Effects of hydrolyzed yeast supplementation in calf starter on immune responses to vaccine challenge in neonatal calves.
The effects of hydrolyzed yeast supplementation on growth performance, health and immune-physiological parameters in neonatal calves challenged with vaccine were investigated. Twelve Holstein calves were started in the experiment at 2 ± 1 days of age and were studied for 35 days. Calves were randomly assigned to each of two dietary treatments, a control (CON) and hydrolyzed yeast (HY) group. The calves in the HY group received control calf starter supplemented with 0.2% HY. All calves were given calf starter ad libitum for 5 weeks starting in week 1. Calves were also given whole milk according to a step-down milking protocol. In order to induce immune responses, all calves were challenged with Hog cholera and Erysipelothrix insidiossa live vaccines by intramuscular injection at 3 weeks of age. Growth performance and feed intake were not affected by dietary treatment throughout the experimental period, except that the HY group had significantly higher (P < 0.05) milk intake than did the CON group at 3 weeks of age. Calves in the HY group showed significantly better (P < 0.05) fecal and health scores at 3 weeks compared to those in the control group. After vaccine challenge, neutropenia, lymphophilia and thrombocytopenia were observed in the CON group, but calves in the HY group did not show significant changes of leukocytes. The average concentration of serum haptoglobin in the HY group was significantly higher (P < 0.05) at 1 and 3 days post-vaccine challenge (DPVC) than that of CON group. Feeding HY supplemented calf starter resulted in a higher (P < 0.05) relative amount of bacterial and viral - specific IgA than in the CON group at 5 DPVC. Although the percentage of CD4+ T cells was significantly (P < 0.05) higher in the HY group than in the CON group at -2 DPVC, significant differences between groups after vaccine challenge was not observed during the experimental period. These results suggest that 0.2% HY supplementation in calf starter can improve the health status and immune-related serum protein production and affect blood cell composition in neonatal calves after vaccine challenge.


[Prevalence and relation of dyspepsia to irritable bowel syndrome in a native community of the Peruvian jungle].
Dyspepsia and irritable bowel syndrome (IBS) are two of the most frequent syndromes in gastroenterology. However, very few epidemiological studies have been conducted in Peru and none in the Peruvian Jungle. The objective of this study is to determine the prevalence of dyspepsia and irritable bowel syndrome in a jungle community of Peru and the recurrence percentage of these syndromes. A sample was taken from 231 persons randomly selected using the "home by home" method, according to the map provided by Punta del Este Medical Center (city of Tarapoto - Department of San Mart n). The persons, considered to best typify the general population of the city, took two tests (Dyspepsia Test and Manning Test) that were previously validated during the months of January through March 1999. The prevalence of dyspepsia was 37.6%, and that of IBS, 22.0%. From those with dyspepsia, 38% had also IBS. From those with IBS, 65% reported dyspepsia symptoms. Prevalence of IBS was higher in individuals with dyspepsia (37.9%) than in individuals without dyspepsia (12.5% p< 0.01). The prevalence of both dyspepsia and IBS decreases as age increases. A statistically significant difference related to ethnicity was found in individuals with IBS. Dyspepsia and ethnicity were associated in 31.4% to individuals having both pathologies (p< 0.0001 and OR=4.28). The dyspepsia/IBS ratio was 1.7/1. There is a high prevalence of IBS and dyspepsia in the study population. The high association found between both syndromes may be due to the common etiopathogenic mechanisms they share such as: a visceral hypersensibility due to peripheral or central mechanisms, bowel motility disturbances or parasitosis. Our study suggests that both dyspepsia and IBS are the manifestations of the same digestive disorder, which has not been fully clarified yet.


[Surgey of tick-borne arboviruses in the Central African Republic (1973-1974). Isolation of Dugbe, CHF/Congo, Jos and Bhanja viruses].
As a complement of the study of the epidemiology of the arboviruses in Central Africa a survey of tick borne viruses has been done, in the Central African Republic, from December 1972 to June 1974; 15.103 ticks were collected, mainly from cattle at the slaughterhouses. They include: 10.085 Ambylomma variegatum, 4.113 Boophilus, 542 Rhipicephalus and 363 Hyalomma. From 892 monospecific pools inoculated into baby mice, 98 isolates of virus were obtained. Among the 57 isolates which have been fully identified (the identification of 41 other isolates is still in progress), 4 different serotypes of arbovirus have been found: Dugbe virus has been the most frequently found with 45 isolates from A. variegatum and I from B. decoloratus; this virus, previously isolated from human cases in Central African Republic in 1967 and 1970 has been isolated from a new human case in 1973. One isolate of CHF/Congo virus has been obtained from Hyalomma nitidum, but this virus has not yet been isolated from human beeings in C.A.R. The two other tick borne viruses isolated during this survey are Jos virus (9 isolates) and Bhanja virus (I isolate), all of them from A variegatum.


Plasma vitamins B2, B6, and B12, and related genetic variants as predictors of colorectal cancer risk.
B-vitamins are essential for one-carbon metabolism and have been linked to colorectal cancer. Although associations with folate have frequently been studied, studies on other plasma vitamins B2, B6, and B12 and colorectal cancer are scarce or inconclusive. We carried out a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, including 1,365 incident colorectal cancer cases and 2,319 controls matched for study center, age, and sex. We measured the sum of B2 species riboflavin and flavin mononucleotide, and the sum of B6 species pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid as indicators for vitamin B2 and B6 status, as well as vitamin B12 in plasma samples collected at baseline. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for colorectal cancer were estimated using conditional logistic regression, adjusted for smoking, education, physical activity, body mass index, alcohol consumption, and intakes of fiber and red and processed meat. The relative risks comparing highest to lowest quintile were 0.71 [95% confidence interval (95% CI), 0.56-0.91; P(trend) = 0.02] for vitamin B2, 0.68 (95% CI, 0.53-0.87; P(trend) <0.001) for vitamin B6, and 1.02 (95% CI, 0.80-1.29; P(trend) = 0.19) for vitamin B12. The associations for vitamin B6 were stronger in males who consumed ≥30 g alcohol/day. The polymorphisms were not associated with colorectal cancer. Higher plasma concentrations of vitamins B2 and B6 are associated with a lower colorectal cancer risk. This European population-based study is the first to indicate that vitamin B2 is inversely associated with colorectal cancer, and is in agreement with previously suggested inverse associations of vitamin B6 with colorectal cancer.


Asymmetric charge patterning on surfaces and interfaces: formation of hexagonal domains.
The structure of soft matter systems at interfaces is of utmost importance in the fields of nanopatterning and self-assembly. It has been shown that lamellar and hexagonal patterns can form on interfaces, for a wide variety of systems. The asphericity of charged domains is considered here for different strengths of the electrostatics, determined by the interface media, relative to the short range van der Waals interactions between the molecular components. The phase behavior of the surface structure is explored by using molecular dynamics simulations, including some dynamical aspects of the interaction between neighboring domains, using the Lindemann criterion [F. Lindemann, Z. Phys. 11, 609 (1910)]. The charge ratio of the electrostatic components influences the shape of the domains, as well as the degree of local order in the interdomain structure.


Discontinuation of outpatient medications: implications for electronic messaging to pharmacies using CancelRx.
Electronic communication of prescription discontinuation, or CancelRx, has the potential to improve medication safety. We aimed to describe the proportion of discontinued outpatient medications that would result in a CancelRx message to understand its impact on medication safety. We used a data report to identify all outpatient medications discontinued in the electronic health record (EHR) of an academic health system in 1 month (October 2018). Among all 63 485 medications discontinued, 23 118 (36.4%) were e-prescribed, 25 982 (40.9%) were patient-reported or reconciled, and the remainder prescribed nonelectronically. Discontinued high-risk medications were more likely to be e-prescribed (2768 of 5896, 47.0%). A discontinuation reason was specified in 37 353 (58.9%) of all discontinued medications. Approximately one-third to one-half of discontinued medications were e-prescribed within the same EHR and would result in a CancelRx message to the pharmacy. Extension of this functionality to medications reconciled in the EHR could significantly expand the impact of CancelRx on medication safety. In addition, complete and accurate discontinuation reasons are needed to optimize CancelRx implementation.


Practice Patterns in Retinopathy of Prematurity Treatment for Disease Milder Than Recommended by Guidelines.
To characterize the frequency of and clinical indications for which experts treat retinopathy of prematurity (ROP) milder than type 1 disease, the recommended threshold for treatment from established consensus guidelines. Descriptive analysis. setting: Multicenter. A database of 1444 eyes generated prospectively from all babies screened for ROP at 1 of 6 major ROP centers whose parents provided informed consent. Retrospective review of the database and charts to identify all patients treated for ROP milder than type 1. Indication(s) for treatment. A total of 137 eyes of 70 infants were treated for ROP. Of these 137 eyes, 13 (9.5%) were treated despite a clinical diagnosis milder than type 1 ROP. Indications for treatment included active ROP with the fellow eye being treated for type 1 ROP (2 eyes, 15.4%); concerning structural changes (9 eyes, 69.2%), including tangential traction with temporal vessel straightening concerning for macular dragging (8 eyes, 61.5%) and thick stage 3 membranes with anteroposterior traction concerning for progression to stage 4 ROP (3 eyes, 23.1%); persistent ROP at an advanced postmenstrual age (4 eyes, 30.8%); and/or vitreous hemorrhage (3 eyes, 23.1%). Experts in this study occasionally recommended treatment in eyes with disease less than type 1 ROP. This study has important clinical implications and highlights the role of individual clinical judgment in situations not covered by evidence-based treatment guidelines.


Prevalence of intimate partner abuse among nurses and nurses' aides in Mexico.
Nurses are the health professionals most frequently involved in the diagnosis and treatment of victims of family violence (FV). Understanding their personal experience with victimization is the key to shaping an appropriate role as advocates for medical recognition of FV and as integral members of the screening teams. We sought to determine the lifetime prevalence of intimate partner abuse among them and identify its risk factors. In our cross-sectional study, 1,150 registered nurses and nurses' aides at 11 urban hospitals in Mexico City self-administered an anonymous survey. We calculated descriptive statistics, Fisher exact tests, and multivariate logistic regression models to analyze physical, sexual, and emotional abuse during adulthood. Physical/sexual abuse during adulthood was 13% for nurses' aides and 18% for nurses. Similar proportions (13% of nurses' aides and 14% of nurses) also reported childhood physical/sexual abuse. Additional respondents (39% nurses' aides, 42% nurses) reported emotional abuse during adulthood. Detecting no significant differences in abuse patterns between the two groups, we combined occupations for all subsequent analyses. Being separated or divorced (vs. married) (Apr = 3.41, 95% confidence interval (CI): 1.81-6.44) and having suffered physical/sexual abuse during childhood (Apr = 3.39, 95% CI: 2.26-5.08) were associated with physical/sexual abuse in adulthood. The same variables were associated with adult emotional abuse (separated/divorced: Apr = 5.33, 95% CI: 2.61-10.85, and childhood physical/sexual abuse: Apr = 2.58, 95% CI: 1.79-3.75). Younger women (between the ages of 23 and 28 years) reported more emotional abuse (Apr = 2.10, 95% CI: 1.48-2.98). Counseling for abused nursing staff may help break the cycle. Physical/sexual partner abuse among nurses appears lower than among the general Mexican population, but remains worrisome. Battling childhood abuse might prevent intimate partner violence.


Selective adsorption, bound states, and potential parameters for He, Ne, and Ar interacting with a Cu(110) surface.
Using nozzle beams of He, Ne, and Ar, we have measured diffractive selective adsorption resonances from a Cu(110) surface kept at 20 K. Bound state energies of the atom-surface potentials have been determined from plots of the measured resonance energies versus incident angle and their fits to calculated kinematical dispersion relations. For 3He and 4He we have found a unique level assignment that is compatible with a single gas-surface potential curve with a well depth of 6.05 meV of the He-Cu(110) potential. This value is about 10% larger than the prediction of 5.55 meV from the current physisorption theory. The Ne and Ar data reveal a large number of closely spaced levels with level separations and estimated van der Waals coefficients that are compatible with available theoretical data.


Escherichia coli O157:H7 strain origin, lineage, and Shiga toxin 2 expression affect colonization of cattle.
Enterohemorrhagic Escherichia coli O157:H7 has evolved into an important human pathogen with cattle as the main reservoir. The recent discovery of E. coli O157:H7-induced pathologies in challenged cattle has suggested that previously discounted bacterial virulence factors may contribute to the colonization of cattle. The objective of the present study was to examine the impact of lineage type, cytotoxin activity, and cytotoxin expression on the amount of E. coli O157:H7 colonization of cattle tissue and cells in vitro. Using selected bovine- and human-origin strains, we determined that lineage type predicted the amount of E. coli O157:H7 strain colonization: lineage I > intermediate lineages > lineage II. All E. coli O157:H7 strain colonization was dose dependent, with threshold colonization at 10(3) to 10(5) CFU and maximum colonization at 10(7) CFU. We also determined that an as-yet-unknown factor of strain origin was the most dominant predictor of the amount of strain colonization in vitro. The amount of E. coli O157:H7 colonization was also influenced by strain cytotoxin activity and the inclusion of cytotoxins from lineage I or intermediate lineage strains increased colonization of a lineage II strain. There was a higher level of expression of the Shiga toxin 1 gene (stx(1)) in human-origin strains than in bovine-origin strains. In addition, lineage I strains expressed higher levels of the Shiga toxin 2 gene (stx(2)). The present study supports a role for strain origin, lineage type, cytotoxin activity, and stx(2) expression in modulating the amount of E. coli O157:H7 colonization of cattle.


Subclinical epileptiform activity and sleep disturbances in Alzheimer's disease.
Subclinical epileptiform activity (SEA) and sleep disturbances are frequent in Alzheimer's disease (AD). Both have an important relation to cognition and potential therapeutic implications. We aimed to study a possible relationship between SEA and sleep disturbances in AD. In this cross-sectional study, we performed a 24-h ambulatory EEG and polysomnography in 48 AD patients without diagnosis of epilepsy and 34 control subjects. SEA, mainly detected in frontotemporal brain regions during N2 with a median of three spikes/night [IQR1-17], was three times more prevalent in AD. AD patients had lower sleep efficacy, longer wake after sleep onset, more awakenings, more N1%, less REM sleep and a higher apnea-hypopnea index (AHI) and oxygen desaturation index (ODI). Sleep was not different between AD subgroup with SEA (AD-Epi+) and without SEA (AD-Epi-); however, compared to controls, REM% was decreased and AHI and ODI were increased in the AD-Epi+ subgroup. Decreased REM sleep and more severe sleep-disordered breathing might be related to SEA in AD. These results could have diagnostic and therapeutic implications and warrant further study at the intersection between sleep and epileptiform activity in AD.


Plasma exosomal miRNAs-based prognosis in metastatic kidney cancer.
Plasma exosomal miRNAs were evaluated for prognosis in an initial set of 44 metastatic renal cell cancer (mRCC) patients by RNA sequencing. Among ∼3.49 million mappable reads per patient, miRNAs accounted for 93.1% of the mapped RNAs. 227 miRNAs with high abundance were selected for survival analysis. Cox regression analysis identified association of 6 miRNAs with overall survival (OS) (P<0.01, False discovery rate (FDR) < 0.3). Five of the associated miRNAs were quantified in an independent follow-up cohort of 65 mRCC patients by TaqMan-based miRNA assays. Kaplan-Meier analysis confirmed the significant OS association of three miRs; miR-let-7i-5p (P=0.018, HR=0.49, 95% CI=0.21-0.84), miR-26a-1-3p (P=0.025, HR=0.43, 95% CI=0.10-0.84) and miR-615-3p (P=0.0007, HR=0.36, 95% CI=0.11-0.54). A multivariate analysis of miR-let-7i-5p with the clinical factor-based Memorial Sloan-Kettering Cancer Center (MSKCC) score improved survival prediction from an area under the curve (AUC) of 0.58 for MSKCC score to an average AUC of 0.64 across 48-month follow-up time. The multivariate model was able to define a high-risk group with median survival of 14 months and low risk group of 39 months (P=0.0002, HR=3.43, 95%CI, 2.73-24.15). Further validation of miRNA-based prognostic biomarkers are needed to improve current clinic-pathologic based prognostic models in patients with mRCC.


Stable, high-affinity streptavidin monomer for protein labeling and monovalent biotin detection.
The coupling between the quaternary structure, stability and function of streptavidin makes it difficult to engineer a stable, high affinity monomer for biotechnology applications. For example, the binding pocket of streptavidin tetramer is comprised of residues from multiple subunits, which cannot be replicated in a single domain protein. However, rhizavidin from Rhizobium etli was recently shown to bind biotin with high affinity as a dimer without the hydrophobic tryptophan lid donated by an adjacent subunit. In particular, the binding site of rhizavidin uses residues from a single subunit to interact with bound biotin. We therefore postulated that replacing the binding site residues of streptavidin monomer with corresponding rhizavidin residues would lead to the design of a high affinity monomer useful for biotechnology applications. Here, we report the construction and characterization of a structural monomer, mSA, which combines the streptavidin and rhizavidin sequences to achieve optimized biophysical properties. First, the biotin affinity of mSA (K(d) = 2.8 nM) is the highest among nontetrameric streptavidin, allowing sensitive monovalent detection of biotinylated ligands. The monomer also has significantly higher stability (T(m) = 59.8 °C) and solubility than all other previously engineered monomers to ensure the molecule remains folded and functional during its application. Using fluorescence correlation spectroscopy, we show that mSA binds biotinylated targets as a monomer. We also show that the molecule can be used as a genetic tag to introduce biotin binding capability to a heterologous protein. For example, recombinantly fusing the monomer to a cell surface receptor allows direct labeling and imaging of transfected cells using biotinylated fluorophores. A stable and functional streptavidin monomer, such as mSA, should be a useful reagent for designing novel detection systems based on monovalent biotin interaction.


Role of autophagy in liver physiology and pathophysiology.
Autophagy is a highly conserved intracellular degradation pathway by which bulk cytoplasm and superfluous or damaged organelles are enveloped by double membrane structures termed autophagosomes. The autophagosomes then fuse with lysosomes for degradation of their contents, and the resulting amino acids can then recycle back to the cytosol. Autophagy is normally activated in response to nutrient deprivation and other stressors and occurs in all eukaryotes. In addition to maintaining energy and nutrient balance in the liver, it is now clear that autophagy plays a role in liver protein aggregates related diseases, hepatocyte cell death, steatohepatitis, hepatitis virus infection and hepatocellular carcinoma. In this review, I discuss the recent findings of autophagy with a focus on its role in liver pathophysiology.


Registered nurses' decision-making regarding documentation in patients' progress notes.
To examine registered nurses' decision-making when documenting care in patients' progress notes. What constitutes effective nursing documentation is supported by available guidelines. However, ineffective documentation continues to be cited as a major cause of adverse events for patients. Decision-making in clinical practice is a complex process. To make an effective decision, the decision-maker must be situationally aware. The concept of situation awareness and its implications for making safe decisions has been examined extensively in air safety and more recently is being applied to health. The study was situated in a naturalistic paradigm. Purposive sampling was used to recruit 17 registered nurses who used think-aloud research methods when making decisions about documenting information in patients' progress notes. Follow-up interviews were conducted to validate interpretations. Data were analysed systematically for evidence of cues that demonstrated situation awareness as nurses made decisions about documentation. Three distinct decision-making scenarios were illuminated from the analysis: the newly admitted patient, the patient whose condition was as expected and the discharging patient. Nurses used mental models for decision-making in documenting in progress notes, and the cues nurses used to direct their assessment of patients' needs demonstrated situation awareness at different levels. Nurses demonstrate situation awareness at different levels in their decision-making processes. While situation awareness is important, it is also important to use an appropriate decision-making framework. Cognitive continuum theory is suggested as a decision-making model that could support situation awareness when nurses made decisions about documenting patient care. Because nurses are key decision-makers, it is imperative that effective decisions are made that translate into safe clinical care. Including situation awareness training, combined with employing cognitive continuum theory as a decision-making framework, provides a powerful means of guiding nurses' decision-making.


Effect of leukotactin-1 on the protection in vivo of myeloid progenitor cells against cytotoxic chemotherapeutics.
Leukotactin-1 (Lkn-1) is a human CC chemokine that induces chemotaxis of neutrophils, monocytes, eosinophils, and lymphocytes and suppresses colony formation of myeloid progenitor cells in vitro. Present studies evaluated the myeloprotective capabilities of Lkn-1 in vivo against Ara-C and 5-fluorouracil (5-FU). The effect of Lkn-1 on myelopoiesis was first assessed in vivo by injecting recombinant Lkn-1 in C3H/HeJ mice. Lkn-1 rapidly decreased cycling rates and absolute numbers of myeloid progenitor cells in marrow. Lkn-1 administration prior to and during the chemotherapeutics treatment resulted in increased progenitors for colony-forming units-granulocyte/macrophage (CFU-GM), colony-forming units-granulocyte/erythroid/megakaryocyte/macrophage (CFU-GEMM), and burst-forming units-erythroid (BFU-E) compared with a saline-treated group. The protective effects lasted until day 3 after the termination of Ara-C administration and until day 7 after the termination of 5-FU administration. The results indicate that Lkn-1 protects bone marrow myeloid progenitor cells when cytotoxic chemotherapeutics are used in a preclinical setting. These results may be of use in clinical treatment for myeloprotection.


A multiscale assessment of bowel impairment in an Italian multiple sclerosis cohort.
Bowel dysfunctions (BD) in multiple sclerosis (MS) are under reported despite their clinical relevance. Scales usually applied do not thoroughly assess constipation and fecal incontinence. Instead, a proper qualitative and quantitative description of these symptoms might have relevant clinical and scientific consequences. The aim of this project is to study the prevalence of BD in a cohort of persons with MS (pwMS). Four-hundred and forty-seven pwMS (330 relapsing-remitting MS-RRMS and 117 progressive MS-PMS) were recruited. Three different questionnaires were administered: the neurogenic bowel dysfunction score (NBDS), the Wexner constipation scale (WexCon) and the Wexner incontinence scale (WexInc). All the scales were divided in subscores according to symptom severity. The prevalence of BD, considered as NBDS > 0, was 53.7%. Mean scores in pwMS group were as follows: NBDS 2.6 (SD 3.5), WexInc 1.1 (SD 2.4), WexCon 4.4 (SD 5.9). NBDS, WexCon and WexInc were significantly higher in PMS vs RRMS (p < 0.001), and significantly associated with disease duration, EDSS, multiple sclerosis severity score (p < 0.001), as well as with each other (p < 0.001). Our study confirms the presence of bowel dysfunctions in a large group of pwMS with a wide range of disability and their association with progressive disease phenotype and clinical disability.


Estimation of Large Motion in Lung CT by Integrating Regularized Keypoint Correspondences into Dense Deformable Registration.
We present a novel algorithm for the registration of pulmonary CT scans. Our method is designed for large respiratory motion by integrating sparse keypoint correspondences into a dense continuous optimization framework. The detection of keypoint correspondences enables robustness against large deformations by jointly optimizing over a large number of potential discrete displacements, whereas the dense continuous registration achieves subvoxel alignment with smooth transformations. Both steps are driven by the same normalized gradient fields data term. We employ curvature regularization and a volume change control mechanism to prevent foldings of the deformation grid and restrict the determinant of the Jacobian to physiologically meaningful values. Keypoint correspondences are integrated into the dense registration by a quadratic penalty with adaptively determined weight. Using a parallel matrix-free derivative calculation scheme, a runtime of about 5 min was realized on a standard PC. The proposed algorithm ranks first in the EMPIRE10 challenge on pulmonary image registration. Moreover, it achieves an average landmark distance of 0.82 mm on the DIR-Lab COPD database, thereby improving upon the state of the art in accuracy by 15%. Our algorithm is the first to reach the inter-observer variability in landmark annotation on this dataset.


Nuclear exchange generates population diversity in the wheat leaf rust pathogen Puccinia triticina.
In clonally reproducing dikaryotic rust fungi, non-sexual processes such as somatic nuclear exchange are postulated to play a role in diversity but have been difficult to detect due to the lack of genome resolution between the two haploid nuclei. We examined three nuclear-phased genome assemblies of Puccinia triticina, which causes wheat leaf rust disease. We found that the most recently emerged Australian lineage was derived by nuclear exchange between two pre-existing lineages, which originated in Europe and North America. Haplotype-specific phylogenetic analysis reveals that repeated somatic exchange events have shuffled haploid nuclei between long-term clonal lineages, leading to a global P. triticina population representing different combinations of a limited number of haploid genomes. Thus, nuclear exchange seems to be the predominant mechanism generating diversity and the emergence of new strains in this otherwise clonal pathogen. Such genomics-accelerated surveillance of pathogen evolution paves the way for more accurate global disease monitoring.


Generation of plasma free cholesterol from circulating lipoprotein-associated cholesteryl ester.
Studies were performed to investigate the contribution of lipoprotein-associated cholesteryl ester (CE) in the monkey to circulating free cholesterol (FC). Monkey plasma was incubated with [14C]- or [3H]cholesteryl ester, and radiolabeled low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were isolated by ultracentrifugation. Animals received labeled LDL or HDL. A rapid transfer of CE between lipoproteins was observed, consistent with an active CE transfer protein activity in the monkey. Within 4 h the percent of plasma radioactivity in FC after injection of CE-labeled LDL or HDL was, respectively, 30 and 7% of that of the ester. To determine whether the generation of FC was due to a circulating plasma cholesteryl ester hydrolase, monkey plasma was incubated with CE-labeled lipoproteins with and without 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). A small amount of FC (less than 3% of the radioactivity) was generated during this incubation but most of the FC production was inhibited by DTNB. Although a small amount of FC can be produced by a plasma cholesteryl esterase (perhaps via reverse action of lecithin-cholesterol acyltransferase), most of the FC in plasma derived from lipoprotein-associated CE is probably due to tissue uptake of lipoproteins and subsequent intracellular hydrolysis of the CE to produce FC.


Self-interference fluorescence microscopy with three-phase detection for depth-resolved confocal epi-fluorescence imaging.
Three-dimensional confocal fluorescence imaging of in vivo tissues is challenging due to sample motion and limited imaging speeds. In this paper a novel method is therefore presented for scanning confocal epi-fluorescence microscopy with instantaneous depth-sensing based on self-interference fluorescence microscopy (SIFM). A tabletop epi-fluorescence SIFM setup was constructed with an annular phase plate in the emission path to create a spectral self-interference signal that is phase-dependent on the axial position of a fluorescent sample. A Mach-Zehnder interferometer based on a 3 × 3 fiber-coupler was developed for a sensitive phase analysis of the SIFM signal with three photon-counter detectors instead of a spectrometer. The Mach-Zehnder interferometer created three intensity signals that alternately oscillated as a function of the SIFM spectral phase and therefore encoded directly for the axial sample position. Controlled axial translation of fluorescent microsphere layers showed a linear dependence of the SIFM spectral phase with sample depth over axial image ranges of 500 µm and 80 µm (3.9 × Rayleigh range) for 4 × and 10 × microscope objectives respectively. In addition, SIFM was in good agreement with optical coherence tomography depth measurements on a sample with indocyanine green dye filled capillaries placed at multiple depths. High-resolution SIFM imaging applications are demonstrated for fluorescence angiography on a dye-filled capillary blood vessel phantom and for autofluorescence imaging on an ex vivo fly eye.


Neonatal necrotizing enterocolitis. Evolution of new principles in management.
Over a three-year period, we have operated on 30 infants with necrotizing enterocolitis. Because of the increased experience with this lesion, we have evolved reliable guidelines for both early diagnosis and operative treatment of necrotizing enterocolitis. Initial therapy was nonsurgical in most cases and included gastrointestinal tract decompression, systemic antibiotics, and correction of fluid, electrolyte, and metabolic abnormalities. Absolute indications for surgery and thought to be prima facie evidence for bowel necrosis were (1) cellulitis of the anterior abdominal wall, (2) free intraperitoneal air, (3) a single dilated intestinal segment present on serial roentgenograms, (4) clinical deteioration in the presence of appropriate medical therapy, and (5) persistent abdominal tenderness. Although all 30 patients operated on had necrotic bowel proved at histologic examination, 21 survived (70%). All patients listed as survivors, with the exception of two, have had intestinal tract continuity reestablished and are doing well.


Construction of a helper cell line for avian reticuloendotheliosis virus cloning vectors.
We wished to construct cell lines that supply the gene products of gag, pol, and env for the growth of replication-defective reticuloendotheliosis retrovirus vectors without production of the helper virus. To do this, first we located by S1 mapping the donor and acceptor splice sites of reticuloendotheliosis virus strain A. The donor splice site is ca. 850 base pairs from the 5' end of proviral DNA. It is close to or overlaps the encapsidation sequences for viral RNA. The splice acceptor site is ca. 5.6 kilobase pairs from the 5' end of proviral DNA. Therefore, the encapsidation sequences and the donor splice site were removed from viral DNA to give expression of the gag and pol genes without virus production. The promoter in the long terminal repeat was fused to a site near the first ATG codon of the env gene, thereby deleting the encapsidation sequences and the gag and pol genes to give expression of the env gene without virus production. The permissive canine cell line D17 was transfected with the two modified viral DNAs. Two cell clones that contain both modified viral DNAs support the production of replication-defective spleen necrosis virus-thymidine kinase recombinant retrovirus vectors without the production of helper virus. To prevent recombination, the vector contains deletions that overlap with deletions in the integrated helper virus DNAs. This helper cell-vector system will be useful to derive infectious recombinant virus stocks of high titer (over 10(5) thymidine kinase transforming units per ml) which are able to infect avian, rat, and dog cells without the aid of helper virus.


Quantification of sarcomere length distribution in whole muscle frozen sections.
Laser diffraction (LD) is a valuable tool for measuring sarcomere length (Ls), a major determinant of muscle function. However, this method relies on few measurements per sample that are often extrapolated to whole muscle properties. Currently it is not possible to measure Ls throughout an entire muscle and determine how Ls varies at this scale. To address this issue, we developed an actuated LD scanner for sampling large numbers of sarcomeres in thick whole muscle longitudinal sections. Sections of high optical quality and fixation were produced from tibialis anterior and extensor digitorum longus muscles of Sprague-Dawley rats (N=6). Scans produced two-dimensional Ls maps, capturing >85% of the muscle area per section. Individual Ls measures generated by automatic LD and bright-field microscopy showed excellent agreement over a large Ls range (ICC>0.93). Two-dimensional maps also revealed prominent regional Ls variations across muscles.


Diagnostic ultrasound-guided excisional testicular biopsy for small (< 1 cm) incidental nodules. A single institution experience.
The widespread use of scrotal ultrasound (SUS) has led to a marked increase in the number of incidentally detected testicular lesions. A small incidental nodule (STN) has defined as a non palpable (< 10 mm), asymptomatic solid lesion with normal levels of oncological testicular markers. Nowadays the lack of agreement on the topic causes managing problems to andrologists. We present our experience consisting in 8 cases of STN discovered by SUS performed for different clinical indications. We retrieved from our ultrasonographic files the clinical information about 717 patients evaluated for andrological problems. Patients with STN underwent to a complete clinical history and physical examination as well as oncological testicular markers measurement and ormonal assessment and then received a diagnostic ultrasound guided excisional biopsy (DEB). Surgical approach was performed through an inguinal incision. Using the coordinates previously obtained from preoperative SUS, STN was localized by intraoperative SUS. The lesion was enucleated and sent to the Pathology department for frozen section examination (FSE). Biopsies of affected testis (TB) were also performed. Post-excision ultrasound has been used to confirm the complete removal of the nodule. Whether pathological findings were benign, testis sparing surgery (TSS) was performed. Immediate radical orchidectomy (IRO) was performed if FSE and TB findings suggested a malignant lesion. STNs were discovered in 8 patients (1,1%). Very small lesions (< 5 mm) were detected in 50% of cases. We performed four IRO and four DEB with consequent TSS. In one case we performed a delayed radical orchidectomy (DRO). At FSE pathologist reported 3 Leydig cell tumor and 3 seminoma and an inflammatory regressive lesion in one case. FSE on TB reported intratesticular neoplasia (TIN) in three cases. In one case nodule wasn't sent to FSE. We observed a concordance between FSE and definitive pathologic report in six cases (75%). The management of STN is still a challenge for the surgical andrologist. A correct diagnosis has a crucial role in making the best treatment and patients outcome. Ultrasound guided excisional biopsy and the close collaboration with a dedicated pathologist are very useful in reducing errors.


A rare case of pleomorphic adenoma with difficult diagnosis using biopsy.
An 85-year-old woman was found to have a nodule in the left S6 of the lung on computed tomography (CT); the pathological diagnosis from the CT-guided biopsy was adenoid cystic carcinoma. We accordingly performed left lower lobectomy. Pathologically, the biphasic cell population showed admixtures in varying proportions of epithelial and stromal elements, thereby indicating pleomorphic adenoma (PA). PA of the lung is extremely rare with reports of only 20 patients so far. Interestingly, this case was difficult to diagnose using CT-guided biopsy because the overview and biphasic cell population obtained on biopsy were garbled. Here we have reported our rare experience of PA.


Spatial and temporal aspects of ACh-induced [Ca2+]i oscillations in porcine tracheal smooth muscle.
This study evaluated the relationship between regional elevation in intracellular calcium concentration ([Ca2+]i) induced by acetylcholine (ACh) and the global cellular responses in porcine tracheal smooth muscle (TSM) cells. Regional (approximately 1.5 microm3) and global (whole cell) changes in [Ca2+]i were measured in fluo-3 loaded TSM cells using real-time confocal microscopy. Regional responses appeared as propagating [Ca2+]i oscillations whereas global responses reflected the spatiotemporal integration of these regional responses. Within a region, [Ca2+]i oscillations were 'biphasic' with initial higher frequencies, followed by slower steady-state oscillations. With increasing ACh concentration, the peak (maximum value relative to 0 nM) of regional [Ca2+]i oscillations remained relatively constant, whereas both frequency and propagation velocity increased. In contrast, the global spatiotemporal integration of the regional oscillatory responses appeared as a concentration-dependent increase in peak as well as mean cellular [Ca2+]i. We conclude that the significance of ACh-induced [Ca2+]i oscillations lies in the establishment of mean [Ca2+]i level for slower Ca2+-dependent physiological processes via modulation of oscillation frequency and propagation velocity.


Projections of giant fibers, a class of reticular interneurons, in the brain of the silver hatchetfish.
Giant fibers are large reticular interneurons that mediate excitatory input from the Mauthner cells to pectoral-fin motoneurons. The present study revealed extensive giant-fiber projections to central targets other than the pectoral-fin motoneurons. Physiologically identified giant fibers were filled intracellularly with Lucifer Yellow. The presence of numerous dendrites suggests that there may be significant integration of non-Mauthner inputs in the giant-fiber cell body. The axon decussates and then bifurcates to form a descending process, that innervates pectoral-fin motoneurons, and an ascending process with collaterals that terminate in the rostral trigeminal, rostral facial and, in some cases, oculomotor and trochlear motor nuclei. The projections are consistent with a role for the giant fibers as mediators of all the cranial components of the Mauthner-initiated startle response. There are also extensive projections to cells near the Mauthner cell and to the medial reticular formation. The latter projections may participate in longer-latency components of the Mauthner-initiated startle response, or they may constitute part of a general arousal pathway. The morphology of giant fibers suggests that they are homologous to cranial relay neurons in the goldfish and T reticular interneurons in zebrafish larvae. Non-Mauthner inputs to giant fibers may participate in non-Mauthner startle responses and contribute to the variability of Mauthner-mediated startle responses.


Toxicological evaluation of honey as an ingredient added to cigarette tobacco.
A tiered testing strategy has been developed to evaluate the potential for new ingredients, tobacco processes, and technological developments to increase or reduce the biological activity that results from burning tobacco. In the manufacture of cigarettes, honey is used as a casing ingredient to impart both aroma and taste. The primary objective of this document is to summarize and interpret chemical and toxicological studies that have been conducted to evaluate the potential impact of honey on the biological activity of either mainstream cigarette smoke or cigarette smoke condensate. As part of ongoing stewardship efforts, cigarettes produced with honey (5% wet weight) as an alternative to invert sugar in tobacco casing material were subjected to extensive evaluation. Principal components of this evaluation were a determination of selected mainstream smoke constituent yields, Ames assay, sister chromatid exchange assay in Chinese hamster ovary cells, a 30-wk dermal tumor promotion evaluation of cigarette smoke condensate in SENCAR mice, and a 13-wk inhalation study of cigarette smoke in Sprague-Dawley rats. Comparative analytical evaluations demonstrated that the substitution of honey for invert sugar as a casing material in cigarettes had no significant impact on mainstream smoke chemistry. In addition, in vitro and in vivo studies demonstrated that cigarettes containing tobacco cased with honey had comparable biological activity to cigarettes containing invert sugar. Collectively, these data demonstrate that the use of honey as an alternative casing material in the manufacture of cigarettes does not alter the potential toxicity of cigarette smoke condensate (CSC) or cigarette smoke; therefore the use of honey as an ingredient added to cigarette tobacco is acceptable from a toxicological perspective.


REDD1 loss reprograms lipid metabolism to drive progression of RAS mutant tumors.
Human cancers with activating RAS mutations are typically highly aggressive and treatment-refractory, yet RAS mutation itself is insufficient for tumorigenesis, due in part to profound metabolic stress induced by RAS activation. Here we show that loss of REDD1, a stress-induced metabolic regulator, is sufficient to reprogram lipid metabolism and drive progression of RAS mutant cancers. Redd1 deletion in genetically engineered mouse models (GEMMs) of KRAS-dependent pancreatic and lung adenocarcinomas converts preneoplastic lesions into invasive and metastatic carcinomas. Metabolic profiling reveals that REDD1-deficient/RAS mutant cells exhibit enhanced uptake of lysophospholipids and lipid storage, coupled to augmented fatty acid oxidation that sustains both ATP levels and ROS-detoxifying NADPH. Mechanistically, REDD1 loss triggers HIF-dependent activation of a lipid storage pathway involving PPARγ and the prometastatic factor CD36. Correspondingly, decreased REDD1 expression and a signature of REDD1 loss predict poor outcomes selectively in RAS mutant but not RAS wild-type human lung and pancreas carcinomas. Collectively, our findings reveal the REDD1-mediated stress response as a novel tumor suppressor whose loss defines a RAS mutant tumor subset characterized by reprogramming of lipid metabolism, invasive and metastatic progression, and poor prognosis. This work thus provides new mechanistic and clinically relevant insights into the phenotypic heterogeneity and metabolic rewiring that underlies these common cancers.


A bioenergetics evaluation of temperature-dependent selection for the spawning phenology by Snake River fall Chinook salmon.
High water temperatures can increase the energetic cost for salmon to migrate and spawn, which can be important for Snake River fall-run Chinook salmon because they migrate great distances (>500 km) at a time when river temperatures (18-24°C) can be above their optimum temperatures (16.5°C). Average river temperatures and random combinations of migration and spawning dates were used to simulate fish travel times and determine the energetic consequences of different thermal experiences during migration. An energy threshold criterion (4 kJ/g) was also imposed on survival and spawning success, which was used to determine how prevailing temperatures might select against certain migration dates and thermal experiences, and in turn, explain the selection for the current spawning phenology of the population. Scenarios of tributary use for thermal refugia under increasing water temperatures (1, 2, and 3°C) were also run to determine which combinations of migration dates, travel rates, and resulting thermal experiences might be most affected by energy exhaustion. As expected, when compared to observations, the model under existing conditions and energy use could explain the onset, but not the end of the observed spawning migration. Simulations of early migrants had greater energy loss than late migrants regardless of the river temperature scenario, but higher temperatures disproportionately selected against a larger fraction of early-migrating fish, although using cold-water tributaries during migration provided a buffer against higher energy use at higher temperatures. The fraction of simulated fish that exceeded the threshold for migration success increased from 58% to 72% as average seasonal river temperatures over baseline temperatures increased. The model supports the conclusion that increases in average seasonal river temperatures as little as 1°C could impose greater thermal constraints on the fish, select against early migrants, and in turn, truncate the onset of the current spawning migration.


The Incidence of Hyponatraemia and Its Effect on the ECOG Performance Status among Lung Cancer Patients.
Hyponatraemia is one of the common electrolytic disorders which are associated with lung cancer. Hyponatraemia may influence the ECOG performance status at presentation. Also, to the best of our knowledge, we found only limited Indian studies where the ECOG score was correlated with the serum sodium status in lung cancer patients on presentation. To assess the incidence of hyponatraemia among the patients of carcinoma of the lung before putting them into the specific treatment category for cancer and to check the effects on their ECOG performance status. A cross-sectional, observational study was conducted on 116 consecutive patients of lung cancer during the period from November 2011 to October 2012. The patients with a histologically proven diagnosis of lung cancer were grouped initially according to their ECOG performance statuses. The serum sodium value of each patient was measured and the hyponatraemic patients were given treatment according to the protocol. The correlation of the ECOG performance status with the serum sodium of the lung cancer patients was measured. To check for any laboratory error in serum sodium, we selected (n = 58) age, sex and socioeconomic matched control patients. At presentation 44.8% of the lung cancer patients showed hyponatraemia [52/116]. The ECOG score was significantly poor in the advanced clinical stages (ECOG ≤2 Vs ECOG ≥ 3 in NSCLC cases, χ(2) =11.25, P=.0008). The ECOG performance status score at admission showed a negative correlation with the serum sodium status which was measured on admission among all the patients (Pearson correlation coefficient = - 0.186). The clinical stage of the lung cancer also showed a positive correlation with the ECOG score at admission in our study (Pearson correlation coefficient = 0.295). Hyponatraemia is not an uncommon condition and it should be suspected and screened in each patient, as it may influence the ECOG performance status score, which serves as an important factor in the prognosis of lung cancer.


The Relationship Between Alcohol Consumption, BMI, and Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis.
Moderate alcohol use may be associated with lower risk of type 2 diabetes mellitus (T2DM). Previous reviews have reached mixed conclusions. To quantify the dose-response relationship between alcohol consumption and T2DM, accounting for differential effects by sex and BMI. Medline, Embase, Web of Science, and one secondary data source. Cohort studies on the relationship between alcohol use and T2DM. Fifty-five studies, and one secondary data source, were included with a combined sample size of 1,363,355 men and 1,290,628 women, with 89,983 and 57,974 individuals, respectively, diagnosed with T2DM. Multivariate dose-response meta-analytic random-effect models were used. For women, a J-shaped relationship was found with a maximum risk reduction of 31% (relative risk [RR] 0.69, 95% CI 0.64-0.74) at an intake of 16 g of pure alcohol per day compared with lifetime abstainers. The protective association ceased above 49 g per day (RR 0.82, 95% CI 0.68-0.99). For men, no statistically significant relationship was identified. When results were stratified by BMI, the protective association was only found in overweight and obese women. Our analysis relied on aggregate data. We included some articles that determined exposure and cases via self-report, and the studies did not account for temporal variations in alcohol use. The observed reduced risk seems to be specific to women in general and women with a BMI ≥25 kg/m2. Our findings allow for a more precise prediction of the sex-specific relationship between T2DM and alcohol use, as our results differ from those of previous studies.


Physiological effects of respiratory failure after paediatric surgery.
Having taking into consideration those pathological conditions in which great difficulties are encountered during the conduction of artificial ventilation the author describes a simple method for investigating the volume of the lungs by means of whole-body plethysmography. A modified Drinker's respirator was used as a plethysmograph. In studies of children after cordiosurgical operations CPAP was found to be particularly useful for improving arterial blood oxgenation in cases with low pulmonary compliance. The method led to a clinically observed reduction of respiratory work. Hypoxia during ventilation with a high-oxygen mixture may depend on a decreased pulmonary volume and the aim of treatment should be to improve this condition.


Generalized melanoses and nonmelanotic pigmentations of the head and neck.
The dentist is in a strategic position to evaluate early color changes of the head and neck. Certain oral and perioral changes of pigmentation are amenable to early diagnosis. Systemically acquired generalized melanoses and nonmelanotic color changes should be periodically reviewed by all examining physicians and dentists. The multiple forms of acanthosis nigricans are described, and the triad of Albright's syndrome is compared with the findings of Peutz-Jegher's syndrome, multiple basal cell nevi, neurofibromatosis, and Addison's disease. The spectrums of changes seen in abnormal nonmelanotic pigmentation are reviewed, and the importance of recognition of drug-induced pigmentation is emphasized.


[Women with atypical, precursor lesions and invasive cervical cancer: behaviors according to the recommendations of the Ministry of Health].
To verify whether women with atypias of undetermined significance and precursor lesions or invasive cervical outcomes were referred to Medium Complexity Units (MCU) following the guidelines recommended by the Brazilian Ministry of Health. Retrospective study based on the cytopathological outcomes of users of the Unified Health System, seen at Basic Health Assistance Units (BHAU) and referred to MCUs in the municipality of Goiânia, state of Goiás, from 2005 to 2006. We assessed 832 records according to the recommendations of the Brazilian Ministry of Health, as established by the Brazilian Nomenclature for Cervical Cytopathologic Outcomes and Recommended Clinical Practice. To check the distribution of variables such as reasons for referral, results of colposcopy and histopathology and clinical procedures we calculated absolute and relative frequencies, mean, minimum and maximum values. We understood 72.7% of the referrals were not in accordance with the recommendations of the Ministry of Health. There were 605 women with test results classified as atypical squamous cells of undetermined significance, possibly non-neoplasms, and squamous intraepithelial lesion of low level which were sent to MCU, and of these 71.8% were submitted to colposcopy, and 64.7% had histopathological examination which results were classified as 31.0% with non-neoplasms and 44.6% as NIC I. Out of 211 women with results classified as more severe squamous lesions, 86.3% were submitted to colposcopy and 68.7% of these had histopathological examinations. The results of this study revealed high rates of inappropriate referrals to MCU, which required a high percentage of unnecessary procedures. The recommendations of the Ministry of Health were followed by BHAU and the majority of women received counseling/treatment as recommended.


Maladaptive Plasticity Masks the Effects of Natural Selection in the Red-Shouldered Soapberry Bug.
Natural selection can produce local adaptation, but local adaptation can be masked by maladaptive plasticity. Maladaptive plasticity may arise as a result of gene flow producing novel gene combinations that have not been exposed to selection. In the 1980s, populations of the red-shouldered soapberry bug (Jadera haematoloma) were locally adapted to feed on the seeds of a native host plant and an introduced host plant; by 2014, local differentiation in beak length had been lost, likely as a consequence of increased gene flow. In this study, I assess the relative contributions of natural selection and plasticity to beak length on these two hosts. I confirm the earlier hypothesis that the host plant seedpod drives divergent natural selection on beak length. I then demonstrate that the proximate cause of the loss of observable differentiation in beak length is maladaptive plasticity, which masks persistent genetic differences between host-associated populations. Maladaptive plasticity is highest in areas where the two plants co-occur; in combination with historical measures of plasticity in hybrids, this indicates that maladaptive plasticity may be a consequence of ongoing gene flow. Although natural selection produced locally adapted genotypes in soapberry bugs, maladaptive plasticity is masking phenotypic differences between populations in nature.


Catalytic conversion of renewable biomass resources to fuels and chemicals.
Lignocellulosic biomass is renewable and cheap, and it has the potential to displace fossil fuels in the production of fuels and chemicals. Biomass-derived carboxylic acids are important compounds that can be used as platform molecules for the production of a variety of important chemicals on a large scale. Lactic acid, a prototypical biomass derivative, and levulinic acid, an important chemical feedstock produced by hydrolysis of waste cellulosic materials, can be upgraded using bifunctional catalysts (those containing metal and acid sites), which allows the integration of several transformations (e.g., oxygen removal and C-C coupling) in a single catalyst bed. This coupling between active sites is beneficial in that it reduces the complexity and cost of the biomass conversion processes. Deoxygenation of biomass derivatives is a requisite step for the production of fuels and chemicals, and strategies are proposed to minimize the consumption of hydrogen from an external source during this process.


Prevalence of different HIV-1 subtypes in sexual transmission in China: a systematic review and meta-analysis.
Sexual transmission has become the primary route of HIV transmission in China. Therefore, a comprehensive overview of HIV-1 subtype distribution is necessary for the prevention and control of the HIV epidemic. The present study aimed to provide a comprehensive prevalence estimate of different HIV-1 subtypes in sexual transmission in China. We conducted a systematic literature review for studies of HIV-1 subtypes in English and Chinese through several databases. Eligible articles were screened and selected by two authors independently. Random-effects model were applied to calculate the pooled prevalence of different HIV-1 subtypes, and subgroup analyses examined prevalence estimates across time, locations, and populations. A total of 130 eligible studies were identified, including 18 752 successfully genotyped samples. The pooled prevalence of CRF01_AE, subtype B, CRF07_BC, CRF08_BC, and subtype C were 44·54% (95% CI 40·81-48·30), 18·31% (95% CI 14·71-22·17), 16·45% (95% CI 13·82-19·25), 2·55% (95% CI 1·56-3·73), 0·37% (95% CI 0·11-0·72), respectively. The prevalence of subtype B in sexual transmission decreased, while the prevalence of CRF01_AE and CRF07_BC in sexual transmission, and CRF08_BC in heterosexual transmission increased. There is significant variation in HIV-1 subtype distribution between regions. The distribution of HIV-1 subtypes and circulating recombinant forms have changed significantly. The high genetic variability of HIV-1 poses a significant challenge for disease control and surveillance in China.


[Findings in the bronchopulmonary system of workers employed in the industrial production and processing of synthetic mineral fibers].
This paper reports on the evaluation of 21 epidemiological studies concerning investigations in the Man-Made Mineral Fibers (MMF) industries. First conditions of exposure were described. Concentrations of respirable fibers at the production and further treatment of MMF in older plants were in average about a few fibers per cm3, today in most cases remarkable below 1 fiber/cm3. In the old factories also there has been an exposure with very fine fibers with a diameter below 1 micron and this is comparable from its amount with the conditions nowadays. About 55000 workers exposed to MMF were investigated, most of them handling glass fibers. Several thousands of this workforce had a duration of exposure of 20 years or more and a latency time of 30 years or more. No case of mesothelioma was found. A most of the identified cases of pneumoconiosis could be attached to a prior or a concomitant exposure to silica if the occupational exposure was carefully examined. At the recent time there is no wellfounded suspicion that pneumoconiosis is caused by the exposure in the MMF-industries. A few authors supposed, that unspecific structural changes of the lung as occuring also in a greater amount in dependency of smoking habits and age are found more frequently among the employees of this industry than among the common population. Neither the workers with such unspecific structural changes of the lung nor the other members of the workforces had prejudices of lung function. At present time a risk due to MMF to get sick with cancer of the bronchopulmonic system, especially with lung cancer can neither be proved nor be excluded. The epidemiological studies carried out until now were not capable to point out a possibly existing risk in such a ordner of magnitude. It is uncertain if it will be feasable to prove such a risk by using more subtilized methods. This depends at one side on the possibility of clearing up and registering the confounding risk factors. On the other side it must be considered, that the exposure with fibrous dusts even in the old MMF-factories was very much lower than the exposure in the asbestos-industry. It is indispensable to take into account the most important confounding risk factors (smoking habits, preexposure and concomitant exposure with dangerous working materials) in further epidemiological investigations.


Adaptation, specialization, and coevolution within phytobiomes.
Growth patterns of individual plants and evolutionary trajectories of plant communities are intimately linked with and are critically affected by host-associated microbiomes. Research across systems has begun to shed light on how these phytobiomes are established under laboratory and natural conditions, and have cultivated hope that a better understanding of the governing principles for host-microbe interactions can guide attempts to engineer microbiomes to boost agricultural yields. One important, yet relatively understudied, parameter in regards to phytobiome membership is the degree to which specialization and coevolution between plant species and microbes provides structure to these communities. In this article, I provide an overview of mechanisms enabling adaptation and specialization of phytobiome communities to host plants as well as the potential for plants themselves to recruit and cultivate beneficial interactions. I further explore the possibility of host-beneficial microbe coevolution and suggest particular situations that could promote the evolution of such close-knit partnerships. It is my hope that this overview will encourage future experiments that can begin to fill in this black box of ecological and evolutionary interactions across phytobiomes.


Consensus recommendations on standardized magnetic resonance imaging protocols for multicenter canine brain tumor clinical trials.
The National Cancer Institute Comparative Brain Tumor Consortium, Patient Outcomes Working Group, propose a consensus document in support of standardized magnetic resonance imaging protocols for canine brain tumor clinical trials. The intent of this manuscript is to address the widely acknowledged need to ensure canine brain tumor imaging protocols are relevant and have sufficient equivalency to translate to human studies such that: (1) multi-institutional studies can be performed with minimal inter-institutional variation, and (2) imaging protocols are consistent with human consensus recommendations to permit reliable translation of imaging data to human clinical trials. Consensus recommendations include pre- and postcontrast three-dimensional T1-weighted images, T2-weighted turbo spin echo in all three planes, T2*-weighted gradient recalled echo, T2-weighted fluid attenuated inversion recovery, and diffusion weighted imaging/diffusion tensor imaging in transverse plane; field of view of ≤150 mm; slice thickness of ≤2 mm, matrix ≥ 256 for two-dimensional images, and 150 or 256 for three-dimensional images.


A Comparison of Forensic Age Prediction Models Using Data From Four DNA Methylation Technologies.
Individual age estimation can be applied to criminal, legal, and anthropological investigations. DNA methylation has been established as the biomarker of choice for age prediction, since it was observed that specific CpG positions in the genome show systematic changes during an individual's lifetime, with progressive increases or decreases in methylation levels. Subsequently, several forensic age prediction models have been reported, providing average age prediction error ranges of ±3-4 years, using a broad spectrum of technologies and underlying statistical analyses. DNA methylation assessment is not categorical but quantitative. Therefore, the detection platform used plays a pivotal role, since quantitative and semi-quantitative technologies could potentially result in differences in detected DNA methylation levels. In the present study, we analyzed as a shared sample pool, 84 blood-based DNA controls ranging from 18 to 99 years old using four different technologies: EpiTYPER®, pyrosequencing, MiSeq, and SNaPshotTM. The DNA methylation levels detected for CpG sites from ELOVL2, FHL2, and MIR29B2 with each system were compared. A restricted three CpG-site age prediction model was rebuilt for each system, as well as for a combination of technologies, based on previous training datasets, and age predictions were calculated accordingly for all the samples detected with the previous technologies. While the DNA methylation patterns and subsequent age predictions from EpiTYPER®, pyrosequencing, and MiSeq systems are largely comparable for the CpG sites studied, SNaPshotTM gives bigger differences reflected in higher predictive errors. However, these differences can be reduced by applying a z-score data transformation.


Isolation and properties of a fluorescent compound, factor 420 , from Methanobacterium strain M.o.H.
A new fluorescent compound, factor(420) (F(420)), which is involved in the hydrogen metabolism of hydrogen-grown Methanobacterium strain M.o.H. has been isolated and purified. Acid hydrolysis of this compound with 6 m HCl for 24 hr releases a ninhydrin-positive compound (glutamic acid), an acid-stable chromophore, phosphate, and an ether-soluble phenolic component. Factor(420) may be reduced by either sodium dithionite or sodium borohydride at pH 7.3 with concomitant loss of its fluorescence and its major absorption peak at 420 nm. Crude cell-free extracts of strain M.o.H. reduce F(420) only under a hydrogen atmosphere. F(420) is photolabile aerobically in neutral and basic solutions, whereas the acid-stable chromophore is not photolabile under these conditions. An approximate molecular weight of 630 +/- 8% for F(420) was determined by Sephadex G-25 chromatography. At the present time, F(420) is proposed as a trivial name for the unknown fluorescent compound because of its strong absorption maximum of 420 nm at pH 7.


Red blood cell phenotype fidelity following glycerol cryopreservation optimized for research purposes.
Intact red blood cells (RBCs) are required for phenotypic analyses. In order to allow separation (time and location) between subject encounter and sample analysis, we developed a research-specific RBC cryopreservation protocol and assessed its impact on data fidelity for key biochemical and physiological assays. RBCs drawn from healthy volunteers were aliquotted for immediate analysis or following glycerol-based cryopreservation, thawing, and deglycerolization. RBC phenotype was assessed by (1) scanning electron microscopy (SEM) imaging and standard morphometric RBC indices, (2) osmotic fragility, (3) deformability, (4) endothelial adhesion, (5) oxygen (O2) affinity, (6) ability to regulate hypoxic vasodilation, (7) nitric oxide (NO) content, (8) metabolomic phenotyping (at steady state, tracing with [1,2,3-13C3]glucose ± oxidative challenge with superoxide thermal source; SOTS-1), as well as in vivo quantification (following human to mouse RBC xenotransfusion) of (9) blood oxygenation content mapping and flow dynamics (velocity and adhesion). Our revised glycerolization protocol (40% v/v final) resulted in >98.5% RBC recovery following freezing (-80°C) and thawing (37°C), with no difference compared to the standard reported method (40% w/v final). Full deglycerolization (>99.9% glycerol removal) of 40% v/v final samples resulted in total cumulative lysis of ~8%, compared to ~12-15% with the standard method. The post cryopreservation/deglycerolization RBC phenotype was indistinguishable from that for fresh RBCs with regard to physical RBC parameters (morphology, volume, and density), osmotic fragility, deformability, endothelial adhesivity, O2 affinity, vasoregulation, metabolomics, and flow dynamics. These results indicate that RBC cryopreservation/deglycerolization in 40% v/v glycerol final does not significantly impact RBC phenotype (compared to fresh cells).


Effect of glutaraldehyde on hydrosmotic response of toad bladder to vasopressin.
The present study investigates the time-, dose-, and temperature-dependence of glutaraldehyde action on the permeability to water of the toad bladder. Bladders preincubated with increasing concentrations of glutaraldehyde become progressively desensitized to the hydrosmotic action of vasopressin (ADH), theophylline, and dibutyryl adenosine 3',5'-cyclic monophosphate (dibutyryl cAMP). The ADH response was reduced by 50% with 0.03% glutaraldehyde applied to the serosal side for 10 min at 4 degrees C. Sixfold higher doses of glutaraldehyde were required with mucosal application. Bladders partially fixed with low-dose glutaraldehyde exhibit a markedly prolonged duration of action of ADH. Bladders fixed with higher doses of glutaraldehyde in the presence of ADH retain a high permeability to water for prolonged periods even in the absence of ADH. This action of glutaraldehyde to stabilize the hormone-induced water channels is also considerably more effective with serosal than with mucosal application. As the rate-limiting permeability barrier for water affected by ADH is known to be located in the apical membrane, these findings suggest that glutaraldehyde exerts its action from an intracellular position. It is postulated that glutaraldehyde stabilizes the ADH-induced channels by cross-linkage of amino groups and other reactive sites at the cytoplasmic surface of the apical membrane and/or by inactivating the intracellular machinery responsible for the dispersal or removal of water channels in the hormone target cell.


Do repeated transurethral procedures under general anesthesia influence mortality in patients with non-invasive urothelial bladder cancer? A Danish national cohort study.
Purpose: To investigate the effect of repeated transurethral procedures under general anesthesia on overall mortality in patients with non-invasive bladder cancer.Materials and methods: All Danish residents with non-invasive papillary urothelial carcinoma or primary urothelial carcinoma in situ diagnosed between 1 January 2000 and 1 January 2011 were included and followed until death or 31 March 2017. All transurethral procedures under general anesthesia, intravesical instillation therapy, recurrences and progression to invasive disease or cystectomy were recorded during follow-up. Associations between treatments and overall mortality were evaluated using multivariable regression analysis adjusted for age, gender, comorbidities and socioeconomic status. The effect of disease progression on mortality was removed by censoring patients at the time of progression or cystectomy.Results: Risk of death increased with the number of transurethral procedures under general anesthesia for Ta low- and high-grade tumors compared to patients who had only one procedure; after eight or more procedures the risk of death increased by 28% and 83%, respectively. There was no similar relationship for carcinomas in situ. In total, 36-52% of procedures under general anesthesia did not identify urothelial neoplasia.Conclusions: Repeated transurethral procedures under general anesthesia appear to be associated with increased risk of death in patients with primary non-invasive papillary urothelial carcinoma. Furthermore, a substantial number of procedures were without findings of neoplasia, indicating that too many patients are admitted for transurethral procedures under GA. Attempts should be taken to reduce unnecessary transurethral procedures under GA, e.g. by improved outpatient diagnosis of urothelial neoplasia.


Loss of α2δ-1 Calcium Channel Subunit Function Increases the Susceptibility for Diabetes.
Reduced pancreatic β-cell function or mass is the critical problem in developing diabetes. Insulin release from β-cells depends on Ca2+ influx through high voltage-gated Ca2+ channels (HVCCs). Ca2+ influx also regulates insulin synthesis and insulin granule priming and contributes to β-cell electrical activity. The HVCCs are multisubunit protein complexes composed of a pore-forming α1 and auxiliary β and α2δ subunits. α2δ is a key regulator of membrane incorporation and function of HVCCs. Here we show that genetic deletion of α2δ-1, the dominant α2δ subunit in pancreatic islets, results in glucose intolerance and diabetes without affecting insulin sensitivity. Lack of the α2δ-1 subunit reduces the Ca2+ currents through all HVCC isoforms expressed in β-cells equally in male and female mice. The reduced Ca2+ influx alters the kinetics and amplitude of the global Ca2+ response to glucose in pancreatic islets and significantly reduces insulin release in both sexes. The progression of diabetes in males is aggravated by a selective loss of β-cell mass, while a stronger basal insulin release alleviates the diabetes symptoms in most α2δ-1-/- female mice. Together, these findings demonstrate that the loss of the Ca2+ channel α2δ-1 subunit function increases the susceptibility for developing diabetes in a sex-dependent manner.


Minimal residual disease.
The study of minimal residual disease has been fueled by the technologic advent of the polymerase chain reaction and basic developments identifying the genetic lesions involved in human malignancies. Thus far advances in identifying, cloning, and the subsequent polymerase chain reaction amplification of relevant genes have outpaced clinical studies designed to tell us the significance of minimal residual disease. It has become clear that the mere detection of minimal residual disease does not foretell relapse; thus, although the presence of minimal residual disease in acute lymphoblastic leukemia and acute prolymphocytic leukemia appears to be associated with a high risk of relapse, the presence of minimal residual disease in t(8;21) acute myeloid leukemia, chronic myeloid leukemia, and t(14;18) non-Hodgkin's lymphoma is not clearly associated with impending relapse. In most situations there is clearly a need for carefully controlled studies to evaluate the predictive value of minimal residual disease.


Sonic hedgehog through Gli2 and Gli3 is required for the proper development of placental labyrinth.
Sonic hedgehog (Shh) functions as a conserved morphogen in the development of various organs in metazoans ranging from Drosophila to humans. Here, we have investigated the potential roles and underlying mechanisms of Shh signaling in murine placentation. Immunostaining revealed the abundant expression of the main components of Shh pathway in both the trophectoderm of blastocysts and developing placentas. Disruption of Shh led to impaired vascularogenesis of yolk sac, less branching and malformation of placental labyrinth, thereby leading to a robust decrease in capacity of transplacental passages. Moreover, placenta-specific gene incorporation by lentiviral transduction of mouse blastocysts and blastocyst transplantation robustly knocked down the expression of Gli3 and Gli2 in placenta but not in embryos. Finally, Gli3 knockdown in Shh(-/-) placentas partially rescued the defects of both yolk sac and placental labyrinth, and robustly restored the capacity of transplacental passages. Gli2 knockdown in Shh(+/)(-) placentas affected neither the capacity of tranplacental passages nor the vascularogenesis of yolk sac, however, it partially phenocopied the labyrinthine defects of Shh(-/-) placentas. Taken together, these results uncover that both Shh/Gli2 and Shh/Gli3 signals are required for proper development of murine placentas and are possibly essential for pregnant maintenance.


Differences between incarcerated and non-incarcerated patients who die in community hospitals highlight the need for palliative care services for seriously ill prisoners in correctional facilities and in community hospitals: A cross-sectional study.
Incarcerated populations worldwide are aging dramatically; in the United States, prisoner mortality rates have reached an all-time high. Little is known about the incarcerated patients who die in community hospitals. Compare incarcerated and non-incarcerated hospital decedents in California. Cross-sectional study. All state hospital decedents ( N = 370,831) from 2009 to 2013, decedent age over time examined with additional data (2001-2013). Overall, 745 incarcerated and 370,086 non-incarcerated individuals died in California hospitals. Incarcerated decedents were more often male (93% vs 51%), Black (19% vs 8%) Latino (27% vs 19%), younger (55 vs 73 years), had shorter hospitalizations (13 vs 16 days), and fewer had an advance care plan (23% vs 36%, p < 0.05). Incarcerated decedents had higher rates of cancer, liver disease, HIV/AIDs, and mental health disorders. Cause of death was disproportionately missing for incarcerated decedents. The average age of incarcerated decedents rose between 2001 and 2013, while it remained stable for others. Palliative care services in correctional facilities should accommodate the needs of relatively young patients and those with mental illness. Given the simultaneous growth in the older prisoner population with the rising age of incarcerated hospital decedents, community hospital clinicians should be prepared to care for seriously ill, incarcerated patients. Significant epidemiologic differences between incarcerated and non-incarcerated decedents in this study suggest the importance of examining the differential palliative care needs of incarcerated patients in all communities.


Impact of ablation of Barrett's esophagus with low-grade dysplasia on patients' illness perception and quality of life: a multicenter randomized trial.
A previous multicenter randomized trial demonstrated that radiofrequency ablation (RFA) significantly reduced the risk of neoplastic progression compared with surveillance (1.5% vs 26.5%) in patients with Barrett's esophagus (BE) and low-grade dysplasia (LGD). In the same population, this study aimed to compare the quality of life (QOL) and illness perception (IP) among patients treated with RFA and patients kept under surveillance. From June 2007 to June 2011, patients with BE and LGD were randomly assigned to RFA or surveillance. QOL and IP were assessed at baseline, 2, 9, 14, 26, and 38 months. Standardized questionnaires were used (SF-36, EORTC QLQ-C30, EORTC QLQ-OES18, and the brief Illness Perception Questionnaire [IPQ]). Forty-seven patients in the ablation group and 49 patients in the surveillance group completed the questionnaires (median follow-up, 36 months). Marginal differences were observed in the SF-36 and the EORTC-QLQ-C30. Based on the EORTC-QLQ-OES18, the ablation group reported more diarrhea (7.8 vs 4.0; P = .018), whereas the surveillance group reported more reflux (15.1 vs 9.0; P < .001) and more problems with speaking (4.3 vs 2.2; P = .019). The IPQ showed that patients in the ablation group perceived their disease lasted for a shorter period of time (P < .001), experienced fewer symptoms (P < .001), had fewer concerns about their condition (P < .001), and tended to be less emotionally affected by their condition (P = .012) than patients in the surveillance group. As a result, patients who underwent ablation experienced their condition as less threatening compared with patients in the surveillance group (P < .001). Patients treated with ablation for BE with LGD reported a QOL comparable with that of patients undergoing endoscopic surveillance; however, the patients in the ablation group had fewer concerns and a less-threatening view of their condition. (Clinical trial registration number [www.trialregister.nl]: NTR1198; 25-1-2008.).


Effects of low-concentration spinetoram wax-based bait stations on Bactrocera dorsalis (Diptera: Tephritidae).
Spinetoram wax-based bait station (SWBB) is a maintenance-free, long-lasting, and eco-friendly management measure for Bactrocera dorsalis. However, the impacts of low-concentration spinetoram on B. dorsalis have not yet been determined. Therefore, our study aimed to determine the impacts of low-concentration SWBBs on the biology, demographics, detoxifying enzymes, and gut microorganisms of B. dorsalis. Our results showed that low-concentration SWBBs posed dose-dependent effects on the lifespan and fecundity of B. dorsalis adults. Both the LC10 and LC30 treatments significantly reduced the fecundity, while only the latter led to significant deleterious effects on the longevity of adults. Transgenerational bioassays revealed that exposure to LC30 significantly affected the development period of larvae and pupae as well as the livability of pre-adult stage of the progeny. However, except for the ovipositional period, no significant effects on the biological traits of F1 adults were observed. In terms of the F1 demographic parameters, dose-dependent effects were observed. Moreover, both the LC10 and LC30 treatments significantly extended the mean generation time, while the latter remarkably decreased the finite and intrinsic rates. Additionally, the significant induction of CarE activity by the LC10 and LC30 treatment was maintained until 24 and 48 h respectively. The CYP450 O-deethylation activity in the LC30 treatment was significantly enhanced at 24 and 48 h intervals when compared to the control. Regarding the intestinal bacterial community, after B. dorsalis adults were exposed to low-concentration SWBBs, the relative abundances of Providencia and Vagococcus were significantly increased, whereas those of Lactococcus and Brachyspira experienced a significant decrease. The obtained results are expected to serve as a foundation for the application of spinetoram in "lure-and-kill" strategies against B. dorsalis.


Video sensor architecture for surveillance applications.
This paper introduces a flexible hardware and software architecture for a smart video sensor. This sensor has been applied in a video surveillance application where some of these video sensors are deployed, constituting the sensory nodes of a distributed surveillance system. In this system, a video sensor node processes images locally in order to extract objects of interest, and classify them. The sensor node reports the processing results to other nodes in the cloud (a user or higher level software) in the form of an XML description. The hardware architecture of each sensor node has been developed using two DSP processors and an FPGA that controls, in a flexible way, the interconnection among processors and the image data flow. The developed node software is based on pluggable components and runs on a provided execution run-time. Some basic and application-specific software components have been developed, in particular: acquisition, segmentation, labeling, tracking, classification and feature extraction. Preliminary results demonstrate that the system can achieve up to 7.5 frames per second in the worst case, and the true positive rates in the classification of objects are better than 80%.


Whole exome sequencing of adenoid cystic carcinoma.
Adenoid cystic carcinoma (ACC) is a rare malignancy that can occur in multiple organ sites and is primarily found in the salivary gland. While the identification of recurrent fusions of the MYB-NFIB genes have begun to shed light on the molecular underpinnings, little else is known about the molecular genetics of this frequently fatal cancer. We have undertaken exome sequencing in a series of 24 ACC to further delineate the genetics of the disease. We identified multiple mutated genes that, combined, implicate chromatin deregulation in half of cases. Further, mutations were identified in known cancer genes, including PIK3CA, ATM, CDKN2A, SF3B1, SUFU, TSC1, and CYLD. Mutations in NOTCH1/2 were identified in 3 cases, and we identify the negative NOTCH signaling regulator, SPEN, as a new cancer gene in ACC with mutations in 5 cases. Finally, the identification of 3 likely activating mutations in the tyrosine kinase receptor FGFR2, analogous to those reported in ovarian and endometrial carcinoma, point to potential therapeutic avenues for a subset of cases.


Association between interleukin-1A polymorphism and cerebral amyloid angiopathy-related hemorrhage.
It has been suggested that the interleukin-1A (IL-1A) allele 2 is a risk factor for Alzheimer's disease (AD). Because cerebral amyloid angiopathy-related hemorrhage (CAAH) often coexists with AD, we examined the IL-1A polymorphism in CAAH. In a case-control study, patients with pathologically verified CAAH, AD patients without intracerebral hemorrhage, and neuropathologically normal control subjects were studied. DNA was extracted from brain tissue, and IL-1A was genotyped. Logistic regression was used to examine the IL-1A polymorphism in CAAH patients with and without AD compared with AD and non-AD control subjects. There were 42 patients with CAAH, 232 AD patients, and 167 non-AD control subjects. In age-adjusted analyses, there was no association between possession of IL-1A allele 2 and risk of CAAH compared with AD control subjects (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.45 to 1.97; P=0.87) or non-AD control subjects (OR, 0.94; 95% CI, 0.47 to 1.87; P=0.86). Stratifying for the presence of apolipoprotein E epsilon2 or epsilon4 demonstrated the known increased risk of CAAH from these lipoprotein E alleles. Subgroup analyses demonstrated a nonsignificant excess of the IL-1A 2,2 genotype in patients with CAAH and AD compared with those CAAH patients who did not have histological evidence indicating AD (OR, 2.17; 95% CI, 0.15 to 122.3; P=0.64). Comparisons between CAAH patients with AD and AD control subjects and between CAAH patients without AD and non-AD control subjects did not demonstrate an association between CAAH and possession of either the IL-1A allele 2 or the 2,2 genotype. The IL-1A allele 2 or 2,2 genotype does not appear to be a major risk factor for CAAH.


Childhood inhibition predicts adolescent social anxiety: Findings from a longitudinal twin study.
An enduring issue in the study of mental health is identifying developmental processes that explain how childhood characteristics progress to maladaptive forms. We examine the role that behavioral inhibition (BI) has on social anxiety (SA) during adolescence in 868 families of twins assessed at ages 8, 13, and 15 years. Multimodal assessments of BI and SA were completed at each phase, with additional measures (e.g., parenting stress) for parents and twins. Analyses were conducted in several steps: first, we used a cross-lagged panel model to demonstrate bidirectional paths between BI and SA; second a biometric Cholesky decomposition showed that both genetic and environmental influences on childhood BI also affect adolescent SA; next, multilevel phenotypic models tested moderation effects between BI and SA. We tested seven potential moderators of the BI to SA prediction in individual models and included only those that emerged as significant in a final conditional model examining predictors of SA. Though several main effects emerged as significant, only parenting stress had a significant interaction with BI to predict SA, highlighting the importance of environmental moderators in models examining temperamental effects on later psychological symptoms. This comprehensive assessment continues to build the prototype for such developmental psychopathology models.


Clinical characteristics, late effects and outcomes in pineoblastomas in children: a single center experience.
Pineoblastomas (PB) are rare tumors of the central nervous system and are more common in children. There is no consensus about standard of care. The objective of this study is to analyze the outcome of children with PB. Six patients with PB who were diagnosed between 1990-2012 were evaluated retrospectively. Demographics, age of diagnosis, first complaint, tumor region, diagnosis type, seeding metastasis to the spinal axis or cerebrospinal fluid (CSF), treatment and survival of these patients were recorded. Three patients had subtotal resection and all patients received chemotherapy and craniospinal irradiation (CSI) after diagnosis. Median follow-up after treatment was 5.5 (range:1-19) years. Two patients are alive with no evidence of disease for 7.5 and 10 years, one of whom was diagnosed with papillary thyroid carcinoma 9.5 years after treatment. One of the patients who died had lived for 19 years after diagnosis. Pineoblastomas are rare but very aggressive tumors; more effective treatment strategies are needed. Survivors should be followed up for late effects such as second malignancies and endocrine deficiencies.


Palladium-decorated hydrogen-gas sensors using periodically aligned graphene nanoribbons.
Polymer residue-free graphene nanoribbons (GNRs) of 200 nm width at 1 μm pitch were periodically generated in an area of 1 cm(2) via laser interference lithography using a chromium interlayer prior to photoresist coating. High-quality GNRs were evidenced by atomic force microscopy, micro-Raman spectroscopy, and X-ray photoelectron spectroscopy measurements. Palladium nanoparticles were then deposited on the GNRs as catalysts for sensing hydrogen gases, and the GNR array was utilized as an electrically conductive path with less electrical noise. The palladium-decorated GNR array exhibited a rectangular sensing curve with unprecedented rapid response and recovery properties: 90% response within 60 s at 1000 ppm and 80% recovery within 90 s in nitrogen ambient. In addition, reliable and repeatable sensing behaviors were revealed when the array was exposed to various gas concentrations even at 30 ppm.


Platelet-rich plasma in bone regeneration: engineering the delivery for improved clinical efficacy.
Human bone is a tissue with a fairly remarkable inherent capacity for regeneration; however, this regenerative capacity has its limitations, and defects larger than a critical size lack the ability to spontaneously heal. As such, the development and clinical translation of effective bone regeneration modalities are paramount. One regenerative medicine approach that is beginning to gain momentum in the clinical setting is the use of platelet-rich plasma (PRP). PRP therapy is essentially a method for concentrating platelets and their intrinsic growth factors to stimulate and accelerate a healing response. While PRP has shown some efficacy in both in vitro and in vivo scenarios, to date its use and delivery have not been optimized for bone regeneration. Issues remain with the effective delivery of the platelet-derived growth factors to a localized site of injury, the activation and temporal release of the growth factors, and the rate of growth factor clearance. This review will briefly describe the physiological principles behind PRP use and then discuss how engineering its method of delivery may ultimately impact its ability to successfully translate to widespread clinical use.


Hormonally controlled ILC antigen presentation potential is reduced during pregnancy.
Strategically located in mucosal barriers, innate lymphoid cells (ILCs) are relevant in local containment and tolerance of commensal microflora. ILCs have been recently described at the fetomaternal interface, where the development of a semi-allogeneic fetus can only succeed in a well-controlled immune environment. We postulate that ILCs adapt their antigen presentation capacity to protect pregnancy from excessive immune responses. Human ILCs were studied in deciduae of term pregnancies, peripheral blood and in in vitro generated ILCs. Fresh isolated lymphocytes or cells treated with pregnancy-related factors were investigated. The fetal antigen rejection-based CBA/J × DBA/2J mouse model (poor outcome pregnant mice; POPM) was used to characterize ILC antigen presentation potential in normal and immunologically disturbed pregnancies. ILC antigen presentation potential was characterized by flow cytometry and qPCR. We discovered that the distribution of ILC subsets changed during both human and murine pregnancy. Moreover, the pregnancy was accompanied by reduced MHCII expression in splenic ILCs during normal pregnancy (CBA/J × BALB/c; good outcome pregnant mice; GOPM) but increased in splenic and intestinal ILCs of CBA/J × DBA/2J mice. In vitro, splenic ILCs from pregnant mice increased MHCII expression after stimulation with IL-1β and IL-23. In contrast, uterine ILCs displayed lower MHCII expression, which remained unchanged after stimulation. Finally, pregnancy-related factors and hormones present in the uterine environment reduced antigen presentation potential of human ILCs in vitro. Together, these data indicate that, during pregnancy, peripheral and especially uterine ILCs adapt their antigen presenting potential to maintain a level of tolerance and support pregnancy.


Anterolateral thigh flap for postmastectomy breast reconstruction.
Most postmastectomy defects are reconstructed by use of lower abdominal-wall tissue either as a pedicled or free flap. However, there are some contraindications for using lower abdominal flaps in breast reconstruction, such as inadequate soft-tissue volume, previous abdominoplasty, lower paramedian or multiple abdominal scars, and plans for future pregnancy. In such situations, a gluteal flap has often been the second choice. However, the quality of the adipose tissue of gluteal flaps is inferior to that of lower abdominal flaps, the pedicle is short, and a two-team approach is not possible because creation of the gluteal flap requires that the patient's position be changed during the operation. In 2000, five cases of breast reconstructions were performed with anterolateral thigh flaps in the authors' institution. Two of them were secondary and three were immediate unilateral breast reconstructions. The mean weight of the specimen removed was 350 g in the three patients who underwent immediate reconstruction, and the mean weight of the entire anterolateral thigh flap was 410 g. Skin islands ranged in size from 4 x 8 cm to 7 x 22 cm, with the underlying fat pad ranging in size from 10 x 12 cm to 14 x 22 cm. The mean pedicle length was 11 cm (range, 7 to 15 cm). All flaps were completely successful, except for one that involved some fat necrosis. The quality of the skin and underlying fat and the pliability of the anterolateral thigh flap are much superior to those of gluteal flaps and are similar to those of lower abdominal flaps. In thin patients, more subcutaneous fat can be harvested by extending the flap under the skin. Use of a thigh flap allows a two-team approach with the patient in a supine position, and no change of patient position is required during the operation. However, the position of the scar may not be acceptable to some patients. Therefore, when an abdominal flap is unavailable or contraindicated, the creation of an anterolateral thigh flap for primary and secondary breast reconstruction is an alternative to the use of lower abdominal and gluteal tissues.


Agreement study between two laboratories of immunofluorescence as a confirmatory test for human immunodeficiency virus type 1 antibody screening.
A total of 114 serum specimens from 76 blood donors, 21 patients with acquired immune deficiency syndrome or acquired immune deficiency syndrome-related complex, 7 multiply transfused patients, 3 hemophiliacs, and 7 others were tested for anti-human immunodeficiency virus type 1 (HIV-1) antibody by enzyme immunoassay (EIA) and Western blot (WB) and then blindly tested by immunofluorescence (IF), independently, in two separate laboratories. The IF technique used acetone-fixed HIV-1-infected E cells and uninfected HUT-78 cells mixed at a 1:3 ratio in one spot on a glass slide and uninfected HUT-78 cells (to assess nonspecific fluorescence) alone in a second spot. Of 114 serum specimens, 85 were repeat EIA positive, and 21 of these were WB positive. A total of 129 of 134 of the IF results (included were 20 duplicates) were identical between laboratories, for a Kappa agreement statistic of 0.93. All five IF results discordant between laboratories were EIA repeat positive and WB negative. Included in the study were eight WB-indeterminate sera, of which five blood donor serum specimens and one hemophiliac serum specimen were IF negative and two acquired immune deficiency syndrome serum specimens were IF positive. As a confirmatory test for HIV-1 antibodies, IF provided a faster alternative or supplementary test for confirming EIA results.