An experimental analysis of the curative action of penicillin in acute bacterial infections. II. The role of phagocytic cells in the process of recovery.
Type I pneumococci injected into the leg muscles of otherwise normal mice reached a maximum total population of approximately 10(6) organisms. In mice rendered severely leucopenic by previous irradiation the maximum bacterial counts recorded were of the order of 10(9). Since the lesions in the latter animals were relatively acellular, the thousandfold difference in the two experiments represented a rough measure of the antibacterial action of the leucocytic exudate. The suppressive effect of the leucocytic exudate was shown by histologie studies to involve phagocytosis. The ingestion of pneumococci was clearly demonstrable within the first 12 to 18 hours. Accordingly, it was attributed to surface phagocytosis. In support of this conclusion was the finding that type III pneumococci reached a significantly higher total population in the myositis lesions than did type I. The type III strain used had been previously shown to be resistant to surface phagocytosis during active growth, whereas the type I strain was known to be susceptible throughout its growth phase. Evidence was also presented that the dense leucocytic exudate probably caused in addition a significant degree of bacteriostasis. When penicillin therapy was begun 9 hours after inoculation, the pneumococci were cleared from the lesions with equal rapidity regardless of the presence or absence of leucocytic exudate. At this early stage the pneumococci were multiplying rapidly in the lesions of both the irradiated and unirradiated mice and therefore were promptly killed by the direct action of the penicillin. When the start of treatment was delayed, however, until 24 hours after inoculation, the bacteria in both sets of lesions had already reached their maximum counts and therefore were presumably resistant to the bactericidal effect of the antibiotic. Under such circumstances the destruction of the bacteria was found to be significantly less prompt in the acellular lesions than in those with a normal cellular exudate. It is concluded from these findings that, in established pneumococcal myositis in mice, the curative effect of penicillin is due, not to the bactericidal action of the antibiotic alone, but rather to the combined effect of the drug and the cellular defenses of the host. The same conclusion also appears to be applicable to analogous acute infections in man, particularly when they are sufficiently advanced to be definitively diagnosed.


Infectious Dose Dictates the Host Response during Staphylococcus aureus Orthopedic-Implant Biofilm Infection.
Staphylococcus aureus is a leading cause of prosthetic joint infections (PJIs) that are typified by biofilm formation. Given the diversity of S. aureus strains and their propensity to cause community- or hospital-acquired infections, we investigated whether the immune response and biofilm growth during PJI were conserved among distinct S. aureus clinical isolates. Three S. aureus strains representing USA200 (UAMS-1), USA300 (LAC), and USA400 (MW2) lineages were equally effective at biofilm formation in a mouse model of PJI and elicited similar leukocyte infiltrates and cytokine/chemokine profiles. Another factor that may influence the course of PJI is infectious dose. In particular, higher bacterial inocula could accelerate biofilm formation and alter the immune response, making it difficult to discern underlying pathophysiological mechanisms. To address this issue, we compared the effects of two bacterial doses (10(3) or 10(5) CFU) on inflammatory responses in interleukin-12p40 (IL-12p40) knockout mice that were previously shown to have reduced myeloid-derived suppressor cell recruitment concomitant with bacterial clearance after low-dose challenge (10(3) CFU). Increasing the infectious dose of LAC to 10(5) CFU negated these differences in IL-12p40 knockout animals, demonstrating the importance of bacterial inoculum on infection outcome. Collectively, these observations highlight the importance of considering infectious dose when assessing immune responsiveness, whereas biofilm formation during PJI is conserved among clinical isolates commonly used in mouse S. aureus infection models.


Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells.
Myb-MuvB (MMB)/dREAM is a nine-subunit complex first described in Drosophila as a repressor of transcription, dependent on E2F2 and the RBFs. Myb, an integral member of MMB, curiously plays no role in the silencing of the test genes previously analyzed. Moreover, Myb plays an activating role in DNA replication in Drosophila egg chamber follicle cells. The essential functions for Myb are executed as part of MMB. This duality of function lead to the hypothesis that MMB, which contains both known activator and repressor proteins, might function as part of a switching mechanism that is dependent on DNA sites and developmental context. Here, we used proliferating Drosophila Kc tissue culture cells to explore both the network of genes regulated by MMB (employing RNA interference and microarray expression analysis) and the genomic locations of MMB following chromatin immunoprecipitation (ChIP) and tiling array analysis. MMB occupied 3538 chromosomal sites and was promoter-proximal to 32% of Drosophila genes. MMB contains multiple DNA-binding factors, and the data highlighted the combinatorial way by which the complex was targeted and utilized for regulation. Interestingly, only a subset of chromatin-bound complexes repressed genes normally expressed in a wide range of developmental pathways. At many of these sites, E2F2 was critical for repression, whereas at other nonoverlapping sites, Myb was critical for repression. We also found sites where MMB was a positive regulator of transcript levels that included genes required for mitotic functions (G2/M), which may explain some of the chromosome instability phenotypes attributed to loss of Myb function in myb mutants.


2017 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 35th Annual Report.
This is the 35th Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 January 2017, 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 8.07 [7.32, 12.65] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system. We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure. In 2017, 2,607,413 closed encounters were logged by NPDS: 2,115,186 human exposures, 51,164 animal exposures, 435,540 information contacts, 5,424 human confirmed nonexposures, and 99 animal confirmed nonexposures. US PCs also made 2,680,625 follow-up calls in 2017. Total encounters showed a 3.79% decline from 2016, while health care facility (HCF) human exposure cases increased by 3.06%. All information contacts decreased by 11.5%, medication identification (Drug ID) requests decreased by 30.2%, and human exposure cases decreased by 2.03%. Human exposures with less serious outcomes have decreased 2.48% per year since 2008, while those with more serious outcomes (moderate, major or death) have increased 4.44% per year since 2000. Consistent with the previous year, the top 5 substance classes most frequently involved in all human exposures were analgesics (11.08%), household cleaning substances (7.43%), cosmetics/personal care products (6.76%), sedatives/hypnotics/antipsychotics (5.74%), and antidepressants (5.02%). As a class, sedative/hypnotics/antipsychotics exposures increased most rapidly, by 1962 cases/year (4.91%/year), over the last 17 years for cases with more serious outcomes. The top 5 most common exposures in children age 5 years or less were cosmetics/personal care products (12.59%), household cleaning substances (10.96%), analgesics (9.18%), foreign bodies/toys/miscellaneous (6.39%), and topical preparations (4.84%). Drug identification requests comprised 22.1% of all information contacts. NPDS documented 3,208 human exposures resulting in death; 2,682 (83.6%) of these were judged as related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory). These data support the continued value of PC expertise and need for specialized medical toxicology information to manage more serious exposures, despite a decrease in cases involving less serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time status of NPDS represents a national public health resource to collect and monitor US exposure cases and information contacts. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, infectious, venomous, chemical agent, or commercial product), and the identification and tracking of significant public health events. NPDS is a model system for the near real-time surveillance of national and global public health.


Biopterin synthesis in mouse spleen during bone marrow transplantation correlates with unimpaired hemopoietic engraftment.
Normal engraftment of bone marrow transplants depends on histocompatibility between donor and recipient. In this case reconstitution of hemopoiesis and lymphopoiesis in the mouse spleen is correlated with transient biopterin synthesis in these cells. Allogeneic bone marrow progeny cells undergo donor cell proliferation in the spleen prior to the incidence of graft-versus-host reaction. These cells are not committed to biopterin synthesis. Thy-1 monoclonal antibody fully repairs engraftment of allogeneic transplants together with biopterin synthesis.


Efficacy of aerosol, intranasal and intramuscular vaccination against selected bovine viral diseases.
An experiment was designed to compare the efficacy of an IM modified live vaccine, an IN temperature-sensitive vaccine, an IN modified live vaccine, and an aerosolized modified live vaccine (two concentrations) to stimulate specific serum antibody and protect calves from a known viral challenge. All vaccines except the IM vaccine contained IBR virus and PI3 virus. The IM vaccine and the IN vaccines provided excellent protection to an IBR challenge, but both concentrations of aerosolized vaccine provided only patial protection. The use of IN modified live vaccine resulted in IBR serum Ab titers in all the test calves (100%), while the IM preparation elicited a response in only 60% of test calves and the IN temperature sensitive vaccine resulted in serum Ab titers in 40% of test calves. The aerosolized vaccine induced IBR serum antibody titers in only 20% of the calves. The use of IN modified live and the aerosolized vaccine resulted in a greater immune response to the PI3 virus (60-80% sero-conversion) than did the temperature sensitive vaccine (20% sero-conversion).


Alleviating Effects of Black Soybean Peptide on Oxidative Stress Injury Induced by Lead in PC12 Cells via Keap1/Nrf2/TXNIP Signaling Pathway.
Many researchers have found that Pb exposure can cause oxidative stress damage to the body's tissue. Black soybean peptide (BSP) has a variety of physiological functions, especially in terms of oxidative stress. Nevertheless, the mitigation function of BSPs on Pb-induced oxidative stress damage in PC12 cells has not been clearly defined. In this study, cell viability was detected by CCK8. Oxidative stress indicators, such as ROS, GSH/GSSG, MDA, SOD, CAT, GPx, and GR, were tested with biochemical kit. Protein expression of Keap1, Nrf2, and TXNIP was measured by Western blot. Compared with the control group, Pb reduced the cell viability of PC12 cells. However, BSP treatment significantly increased the viability of PC12 cells induced by lead exposure (p < 0.05). Lead can enrich the contents of MDA and ROS, but decrease the amount of CAT, SOD, GR, GPx, and GSH/GSSG in PC12 cells, while BSP can alleviate it (p < 0.05). Lead can enhance the expression of Keap1 and TXNIP proteins, but reduce Nrf2 expression. In contrast, BSPs reversed this phenomenon (p < 0.05). BSPs can alleviate oxidative stress injury induced by lead in PC12 cells through the Keap1/Nrf2/TXNIP signaling pathway.


Identification of candidate Klf4 target genes reveals the molecular basis of the diverse regulatory roles of Klf4 in the mouse cornea.
Krüppel-like factor 4 (Klf4) plays a crucial role in the development and maintenance of the mouse cornea. In the current study, wild-type (WT) and Klf4-conditional null (Klf4CN) corneal gene expression patterns were examined, to gain understanding of the molecular basis of the Klf4CN corneal phenotype. Expression of more than 22,000 genes in 10 WT and Klf4CN corneas was compared by microarrays, analyzed using BRB ArrayTools (National Cancer Institute, Bethesda, MD) and validated by Q-RT-PCR. Transient cotransfections were used to test whether Klf4 activates the aquaporin-3, Aldh3a1, and TKT promoters. Scatterplot analysis identified 740 and 529 genes up- and downregulated by more than twofold, respectively, in the Klf4CN corneas. Cell cycle activators were upregulated, whereas the inhibitors were downregulated, consistent with the increased Klf4CN corneal epithelial cell proliferation. Desmosomal components were downregulated, consistent with the Klf4CN corneal epithelial fragility. Downregulation of aquaporin-3, detected by microarray, was confirmed by immunoblot and immunohistochemistry. Aquaporin-3 promoter activity was stimulated 7- to 10-fold by cotransfection with pCI-Klf4. The corneal crystallins Aldh3A1 and TKT were downregulated in the Klf4CN cornea, and their respective promoter activities were upregulated 16- and 9-fold by pCI-Klf4 in cotransfections. The expression of epidermal keratinocyte differentiation markers was affected in the Klf4CN cornea. Although the cornea-specific keratin-12 was downregulated, most other keratins were upregulated, suggesting hyperkeratosis. Functionally diverse candidate Klf4 target genes were identified, revealing the molecular basis of the diverse aspects of the Klf4CN corneal phenotype. These results establish Klf4 as an important node in the genetic network of transcription factors regulating the corneal homeostasis.


Hydroxylation of phenol to catechol by Candida tropicalis: involvement of cytochrome P450.
Microsomal preparations isolated from yeast Candida tropicalis (C. tropicalis) grown on three different media with or without phenol were isolated and characterized for the content of cytochrome P450 (CYP) (EC 220.127.116.11). While no CYP was detected in microsomes of C. tropicalis grown on glucose as the carbon source, evidence was obtained for the presence of the enzyme in the microsomes of C. tropicalis grown on media containing phenol. Furthermore, the activity of NADPH: CYP reductase, another enzyme of the microsomal CYP-dependent system, was markedly higher in cells grown on phenol. Microsomes of these cells oxidized phenol. The major metabolite formed from phenol by microsomes of C. tropicalis was characterized by UV/vis absorbance and mass spectroscopy as well as by the chromatographic properties on HPLC. The characteristics are identical to those of catechol. The formation of catechol was inhibited by CO, the inhibitor of CYP, and correlated with the content of cytochrome P450 in microsomes. These results, the first report showing the ring hydroxylation of phenol to catechol with the microsomal enzyme system of C. tropicalis, strongly suggest that CYP-catalyzed reactions are responsible for this hydroxylation. The data demonstrate the progress in resolving the enzymes responsible for the first step of phenol degradation by the C. tropicalis strain.


Evaluation of a classroom-based physical activity promoting programme.
The purpose of the present study was to evaluate the effect of the Happy 10 programme on the promotion of physical activity, physical growth and development of primary school students, and on obesity control and prevention. Two similar primary schools from one district of Beijing, China were selected, one as an intervention school and the other as a control school. A Happy 10 programme was implemented at least once every school day in the intervention school for two semesters, whereas no intervention was adopted in the control school. The information on energy expenditure and duration of physical activity was collected by a validated 7-day physical activity questionnaire. Height and weight were measured by the trained investigators following standardized procedure. Energy expenditure and intensity of each Happy 10 session were measured by a physical activity monitor. The average energy expenditure and duration of total physical activity per day among students in the intervention school increased significantly from 15.0 to 18.2 kcal kg(-1) and 2.8 to 3.3 h, respectively, whereas the figures significantly decreased in the control school. There was a significant difference in change of weight and body mass index between girls in the intervention and control school (2.4 kg vs. 4.6 kg; 0.47 kg m(-2) vs. 0.66 kg m(-2)). The prevalence of overweight and obesity in the intervention school decreased by 0.4-5.6%, as compared with the increase by 0.6-4.5% in the control school. The average energy expenditure and intensity per 10-min session ranged from 25.0 to 35.1 kcal and from 4.8 to 6.2 kcal kg(-1) h(-1), respectively, in grades 1-5. The Happy 10 programme provides a useful strategy to promote physical activity among school children, and also plays a positive role in building up physical growth and development of girls.


Activation and repression of glucose-stimulated ChREBP requires the concerted action of multiple domains within the MondoA conserved region.
Carbohydrate response element-binding protein (ChREBP) is a glucose-dependent transcription factor that stimulates the expression of glycolytic and lipogenic genes in mammals. Glucose regulation of ChREBP has been mapped to its conserved NH(2)-terminal region of 300 amino acids, designated the MondoA conserved region (MCR). Within the MCR, five domains (MCR1-5) have a particularly high level of conservation and are likely to be important for glucose regulation. We carried out a large-scale deletion and substitution mutational analysis of the MCR domain of ChREBP. This analysis revealed that MCRs 1-4 function in a concerted fashion to repress ChREBP activity in basal (nonstimulatory) conditions. Deletion of the entire MCR1-4 segment or the combination of four specific point mutations located across this region leads to a highly active, glucose-independent form of ChREBP. However, deletion of any individual MCR domain and the majority of point mutations throughout MCR1-4 rendered ChREBP inactive. These observations suggest that the MCR1-4 region interacts with an additional coregulatory factor required for activation. This possibility is supported by the observation that the MCR1-4 region can compete for activity with wild-type ChREBP in stimulatory conditions. In contrast, mutations in the MCR5 domain result in increased activity, suggesting that this domain may be the target of intramolecular repression in basal conditions. Thus, the MCR domains act in a complex and coordinated manner to regulate ChREBP activity in response to glucose.


Collaborative partners in nursing education: a preceptorship model for BScN students.
This article depicts and describes five significant steps in the process of establishing and maintaining a nursing student preceptor programme in a psychiatric unit. Specific collaborative relationships, roles, strategies, important qualities, and suggestions are identified to enhance the success and contributions of each of the three learning partners--student, preceptor, and clinical faculty tutor. The steps and processes highlighted in this model are based on the actual experience of a nurse educator in a university school of nursing, in collaboration with the director of psychiatry (also a nurse) at a community hospital in southern Ontario, Canada. The authors jointly share their perceptions of the strengths, limitations, and mutual benefits experienced throughout all phases of this collaborative partnership. In addition, student and preceptor feedback on the placement are described, demonstrating the usefulness of ongoing feedback from all the participants. This article will be of interest to other nurse educators planning to initiate and maintain clinical preceptorship programs.


Comparison of two methods for assessing injuries among preschool children.
Most studies of injuries use health services records or recall rather than prospective methods, and there is no information on how these different methods compare. This study was aimed at comparing a report (retrospective) with a diary (prospective) for recording childhood injuries. The study included 1,273 and 620 children, the retrospective and prospective subsamples, respectively, from a population based birth cohort in Pelotas, southern Brazil. The reported incidence of injuries in the preceding month were compared with those reported over month by diary (prospective study). Both methods were well accepted and 92.7% of the diaries were returned. One or more injuries per child month were reported for 20.8% (retrospective) and 48.4% (prospective) of the children. The total number of reported injuries for the 620 children were 145 (retrospective) and 715 (prospective). Using the prospective method as the gold standard, the retrospective method detected only 20.2% of all injuries. Under-reporting did not vary significantly with maternal education, but was greater (51.8%) for injuries requiring medical care than for those managed at home (18.3%; p=0.003). The diary was well accepted and resulted in higher incidences of reported injuries than the recall method, particularly for injuries that did not require medical care. Use of this method should be promoted to provide more complete epidemiological information to guide preventive strategies.


Transformation of mouse fibroblasts by Jaagsiekte sheep retrovirus envelope does not require phosphatidylinositol 3-kinase.
Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma, a transmissible lung cancer of sheep. The envelope of JSRV may have oncogenic properties, since it can morphologically transform mouse NIH 3T3 cells and other fibroblast lines. Recently, we found that the cytoplasmic tail of the envelope transmembrane (TM) protein is necessary for transformation, and in particular a consensus binding motif (YXXM) for phosphatidylinositol 3-kinase (PI3K) is important. Moreover, JSRV-transformed cells show phosphorylation (activation) of Akt/protein kinase B, a downstream target of PI3K. In these studies, we directly tested for the involvement of PI3K in transformation by JSRV. Contrary to expectations, four different experiments indicated that PI3K is not necessary for JSRV-induced transformation: (i) cotransfection with a dominant negative truncated form of the PI3K regulatory subunit (Deltap85) did not affect transformation frequency, (ii) cells stably expressing Deltap85 showed the same frequencies of transformation as parental NIH 3T3 cells, (iii) fibroblasts established from double-knockout mice lacking PI3K p85alpha and p85beta could be transformed with JSRV envelope, and (iv) incubation of cells with the PI3K inhibitor LY294002 did not specifically inhibit transformation, nor did the drug reverse transformation of JSRV-transformed cells. One alternate explanation for the lack of transformation by YXXM mutants could be that they were defective in intracellular trafficking. However, confocal microscopy of epitope-tagged envelope proteins of both wild-type and nontransforming YXXM mutants showed a cell surface or plasma membrane localization. While PI3K is not required for JSRV-induced transformation of NIH 3T3 cells, the downstream target Akt kinase was found to be activated (phosphorylated) in JSRV-transformed PI3K-negative cells. Therefore, JSRV envelope can induce PI3K-independent phosphorylation of Akt.


Localization on Certain Graphs with Strongly Correlated Disorder.
Many-body localization in interacting quantum systems can be cast as a disordered hopping problem on the underlying Fock-space graph. A crucial feature of the effective Fock-space disorder is that the Fock-space site energies are strongly correlated-maximally so for sites separated by a finite distance on the graph. Motivated by this, and to understand the effect of such correlations more fundamentally, we study Anderson localization on Cayley trees and random regular graphs, with maximally correlated disorder. Since such correlations suppress short distance fluctuations in the disorder potential, one might naively suppose they disfavor localization. We find however that there exists an Anderson transition, and indeed that localization is more robust in the sense that the critical disorder scales with graph connectivity K as sqrt[K], in marked contrast to KlnK in the uncorrelated case. This scaling is argued to be intimately connected to the stability of many-body localization. Our analysis centers on an exact recursive formulation for the local propagators as well as a self-consistent mean-field theory; with results corroborated using exact diagonalization.


[Effect of space flight on cosmonaut peripheral blood lymphocyte blast transformation].
The postflight investigation of cell mediated immunity of seven cosmonauts showed significant increase in spontaneous activity of lymphocytes of peripheral blood and decrease in stimulation of lymphocytes cultured with PHA at R + O. Variations in these parameters were transient, remaining within physiological limits. Two cosmonauts displayed a stable increase in lymphocyte activity during blast transformation test with Staphylococcus aureus culture filtrate.


Visual receptive fields and their images in superior colliculus of the cat.
1. The receptive fields of collicular neurons in the cat, recorded in a single microelectrode penetration, were not centered on a point in visual space, but nested eccentrically with the smaller fields displaced toward the area centralis. The eccentric nesting was not eliminated by correcting the fields for the tangent screen distortion or by making penetrations normal to the collicular surface in coronal and parasagittal planes. These findings do not support the idea that collicular cells form topographically organized columns oriented normal to the collicular surface. 2. When the receptive fields were plotted in the visual coordinate system of the collicular map, the nesting became much more concentric, suggesting that the eccentric nesting of the receptive fields in visual space was largely a product of the retinotectal coordinate transformation. 3. The profile of a collicular receptive field, plotted in the collicular visual coordinate system is called the receptive-field image. Receptive-field images tended to have oval shapes with the long axis oriented mediolaterally. Clusters of receptive-field images, plotted for single penetrations, appeared similar wherever they occurred in the collicular map, suggesting that a common pattern of neural convergence determines the geometry of the receptive-field images in all parts of the colliculus. 4. The neural substrate of the receptive-field images was examined by tracing the theoretical patterns of neural activity which a point stimulus would produce in the retinotectal system. This analysis suggested that the shape and dimensions of the receptive-field images, and consequently the receptive fields, might be accounted for in large part by the geometry of collicular dendritic fields, the dimensions of the visual receptive fields of afferent fibers, and the retinotectal coordinate transformation. 5. Because it adjusts for the retinotectal distortion of visual space, the receptive-field image may be used to outline the distribution of collicular cells excited by a point stimulus. This makes it possible to show that a point stimulus activates large-field cells in the superficial gray layer over an area of about 2.5 by 1.5 mm in the central parts of the colliculus. It is suggested that such cells may organize the directional signals required by the oculomotor system for visual orienting behavior.


Identification of genes targeted by CpG island methylator phenotype in neuroblastomas, and their possible integrative involvement in poor prognosis.
CpG island (CGI) methylator phenotype (CIMP) is strongly associated with poor prognosis in neuroblastomas (NBLs; hazard ratios 7-22). Methylation of nonpromoter CGIs is useful to detect the presence of the CIMP, while the poor prognosis is considered to be caused by gene silencing due to promoter methylation. Here, promoter CGIs targeted by the CIMP were searched for. A genome-wide screening was performed by methylation-sensitive representational difference analysis of CIMP(+) and CIMP(-) NBLs. Promoter CGIs of 9 genes were methylated in CIMP(+) NBL cell lines and caused silencing of their downstream genes. On analysis of 90 clinical specimens, CYP26C1,FERD3L (N-TWIST), CRYBA2 and PCDHGC4 were methylated at significantly higher incidences in CIMP(+) NBLs than CIMP(-) NBLs, while the difference was unclear for NPY, SPAG6, DDIT4L, CHR3SYT and C6Orf141. Methylation of CYP26C1 and FERD3L was significantly associated with poor prognosis, but weaker than the presence of the CIMP. Treatment of an NBL cell line with a demethylating agent caused demethylation of multiple promoter CGIs, and enhanced 13-cis-retinoic acid-induced neuronal differentiation. Our results indicate that the CIMP causes poor prognosis of NBLs by inducing methylation of multiple promoter CGIs with various incidences.


Potential Use of Marine Seaweeds as Prebiotics: A Review.
Human gut microbiota plays an important role in several metabolic processes and human diseases. Various dietary factors, including complex carbohydrates, such as polysaccharides, provide abundant nutrients and substrates for microbial metabolism in the gut, affecting the members and their functionality. Nowadays, the main sources of complex carbohydrates destined for human consumption are terrestrial plants. However, fresh water is an increasingly scarce commodity and world agricultural productivity is in a persistent decline, thus demanding the exploration of other sources of complex carbohydrates. As an interesting option, marine seaweeds show rapid growth and do not require arable land, fresh water or fertilizers. The present review offers an objective perspective of the current knowledge surrounding the impacts of seaweeds and their derived polysaccharides on the human microbiome and the profound need for more in-depth investigations into this topic. Animal experiments and in vitro colonic-simulating trials investigating the effects of seaweed ingestion on human gut microbiota are discussed.


Co-administration of Cyclosporin A and Ondansetron decreases transient local cerebral ischemic injury in the mouse.
Several studies indicate that cyclosporin A has a protective effect against brain infarction. In this study, we aimed to determine if co-administration of cyclosporin A and ondansetron could reduce damage caused by cerebral ischemia. ICR (Charles River Laboratories) mice were subjected to transient focal cerebral ischemia and divided into 4 groups (O, V, C, and Mix). Immediately after reperfusion, each ligand was administered intravenously through the external jugular vein. Group V animals received 0.9% saline alone, group O animals received 0.1 mg/kg ondansetron solution, group C animals received 10 mg/kg cyclosporin A solution, and group Mix received 0.1 mg/kg ondansetron solution and 10 mg/kg cyclosporin A solution. Our results showed that the volume of brain infarction induced by middle cerebral artery occlusion in group Mix was significantly smaller than that seen in group V. Forty-eight hours after ischemia, the neurological scores of rats from group Mix significantly improved when compared to group V. Overall, our study showed that a combination of cyclosporin A and ondansetron may be a practical clinical method to treat brain infarction. However, further studies are required to investigate the cerebroprotective mechanism of action, the possible side effects of co-administration of these drugs, and the ability of these ligands to cross the blood brain barrier.


Paget's disease of the temporal bone.
Osteitis deformans Paget is a fairly common, heritable, sometimes progressive disease of bone which affects primarily the axial skeleton and may lead to deformity and weakness. It affects 3% of the population over forty years of age and males more frequently than females. The skull and temporal bones become involved in about two-thirds of the patients. Progressive involvement of the temporal bones may lead to alteration of position, increase in size and change of architecture of the petrous pyramid, external canal, middle ear and inner ear capsule. These changes in turn may produce impairment of hearing (about 30-50% of cases) and vestibular function (20-25%). The clinical, radiological, and pathological manifestations of Paget's disease of the temporal bone are discussed in detail and explained with photomicrographs. Examples of tumor formations and vascular changes are presented.


Efficient delivery of methotrexate to MDA-MB-231 breast cancer cells by a pH-responsive ZnO nanocarrier.
Methotrexate (MTX), an efficient chemotherapy medication is used in treating various malignancies. However, the breast cancer cell line MDA-MB-231 has developed resistance to it due to low levels of the MTX transport protein, and reduced folate carrier (RFC), making it less effective against these cancer cells. Here we designed a very simple, biocompatible, and non-toxic amine-capped ZnO quantum dots to overcome the MTX resistance on the MDA-MB-231 breast cancer cell line. The QD was characterized by HRTEM, DLS EDX, FT-IR, UV-Vis, and Fluorescence spectroscopy. MTX loading onto the QD was confirmed through fluorescence and UV-Vis spectroscopy. Additionally, extensive confocal microscopic investigations were carried out to determine whether the MTX was successfully released on the MDA-MB-231 cell line. It was discovered that QD is a better pH-responsive delivery system than the previous ones because it successfully delivers MTX to the MDA-MB-231 at a higher rate on an acidic pH than it does at a physiological pH. QD also has anticancer activity and can eradicate cancer cells on its own. These factors make the QD to be an effective pH-responsive delivery system that can improve the efficacy of the medication in therapeutic diagnosis.


A comprehensive molecular phylogeny of Geometridae (Lepidoptera) with a focus on enigmatic small subfamilies.
Our study aims to investigate the relationships of the major lineages within the moth family Geometridae, with a focus on the poorly studied Oenochrominae-Desmobathrinae complex, and to translate some of the results into a coherent subfamilial and tribal level classification for the family. We analyzed a molecular dataset of 1,206 Geometroidea terminal taxa from all biogeographical regions comprising up to 11 molecular markers that includes one mitochondrial (COI) and 10 protein-coding nuclear gene regions (wingless, ArgK, MDH, RpS5, GAPDH, IDH, Ca-ATPase, Nex9, EF-1alpha, CAD). The molecular data set was analyzed using maximum likelihood as implemented in IQ-TREE and RAxML. We found high support for the subfamilies Larentiinae, Geometrinae and Ennominae in their traditional scopes. Sterrhinae becomes monophyletic only if Ergavia Walker, Ametris Hübner and Macrotes Westwood, which are currently placed in Oenochrominae, are formally transferred to Sterrhinae. Desmobathrinae and Oenochrominae are found to be polyphyletic. The concepts of Oenochrominae and Desmobathrinae required major revision and, after appropriate rearrangements, these groups also form monophyletic subfamily-level entities. Oenochrominae s.str. as originally conceived by Guenée is phylogenetically distant from Epidesmia and its close relatives. The latter is hereby described as the subfamily Epidesmiinae Murillo-Ramos, Sihvonen & Brehm, subfam. nov. Epidesmiinae are a lineage of "slender-bodied Oenochrominae" that include the genera Ecphyas Turner, Systatica Turner, Adeixis Warren, Dichromodes Guenée, Phrixocomes Turner, Abraxaphantes Warren, Epidesmia Duncan & Westwood and Phrataria Walker. Archiearinae are monophyletic when Dirce and Acalyphes are formally transferred to Ennominae. We also found that many tribes were para- or polyphyletic and therefore propose tens of taxonomic changes at the tribe and subfamily levels. Archaeobalbini stat. rev. Viidalepp (Geometrinae) is raised from synonymy with Pseudoterpnini Warren to tribal rank. Chlorodontoperini Murillo-Ramos, Sihvonen & Brehm, trib. nov. and Drepanogynini Murillo-Ramos, Sihvonen & Brehm, trib. nov. are described as new tribes in Geometrinae and Ennominae, respectively.


Relationship Between Metabolic Syndrome and Clinical Features, and Its Personal-Social Performance in Patients with Schizophrenia.
The aim of this study was to evaluate the metabolic syndrome (MS) criteria and also to investigate the effects of MS on medical treatment, clinical course and personal and social performance in patients with schizophrenia. One hundred-sixteen patients with schizophrenia were included in the study. Measurements of MS were calculated in all patients. Brief Psychiatric Rating Scale, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia, Personal and Social Performance Scale (PSP) were applied. The frequency of MS according to IDF criteria was 42.2 % among the patients. There was no significant difference between patients with and without MS in terms of age. The ratios of MS were 62.5 % for the group taking typical and atypical antipsychotics together and 35.7 % for the group taking two or more atypical antipsychotics together. The duration of disorder in patients with MS was higher than those without MS. Furthermore there was no significant difference between the schizophrenic patients with and without MS, in terms of PSP scores. Our findings showed that the duration of illness, high scores of BMI, use of clozapine or concurrent use of typical and atypical antipsychotics, depressive and negative symptoms of schizophrenia were significant risk factors for the development of MS.


Auditory versus visual processing of three sets of simultaneous digit pairs.
Two experiments were conducted to determine whether the auditory and visual systems process simultaneously presented pairs of alphanumeric information differently. In Experiment 1, different groups of subjects were given extensive practice recalling pairs of superimposed visual or auditory digits in simultaneous order (the order of arrival) or successive order (one member of each digit pair in turn, followed by the other pair member). For auditory input, successive order of recall was more accurate, particularly for the last two of three pairs presented, whereas for visual input, simultaneous order of recall was more accurate. In Experiment 2, subjects were cued to recall in one or the other order either immediately before or after stimulus input. Recall order results were the same as for Experiment 1, and precuing did not facilitate recall in either order for both modalities. These results suggest that processing in the auditory system can only occur successively across time, whereas as in the visual system processing can only occur simultaneously in space.


Stimulating the anaerobic degradation of aromatic hydrocarbons in contaminated sediments by providing an electrode as the electron acceptor.
The possibility that electrodes might serve as an electron acceptor to simulate the degradation of aromatic hydrocarbons in anaerobic contaminated sediments was investigated. Initial studies with Geobacter metallireducens demonstrated that although toluene was rapidly adsorbed onto the graphite electrodes it was rapidly oxidized to carbon dioxide with the electrode serving as the sole electron acceptor. Providing graphite electrodes as an electron acceptor in hydrocarbon-contaminated sediments significantly stimulated the removal of added toluene and benzene. Rates of toluene and benzene removal accelerated with continued additions of toluene and benzene. [(14)C]-Toluene and [(14)C]-benzene were quantitatively recovered as [(14)C]-CO(2), demonstrating that even though the graphite adsorbed toluene and benzene they were degraded. Introducing an electrode as an electron acceptor also accelerated the loss of added naphthalene and [(14)C]-naphthalene was converted to [(14)C]-CO(2). The results suggest that graphite electrodes can serve as an electron acceptor for the degradation of aromatic hydrocarbon contaminants in sediments, co-localizing the contaminants, the degradative organisms and the electron acceptor. Once in position, they provide a permanent, low-maintenance source of electron acceptor. Thus, graphite electrodes may offer an attractive alternative for enhancing contaminant degradation in anoxic environments.


Predicting sepsis-related mortality and ICU admissions from telephone triage information of patients presenting to out-of-hours GP cooperatives with acute infections: A cohort study of linked routine care databases.
General practitioners (GPs) often assess patients with acute infections. It is challenging for GPs to recognize patients needing immediate hospital referral for sepsis while avoiding unnecessary referrals. This study aimed to predict adverse sepsis-related outcomes from telephone triage information of patients presenting to out-of-hours GP cooperatives. A retrospective cohort study using linked routine care databases from out-of-hours GP cooperatives, general practices, hospitals and mortality registration. We included adult patients with complaints possibly related to an acute infection, who were assessed (clinic consultation or home visit) by a GP from a GP cooperative between 2017-2019. We used telephone triage information to derive a risk prediction model for sepsis-related adverse outcome (infection-related ICU admission within seven days or infection-related death within 30 days) using logistic regression, random forest, and neural network machine learning techniques. Data from 2017 and 2018 were used for derivation and from 2019 for validation. We included 155,486 patients (median age of 51 years; 59% females) in the analyses. The strongest predictors for sepsis-related adverse outcome were age, type of contact (home visit or clinic consultation), patients considered ABCD unstable during triage, and the entry complaints"general malaise", "shortness of breath" and "fever". The multivariable logistic regression model resulted in a C-statistic of 0.89 (95% CI 0.88-0.90) with good calibration. Machine learning models performed similarly to the logistic regression model. A "sepsis alert" based on a predicted probability >1% resulted in a sensitivity of 82% and a positive predictive value of 4.5%. However, most events occurred in patients receiving home visits, and model performance was substantially worse in this subgroup (C-statistic 0.70). Several patient characteristics identified during telephone triage of patients presenting to out-of-hours GP cooperatives were associated with sepsis-related adverse outcomes. Still, on a patient level, predictions were not sufficiently accurate for clinical purposes.


Development of a Hypersensitivity Evaluation Method for Cultured Sensory Neurons Using Electrical Activity Recording.
Investigation of hypersensitivity caused by peripheral sensitization progression is important for developing novel pain treatments. Existing methods cannot record plastic changes in neuronal activity because they occur over a few days. We aimed to establish an efficient method to evaluate neuronal activity alterations caused by peripheral sensitization on high-density microelectrode arrays (HD-MEAs) which can record neuronal activity for a long time. Rat dorsal root ganglion (DRG) neurons were dissected from rat embryos and cultured on HD-MEAs. DRG neurons were labeled with NeuO, live staining dye. Neurons were detected with the fluorescence signal and electrodes were selected with the fluorescence images. The number of DRG neurons, whose activity were recorded, detected based on fluorescence observation was five times greater than that based on neuronal activity. Analysis of changes in neuronal activity observed in pharmacological stimulation experiments suggested that substance P induced peripheral sensitization and enhanced capsaicin sensitivity. In addition, results of immunofluorescence staining suggested that peripheral sensitization occurred mostly in neurons that co-expressed transient receptor potential vanilloid 1 (TRPV1) and neurokinin 1 receptor (NK1R). In conclusion, we established an efficient method for assessing the effects of peripheral sensitization on DRG neurons cultured on HD-MEAs.


A gene-based linkage map for Bicyclus anynana butterflies allows for a comprehensive analysis of synteny with the lepidopteran reference genome.
Lepidopterans (butterflies and moths) are a rich and diverse order of insects, which, despite their economic impact and unusual biological properties, are relatively underrepresented in terms of genomic resources. The genome of the silkworm Bombyx mori has been fully sequenced, but comparative lepidopteran genomics has been hampered by the scarcity of information for other species. This is especially striking for butterflies, even though they have diverse and derived phenotypes (such as color vision and wing color patterns) and are considered prime models for the evolutionary and developmental analysis of ecologically relevant, complex traits. We focus on Bicyclus anynana butterflies, a laboratory system for studying the diversification of novelties and serially repeated traits. With a panel of 12 small families and a biphasic mapping approach, we first assigned 508 expressed genes to segregation groups and then ordered 297 of them within individual linkage groups. We also coarsely mapped seven color pattern loci. This is the richest gene-based map available for any butterfly species and allowed for a broad-coverage analysis of synteny with the lepidopteran reference genome. Based on 462 pairs of mapped orthologous markers in Bi. anynana and Bo. mori, we observed strong conservation of gene assignment to chromosomes, but also evidence for numerous large- and small-scale chromosomal rearrangements. With gene collections growing for a variety of target organisms, the ability to place those genes in their proper genomic context is paramount. Methods to map expressed genes and to compare maps with relevant model systems are crucial to extend genomic-level analysis outside classical model species. Maps with gene-based markers are useful for comparative genomics and to resolve mapped genomic regions to a tractable number of candidate genes, especially if there is synteny with related model species. This is discussed in relation to the identification of the loci contributing to color pattern evolution in butterflies.


Trajectories of kidney function and risk of mortality.
We aimed to identify patterns within the rate of kidney function decline, determinants of these patterns and their association with all-cause mortality risk in the general population. Participants aged ≥ 45 years with at least one assessment of creatinine-based estimated glomerular filtration rate (eGFR) taken between 1997 and 2018 were selected from a population-based cohort study. Analyses were performed using several distinct latent class trajectory modelling methods. Cumulative incidences were calculated with 45 years of age as the starting point. In 12 062 participants (85 922 eGFR assessments, mean age 67.0 years, 58.7% women, median follow-up 9.6 years), four trajectories of eGFR change with age were identified: slow eGFR decline [rate of change in mL/min/1.73 m2 per year (RC), -0.9; 95% CI, -0.9 to -0.9; reference group], intermediate eGFR decline (RC, -2.5; 95% CI, -2.7 to -2.5) and fast eGFR decline (RC, -4.3; 95% CI, -4.4 to -4.1), and an increase/stable eGFR (RC, 0.3; 95% CI, 0.3 to 0.4). Women were more likely to have an increase/stable eGFR [odds ratio (OR), 1.94; 95% CI, 1.53 to 2.46] whereas men were more likely to have a fast eGFR decline (OR, 1.86; 95% CI, 1.33 to 2.60). Participants with diabetes, cardiovascular disease (CVD) or hypertension were more likely to have an intermediate or fast eGFR decline. All-cause mortality risks (cumulative incidence at age of 70 years) were 32.3% (95% CI, 21.4 to 47.9, slow eGFR decline), 6.7% (95% CI, 3.5 to 12.4, intermediate eGFR decline), 68.8% (95% CI, 44.4 to 87.8, fast eGFR decline) and 9.5% (95% CI, 5.5 to 15.7, increase/stable eGFR). Sex, hypertension, diabetes and CVD were identified as trajectory membership determinants. Having fast eGFR decline was associated with the highest risk of all-cause mortality, highlighting the need for extensive monitoring and prevention of kidney function decline in individuals at risk of having fast eGFR decline.


Nicotine and carbon monoxide content of cigarette smoke and the risk of myocardial infarction in young men.
To evaluate whether the nicotine and carbon monoxide content of cigarette smoke is related to the risk of nonfatal first myocardial infarction in young men, we compared 502 cases with 835 hospital controls, all between the ages of 30 and 54 years. As expected, the estimated risk of myocardial infarction increased with the number of cigarettes smoked; overall, the relative-risk estimate for current smokers was 2.8 (95 per cent confidence interval, 2.0 to 4.0). The risk did not appear to vary according to the amount of nicotine or carbon monoxide in the cigarette, and the mean amounts of both substances per cigarette were similar for the cases and controls. The results suggest that men who smoke the newer cigarettes with reduced amounts of nicotine and carbon monoxide do not have a lower risk of myocardial infarction than those who smoke cigarettes containing larger amounts of these substances.


[Public health structures in Spain: a changing panorama].
In the last years the health care system in Spain has undergone very important transformations. However, the public health services have not followed a comparable process. Until 1979 public health structures were based in central services and their provincial units, on one side, and in the resources of local governments on the other. From then on began the process of transferring responsibilities and resources to the regional governments of Autonomous Communities (AC), which today manage most public health services, while the central government keeps as its responsibility the development of basic norms, the administration of public health services at borders and customs, and the general health coordination. The situation in 1995 resembles that of a Federal Country, although the Kingdom of Spain is not formally defined as such. The role of central government services is visibly reoriented towards coordination and the building of consensual and shared structures for health information, for need evaluation, and for policy formulation and evaluation. Although the General Health Law of 1986 considered public health as a main axis for all health agencies, its actual development has been more patchy. Several AC with an Autonomous Health Service have kept public health services separated from it. Besides, many public health functions and activities are developed today from other structures. The processes of change reveal two contradictory aspects. On one side, structures have been upgraded after decentralization, and teams reinforced, with trained and full-time staff. However, there is some dilution of public health responsibility in the periphery, and a lower visibility of the health authority.


Morphological variations in Onchocerca sp. from atypical hosts and sites: the validity of O. stilesi.
Minor morphological variations occur in some specimens of Onchocerca gutturosa and O. lienalis developing in unusual anatomical sites in their normal hosts and in unusual Hosts. These variations may affect characters usually considered to be important diagnostic features. Variations in O. lienalis show a range which encompass the features used by Eberhard (1979) to distinguish a new species, O. stilesi. Further studies on fresh material are needed before O. stilesi can be accepted as a valid species.


[Rapid time-resolved fluoroimmunometric analysis of myoglobin].
High performance quantitative procedure for evaluation of myoglobin in blood serum is developed. The principle of two-site immunometry was used involving monoclonal antibodies against nonoverlapping epitopes of myoglobin molecule. The fluorescent compound containing europium served as a label of the antibody. Modification of the single-step assay enabled to increase the velocity of the assay to about 30 min and simplify it. The assay allowed estimation of myoglobin over a broad range of concentrations from 2 ng up to 1,000 ng/ml. The assay may be recommended for use in clinical practice for express diagnosis of myocardium infarction.


A Facile Colorimetric and Spectrophotometric Method for Sensitive Determination of Metformin in Human Serum Based on Citrate-Capped Gold Nanoparticles: Central Composite Design Optimization.
For the determination of Metformin in human serum, a facile colorimetric and spectrophotometric sensor was designed based on citrate-capped gold nanoparticles (citrate-GNPs). In this probe, the addition of Metformin to GNP solution generates a naked-eye color change resulting from the aggregation of GNPs. Study of this color conversion and quantity analysis of analyte is operated by spectrophotometric instruments. The three factors pH, time, and GNP ratio were selected to examine their effects on sensing results and their values optimization. The optimization of parameters was done by means of central composite design and one-at-a-time methods. The sensing results proved the highly selective and sensitive performance of the sensor for Metformin in a linear range of 6.25-133.3 ppm with a detection limit of 1.79 ppm. The relative standard deviation (RSD) of the reported method is 2.53%.


Disease burden of herpes zoster in Korea.
The occurrence of herpes zoster can deteriorate the quality of life considerably, resulting in high disease burden. While Korea is assumed to have high disease burden of herpes zoster, there has been no researches analyzing this. We performed this study to investigate the disease burden of herpes zoster in the Korean population as a whole. We used the database of the Health Insurance Review & Assessment Service of Korea and analyzed the data of patients who had herpes zoster as a principal diagnosis during the period from 2003 to 2007. We investigated the annual prevalence, rate of clinical visits, rate of hospitalization, and the pattern of medical services use. The socioeconomic burden of herpes zoster was calculated by a conversion into cost. Rates of clinic visits and hospitalizations due to herpes zoster during the 5-year period from 2003 to 2007 were 7.93-12.54 per 1000 population and 0.22-0.32 per 1000 population, respectively. Prevalence rates according to age increased sharply after 50 years and reached a peak at 70 years. The total socioeconomic cost of herpes zoster was $75.9-143.8 million per year, increasing every year by 14-20%. There is a heavy socioeconomic burden due to herpes zoster in Korea and indicate that appropriate policies need to be established to reduce this burden. Additional researches are also necessary to assess the safety, efficacy and cost-effectiveness of a herpes zoster vaccine in the Korean population.


Safety of and response to electroconvulsive therapy during pregnancy: Results from population-based nationwide registries.
Psychiatric disorders are common during pregnancy, affecting up to 16% of pregnant women. Severe depression and anxiety have significant negative effects on the health of both the mother and the developing fetus. Electroconvulsive therapy (ECT) is considered a treatment option for pregnant women with severe psychiatric disorders when other treatments have been ineffective or pose risks to the fetus. Knowledge of the safety and efficacy of ECT during pregnancy, however, remains limited. Data were obtained from nationwide registries of pregnant women in Sweden who received ECT for a severe psychiatric disorder from January 2008 to December 2021. ECT-related outcomes in pregnant women were compared by propensity score matching with a group of non-pregnant women who also received ECT. Pregnancy-related outcomes were compared with two additional control groups: one consisting of the same group of women who did not receive ECT during another pregnancy and the other composed of pregnant women admitted to inpatient psychiatric care but who did not receive ECT, matched based on propensity score. Ninety-five pregnant women received ECT during the study period, accounting for 97 pregnancies. The response rate to ECT in pregnant women (n = 54) was similar to the matched control group of non-pregnant women (74% vs. 65%; OR 1.61; 95% CI 0.79-3.27). Rates of adverse events related to ECT were similar to those in the control group. There were no pre-term births or severe adverse outcomes related to the pregnancy, that were close in time to ECT. Therefore, no adverse outcomes related to pregnancy and childbirth could be directly attributed to ECT. The likelihood of premature birth and a 5-min Apgar score <7 in the newborn were both significantly higher in the ECT group, compared with the matched non-ECT group (OR 2.33, 95% CI 1.15-4.73, p = 0.008, and OR 3.68, 95% CI 1.58-8.55, p < 0.001, respectively). By contrast, no significant differences were observed when women in the pregnant ECT group were compared with the same group lacking ECT during another pregnancy. ECT was associated with a positive treatment response in pregnant women with severe psychiatric disorders. The response rate to ECT was similar in pregnant and non-pregnant women. Nevertheless, the risks of premature birth and of a slightly poorer condition in newborns were higher in women who did than did not receive ECT, emphasizing the need for increased attention to severe psychiatric disorders during pregnancy.


Static compliance of the respiratory system in healthy infants.
We recorded static deflation pressure-volume (PV) curves from near TLC to FRC in 49 healthy, sedated, spontaneously breathing infants of 1 to 104 wk of age. Respiratory activity was transiently inhibited by inflating the respiratory system several times to a volume at an airway pressure of 30 cm H2O (V30). Passive deflation from V30 to FRC was then interrupted by multiple brief occlusions at the airway opening, in order to measure static recoil pressures. The expired volume from V30 to FRC was defined as V30E. Compliance of the respiratory system (Crs) was calculated as the slope of the linear portion of the PV curve from 5 to 15 cm H2O. Crs and V30E increased with increasing body length (p < 0.001). After adjustment for body length, males had greater Crs values than did females (p < 0.01). V30E was smaller in female infants (p < 0.05) and in infants whose mothers smoked during pregnancy (p < 0.04). Specific compliance (Crs/V30E) declined with increasing age (p < 0.01), but there were no differences related to sex or maternal smoking. We conclude that static deflation PV curves can be recorded in the age range from 1 to 104 wk, and that maternal smoking may produce hypoplastic lungs.


High suPAR and Low Blood Eosinophil Count are Risk Factors for Hospital Readmission and Mortality in Patients with COPD.
The biomarker soluble urokinase plasminogen activator receptor (suPAR) has been associated with increased mortality in chronic obstructive pulmonary disease (COPD), while elevated blood eosinophils have been associated with better survival. We hypothesized that suPAR and blood eosinophil count are independent risk factors for readmission and mortality after an acute admission in patients with COPD. This retrospective cohort study comprised 4022 patients with prevalent COPD acutely admitted to Hvidovre Hospital, Denmark. Irrespective of cause of admission, suPAR and blood eosinophils were measured, and patients were followed up to 365 days. Associations with 365-day respiratory readmission, all-cause readmission and all-cause mortality were investigated by Cox regression analyses adjusted for age, sex, Charlson score and C-reactive protein. suPAR was significantly elevated in patients who later experienced readmission or died. At 365 days, hazard ratios (HRs) for all-cause readmission and mortality reached 1.61 (95% CI 1.40-1.85; p<0.0001) and 3.40 (95% CI 2.64-4.39; p<0.0001), respectively, for COPD patients in the fourth suPAR quartile compared to patients in the first suPAR quartile. High blood eosinophils (>300 cells/μL) were associated with lower risk of mortality (HR 0.49, 95% CI 0.39-0.62; p<0.0001) compared with patients with <150 cells/μL. When stratifying patients by suPAR quartiles and blood eosinophil counts, the highest relative mortality rate was found in patients belonging to both the fourth suPAR quartile and the low blood eosinophil (<150 cells/μL) group. In this cohort of COPD patients acutely admitted to a hospital, elevated suPAR concentrations were associated with both higher risk of all-cause readmission and mortality, whereas higher blood eosinophil count was associated with lower risk of mortality.


Neutrophil stimulation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) results in the release of functional soluble TRAIL/Apo-2L.
Mycobacterium bovis bacillus Calmette-Guérin (BCG) has been used to treat bladder cancer for almost 30 years; however, the effector mechanism of the BCG-induced antitumor response remains enigmatic. Most BCG research has focused on the mononuclear-cell infiltrate, but growing evidence supports a role for neutrophils in the antitumor response. Previously, we demonstrated increased urinary tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo-2L) levels from BCG-responsive patients compared to nonresponders. Interestingly, neutrophils isolated from the urine expressed TRAIL/Apo-2L, leading us to investigate the neutrophil response to BCG. BCG-stimulated neutrophils expressed surface-bound and released functional soluble TRAIL/Apo-2L. Whereas neither interferon alpha (IFN-alpha) nor IFN-gamma directly induced TRAIL/Apo2L expression by neutrophils, IFN-alpha did stimulate TRAIL gene transcription, and IFN-primed neutrophils contained and released more TRAIL/Apo-2L after BCG stimulation than did unprimed neutrophils. In unstimulated neutrophils TRAIL/Apo-2L was present predominantly in the azurophilic granules and plasma-membrane-enriched/secretory-granule fraction. Finally, we observed that killed BCG, Toll-like receptor 2 (TLR2) and TLR4 agonists, and an M tuberculosis cell-wall fraction were each capable of inducing the release of soluble TRAIL/Apo-2L from neutrophils. These results further characterize the potential role neutrophils may play in initiating the antitumor response described with BCG treatment for superficial bladder cancer.


Defining Outcome Measures for Psoriasis: The IDEOM Report from the GRAPPA 2016 Annual Meeting.
The International Dermatology Outcome Measures (IDEOM) psoriasis working group was established to develop core domains and measurements sets for psoriasis clinical trials and ultimately clinical practice. At the 2016 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, the IDEOM psoriasis group presented an overview of its progress toward developing this psoriasis core domain set. First, it summarized the February 2016 meeting of all involved with the IDEOM, highlighting patient and payer perspectives on outcome measures. Second, the group presented an overview of the consensus process for developing the core domain set for psoriasis, including previous literature reviews, nominal group exercises, and meeting discussions. Future plans include the development of working groups to review candidate measures for at least 2 of the domains, including primary pathophysiologic manifestations and patient-reported outcomes, and Delphi surveys to gain consensus on the final psoriasis core domain set.


Eyelid laxity, obesity, and obstructive sleep apnea in keratoconus.
The association between floppy eyelid syndrome and keratoconus (KCN) has been well established, but the converse relationship has not yet been examined and is the objective of this study. The study also investigates the prevalence of obesity and obstructive sleep apnea (OSA) in KCN patients. A prospective case-control study of KCN patients with age-, sex-, race-, and body mass index-matched controls was conducted at the Ross Eye Institute, Buffalo, NY. Fifteen patients were enrolled in each group. Extensive eyelid laxity measurements were performed on both groups. Complete medical/ophthalmic history and Epworth Sleepiness Scales were completed on 50 KCN patients and were compared with the normal population. Increased eyelid measurements of the vertical lid pull, lower lid pull, medial canthal tendon distraction, and palpebral width were found in the KCN group compared with the matched control group (P = 0.001, 0.005, 0.04, and 0.01, respectively), and a more rubbery tarsus (P = 0.03), increased corneal diameter (P = 0.02), and increased exophthalmometry measurements (P = 0.01) were also found. The prevalence of OSA (24%, 14/50) and obesity (52%, 26/50) were higher in the KCN patients versus the normal population. KCN patients have increased laxity to their eyelids, along with a more rubbery tarsus, which may be along the spectrum of floppy eyelid syndrome. KCN patients had a high prevalence of OSA and obesity. The high prevalence of OSA in KCN patients is an important association that carries an increased risk of death from any cause and stroke.


The experience of beta-thalassaemiaand its prevention in Cyprus.
Haemoglobinopathies are a series of hereditary genetic diseases which, if left untreated, usually prove fatal. The present paper discusses how one of the most important of these, beta-thalassaemia, afflicted the island of Cyprus in the last century and almost threatened to eliminate the whole population. In narrating the medical facts of the disease we point out the moral dilemmas which medical personnel, the state and the church had to deal with before they embarked on a program for the treatment and prevention of beta-thalassaemia. After careful study of the program we conclude that, although in the given case it proved a successful model for the management of beta-thalassaemia, it bears no resemblance whatsoever to eugenics.


Automated lung nodule classification following automated nodule detection on CT: a serial approach.
We have evaluated the performance of an automated classifier applied to the task of differentiating malignant and benign lung nodules in low-dose helical computed tomography (CT) scans acquired as part of a lung cancer screening program. The nodules classified in this manner were initially identified by our automated lung nodule detection method, so that the output of automated lung nodule detection was used as input to automated lung nodule classification. This study begins to narrow the distinction between the "detection task" and the "classification task." Automated lung nodule detection is based on two- and three-dimensional analyses of the CT image data. Gray-level-thresholding techniques are used to identify initial lung nodule candidates, for which morphological and gray-level features are computed. A rule-based approach is applied to reduce the number of nodule candidates that correspond to non-nodules, and the features of remaining candidates are merged through linear discriminant analysis to obtain final detection results. Automated lung nodule classification merges the features of the lung nodule candidates identified by the detection algorithm that correspond to actual nodules through another linear discriminant classifier to distinguish between malignant and benign nodules. The automated classification method was applied to the computerized detection results obtained from a database of 393 low-dose thoracic CT scans containing 470 confirmed lung nodules (69 malignant and 401 benign nodules). Receiver operating characteristic (ROC) analysis was used to evaluate the ability of the classifier to differentiate between nodule candidates that correspond to malignant nodules and nodule candidates that correspond to benign lesions. The area under the ROC curve for this classification task attained a value of 0.79 during a leave-one-out evaluation.


Detecting epistasis from an ensemble of adapting populations.
The role that epistasis plays during adaptation remains an outstanding problem, which has received considerable attention in recent years. Most of the recent empirical studies are based on ensembles of replicate populations that adapt in a fixed, laboratory controlled condition. Researchers often seek to infer the presence and form of epistasis in the fitness landscape from the time evolution of various statistics averaged across the ensemble of populations. Here, we provide a rigorous analysis of what quantities, drawn from time series of such ensembles, can be used to infer epistasis for populations evolving under weak mutation on finite-site fitness landscapes. First, we analyze the mean fitness trajectory-that is, the time course of the ensemble average fitness. We show that for any epistatic fitness landscape and starting genotype, there always exists a non-epistatic fitness landscape that produces the exact same mean fitness trajectory. Thus, the presence of epistasis is not identifiable from the mean fitness trajectory. By contrast, we show that two other ensemble statistics-the time evolution of the fitness variance across populations, and the time evolution of the mean number of substitutions-can detect certain forms of epistasis in the underlying fitness landscape.


The Application of Systems Science in Nutrition-Related Behaviors and Outcomes Implementation Research: A Scoping Review.
Use of systems science can improve the dissemination and implementation (D&I) process. However, little is known about use of systems science in nutrition D&I research. The purpose of this article is to synthesize the ways in which systems science methodology is applied in nutrition D&I research. Scoping review methodology involved searching 6 academic databases for full-text, peer-reviewed, English articles published between 1970 and 2020 that employed systems science within nutrition D&I research. Data extraction included intervention type, population, study aim, methods, theoretical approach, outcomes, and results. Descriptive statistics and qualitative thematic analysis followed. Thirty-four retained articles qualitatively identified benefits (successful planning and organization of complex interventions) and challenges (limited resources, trainings, and lack of knowledge) to utilizing systems science in nutrition D&I research. Future research should work toward building knowledge capacity among nutrition practitioners by increasing available trainings and resources to enhance the utilization of systems science in nutrition D&I research.


[A solid-pseudopapillary tumors of the pancreas].
The review presents an update of solid-pseudopapillary pancreatic tumors, a rare and inadequately studied type of tumors that are predominantly encountered in girls and young women. It discusses the problems in the diagnosis based on the histological and imunophenotypical uniqueness of these tumors, which allows them to be differentiated from other types of pancreatic tumors with a less favorable prognosis. The correct diagnosis of a solid-pseudopapillary tumor determines the management tactic that requires no radiation or chemotherapy in the vast majority.


Real-world costing analysis for diffuse large B-cell lymphoma in British Columbia.
Diffuse large B-cell lymphoma (dlbcl) accounts for 30%-40% of all non-Hodgkin lymphomas. Approximately 60% of patients are cured with standard treatment. Targeted treatments are being investigated and might improve disease outcomes; however, their effect on cancer drug budgets will be significant. For the present study, we conducted an analysis of real-world costs for dlbcl patients treated in British Columbia, useful for health care system planning. Patient records from a retrospective cohort of patients diagnosed with dlbcl in British Columbia during 2004-2013 were anonymously linked across multiple administrative data sources: systemic therapy, radiotherapy, hospitalizations, oncologist services, outpatient medications, and fee-for-service physician services. Using generalized linear modelling regression, time-dependent costs (in 2015 Canadian dollars) were estimated in 6-month intervals over a 5-year period. The inverse probability weighting method was applied to account for censored observations. Nonparametric bootstrapping was used to estimate standard errors for the mean cost at each time interval. The cohort consisted of 678 patients (5-year overall survival: 67%). Mean age at diagnosis was 64 ± 14 years; median follow-up was 3.2 years. Mean total cost of care was highest in the first 6 months after diagnosis ($29,120; 95% confidence interval: $28,986 to $29,170) and after disease progression ($18,480; 95% confidence interval: $15,187 to $24,772). Systemic therapy and hospitalization costs were the largest cost drivers. At each time interval, costs were observed to be positively skewed. Our results depict real-world costs for the treatment of dlbcl patients with standard chop-r therapy. Cost-model parameters are also provided for economic modelling of dlbcl interventions.


Vitamin D: metabolism, molecular mechanisms, and mutations to malignancies.
The potential protective effects of vitamin D against cutaneous carcinogenesis are still poorly understood. The inhibition, by vitamin D, of various cancers in in vitro and in vivo models has triggered detailed investigation of vitamin D effects on neoplastic behavior. Recent studies highlight that such neoplastic features as the tumor microenvironment, angiogenesis, DNA mutagenesis, and apoptosis are all connected to vitamin D metabolic pathways. This review discusses these connections. Vitamin D modulation of the cell cycle, DNA repair and apoptosis via its receptors (VDRs) may have a suppressive effect on skin cancer as some studies suggest. The regulation of multiple tumor signaling pathways by vitamin D may have an implication in cutaneous carcinogenesis and tumor progression to malignancy.


Closing and inactivation potentiate the cocaethylene inhibition of cardiac sodium channels by distinct mechanisms.
Cocaethylene, a metabolite of cocaine and alcohol, is a potent inhibitor of the cardiac (Nav1.5) sodium channel heterologously expressed in Xenopus laevis oocytes. Cocaethylene produces minimal tonic block under resting conditions but causes a potent use-dependent inhibition during repetitive depolarization and a hyperpolarizing shift in the steady-state inactivation. The data are consistent with a state-dependent binding mechanism, which has high affinity for inactivated channels (KI = 17 microM) and low affinity for resting channels (KR = 185 micro). Mutations of the interdomain D3-D4 linker eliminated rapid inactivation and weakened the cocaethylene inhibition, consistent with an important role for fast inactivation in cocaethylene binding. A rapid component of cocaethylene inhibition was observed in a noninactivating mutant of Nav1.5 that was tightly linked to channel opening and displayed properties consistent with a pore blocking mechanism. Hyperpolarization caused the noninactivating mutant channel to close, trapping cocaethylene and slowing the recovery. Mutation of a conserved isoleucine (I1756C) located near the extracellular end of the D4S6 segment accelerated the recovery of the noninactivating channel, suggesting that this mutation facilitates cocaethylene untrapping, which seems to be the rate-limiting step in the recovery when the channel is closed. This contrasts with the rapidly inactivating channel, where the I1756C mutation did not alter the recovery from cocaethylene inhibition. The data suggest that additional mechanisms, such as more stable cocaethylene binding, may be a more important determinant of recovery kinetics when the channels are inactivated. The data indicate that deactivation and inactivation slow the recovery and potentiate the cocaethylene inhibition of the Nav1.5 channel by distinct mechanisms.


Myeloid sarcoma involving the breast.
Myeloid sarcoma is a tumor mass with extramedullary growth pattern, composed of myeloblasts or immature myeloid cells. The development of myeloid sarcoma may precede or concur with acute or chronic myeloid leukemia (AML or CML) or other myeloproliferative diseases or myelodysplastic syndromes (MDS). Isolated myeloid sarcoma of the breast is very rare. A case is presented of a 25-year-old, previously healthy woman that presented to our department for a palpable node, 5 x 2 cm in size, in the upper medial quadrant of her left breast. Fine needle aspiration (FNA) produced a sample consisting of medium sized blasts. Additional work-up revealed anemia, thrombocytopenia and leukocytosis, along with atypical blasts detected in peripheral blood and bone marrow smear. Based on the morphology, cytochemical characteristics and immature cell immunophenotype, it was considered a case of acute myeloid leukemia without maturation. In spite of intensive chemotherapy, the patient died within a year of diagnosis. In cases of isolated breast myeloid sarcoma, the diagnosis can be missed if the possibility of myeloid sarcoma is not remembered on differential diagnosis of a breast neoplasm.


Detection of an isoform of alpha(1)-antitrypsin in serum samples from foals with gastric ulcers.
The objective of this study was to find serum indicators of gastric ulcers in foals. By using two-dimensional electrophoresis of serum proteins, three distinct spots were detected in samples from foals with gastric ulcers detected endoscopically. One of them appeared with high frequency and was identified by partial digestion with trypsin and subsequent nano-electrospray ionisation-tandem mass spectrometry (nanoesi-ms/ms) analysis as an alpha(1)-antitrypsin. Western blot analysis, using an antibody against human alpha(1)-antitrypsin, revealed at least two bands, of molecular weight 58 kDa and 55 kDa, in the sera. The 55 kDa band was detected in 44 of 47 serum samples from foals with gastric ulcers, but in only three of 22 serum samples from healthy foals.


Boosting Ammonium Oxidation in Wastewater by the BiOCl-Functionalized Anode.
Mixed metal oxide (MMO) anodes are commonly used for electrochlorination of ammonium (NH4+) in wastewater treatment, but they suffer from low efficiency due to inadequate chlorine generation at low Cl- concentrations and sluggish reaction kinetics between free chlorine and NH4+ under acidic pH conditions. To address this challenge, we develop a straightforward wet chemistry approach to synthesize BiOCl-functionalized MMO electrodes using the MMO as an efficient Ohmic contact for electron transfer. Our study demonstrates that the BiOCl@MMO anode outperforms the pristine MMO anode, exhibiting higher free chlorine generation (24.6-60.0 mg Cl2 L-1), increased Faradaic efficiency (75.5 vs 31.0%), and improved rate constant of NH4+ oxidation (2.41 vs 0.76 mg L-1 min-1) at 50 mM Cl- concentration. Characterization techniques including electron paramagnetic resonance and in situ transient absorption spectra confirm the production of chlorine radicals (Cl• and Cl2•-) by the BiOCl/MMO anode. Laser flash photolysis reveals significantly higher apparent second-order rate constants ((4.3-4.9) × 106 M-1 s-1 at pH 2.0-4.0) for the reaction between NH4+ and Cl•, compared to the undetectable reaction between NH4+ and Cl2•-, as well as the slower reaction between NH4+ and free chlorine (102 M-1 s-1 at pH < 4.0) within the same pH range, emphasizing the significance of Cl• in enhancing NH4+ oxidation. Mechanistic studies provide compelling evidence of the capacity of BiOCl for Cl- adsorption, facilitating chlorine evolution and Cl• generation. Importantly, the BiOCl@MMO anode exhibits excellent long-term stability and high catalytic activity for NH4+-N removal in a real landfill leachate. These findings offer valuable insights into the rational design of electrodes to improve electrocatalytic NH4+ abatement, which holds great promise for wastewater treatment applications.


Inhaled anticholinergic drug therapy and the risk of acute urinary retention in chronic obstructive pulmonary disease: a population-based study.
Inhaled anticholinergic medications (IACs) are widely used treatments for chronic obstructive pulmonary disease (COPD). The systemic anticholinergic effects of IAC therapy have not been extensively studied. This study sought to determine the risk of acute urinary retention (AUR) in seniors with COPD using IACs. A nested case-control study of individuals with COPD aged 66 years or older was conducted from April 1, 2003, to March 31, 2009, using population-based linked databases from Ontario, Canada. A hospitalization, same-day surgery, or emergency department visit for AUR identified cases, which were matched with up to 5 controls. Exposure to IACs was determined using a comprehensive drug benefits database. Conditional logistic regression analysis was conducted to determine the association between IAC use and AUR. Of 565,073 individuals with COPD, 9432 men and 1806 women developed AUR. Men who just initiated a regimen of IACs were at increased risk for AUR compared with nonusers (adjusted odds ratio [OR], 1.42; 95% confidence interval [CI], 1.20-1.68). In men with evidence of benign prostatic hyperplasia, the risk was increased further (OR, 1.81; 95% CI, 1.46-2.24). Men using both short- and long-acting IACs had a significantly higher risk of AUR compared with monotherapy users (OR, 1.84; 95% CI, 1.25-2.71) or nonusers (2.69; 1.93-3.76). Use of short- and long-acting IACs is associated with an increased risk of AUR in men with COPD. Men receiving concurrent treatment with both short- and long-acting IACs and those with evidence of benign prostatic hyperplasia are at highest risk.


Autoimmune hemolytic anemia terminating seven years later in Hodgkin's disease.
A 64-year-old woman was treated during 7(1/2) years for an isolated AIHA by transfusions, prednisone and splenectomy. The autoantibody was a warm-type IgG with anti-e specificity. At autopsy, generalized Hodgkin's disease of mixed cellularity was found. Only 11 similar cases of hemolytic anemia preceding the development of Hodgkin's disease have been reported in the literature. This association suggests a possible underlying defect in the immune system of the host.


Genomic approaches to identify hybrids and estimate admixture times in European wildcat populations.
The survival of indigenous European wildcat (Felis silvestris silvestris) populations can be locally threatened by introgressive hybridization with free-ranging domestic cats. Identifying pure wildcats and investigating the ancestry of admixed individuals becomes thus a conservation priority. We analyzed 63k cat Single Nucleotide Polymorphisms (SNPs) with multivariate, Bayesian and gene-search tools to better evaluate admixture levels between domestic and wild cats collected in Europe, timing and ancestry proportions of their hybrids and backcrosses, and track the origin (wild or domestic) of the genomic blocks carried by admixed cats, also looking for possible deviations from neutrality in their inheritance patterns. Small domestic ancestry blocks were detected in the genomes of most admixed cats, which likely originated from hybridization events occurring from 6 to 22 generations in the past. We identified about 1,900 outlier coding genes with excess of wild or domestic ancestry compared to random expectations in the admixed individuals. More than 600 outlier genes were significantly enriched for Gene Ontology (GO) categories mainly related to social behavior, functional and metabolic adaptive processes (wild-like genes), involved in cognition and neural crest development (domestic-like genes), or associated with immune system functions and lipid metabolism (parental-like genes). These kinds of genomic ancestry analyses could be reliably applied to unravel the admixture dynamics in European wildcats, as well as in other hybridizing populations, in order to design more efficient conservation plans.


New theoretical formulation for the determination of radiance transmittance at the water-air interface.
Radiative transfer across the water-air interface has important implications for optics and remote sensing of natural waters. The upward radiance emerging from the water suffers a critical change when it passes through the water-air interface. Upwelling radiance transmittance τw,a is an optical process occurring at the water-air interface that determines the in-water radiances propagating through the interface. In previous studies, τw,a was successfully derived for determining the water-leaving radiances in open ocean waters, despite being oversimplified with a constant value. The constant τw,a value becomes rapidly invalid in high scattering and absorbing waters within nearshore and inland environments. In this study, we attempt to quantitatively solve the upwelling radiance transmittance τw,a (i.e., the percentage of in-water photons that escape through the water-air interface) for varying coefficients of scattering and absorption within the range of natural waters. The two important optical phenomena which are ignored in the previous studies have been fully accounted: (i) the particulate contribution to the refractive index (RI) of seawater and (ii) the multiple interactions of the upwelling photons with the water-air interface. As a result, this study leads to a new theoretical formulation of the upwelling radiance transmittance applicable to all natural waters. The effect and variation of the new formulation on the water-leaving radiance and remote sensing reflectance is further studied for coastal and inland waters. Particular attention is also focused on the conversion of sub-surface remote sensing reflectance (rrs) to above-surface remote sensing reflectance (Rrs), which is important for calibration and validation of the remote sensing algorithms. The results show substantial improvement in the ocean color quantities (Lw and Rrs) by up to factor 33% for scattering waters and <5% for absorbing waters.


Aldol sensors for the rapid generation of tunable fluorescence by antibody catalysis.
The synthesis of novel fluorogenic retro-aldol substrates for aldolase antibody 38C2 is described. These substrates are efficiently and specifically processed by antibody aldolases but not by natural cellular enzymes. Together, the fluorogenic substrates and antibody aldolases provide reporter gene systems that are compatible with living cells. The broad scope of the antibody aldolase allows for the processing of a range of substrates that can be designed to allow fluorescence monitoring at a variety of wavelengths. We also have developed the following concept in fluorescent protein tags. beta-Diketones bearing a fluorescent tag are bound covalently by the aldolase antibody and not other proteins. We anticipate that proteins fused with the antibody can be tagged specifically and covalently within living cells with fluorophores of virtually any color, thereby providing an alternative to green fluorescent protein fusions.


Interventions to improve care related to colorectal cancer among racial and ethnic minorities: a systematic review.
To systematically review the literature to identify interventions that improve minority health related to colorectal cancer care. MEDLINE, PsycINFO, CINAHL, and Cochrane databases, from 1950 to 2010. Interventions in US populations eligible for colorectal cancer screening, and composed of ≥50 % racial/ethnic minorities (or that included a specific sub-analysis by race/ethnicity). All included studies were linked to an identifiable healthcare source. The three authors independently reviewed the abstracts of all the articles and a final list was determined by consensus. All papers were independently reviewed and quality scores were calculated and assigned using the Downs and Black checklist. Thirty-three studies were included in our final analysis. Patient education involving phone or in-person contact combined with navigation can lead to modest improvements, on the order of 15 percentage points, in colorectal cancer screening rates in minority populations. Provider-directed multi-modal interventions composed of education sessions and reminders, as well as pure educational interventions were found to be effective in raising colorectal cancer screening rates, also on the order of 10 to 15 percentage points. No relevant interventions focusing on post-screening follow up, treatment adherence and survivorship were identified. This review excluded any intervention studies that were not tied to an identifiable healthcare source. The minority populations in most studies reviewed were predominantly Hispanic and African American, limiting generalizability to other ethnic and minority populations. Tailored patient education combined with patient navigation services, and physician training in communicating with patients of low health literacy, can modestly improve adherence to CRC screening. The onus is now on researchers to continue to evaluate and refine these interventions and begin to expand them to the entire colon cancer care continuum.


Marijuana for Parkinson's Disease?
Marijuana is popular in the United States and is being widely legalized for recreational and medicinal purposes. It remains a Schedule 1 substance without fully proven risks and benefits; yet, it is increasingly available in many US states and territories. Cannabis might have medicinal efficacy in Parkinson's disease as a form of medical marijuana. Endocannabinoid receptors exist throughout the nervous system and are documented to influence receptors affecting a wide variety of areas. Neuroprotective aspects might be induced by cannabis exposure that might yield benefit against the nigrostriatal degeneration of patients with Parkinson's disease. Animal investigations support suggestions of improvement in bradykinesia and/or tremors, but this is unsubstantiated in human studies. However, some patient surveys and anecdotal or case reports indicate that marijuana attenuates some motor manifestations of parkinsonism and also of non-motor, mood and/or cognitive symptoms. Medical marijuana might benefit motor and nonmotor aspects of Parkinson's disease patients. Currently, these assertions are not substantiated in human investigations and cannabis can also induce side effects. Until studies clarify the safety and efficacy of pharmacotherapy with cannabis products, medical marijuana remains largely without scientific endorsement. Research has yet to document the full benefits, risks, and clinical applications of marijuana as a treatment for patients with Parkinson's disease.


Comparative morphology and phylogenetic placement of two microsclerotial black fungi from Sphagnum.
Capnobotryella renispora and Scleroconidioma sphagnicola form black, irregularly shaped microsclerotia that are indistinguishable in gross morphology on leaves of Sphagnum fuscum. In culture, microsclerotia of these fungi were similar, in that mature component cells possessed thick, highly melanized cell walls, poorly defined organelles, large lipid bodies and simple septa. They were different in morphogenesis, in the way their component cells were organized and in disseminative propagules. Microsclerotia of S. sphagnicola formed phialidic conidiogenous cells on their surface, whereas in C. renispora, adjacent cells in mature microsclerotia often separated from each other by septum schizolysis and formed chlamydospores. The identification of C. renispora from Sphagnum is provisional despite a 100% ITS sequence match with data for a culture derived from the type strain. No holoblastic, reniform conidia typical of the species were formed in nature or in culture, and the SSU sequence for a separately preserved culture of the ex-type strain was markedly divergent. Parsimony analyses of nuclear ribosomal DNA sequences showed that these two fungi were related to separate orders of Dothideomycetes. Both SSU and ITS data supported a close relationship for S. sphagnicola to the Dothideales sensu stricto, while the closest ITS match was to Rhizosphaera spp. In the SSU analyses, C. renispora was nested within the Capnodiales.


Acute immunologic pulmonary alveolitis.
Acute immunologic injury of rat lung has been induced by the intrabronchial injection of heterologous antibody and the intravenous injection of radiolabeled antigen. Within 4 h an acute hemorrhagic neutrophil-rich exudate develops in alveolar and interstitial areas and then gradually fades. Lung injury in this model can be quantitated by measurements of increased vascular permeability and extractable hemoglobin. By the use of immunofluorescent techniques, alveolar and interstitial deposits of antigen and antibody have been demonstrated, but not the third component of complement (C3). Although not found in relation to immune complexes, C3 is nevertheless present in damaged lung as measured by accumulation of radiolabeled C3 from the circulation. Ablation experiments indicate the requirement for both circulating neutrophils and C3 for the development of lung injury. These studies provide definition for the development of lung damage induced by immune complexes.


Role of LC-MS/MS in hair testing for the determination of common drugs of abuse and other psychoactive drugs.
Hair testing has been used in toxicological investigations for the last two decades, but only recently a remarkable extension of hair analysis to a variety of application fields was observed, besides drug abuse recognition. The dramatic improvements of LC-MS/MS instrumentation make the detection of tiny amounts of almost whatever drug in hair possible, even after single-dose intake. The progresses observed during the last 5 years in the detection of psychoactive substances in hair are reviewed herein. The literature is partitioned according to the target compounds, namely traditional drugs of abuse, new psychoactive substances and pharmaceutical psychoactive substances. The LC-MS/MS methods presented are addressed to determine a single class of drugs, with the primary aim of accurate quantitation, or to perform multiclass analysis, for rapid and effective screening protocols.


[Thyroid cancer].
The prevalence of nodular lesions of the thyroid gland (thyroid gland), according to various researchers, ranges from 3 to 7%]. The widespread introduction of ultrasound (ultrasound) in clinical practice, as well as the results of autopsy studies, showed that the prevalence of nodular lesions of the thyroid gland is much higher and is about 50%, especially at the age of over 50. In women, thyroid nodes are detected 2-4 times more often than in men. Children suffer from nodular lesions extremely rarely. The incidence of nodular goiter is directly proportional to age. The increase in the incidence of nodular goiter is approximately 0.1% per year at a young age and gradually reaches 2%. The prevalence of thyroid cancer (thyroid cancer) among nodular goiter, according to various authors, is from 1 to 6%. It should be noted that the prevalence in the population of nodular goiter is so high both in the regions of iodine deficiency and with normal iodine supply, but in the first case it is slightly higher. The incidence of thyroid cancer in absolute terms does not depend on the level of iodine supply. Thus, in a situation of a slightly higher incidence of banal nodular colloid goiter in the regions of iodine deficiency, the proportion of cancer among all cases of nodular goiter will be less. It is important to note that these data make it possible to equally use the results of studies on thyroid cancer obtained in regions with different iodine supply.


Time-resolved diffuse optical spectroscopy up to 1700 nm by means of a time-gated InGaAs/InP single-photon avalanche diode.
We present a new compact system for time-domain diffuse optical spectroscopy of highly scattering media operating in the wavelength range from 1100 nm to 1700 nm. So far, this technique has been exploited mostly up to 1100 nm: we extended the spectral range by means of a pulsed supercontinuum light source at a high repetition rate, a prism to spectrally disperse the radiation, and a time-gated InGaAs/InP single-photon avalanche diode working up to 1700 nm. A time-correlated single-photon counting board was used as processing electronics. The system is characterized by linear behavior up to absorption values of about 3.4 cm(-1) where the relative error is 17%. A first measurement performed on lipids is presented: the absorption spectrum shows three major peaks at 1200 nm, 1400 nm, and 1700 nm.