduct a multicentre prospective randomised controlled trial, Mental health of Urban Mothers trial. Pregnant women living in large metropolitan cities will be recruited using internet-based application through non-profit organisations' websites. The women who consent will be randomised to receive a web-based peer-to-peer support intervention or usual care. Data will be analysed to identify the effects of intervention on Edinburgh Postnatal Depression Score and Generalised Anxiety Disorder 7 scores as well as pregnancy outcomes. The impact of COVID-19 pandemic on maternal stress will be assesed using Impact Event Scale-R. Any differences in outcomes between cities will be addressed in subgroup analyses. The study will be conducted according to the principles of Good Clinical Practice and will follow the ethical principles of the Declaration of Helsinki. The study protocol has been approved by the ethical review board of Chinese University of Hong Kong (IRB number 2019-8170) and Shanghai Center for Women's and Children's Health (international review board (IRB) number 2020-F001-12). The results will be disseminated at national and international scientific conferences, published in peer-reviewed medical journals and spread to the public through social media, news outlets and podcasts. NCT04363177; Trial sponsor Karolinska Institute, CLINTEC, Stockholm, Sweden.


Curcumin: a potential candidate in prevention of cancer via modulation of molecular pathways.
Cancer is the most dreadful disease worldwide in terms of morbidity and mortality. The exact cause of cancer development and progression is not fully known. But it is thought that cancer occurs due to the structural and functional changes in the genes. The current approach to cancer treatment based on allopathic is expensive, exhibits side effects; and may also alter the normal functioning of genes. Thus, a safe and effective mode of treatment is needed to control the cancer development and progression. Some medicinal plants provide a safe, effective and affordable remedy to control the progression of malignant cells. The importance of medicinal plants and their constituents has been documented in Ayurveda, Unani medicine, and various religious books. Curcumin, a vital constituent of the spice turmeric, is an alternative approach in the prevention of cancer. Earlier studies have shown the effect of curcumin as an antioxidant, antibacterial, antitumor and it also has a noteworthy role in the control of different diseases. In this review, we summarize the understanding of chemopreventive effects of curcumin in the prevention of cancer via the regulation of various cell signaling and genetic pathways.


Intraoperative monitoring and use of the internal shunt during carotid endarterectomy.
Carotid endarterectomy can be an effective form of therapy in stroke prevention in patients with carotid artery disease. A perioperative stroke is not only a devastating complication but negates the beneficial effects of the procedure. Careful attention to detail will prevent embolization during carotid endarterectomy and thus avoid the most common cause of perioperative cerebral infarction. The maintenance of adequate cerebral perfusion during carotid endarterectomy can be provided with the use of a shunt during carotid cross-clamping. This is necessary in approximately 15% of patients. Different approaches to the use of a shunt during carotid endarterectomy are discussed with their merits and disadvantages. Assessment of the technical results prior to completion of the operation should be an integral part of the procedure. The available methods, with their inherent limitations, are briefly discussed.


Realization of time gating by use of spatial filtering.
A method for simulating conventional time gating in low-coherence optical imaging processes in highly scattering media is given. The method uses monochromatic instead of broadband light, and spatial filtering is substituted for time gating. The process enables the study of imaging techniques in scattering media to be carried out in an easy and highly controllable way. Experimental results are given.


Children's Experience of Posttraumatic Growth: Distinguishing General from Domain-Specific Correlates.
Although the five domains of posttraumatic growth (new possibilities, relating to others, personal strength, spiritual change and appreciation of life) have been studied extensively in adults, little is known about these domains and their correlates in children. We aimed to examine whether demographic and/or social characteristics are related to children's reports of overall posttraumatic growth and of growth in specific domains. In a general population study, children aged 8-12 years who had been exposed to adverse events (N = 1290) filled out questionnaires on their experiences, demographic characteristics (gender, age, time lag since event), stress reactions, peer support, religiosity and posttraumatic growth. All demographic and social characteristics were related to overall posttraumatic growth, except time lag. Associations varied across the five domains with the strongest effects being found for stress reactions and religiosity. A higher level of stress reactions was related to more growth in all domains (general effect), whereas religious children experienced more spiritual growth than non-religious children without differences on other domains (domain specific effect). Other effects were small, and some did not remain significant after Bonferroni corrections. These findings suggest the presence of both general and domain-specific correlates of child posttraumatic growth. Although effects were generally small, the current findings show the need to differentiate between the domains of posttraumatic growth in both further research and clinical practice. This will allow a better understanding of the mechanisms of posttraumatic growth in children as well as more tailored assessment and intervention.


The genomic landscape, causes, and consequences of extensive phylogenomic discordance in Old World mice and rats.
A species tree is a central concept in evolutionary biology whereby a single branching phylogeny reflects relationships among species. However, the phylogenies of different genomic regions often differ from the species tree. Although tree discordance is often widespread in phylogenomic studies, we still lack a clear understanding of how variation in phylogenetic patterns is shaped by genome biology or the extent to which discordance may compromise comparative studies. We characterized patterns of phylogenomic discordance across the murine rodents (Old World mice and rats) - a large and ecologically diverse group that gave rise to the mouse and rat model systems. Combining new linked-read genome assemblies for seven murine species with eleven published rodent genomes, we first used ultra-conserved elements (UCEs) to infer a robust species tree. We then used whole genomes to examine finer-scale patterns of discordance and found that phylogenies built from proximate chromosomal regions had similar phylogenies. However, there was no relationship between tree similarity and local recombination rates in house mice, suggesting that genetic linkage influences phylogenetic patterns over deeper timescales. This signal may be independent of contemporary recombination landscapes. We also detected a strong influence of linked selection whereby purifying selection at UCEs led to less discordance, while genes experiencing positive selection showed more discordant and variable phylogenetic signals. Finally, we show that assuming a single species tree can result in high error rates when testing for positive selection under different models. Collectively, our results highlight the complex relationship between phylogenetic inference and genome biology and underscore how failure to account for this complexity can mislead comparative genomic studies.


Bi-directional replication and random termination.
Two-dimensional (2D) agarose gel electrophoresis was used to study termination of DNA replication in a shuttle vector, YRp7', when it replicated in Escherichia coli, Saccharomyces cerevisiae and Xenopus egg extracts. In E. coli, the 2D gel patterns obtained were consistent with uni-directional replication initiated at a specific site, the ColE1 origin. In consequence, termination also occurred precisely at the ColE1 origin. In Xenopus egg extracts, the particular shape of the bubble arc as well as the triangular smear detected to the left of the simple-Y pattern indicated random initiation and termination. In S.cerevisiae, initiation occurred at the ARS1 origin and replication proceeded in a bi-directional manner. However, termination did not always occur at a specific site 180 degrees across from the origin, but almost all along the south hemisphere of the plasmid. Inversion, deletion or replacement of DNA sequences located throughout this hemisphere did not eliminate random termination. Analysis of the replication intermediates of another yeast plasmid bearing a different origin, ARS305, also exhibited random termination. We propose that the random termination events observed in S.cerevisiae could be due to an asynchronous departure of both forks from the bi-directional origin in addition to differences in the rate of fork progression. These observations could be extended to all bi-directional origins.


Will the "Fixes" Fall Flat? Prospects for Quality Measures and Payment Incentives to Control Healthcare Spending.
Payment systems in the US healthcare system have rewarded physicians for services and attempted to control healthcare spending, with rewards and penalties based upon projected goals for future spending. The incorporation of quality goals and alternatives to fee-for-service was introduced to replace the previous system of rewards and penalties. We describe the history of the US healthcare payment system, focusing on Medicare and the efforts to control spending through the Sustainable Growth Rate. We describe the latest evolution of the payment system, which emphasizes quality measurement and alternative payment models. We conclude with suggestions for how to influence physician behavior through education and payment reform so that their behavior aligns with alternative care models to control spending in the future.


Seroprevalence of antibodies against rubella virus in pregnant women in Haiti.
To assess the seroprevalence of immunity to the rubella virus in pregnant women in Haiti attending the Obstetrics and Gynecology Department of the State University Hospital, in the capital city of Port-au-Prince, in order to help with the introduction of the rubella vaccine for the population and provide protection for women of reproductive age in the country. This cross-sectional study was done between February 2002 and May 2002. A total of 503 pregnant women were tested for rubella-specific immunoglobulin G antibodies, using enzyme immunoassay; 8 of those women were later excluded because they did not know their age, leaving 495 women in the analysis. Of the 495 participants included in our analysis, 471 of them (95.2%) were seropositive; only 24 of them (4.8%) were seronegative (susceptible). A statistically significant difference (P = 0.02) was found in the rate of seronegativity for rubella virus between the pregnant women living in the Port-au-Prince area (17 of 426 women, or 4.0%) and those living in rural areas (7 of 69 women, or 10.1%). In terms of age, 81 of the 495 (16.4%) women were under 21 years ld. This study is an important first step in addressing the issue of prevalence of rubella virus infection among Haitian women and in dealing with the still-underrecognized public health problem of congenital rubella syndrome in Haiti. We recommend additional research that uses randomized sampling and includes a significant proportion of women from rural areas of the country.


A comparison of clinical and objective measures of freezing of gait in Parkinson's disease.
Freezing of gait, a paroxysmal motor block, is common in the latter stages of Parkinson's disease. The current 'gold standard' of assessing the severity of freezing is based on clinical identification (by up to 3 raters) of the number of episodes from video. The aims of this study were to systematically assess this 'gold standard' across multiple Parkinson's disease centers, and to compare these clinical ratings with objective measures derived from lower limb acceleration data. Video recordings were acquired during a timed up-and-go task from 10 Parkinson's disease patients (with a clinical history of freezing) in the 'off' state. Patients were instrumented with accelerometers on the lateral aspect of each shank. Ten experienced clinicians were recruited from four Parkinson's disease centers to independently assess the videos for number and duration of freezing events. The reliability of clinical video assessment for number of freezing events was moderate (intraclass correlation coefficient 0.63). Percent time frozen (cumulative duration of freezing episodes/total duration of the walking task) demonstrated stronger agreement between raters (0.73). Agreement of accelerometry-derived measures of freezing severity with mean clinician ratings was strong for number of episodes (0.78) and very strong for percent time frozen (0.93). The results demonstrate the viability of objective measures of freezing, and that percent time frozen is a more reliable metric of severity than number of freezing events for both clinical and objective measures. The large variability between clinicians suggests that caution should be used when comparing subjective ratings across centers.


Clinicopathological and histochemical studies of linitis plastica type gastric cancer with special reference to early gastric cancer in the region of the fundic gland.
In this study, early gastric cancer in the region of the fundic gland was found to occur predominantly in women. Many lesions of this type were identified in the posterior wall of the middle portion of the stomach. Histologically, the lesions were classified as poorly differentiated carcinomas in all cases of early cancer. On the other hand, in 9 patients with cancer of linitis plastica type having IIc lesions (less than 2.0 cm in diameter) located in the region of the fundic gland, the tumor focus was also in the posterior wall of the middle portion of the stomach. Giant folds were present diffusely in all other portions of the gastric mucosa in these latter cases. These cases also had diffuse infiltration of cancer cells into the submucosa, muscle layer and extraserosal regions. Histologically, the lesions were classified, in all cases of linitis plastica type, as poorly differentiated carcinomas including signet ring cells. Acid mucopolysaccharides (AMPS) and sialic acid were histochemically detected in the interstitial tissues of early gastric carcinomas and linitis plastica type gastric cancers. The AMPS digestion rates were higher for early cancer tissue. The present results support the hypothesis that early gastric cancer in the region of the fundic gland may occur in conditions favorable to tumor growth and may develop into cancer of linitis plastica type.


Zebrafish Hagoromo mutants up-regulate fgf8 postembryonically and develop neuroblastoma.
We screened an existing collection of zebrafish insertional mutants for cancer susceptibility by histologic examination of heterozygotes at 2 years of age. As most mutants had no altered cancer predisposition, this provided the first comprehensive description of spontaneous tumor spectrum and frequency in adult zebrafish. Moreover, the screen identified four lines, each carrying a different dominant mutant allele of Hagoromo previously linked to adult pigmentation defects, which develop tumors with high penetrance and that histologically resemble neuroblastoma. These tumors are clearly neural in origin, although they do not express catecholaminergic neuronal markers characteristic of human neuroblastoma. The zebrafish tumors result from inappropriate maintenance of a cell population within the cranial ganglia that are likely neural precursors. These neoplasias typically remain small but they can become highly aggressive, initially traveling along cranial nerves, and ultimately filling the head. The developmental origin of these tumors is highly reminiscent of human neuroblastoma. The four mutant Hagoromo alleles all contain viral insertions in the fbxw4 gene, which encodes an F-box WD40 domain-containing protein. However, although one allele clearly reduced the levels of fbxw4 mRNA, the other three insertions had no detectable effect on fbw4 expression. Instead, we showed that all four mutations result in the postembryonic up-regulation of the neighboring gene, fibroblast growth factor 8 (fgf8). Moreover, fgf8 is highly expressed in the tumorigenic lesions. Although fgf8 overexpression is known to be associated with breast and prostate cancer in mammals, this study provides the first evidence that fgf8 misregulation can lead to neural tumors.


Tumor-related epilepsy and epilepsy surgery.
Tumor-related epilepsy (TRE) is a major etiologic category of epilepsy. TRE is heterogeneous, and the epidemiology, pathology, pathophysiology, clinical features, treatment, and outcomes vary accordingly. In addition, treatment imperatives vary between almost purely epilepsy considerations and those that are primarily oncologic. Often, there is no clear separation of imperatives, and there is a relatively scant evidence base that underpins management decisions in such cases. Given a diverse molecular as well as clinical landscape and the rapid pace with which new knowledge accrues, there are relatively few recent literature resources on TRE that provide neurologists, neurosurgeons, epileptologists, and oncologists with an up-to-date, state-of-the-art review of the field in all of its important aspects. The proceedings of the Sixth International Epilepsy Colloquium in Cleveland in Ohio, U.S.A., in May 2013 on Tumoral Epilepsy and Epilepsy Surgery address, at least in part, several TRE aspects crucial to modern epilepsy and oncology practice.


Relationship of alcohol and illicit drug use with high blood pressure care and control among urban hypertensive Black men.
To examine the relationships among alcohol and illicit drug use and high blood pressure (HBP) care and control. Baseline cross-sectional data from an ongoing clinical trial evaluating the effectiveness of a HBP care program was utilized. Data collected at baseline on 309 urban hypertensive Black men, aged 18-54, included: socio-demographics, health status, HBP care behaviors, alcohol and illicit drug use, urine screen for illicit drug use, and blood pressure (BP). Men using alcohol and illicit drugs were less likely to report having medical insurance, having a doctor for HBP care, engaging in critical patient behaviors for HBP control, being on HBP medications, and compliance with HBP medication regimen. Alcohol and illicit drug users were more likely to eat high fat/high salt foods and significantly more likely to smoke cigarettes. In comparison to abstainers, men who used both alcohol and illicit drugs were significantly more likely to have uncontrolled BP and higher systolic blood pressure (SBP). Alcohol and illicit drug use were negatively associated with HBP care behaviors. Thus, BP was poorly controlled in this group of alcohol and illicit drug users. Screening, counseling, and treatment for alcohol and illicit drug use should be essential components in comprehensive HBP care.


Comparative analysis of mycobacterial truncated hemoglobin promoters and the groEL2 promoter in free-living and intracellular mycobacteria.
The success of Mycobacterium tuberculosis depends on its ability to withstand and survive the hazardous environment inside the macrophages that are created by reactive oxygen intermediates, reactive nitrogen intermediates, severe hypoxia, low pH, and high CO(2) levels. Therefore, an effective detoxification system is required for the pathogen to persist in vivo. The genome of M. tuberculosis contains a new family of hemoproteins named truncated hemoglobin O (trHbO) and truncated hemoglobin N (trHbN), encoded by the glbO and glbN genes, respectively, important in the survival of M. tuberculosis in macrophages. Mycobacterial heat shock proteins are known to undergo rapid upregulation under stress conditions. The expression profiles of the promoters of these genes were studied by constructing transcriptional fusions with green fluorescent protein and monitoring the promoter activity in both free-living and intracellular milieus at different time points. Whereas glbN showed an early response to the oxidative and nitrosative stresses tested, glbO gave a lasting response to lower concentrations of both stresses. At all time points and under all stress conditions tested, groEL2 showed higher expression than both trHb promoters and expression of both promoters showed an increase while inside the macrophages. Real-time PCR analysis of trHb and groEL2 mRNAs showed an initial upregulation at 24 h postinfection. The presence of the glbO protein imparted an increased survival to M. smegmatis in THP-1 differentiated macrophages compared to that imparted by the glbN and hsp65 proteins. The comparative upregulation shown by both trHb promoters while grown inside macrophages indicates the importance of these promoters for the survival of M. tuberculosis in the hostile environment of the host.


Sub-100-nm precision distance measurement by means of all-fiber photonic microwave mixing.
The importance of dimensional metrology has gradually emerged from fundamental research to high-technology industries. In the era of the fourth industrial revolution, absolute distance measurements are required to cope with various applications, such as unmanned vehicles, intelligent robots, and positioning sensors for smart factories. In such cases, the size, weight, power, and cost (SWaP-C) should essentially be restricted. In this paper, sub-100 nm precision distance measurements based on an amplitude-modulated continuous-wave laser (AMCW) with an all-fiber photonic microwave mixing technique is proposed and realized potentially to satisfy SWaP-C requirements. Target distances of 0.879 m and 8.198 m were measured by detecting the phase delay of 15 GHz modulation frequencies. According to our measurement results, the repeatability could reach 43 nm at an average time of 1 s, a result not previously achieved by conventional AMCW laser distance measurement methods. Moreover, the performance by the proposed method in terms of Allan deviation is competitive with most frequency-comb-based absolute distance measurement methods, even with a simple configuration. Because the proposed method has a simple configuration such that it can be easily utilized and demonstrated on a chip-scale platform using CMOS-compatible silicon photonics, it is expected to herald new possibilities, leading to the practical realization of a fully integrated chip-scale LIDAR system.


Imaging of transgenic cricket embryos reveals cell movements consistent with a syncytial patterning mechanism.
The mode of insect embryogenesis varies among species, reflecting adaptations to different life history strategies [1, 2]. In holometabolous insects, which include the model systems, such as the fruit fly and the red flour beetle, a large proportion of the blastoderm produces an embryo, whereas hemimetabolous embryos generally arise from a small region of the blastoderm [3]. Despite their importance in evolutionary studies, information of early developmental dynamics of hemimetabolous insects remains limited. Here, to clarify how maternal and gap gene products act in patterning the embryo of basal hemimetabolous insects, we analyzed the dynamic segmentation process in transgenic embryos of an intermediate-germ insect species, the cricket, Gryllus bimaculatus. Our data based on live imaging of fluorescently labeled embryonic cells and nuclei suggest that the positional specification of the cellular blastoderm may be established in the syncytium, where maternally derived gradients could act fundamentally in a way that is similar to that of Drosophila, namely throughout the egg. Then, the blastoderm cells move dynamically, retaining their positional information to form the posteriorly localized germ anlage. Furthermore, we find that the anterior head region of the cricket embryo is specified by orthodenticle in a cellular environment earlier than the gnathal and thoracic regions. Our findings imply that the syncytial mode of the early segmentation in long-germ insects evolved from a dynamic syncytial-to-cellular mode found in the present study, accompanied by a heterochronic shift of gap gene action.


Evidence for the involvement of protein kinase C in acidic pH-induced contraction in spontaneously hypertensive rat aorta.
This study was performed to test the hypothesis that activation of protein kinase C (PKC) is a mechanism underlying the acidic pH-induced contraction (APIC) in spontaneously hypertensive rat (SHR) aorta. Changing pH of the bathing solution from 7.4 to 6.5 induced a marked contraction of SHR aorta. PKC inhibitors, GF109203X and calphostin C markedly inhibited the APIC selectively, without having a marked effect on the KCl-induced contraction. Inhibitors of mitogen-activated protein kinase kinase, U0126 and PD98059 mildly but significantly attenuated the APIC. However, at the similar concentrations both U0126 and PD98059 inhibited the KCl-induced contraction in a manner similar to that observed in APIC. D-609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC) markedly inhibited the APIC and the extent of inhibition by this compound was similar to that shown by PKC inhibitors. Whereas, U-73122 and propranolol, inhibitors of phosphatidylinositol-specific PLC and phosphatidate phosphohydrolase, respectively, had no affect on the APIC. A tyrosine kinase inhibitor, tyrphostin 23 and GF109203X inhibited the APIC in an additive manner, and together they abolished the contractile response. From all these results, it is suggested that a significant component of the contraction observed in response to acidosis in SHR aorta is dependent upon the activation of PKC that seems to be the downstream event of the activation of PC-PLC. Furthermore, PKC- and tyrosine kinase-dependent pathways underlying the APIC are independent of each other.


Characterization of α-Glucosidases From Lutzomyia longipalpis Reveals Independent Hydrolysis Systems for Plant or Blood Sugars.
Lutzomyia longipalpis is the main vector of Leishmania infantum and exploits different food sources during development. Adults have a diet rich in sugars, and females also feed on blood. The sugar diet is essential for maintaining longevity, infection, and Leishmaniasis transmission. Carbohydrases, including α-glucosidases, are the main enzymes involved in the digestion of sugars. In this context, we studied the modulation of α-glucosidase activities in different feeding conditions and compartments of Lutzomyia longipalpis females, in order to characterize in detail their roles in the physiology of this insect. All tissues showed activity against MUαGlu and sucrose, with highest activities in the midgut and crop. Activity was 1,000 times higher on sucrose than on MUαGlu. Basal activities were observed in non-fed insects; blood feeding induced activity in the midgut contents, and sugar feeding modulated activity in midgut tissues. α-glucosidase activity changed after female exposure to different sugar concentrations or moieties. α-glucosidases from different tissues showed different biochemical properties, with an optimum pH around 7.0-8.0 and K M between 0.37 and 4.7 mM, when MUαGlu was used as substrate. Using sucrose as substrate, the optimum pH was around 6.0, and K M ranges between 11 and 800 mM. Enzymes from the crop and midgut tissues showed inhibition in high substrate concentrations (sucrose), with K I ranging from 39 to 400 mM, which explains the high K M values found. Chromatographic profiles confirmed that different α-glucosidases are been produced in L. longipalpis in different physiological contexts, with the distinction of at least four α-glucosidases. The results suggest that some of these enzymes are involved in different metabolic processes, like digestion of plant sugars, digestion of blood glycoproteins or glycolipids, and mobilization of energetic storages during starvation.


Development of Obesity: The Driver and the Passenger.
Obesity has reached epidemic proportions and is one of the greatest challenges for public health in the twenty-first century. The macronutrient composition of diets, in particular the amount and ratio of carbohydrates, fat and protein, have received considerable attention in recent decades due to its potential relevance to the development of obesity and weight loss. The effects of various macronutrients on body weight regulation are still under debate. High-carbohydrate diets, and particularly high-fat diets, have been blamed for the increase in the prevalence of obesity. This paper shows that neither fat nor carbohydrates are fattening per se. Mixed diets with substantial amounts of fat and high-glycemic carbohydrates, like current WDs, are required to promote weight gain and obesity. High-glycemic carbohydrates are the active partner (the "driver"), which promotes fat storage through its insulinogenic effect, while fat is the passive partner (the "passenger") on the way to obesity. Elevated insulin levels (postprandial, but more importantly due to hypersecretion and hyperinsulinemia) promote fat storage and play a key role in obesogenesis and the obesity epidemic. Furthermore, mixed diets high in high-glycemic carbohydrates and fat promote fetal programming, with long-term adverse impacts on the offspring, including insulin hypersecretion, (childhood) obesity and metabolic diseases. Maternal obesity and high weight gain during pregnancy have also been linked to deleterious effects on fetal programming. As the global obesity epidemic increasingly affects women of reproductive age, a significant percentage of fetuses will experience fetal programming with a tendency towards obesity - a self-reinforcing process that further fuels the epidemic. A change in lifestyle and diet composition is needed to prevent or limit the development of obesity and related diseases.


Detection of circumstellar material in a normal type Ia supernova.
Type Ia supernovae are important cosmological distance indicators. Each of these bright supernovae supposedly results from the thermonuclear explosion of a white dwarf star that, after accreting material from a companion star, exceeds some mass limit, but the true nature of the progenitor star system remains controversial. Here we report the spectroscopic detection of circumstellar material in a normal type Ia supernova explosion. The expansion velocities, densities, and dimensions of the circumstellar envelope indicate that this material was ejected from the progenitor system. In particular, the relatively low expansion velocities suggest that the white dwarf was accreting material from a companion star that was in the red-giant phase at the time of the explosion.