Manually operated low-coherence interferometer for optical information hiding.
A low-coherence interferometer for optical information hiding that ensures security of an optical image by hiding the image behind a light-scattering medium is demonstrated. The interferometer has a distinctive feature in that modulation of the optical-path difference between the object and reference arms is performed with a manual operation. The main advantage of the operation method is the absence of expensive optomechanical parts in the interferometer.


Dissecting the role of milk components on gut microbiota composition.
The composition of human milk is tailored to contribute to the development of the gastrointestinal (GI) tract of newborns and infants. Importantly, human milk contains the antimicrobial compounds lysozyme and lactoferrin that are thought to contribute to the formation of a health-promoting microbiota. As these protective factors are lacking in the milk of dairy animals, we genetically engineered goats expressing human lysozyme in their milk and have recently reported a new animal model to dissect out the role of milk components on gut microbiota formation. Using the pig as a more human-relevant animal model, we demonstrated that consumption of lysozyme-rich milk enriched the abundance of bacteria associated with GI health and decreased those associated with disease, much like human milk. This work demonstrated that the pig is a valid animal model for gut microbiome studies on the effects of dietary components on microbiota composition, host-microbe interactions and state of the intestine.


Effects of 2 weeks hypergravity on the composition of the intervertebral disc.
The effects of loading on connective tissues similar to the intervertebral disk have primarily been studied using articular cartilage organ culture in vitro techniques. The effects of in vivo loading on the intervertebral disk are less well documented. The lumbar annuli of rats centrifuged at 2G for 2 wk were compared with those of similar rats kept under analogous conditions at 1G. The studies involved the water, hydroxyproline (collagen), and uronic acid (proteoglycan, PG) content of the L4-5 and L5-6 annuli. Comparisons were also made between the 2G animals and the previous Cosmos 2044 spaceflight animals at 0G. The water content of annuli did not differ between the control and 2G annuli; however, the PG content of the tissue was decreased in the 2G animals and the collagen content slightly increased, resulting in an increased collagen-PG ratio in the 2G animals. When the annuli were immersed in water for 2 h, more PG leached from the annuli of the 2G animals than the control animals, suggesting an alteration in the nature of the PG population comprising the annuli. Interestingly, the direction of changes in the 2G annuli was identical to that of the previous Cosmos 2044 0G animals when they were compared with their respective controls. Therefore, directly opposite experimental conditions (2G and 0G) produced similar results. Previous studies regarding PG synthesis and content in cartilaginous tissues suggest alterations in intratissue pH and hydration to be among the factors involved in controlling the PG population. If the observed changes are permanent, they may affect the integrity of the intervertebral disk although it is likely they are totally reversible on return to 1G after an interim period, providing injuries are avoided.


Effect of vitamin A and undernutrition on the susceptibility of rodents to a malarial parasite Plasmodium berghei.
The ability of vitamin A deficient rats to resist infection with P. berghei was investigated. When 10 X 10(6) erythrocytes bearing the parasite/100 g body weight were given to the vitamin A protein energy undernourished rats, parasitemia developed in these animals at a faster pace than the controls. A high number (60% to 95%) of red blood cells (RBC) carrying the parasite were noticeable within 6 to 7 days after infection, at which time most animals in this group died. The pair-fed controls (protein-energy undernourished but supplemented with vitamin A) fared perceptibly better with an equivalent load of infection. Control ad libitum fed littermates were able to restrict the infection and neither high parasitemia nor death was noted in this group. Oral supplements of retinyl acetate to vitamin A deficient rats enabled the animals to recover from infection. A subclinical dose of 500 parasitized RBC given at an early stage of the vitamin A deficiency precipitated the deficiency symptoms at a faster rate and led to the development of higher order of parasitemia in these rats beginning from the 10th day after infection as compared to pair fed controls. The yield of glass adhering cells obtainable from peritoneal exudates was low in deficient rats. In vitro experiments further suggest a decrease in the capacity of the glass adhering peritoneal exudate cells in vitamin A deficient mice to clear the infection. This capacity was improved by addition of non glass adhering cells from sensitized control mice.


Downregulation of RBMS3 is associated with poor prognosis in esophageal squamous cell carcinoma.
Deletions on chromosome 3p occur often in many solid tumors, including esophageal squamous cell carcinoma (ESCC), suggesting the existence at this location of one or more tumor suppressor genes (TSG). In this study, we characterized RBMS3 gene encoding an RNA-binding protein as a candidate TSG located at 3p24. Downregulation of RBMS3 mRNA and protein levels was documented in approximately 50% of the primary ESCCs examined. Clinical association studies determined that RBMS3 downregulation was associated with poor clinical outcomes. RBMS3 expression effectively suppressed the tumorigenicity of ESCC cells in vitro and in vivo, including by inhibition of cell growth rate, foci formation, soft agar colony formation, and tumor formation in nude mice. Molecular analyses revealed that RBMS3 downregulated c-Myc and CDK4, leading to subsequent inhibition of Rb phosphorylation. Together, our findings suggest a tumor suppression function for the human RBMS3 gene in ESCC, acting through c-Myc downregulation, with genetic loss of this gene in ESCC contributing to poor outcomes in this deadly disease.


Postnatal Development of the Spheno-occipital Synchondrosis: A Histological Analysis.
The spheno-occipital synchondrosis (SOS) in cranial base is an important growth center for the craniofacial skeleton, and also is a guide rail for development of the maxilla, midface, and mandible. Previous studies showed that SOS may be a treatment target for youngsters with midfacial hypoplasia and small cranial vault secondary to craniosynostosis. However, most of studies about the SOS are based on imaging data. In this study, we try to explore the characteristics of postnatal development of the mouse SOS based on histological analysis. Our findings showed that the width of the SOS in mice were gradually decreased from newborn mice to adult mice, and the SOS cartilage was gradually became small, then almost completely ossificated in adult mice. The resting and proliferative layers in SOS cartilage were gradually decreased, and almost only hypertrophic chondrocytes while no resting and proliferative layer chondrocytes in adult mice. The proliferative ability of SOS chondrocytes also gradually decreased. These findings will be of benefit for the further clinical treatment for patients with midfacial hypoplasia or small cranial vault secondary to craniosynostosis. Further evidence-based research about the clinical implication is necessary in future.


Time for You: A process evaluation of the rapid implementation of a multi-level mental health support intervention for frontline workers during the COVID-19 pandemic.
The coronavirus (COVID-19) pandemic had wide-ranging negative impacts on mental health. The pandemic also placed extraordinary strain on frontline workers who were required to continue working and putting themselves at risk to provide essential services at a time when their normal support mechanisms may not have been available. This paper presents an evaluation of the Time for You service, a rapidly developed and implemented intervention aimed at providing frontline workers with quick access to flexible online mental health support. Time for You provided service users with three service options: self-guided online cognitive behavioural therapy (CBT) resources; guided engagement with online CBT resources; 1-1 psychological therapy with trainee sport and exercise psychologists and trainee health psychologists. A process evaluation informed by the Consolidated Framework for Implementation Research considered service fidelity, adaptations, perceived impact, reach, barriers, and facilitators. Interviews with project managers (n = 5), delivery staff (n = 10), and service users (n = 14) explored perceptions of the service implementation and outcomes, supported by data regarding engagement with the online CBT platform (n = 217). Findings indicated that service users valued the flexibility of the service and the speed with which they were able to access support. The support offered by Trainee Psychologists was perceived to be of high quality, and the service was perceived by service users to have improved mental health and wellbeing. The rapid implementation contributed to issues regarding appropriate service user screening that led to trainee psychologists being unable to provide the service users with the support they needed as the presenting issues were outside of trainees' competencies. Overall, the findings suggest that interventions offering flexible, online psychological support to frontline workers can be an effective model for future interventions. Trainee psychologists are also able to play an important role in delivering such services when clear screening processes are in place.


Nicotinamide for the treatment of heart failure with preserved ejection fraction.
Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent and intractable form of cardiac decompensation commonly associated with diastolic dysfunction. Here, we show that diastolic dysfunction in patients with HFpEF is associated with a cardiac deficit in nicotinamide adenine dinucleotide (NAD+). Elevating NAD+ by oral supplementation of its precursor, nicotinamide, improved diastolic dysfunction induced by aging (in 2-year-old C57BL/6J mice), hypertension (in Dahl salt-sensitive rats), or cardiometabolic syndrome (in ZSF1 obese rats). This effect was mediated partly through alleviated systemic comorbidities and enhanced myocardial bioenergetics. Simultaneously, nicotinamide directly improved cardiomyocyte passive stiffness and calcium-dependent active relaxation through increased deacetylation of titin and the sarcoplasmic reticulum calcium adenosine triphosphatase 2a, respectively. In a long-term human cohort study, high dietary intake of naturally occurring NAD+ precursors was associated with lower blood pressure and reduced risk of cardiac mortality. Collectively, these results suggest NAD+ precursors, and especially nicotinamide, as potential therapeutic agents to treat diastolic dysfunction and HFpEF in humans.


Novel robust biomarkers for human bladder cancer based on activation of intracellular signaling pathways.
We recently proposed a new bioinformatic algorithm called OncoFinder for quantifying the activation of intracellular signaling pathways. It was proved advantageous for minimizing errors of high-throughput gene expression analyses and showed strong potential for identifying new biomarkers. Here, for the first time, we applied OncoFinder for normal and cancerous tissues of the human bladder to identify biomarkers of bladder cancer. Using Illumina HT12v4 microarrays, we profiled gene expression in 17 cancer and seven non-cancerous bladder tissue samples. These experiments were done in two independent laboratories located in Russia and Canada. We calculated pathway activation strength values for the investigated transcriptomes and identified signaling pathways that were regulated differently in bladder cancer (BC) tissues compared with normal controls. We found, for both experimental datasets, 44 signaling pathways that serve as excellent new biomarkers of BC, supported by high area under the curve (AUC) values. We conclude that the OncoFinder approach is highly efficient in finding new biomarkers for cancer. These markers are mathematical functions involving multiple gene products, which distinguishes them from "traditional" expression biomarkers that only assess concentrations of single genes.


Does the extent of surgery have an impact on the survival of patients who receive postoperative radiation therapy for supratentorial low-grade gliomas?
We evaluate the impact of extent of surgery (EOS) on survival of patients with supratentorial nonpilocytic low-grade gliomas (LGG) treated with postoperative radiation therapy (PORT). Sixty-five patients with pathologically confirmed supratentorial nonpilocytic LGG (36 astrocytomas and 29 oligodendrogliomas) were treated with PORT after different extents of surgery: 12 gross total resections (GTR), 27 minimal or subtotal resections (MR/SR), and 26 biopsies (B). EOS was confirmed with postoperative imaging. The median radiation dose delivered was 5,940 cGy (range, 4,950-6,620 cGy). One of 12 patients (8%) in the GTR group and 12 of 53 patients (23%) in the less than GTR group demonstrated contrast enhancement. The median follow-up was 61 months (range 5-194 month). The 10-year overall survival (OS) was 82.5% and 32% for the GTR and the less than GTR groups, respectively (P = 0.0008). The corresponding 10-year disease-specific survival (DSS) was 90% and 41.4%%, respectively (P = 0.001). Multivariate analysis showed that only contrast enhancement and EOS were predictors for OS and DSS. Our data suggest that EOS correlates with OS and DSS in patients who have PORT. GTR should be the goal if technically achievable without causing significant morbidity, and its combination with PORT is compatible with long-term survival.


Phenotype-genotype correlation in haemoglobin H disease in childhood.
In this study we used restriction endonuclease mapping to characterise the molecular defect responsible for haemoglobin H disease in 14 Sardinian children. The resulting genotypes were then correlated with the respective clinical and haematological phenotypes. We found that patients with the combination of non-deletion alpha(+)-thalassaemia [(alpha alpha)th] and deletion alpha(0)-thalassaemia (-Med) have a more severe phenotype than that resulting from the interaction of deletion alpha(0)-thalassaemia (-Med) and alpha(+)-thalassaemia (-alpha) determinants. Clinically, presentation was earlier and with moderate anaemia or haemolytic crisis, enlargement of the liver and spleen, and thalassaemic bone changes. Haematologically, the anaemia was more severe and there were higher bilirubin levels, reticulocyte counts, Hb H levels, and percentage of red blood cells with inclusion bodies. These results suggest that in those Hb H disease patients with the non-deletion [(alpha alpha)th] determinant, two alpha globin genes produce fewer alpha globin chains than a single alpha globin locus.


Utilizing museomics to trace the complex history and species boundaries in an avian-study system of conservation concern.
A taxonomic classification that accurately captures evolutionary history is essential for conservation. Genomics provides powerful tools for delimiting species and understanding their evolutionary relationships. This allows for a more accurate and detailed view on conservation status compared with other, traditionally used, methods. However, from a practical and ethical perspective, gathering sufficient samples for endangered taxa may be difficult. Here, we use museum specimens to trace the evolutionary history and species boundaries in an Asian oriole clade. The endangered silver oriole has long been recognized as a distinct species based on its unique coloration, but a recent study suggested that it might be nested within the maroon oriole-species complex. To evaluate species designation, population connectivity, and the corresponding conservation implications, we assembled a de novo genome and used whole-genome resequencing of historical specimens. Our results show that the silver orioles form a monophyletic lineage within the maroon oriole complex and that maroon and silver forms continued to interbreed after initial divergence, but do not show signs of recent gene flow. Using a genome scan, we identified genes that may form the basis for color divergence and act as reproductive barriers. Taken together, our results confirm the species status of the silver oriole and highlight that taxonomic revision of the maroon forms is urgently needed. Our study demonstrates how genomics and Natural History Collections (NHC) can be utilized to shed light on the taxonomy and evolutionary history of natural populations and how such insights can directly benefit conservation practitioners when assessing wild populations.


[Cardiovascular prevention: current progress and the long road to travel].
This article describes the limitations of the currently available screening modalities used for determining cardiovascular risk in the general population. In addition, it contains an analysis of the potential ways in which the predictive and classificatory abilities of the cardiovascular risk charts used in primary care can be improved to enable them to function more effectively. Also included are discussions of existing opportunities for improving current strategies for screening and cardiovascular prevention, of the value of measuring new biomarkers in individual patients, including genetic predisposition to coronary heart disease, and of some of the clinical measures used in practice, such as the ankle-brachial index and the carotid intima-media thickness. In addition, the most important subgroups of individuals at a high cardiovascular risk, as judged by their size and the number of cardiovascular events experienced at 10 years, are described. Finally, there is a brief review of the potential role that image modalities currently being developed could play in particular subgroups of asymptomatic individuals with an elevated disease risk.


An iterative type I polyketide synthase initiates the biosynthesis of the antimycoplasma agent micacocidin.
Micacocidin is a thiazoline-containing natural product from the bacterium Ralstonia solanacearum that shows significant activity against Mycoplasma pneumoniae. The presence of a pentylphenol moiety distinguishes micacocidin from the structurally related siderophore yersiniabactin, and this residue also contributes to the potent antimycoplasma effects. The biosynthesis of the pentylphenol moiety, as deduced from bioinformatic analysis and stable isotope feeding experiments, involves an iterative type I polyketide synthase (iPKS), which generates a linear tetraketide intermediate from acyl carrier protein-tethered hexanoic acid by three consecutive, decarboxylative Claisen condensations with malonyl-coenzyme A. The final conversion into 6-pentylsalicylic acid depends on a ketoreductase domain within the iPKS, as demonstrated by heterologous expression in E. coli and subsequent site-directed mutagenesis experiments. Our results unveil the early steps in micacocidin biosynthesis and illuminate a bacterial enzyme that functionally resembles fungal polyketide synthases.


[Effect of cycloferon on tonsils microflora in often ill children].
To estimate the ability of cycloferon to influence a microbiological landscape of tonsils surface in often ill children (OIC), the microflora of tonsils before and after a standard course of this preparation in a group of 68 preschool children classified into OIC category. It is established that the microbe landscape of tonsils surface after a course of cycloferon therapy is characterized by reduction of microflora variety, decrease in bacteria titer (including S. aureus), and reduction ion then number of strains resistant to benzylpenicillin, clindamycin, and vancomycin. Thus, it is possible to recommend cycloferon for rehabilitation of OIC.


Lysozyme-catalysed hydrolysis of some beta-aryl di-N-acetylchitobiosides.
1. Four beta-aryl di-N-acetylchitobiosides and beta-S-phenyl di-N-acetylthiochitobioside have been prepared and shown to be substrates for hen's-egg-white lysozyme. 2. The lysozyme-catalysed hydrolysis of these substrates obeys Michaelis-Menten kinetics. 3. The Michaelis constants, K(m), for the beta-aryl di-N-acetyl-chitobiosides are almost independent of the aglycone, whereas the catalytic constants, k(cat.), show a marked dependence, giving a Hammett reaction constant, rho, equal to 1.2; this suggests the rate-determining step involves concerted acid-base or acid-nucleophilic catalysis. 4. This conclusion is supported by the Michaelis-Menten constants found for beta-S-phenyl di-N-acetylthiochitobioside. 5. A three-step reaction pathway is proposed, and mechanisms are suggested that would account for the evidence currently available.


Risk Factors, Diagnosis, Management, and Outcome of Splanchnic Vein Thrombosis: A Retrospective Analysis.
This study aims to determine the risk factors, diagnostic methods employed, treatment modalities, and outcome in patients with splanchnic vein thrombosis (SVT). A retrospective chart review of patients, age 18 to 90 years, diagnosed with SVT at a single institution from January 1, 2010 to November 10, 2012. They were grouped as portal vein thrombosis (PVT)-including those combined with splenic vein thrombosis (SPVT) or mesenteric vein thrombosis (MVT)-and Budd-Chiari syndrome (BCS). Overall 246 SVT patients were identified, including 225 PVT and 21 BCS. Risk factors were liver disease, upper abdominal (regional) cancer and surgery, pancreatitis, and hereditary thrombophilia. The most common symptom was abdominal pain and most patients had abnormal liver function. Among those tested, the JAK2 V617F mutation was present in only 20% of the patients with PVT and 14% of the patients with BCS. Most patients were diagnosed by computed tomography. Anticoagulants were given to 30% of the patients with PVT and to 60% of the patients with BCS, with recurrence of SVT in 15% of the patients with PVT and 24% of the patients with BCS, regardless of anticoagulation. As compared with published literature on SVT, we found a higher incidence of regional cancer and surgery and a lower incidence of the JAK2 V617F mutation.


Unsupervised Methods for Detection of Neural States: Case Study of Hippocampal-Amygdala Interactions.
The hippocampus and amygdala are functionally coupled brain regions that play a crucial role in processes involving memory and learning. Because interareal communication has been reported both during specific sleep stages and in awake, behaving animals, these brain regions can serve as an archetype to establish that measuring functional interactions is important for comprehending neural systems. To this end, we analyze here a public dataset of local field potentials (LFPs) recorded in rats simultaneously from the hippocampus and amygdala during different behaviors. Employing a specific, time-lagged embedding technique, named topological causality (TC), we infer directed interactions between the LFP band powers of the two regions across six frequency bands in a time-resolved manner. The combined power and interaction signals are processed with our own unsupervised tools developed originally for the analysis of molecular dynamics simulations to effectively visualize and identify putative, neural states that are visited by the animals repeatedly. Our proposed methodology minimizes impositions onto the data, such as isolating specific epochs, or averaging across externally annotated behavioral stages, and succeeds in separating internal states by external labels such as sleep or stimulus events. We show that this works better for two of the three rats we analyzed, and highlight the need to acknowledge individuality in analyses of this type. Importantly, we demonstrate that the quantification of functional interactions is a significant factor in discriminating these external labels, and we suggest our methodology as a general tool for large, multisite recordings.


Tracing our roots: a new era in clinical laboratory science education.
To describe the emergence of laboratory personnel at the technician and assistant levels and discuss educational issues that arose between 1962 and 1977. A survey of literature on the history of clinical laboratory science (CLS) was conducted. References consulted include various books and professional journals. Advances in scientific and medical knowledge and the development of new technologies created new roles and responsibilities for medical technologists (MTs) in the areas of education, research, and laboratory management. At the same time, the certified laboratory assistant (CLA) category was established as a means of providing competent personnel to work in physician office laboratories and small community hospitals in lieu of a certified MT. The growth in popularity of two-year colleges and the availability of federal funding for the development of allied health programs led to the establishment of yet another category of laboratory personnel: the medical laboratory technician (MLT). These developments prompted educators to modify their CLS curricula, develop educational programs at the CLA and MLT levels, and provide opportunities to CLAs, and MLTs for upward mobility. Furthermore, once the Board of Registry (BOR) established the baccalaureate degree as the prerequisite for MT certification, educators also began to restructure and more closely integrate the academic and clinical components of MT programs.


Bisexual behavior among Chinese young migrant men who have sex with men: implications for HIV prevention and intervention.
Data from 307 young migrant men who have sex with men (MSM) in Beijing were analyzed to examine bisexual behavior and the associated sociodemographic and behavioral factors among Chinese young migrant MSM. More than one-fourth (27%) of the MSM were also concurrently engaged in sexual behavior with women (MSMW). Among MSMW, 8.4% were infected with HIV, and 10.8% with Syphilis, compared to 4.9% and 23.7%, respectively, among men who have sex with men only (MSM-only). Various HIV-related risk behaviors among MSMW were similar to those of MSM-only, such as unprotected anal sex, multiple sexual partners, involvement in commercial sex, and substance use. Compared with MSM-only, MSMW were less likely to have tested for HIV, to participate in HIV prevention activities, and were less knowledgeable about condom use and HIV/AIDS. MSMW also had a higher rate of unprotected sex with female stable sexual partners than with male stable sexual partners (79.5% vs. 59.5%). Results indicated that MSMW were at a very high risk for both HIV infection and transmission. Intervention efforts are needed to target this subgroup of MSM and promote AIDS knowledge and HIV/STD testing among MSMW, and to reduce HIV transmission through MSM's bisexual behavior.


Ionosphere of venus: first observations of the dayside ion composition near dawn and dusk.
The first in situ measurements of the composition of the ionosphere of Venus are provided by independent Bennett radio-frequency ion mass spectrometers on the Pioneer Venus bits and orbiter spacecraft, exploring the dawn and duskside regions, respectively. An extensive composition of ion species, rich in oxygen, nitrogen, and carbon chemistry is idenitified. The dominant topside ion is O(+), with C(+), N(+), H(+), and He(+) as prominent secondary ions. In the lower ionosphere, the ionzization peak or F(1) layer near 150 kilometers reaches a concentration of about 5 x l0(3) ions per cubic centimeter, and is composed of the dominant molecular ion, O(2)(+), with NO(+), CO(+), and CO(2)(+), constituting less than 10 percent of the total. Below the O(+) peak near 200 kilometers, the ions exhibit scale heights consistent with a neutral gas temperature of about 180 K near the terminator. In the upper ionosphere, scale heights of all species reflect the effects of plasma transport, which lifts the composition upward to the often abrupt ionopause, or thermal ion boundary, which is observed to vary in height between 250 to 1800 kilometers, in response to solar wind dynamics.


Severe parainfluenza pneumonia in a case of transient hypogammalobulinemia of infancy.
Human parainfluenza viruses (HPIVs) infection, largely known to cause self-limiting bronchiolitis and pneumonia in immune competent patients, can lead to severe to fatal pulmonary disease in immune disorders, such as primary or acquired-immune deficiencies. We report the case of a 1-year-old child who developed an acute respiratory distress syndrome. Because of a progressive respiratory failure unresponsive to conventional treatment extracorporeal membrane oxygenation (ECMO) was rapidly started. HPIV-3 infection was diagnosed on the rhinopharyngeal fluid and immunological examinations revealed a hypogammaglobulinemia. A combination therapy with ribavirin, intravenous immunoglobulin (IVIG) and steroid under ECMO support was started with considerable improvement. Subsequent analysis and more specific immunological assessment resulted normal confirming the diagnosis of transient hypogammaglobulinemia of infancy (THI). This case highlights the importance of prompt therapy with early ECMO support in combination with ribavirin, IVIG and steroids in patients affected by severe HPIV-3 pneumonia and THI.


Selection of yeast strains in naturally fermented cured meat as promising starter cultures for fermented cured beef, a traditional fermented meat product of northern China.
Fermented meat products are meat products with a unique flavor, color, and texture as well as an extended shelf life under natural or artificially controlled conditions. Microorganisms or enzymes are used to ferment the raw meat so that it undergoes a series of biochemical and physical changes. Common fermentation strains are lactic acid bacteria, yeasts, staphylococci, molds, and so forth. Studies on the inhibitory effect of yeast fermentation strain on N-nitrosamines in fermented meat products have not been reported. Two excellent yeast starters were identified to solve the problem of nitrosamines in fermented meat products. Meyerozyma guilliermondii and Debaryomyces hansenii led to weak acid production, strong resistance to NaCl and NaNO2 , and high tolerance to low acidic conditions. The inoculated fermented beef exhibited decreased lightness, moisture content, water activity, pH, protein content, nitrite content, and N-nitrosamine content in comparison with the control group fermented bacon. M. guilliermondii had a better effect, reducing pH from 5.69 to 5.41, protein content from 254.24 to 221.92 g·kg-1 , nitrite content from 28.61 to 25.33 mg·kg-1 and N-nitrosamine by 18.97%, and giving the fermented beef the desired meat color, mouthfeel, odor, taste, and tissue quality. In this study, two strains of yeast fermenters that can degrade N-nitrosamine precursors were identified, which to some extent solves the problem of the high risk of generating nitrosamines such as N-nitrosodiethylamine (NDEA) by processing fermented meat products with nitrites as precursors. These two strains are likely to be used as starter cultures for fermented meat products. © 2023 Society of Chemical Industry.


Chimeric coxsackie B3 virus genomes that express hybrid coxsackievirus-poliovirus 2B proteins: functional dissection of structural domains involved in RNA replication.
The 2B proteins of coxsackievirus and poliovirus (PV) share significant structural similarity and exhibit similar biochemical activities, namely inhibition of protein secretion and modification of membrane permeability. Both proteins contain two hydrophobic domains in the carboxy-terminal two-thirds of their sequence, of which one has the potential to form a cationic amphipathic alpha-helix. To gain more insight into the structural requirements of enterovirus protein 2B for its functioning in viral RNA replication, a chimeric cDNA approach was used. Chimeric coxsackie B3 virus (CBV3) genomes were constructed that expressed either the entire PV 2B protein or hybrid proteins in which specific segments of CBV3 2B were substituted by their corresponding PV counterparts. In vitro synthesis and processing of the chimeric polyproteins showed no abnormalities. CBV3 genomes carrying the entire PV 2B gene failed to replicate. A chimeric genome that expressed a hybrid 2B protein consisting of the amino-terminal one-third of PV and the remainder of CBV3 yielded viable viruses. In contrast, a 2B protein consisting of the amino-terminal one-third of CBV3 and the remainder of PV failed to drive replication. These data imply that a sequence-specific interaction with another viral protein is required to drive RNA replication and suggest that the proposed sites of contact reside in the carboxy-terminal two-thirds of 2B. Hybrid genomes in which either the amphipathic alpha-helix or the other hydrophobic domain was replaced failed to replicate. The potential contribution of these domains to the structure and functioning of protein 2B are discussed.


[Role of R-(-)-deprenyl in adhesion of neuronal and non-neuronal cells].
Role of R-(-)-deprenyl in adhesion of neuronal and non-neuronal cells. The beneficial effect of the anti-parkinsonian monoamine oxidase-B inhibitor, R-(-)-deprenyl has been shown in a number of different diseases, such as Parkinson's and Alzheimer's disease, atherosclerosis or tumor formation. The role of the cytoskeleton, the main component of cell adhesion, has been suggested in the development of these diseases. Nevertheless, the effect of the drug on cell adhesion has never been examined. In the present study, the authors studied the effect of R-(-)-deprenyl on cell-cell adhesion of neuronal (PC12, rat phaeochromocytoma) and non-neuronal (NIH3T3, NIH3T3/EGFR, NIH3T3/EGFR-e3B1 mouse embryo fibroblasts, and 5180 mouse sarcoma) cells using cell association assay. R-(-)-deprenyl treatment resulted in a cell type- and concentration-dependent increase in cell-cell adhesion of PC12 cells, which contain no monoamine oxidase-B, and we observed the same effect in NIH3T3 cells at concentrations lower than those needed for monoamine oxidase-B inhibition. Interestingly, R-(-)-deprenyl increased cell-cell adhesion of tumor cell lines as well. The effect of R-(-)-deprenyl was not reversible during a 24-hour recovery period. At the same time, the monoamine oxidase-B inactive isomer of the drug, S-(+)-deprenyl had no effect on cell-cell adhesion in PC12 and NIH3T3 cells. In this study, the authors described a new, monoamine oxidase-B independent effect of R-(-)-deprenyl on cell-cell adhesion both in neuronal and non neuronal cells. The authors' results with S-(+)-deprenyl suggest that the sterical structure of the drug is an important factor of the observed effect, which is probably a consequence of an irreversible change in the cells.


Human C-reactive protein does not protect against acute lipopolysaccharide challenge in mice.
The physiological and pathophysiological functions of C-reactive protein (CRP), the classical acute-phase protein, are not well established, despite many reports of biological effects of CRP in vitro and in model systems in vivo. Limited, small scale experiments have suggested that rabbit and human CRP may both protect mice against lethal toxicity of Gram-negative bacterial LPS. However, in substantial well-controlled studies in C57BL/6 mice challenged with Escherichia coli O111:B4 LPS, we show in this work that significant protection against lethality was conferred neither by an autologous acute-phase response to sterile inflammatory stimuli given to wild-type mice 24 h before LPS challenge, nor by human CRP, whether passively administered or expressed transgenically. Male mice transgenic for human CRP, which mount a major acute-phase response of human CRP after LPS injection, were also not protected against the lethality of LPS from either E. coli O55:B5 or Salmonella typhimurium. Even when the acute-phase human CRP response was actively stimulated in transgenic mice before LPS challenge, no protection against LPS toxicity was observed. Indeed, male mice transgenic for human CRP that were pretreated with casein to stimulate an acute-phase response 24 h before LPS challenge suffered significantly greater mortality than unstimulated human CRP transgenic controls. Rather than being protective in this situation, human CRP may thus have pathogenic proinflammatory effects in vivo.


Use of Oral Contraceptives to Manipulate Menstruation in Young, Physically Active Women.
Menstruation and menstrual symptoms are commonly cited barriers to physical activity in women. The delay or avoidance of menstruation through extended oral-contraceptive (OC) regimens may mitigate these barriers, yet information on menstrual-manipulation practices in young physically active women is sparse. The objective of this study was to investigate prevalence of, and reasons for, menstrual manipulation with OCs in recreationally and competitively active women. One hundred ninety-one recreationally active (self-reported moderate to vigorous physical activity 150-300 min/wk) women (age 23 ± 5 y), 160 subelite recreationally active (self-reported moderate to vigorous physical activity >300 min/wk) women (age 23 ± 5 y), and 108 competitive (state-, national- or international-level) female athletes (age 23 ± 4 y) completed a self-administered questionnaire assessing OC-regimen habits and reasons for manipulation of menstruation. The majority (74%) of OC users reported having deliberately manipulated menstruation at least once during the previous year, with 29% reporting having done so at least 4 times. Prevalence of menstrual manipulation (at least once in the previous year) was not different between competitive athletes, subelite recreationally active women, and recreationally active women (77% vs 74% vs 72%; P > .05). The most cited reasons for manipulating menstruation were special events or holidays (rated by 75% as important/very important), convenience (54%), and sport competition (54%). Menstrual manipulation through extended OC regimens is common practice in recreationally and competitively active young women, for a range of reasons relating to convenience that are not limited to physical activity. This strategy may help reduce hormone-related barriers to exercise participation, thereby positively affecting participation and performance.


Health literacy of hospital patients using a linguistically validated Croatian version of the Newest Vital Sign screening test (NVS-HR).
The Newest Vital Sign (NVS) is a simple, quick and accurate screening test for health literacy (HL). It has been validated for different languages but, to date, not for the Croatian language. The aim of this study was to develop a linguistically validated Croatian version of the NVS and to use it at a later stage in a pilot study of health literacy assessment of hospital patients in Croatia. A full linguistic validation procedure was applied, including forward and backward translation, expert panel review, cognitive interview with 10 respondents from general population, and full involvement in the procedure of one of the screening test developers, the lead author of the NVS-UK version. HL testing on 100 hospital patients (55% women, median age 63.5 years) revealed 58% of patients had less than adequate HL level (scores less than 4), and mean NVS total score was 3.34. A positive significant association was observed between HL and educational level (p = 0.002). A high percentage of patients (92%) did not object to being tested for HL by their primary care physician or in hospital, and 99% of patients would recommend HL testing among patients in general. The respondents' positive views on HL testing and mean completion time of 4 minutes indicate that the Croatian version of the NVS (NVS-HR) could be recommended for use in both clinical and research settings in Croatia.


[The Tobacco-Free Generation].
In the Netherlands, every day some 100 adolescents become addicted to cigarettes. These new smokers fill the gap left by the 25% of smokers who die before reaching retirement age. The State Secretary for Health, Welfare and Sport in the Netherlands, the Royal Dutch Medical Association (KNMG), and the Dutch Cancer Society, Lung Foundation and Heart Foundation all support the concept of a tobacco-free generation. The concept is that, by applying public health interventions and restriction of tobacco accessibility through price hikes, in the near future none of the children in the Netherlands born in 2017 and beyond will take up smoking. This appealing plan can be phased in gradually, reaching full implementation by 2035. That gives politicians time to take evidence-based measures. The roadmap for this 'tobacco endgame' starts today with tobacco-free conception and pregnancy, and will follow the life of a child from then on. In this comment, I discuss the concept of a tobacco-free generation and focus on the responsibility of the government to take effective measures.


The fragile X continuum: new advances and perspectives.
Fragile X syndrome is the world's most common hereditary cause of intellectual disability in men and to a lesser extent in women. The disorder is caused by the silencing of a single gene on the X chromosome, the Fragile X Mental Retardation Gene-1. A substantial body of research across the disciplines of molecular genetics, child psychiatry and developmental neuroscience bears testament to a decade of exciting and innovative science that has advanced our knowledge about the fragile X 'signature' or influence across cognitive and social development. The core aims of this review are to first discuss fragile X syndrome and premutation involvement in the context of current advances that demonstrate the dynamic nature of the genotype on phenotypic outcomes. Second, to discuss the implications of these recent advances for the development of clinical and educational interventions and resource tools that target specific phenotypic 'signatures' within the fragile X continuum.


When left means right: an explanation of the left cradling bias in terms of right hemisphere specializations.
Previous research has indicated that 70-85% of women and girls show a bias to hold infants, or dolls, to the left side of their body. This bias is not matched in males (e.g. deChateau, Holmberg & Winberg, 1978; Todd, 1995). This study tests an explanation of cradling preferences in terms of hemispheric specialization for the perception of facial emotional expression. Thirty-two right-handed participants were given a behavioural test of lateralization and a cradling task. Females, but not males, who cradled a doll on the left side were found to have significantly higher laterality quotients than right cradlers. Results indicate that women cradle on the side of the body that is contralateral to the hemisphere dominant for face and emotion processing and suggest a possible explanation of gender differences in the incidence of cradling.


Soft color segmentation and its applications.
We propose an automatic approach to soft color segmentation, which produces soft color segments with appropriate amount of overlapping and transparency essential to synthesizing natural images for a wide range of image-based applications. While many state-of-the-art and complex techniques are excellent at partitioning an input image to facilitate deriving a semantic description of the scene, to achieve seamless image synthesis, we advocate to a segmentation approach designed to maintain spatial and color coherence among soft segments while preserving discontinuities, by assigning to each pixel a set of soft labels corresponding to their respective color distributions. We optimize a global objective function which simultaneously exploits the reliability given by global color statistics and flexibility of local image compositing, leading to an image model where the global color statistics of an image is represented by a Gaussian Mixture Model (GMM), while the color of a pixel is explained by a local color mixture model where the weights are defined by the soft labels to the elements of the converged GMM. Transparency is naturally introduced in our probabilistic framework which infers an optimal mixture of colors at an image pixel. To adequately consider global and local information in the same framework, an alternating optimization scheme is proposed to iteratively solve for the global and local model parameters. Our method is fully automatic, and is shown to converge to a good optimal solution. We perform extensive evaluation and comparison, and demonstrate that our method achieves good image synthesis results for image-based applications such as image matting, color transfer, image deblurring, and image colorization.


Cervical laminoplasty versus laminectomy and fusion: An umbrella review of postoperative outcomes.
While multiple studies exist comparing cervical laminoplasty (CLP) and posterior cervical laminectomy with fusion (PCF), no clear consensus exists on which intervention is better. An umbrella review helps provide an overall assessment by analyzing a given condition's multiple interventions and outcomes. It integrates all available information on a topic and allows a consensus to be reached on the intervention of choice. A literature search was conducted using specific search criteria in PubMed, Scopus, and Web of Science databases. Titles and abstracts were screened based on inclusion criteria. A full-text review of articles that passed the initial inclusion criteria was performed. Nine meta-analyses were deemed eligible for the umbrella review. Data was extracted on reported variables from these meta-analyses. Subsequent quality assessment using AMSTAR2 and data analysis using the R package metaumbrella were used to determine the significance of postoperative outcomes. When the meta-analyses were pooled, statistically significant differences between CLP and PCF were found for postoperative overall complications rate and postoperative JOA score. PCF was associated with a lower overall complication rate and a higher postoperative JOA score, both supported by a weak level of evidence (class IV). Data regarding all other outcomes were non-significant. Our umbrella review investigates CLP and PCF by providing a comprehensive overview of existing evidence and evaluating inconsistencies within the literature. This umbrella review revealed that PCF had better outcomes for overall complications rate and postoperative JOA than CLP, but they were classified as being of weak significance.


Identifying learning disabilities through a cognitive deficit framework: can verbal memory deficits explain similarities between learning disabled and low achieving students?
Traditionally, students with learning disabilities (LD) have been identified using an aptitude-achievement discrepancy or response to intervention approach. As profiles of the cognitive deficits of discrepancy-defined students with LD have already been developed using these approaches, these deficits can in turn be used to identify LD using the discrepancy approach as a benchmark for convergent validity. Australian Grade 3 (N = 172) students were administered cognitive processing tests to ascertain whether scores in these tests could accurately allocate students into discrepancy-defined groups using discriminant function analysis. Results showed that 77% to 82% of students could be correctly allocated into LD, low achievement, and regular achievement groups using only measures of phonological processing, rapid naming, and verbal memory. Furthermore, verbal memory deficits were found, along with phonological processing and rapid naming deficits, in students that would be designated as low achieving by the discrepancy method. Because a significant discrepancy or lack of response to intervention is a result of cognitive deficits rather than the other way around, it is argued that LD should be identified via cognitive deficits.


Ethylene-Induced Hydrogen Sulfide Negatively Regulates Ethylene Biosynthesis by Persulfidation of ACO in Tomato Under Osmotic Stress.
A number of recent studies identified hydrogen sulfide (H2S) as an important signal in plant development and adaptation to environmental stress. H2S has been proven to participate in ethylene-induced stomatal closure, but how the signaling pathways of H2S and ethylene interact is still unclear. Here, we reveal how H2S controls the feedback-regulation of ethylene biosynthesis in tomato (Solanum lycopersicum) under osmotic stress. We found that ethylene induced the production of H2S in guard cells. The supply of hypotaurine (HT; a H2S scavenger) or DL-pro-pargylglycine (PAG; a synthetic inhibitor of H2S) removed the effect of ethylene or osmotic stress on stomatal closure. This suggests that ethylene-induced H2S is a downstream component of osmotic stress signaling, which is required for ethylene-induced stomatal closure under osmotic stress. We further found that H2S inhibited ethylene synthesis through inhibiting the activity of 1-aminocyclopropane-1-carboxylic acid (ACC) oxidases (ACOs) by persulfidation. A modified biotin-switch method (MBST) showed that H2S can induce persulfidation of LeACO1 and LeACO2 in a dose-dependent manner, and that persulfidation inhibits the activity of LeACO1 and LeACO2. We also found that LeACO1 is persulfidated at cysteine 60. These data suggested that ethylene-induced H2S negatively regulates ethylene biosynthesis by persulfidation of LeACOs. In addition, H2S was also found to inhibit the expression of LeACO genes. The results provide insight on the general mode of action of H2S and contribute to a better understanding of a plant's response to osmotic stress.


Testosterone trajectories and reference ranges in a large longitudinal sample of male adolescents.
Pubertal dynamics plays an important role in physical and psychological development of children and adolescents. We aim to provide reference ranges of plasma testosterone in a large longitudinal sample. Furthermore, we describe a measure of testosterone trajectories during adolescence that can be used in future investigations of development. We carried out longitudinal measurements of plasma testosterone in 2,216 samples obtained from 513 males (9 to 17 years of age) from the Avon Longitudinal Study of Parents and Children. We used integration of a model fitted to each participant's testosterone trajectory to calculate a measure of average exposure to testosterone over adolescence. We pooled these data with corresponding values reported in the literature to provide a reference range of testosterone levels in males between the ages of 6 and 19 years. The average values of total testosterone in the ALSPAC sample range from 0.82 nmol/L (Standard Deviation [SD]: 0.09) at 9 years of age to 16.5 (SD: 2.65) nmol/L at 17 years of age; these values are congruent with other reports in the literature. The average exposure to testosterone is associated with different features of testosterone trajectories such as Peak Testosterone Change, Age at Peak Testosterone Change, and Testosterone at 17 years of age as well as the timing of the growth spurt during puberty. The average exposure to testosterone is a useful measure for future investigations using testosterone trajectories to examine pubertal dynamics.


Macromolecular metallurgy of binary mesocrystals via designed multiblock terpolymers.
Self-assembling block copolymers provide access to the fabrication of various ordered phases. In particular, the ordered spherical phases can be used to engineer soft mesocrystals with domain size at the 5-100 nm scales. Simple block copolymers, such as diblock copolymers, form a limited number of mesocrystals. However multiblock copolymers are capable to form more complex mesocrystals. We demonstrate that designed B1AB2CB3 multiblock terpolymers, in which the A- and C-blocks form spherical domains and the packing of these spheres can be controlled by changing the lengths of the middle and terminal B-blocks, self-assemble into various binary mesocrystals with space group symmetries of a large number of binary ionic crystals, including NaCl, CsCl, ZnS, α-BN, AlB2, CaF2, TiO2, ReO3, Li3Bi, Nb3Sn(A15), and α-Al2O3. This approach can be generalized to other terpolymers as well as to tetrapolymers to obtain ternary mesocrystals. Our study provides a new concept of macromolecular metallurgy for producing crystal phases in a mesoscale and thus makes multiblock copolymers a robust platform for the engineering of functional materials.


Wings as impellers: honey bees co-opt flight system to induce nest ventilation and disperse pheromones.
Honey bees (Apis mellifera) are remarkable fliers that regularly carry heavy loads of nectar and pollen, supported by a flight system - the wings, thorax and flight muscles - that one might assume is optimized for aerial locomotion. However, honey bees also use this system to perform other crucial tasks that are unrelated to flight. When ventilating the nest, bees grip the surface of the comb or nest entrance and fan their wings to drive airflow through the nest, and a similar wing-fanning behavior is used to disperse volatile pheromones from the Nasonov gland. In order to understand how the physical demands of these impeller-like behaviors differ from those of flight, we quantified the flapping kinematics and compared the frequency, amplitude and stroke plane angle during these non-flight behaviors with values reported for hovering honey bees. We also used a particle-based flow visualization technique to determine the direction and speed of airflow generated by a bee performing Nasonov scenting behavior. We found that ventilatory fanning behavior is kinematically distinct from both flight and scenting behavior. Both impeller-like behaviors drive flow parallel to the surface to which the bees are clinging, at typical speeds of just under 1 m s-1 We observed that the wings of fanning and scenting bees frequently contact the ground during the ventral stroke reversal, which may lead to wing wear. Finally, we observed that bees performing Nasonov scenting behavior sometimes display 'clap-and-fling' motions, in which the wings contact each other during the dorsal stroke reversal and fling apart at the start of the downstroke. We conclude that the wings and flight motor of honey bees comprise a multifunctional system, which may be subject to competing selective pressures because of its frequent use as both a propeller and an impeller.


Coordinate redeployment of PRC1 proteins suppresses tumor formation during Drosophila development.
Polycomb group proteins form two main complexes, PRC2 and PRC1, which generally coregulate their target genes. Here we show that PRC1 components act as neoplastic tumor suppressors independently of PRC2 function. By mapping the distribution of PRC1 components and trimethylation of histone H3 at Lys27 (H3K27me3) across the genome, we identify a large set of genes that acquire PRC1 in the absence of H3K27me3 in Drosophila larval tissues. These genes massively outnumber canonical targets and are mainly involved in the regulation of cell proliferation, signaling and polarity. Alterations in PRC1 components specifically deregulate this set of genes, whereas canonical targets are derepressed in both PRC1 and PRC2 mutants. In human embryonic stem cells, PRC1 components colocalize with H3K27me3 as in Drosophila embryos, whereas in differentiated cell types they are selectively recruited to a large set of proliferation and signaling-associated genes that lack H3K27me3, suggesting that the redeployment of PRC1 components during development is evolutionarily conserved.


Derlin-dependent accumulation of integral membrane proteins at cell surfaces.
Quality-control mechanisms of protein folding of transmembrane and secreted proteins is mediated by endoplasmic-reticulum-associated degradation (ERAD), which is used to detect and to degrade misfolded proteins in the ER. The ERAD machinery consists of chaperones, transmembrane proteins and ubiquitin-associated enzymes that detect, modify, and retro-translocate the misfolded proteins to the cytoplasm for degradation by the proteasome. In contrast to ERAD, little is known about the fates of integral membrane and secreted proteins that become misfolded at the plasma membrane or in the extracellular space. Derlin proteins are a family of proteins that are conserved in all eukaryotes, where they function in ERAD. Here, we show that loss of Derlin function in Caenorhabditis elegans and in mouse macrophages results in the accumulation of integral membrane proteins at the plasma membrane. Induction of LDL receptor misfolding at the plasma membrane results in a sharp decrease in its half-life, which can be rescued by proteasomal inhibitors or by reduction of Derlin-1 levels. We also show that Derlin proteins localize to endosomes as well as to the ER. Our data are consistent with a model where Derlin proteins function in a spatially segregated quality control pathway that is used for the recognition and degradation of transmembrane proteins that become misfolded at the plasma membrane and/or in endosomes.


A Realist Review of How Community-Based Drug Checking Services Could Be Designed and Implemented to Promote Engagement of People Who Use Drugs.
With rising numbers of drug-related deaths in the UK and globally, exploration of interventions that seek to reduce drug-related harm is essential. Drug checking services (DCS) allow people to submit drug samples for chemical analysis and receive feedback about the sample, as well as harm reduction advice. The use of DCS is often linked to festival and/or nightlife settings and to so-called 'recreational' drug use, but research has also shown the potential of community-based DCS as an intervention serving more varied demographics of people who use drugs, including more marginalised individuals and those experiencing drug dependence. Whilst there is a growing evidence base on the effectiveness of drug checking as a harm reduction intervention, there is still limited evidence of the underlying mechanisms and processes within DCS which may aid implementation and subsequent engagement of people who use drugs. This presents a challenge to understanding why engagement differs across types of DCS, and how best to develop and deliver services across different contexts and for different populations. To explore the contexts and mechanisms which impact engagement in community-based DCS, a realist review was undertaken to synthesise the international evidence for the delivery and implementation of DCS. There were 133 sources included in the review. From these sources the underlying contexts, mechanisms, and outcomes relating to DCS implementation and engagement were developed and refined into seven programme theories. The findings of this review are theoretically novel and hold practical relevance for the design of DCS, with implications for optimisation, tailoring, and implementing services to reach individuals in different settings.


[What kind of information is expected to be provided by medical information services?].
The improvement of health-related information services is one major issue in reforming the German health care system to provide more transparency in health care services for patients and persons covered by the German statutory health insurance system. To meet the general need for specific medical information a telephone-based health information service may give individual advice and provide a helpful selection of information. The study aims at users expectations and preferences with regard to health information services. More particularly, users perception concerning the type of health information and the ways of choosing the information were to be explored. The study included 160 participants of different ages. Prototypical medical advice conversations were presented to the participants consisting of/identifying the consumer's inquiry, followed by the expert's answering sequence. The answers were based on typical inquiries from medical information providers focussing on treatment methods and illnesses. Health information from these conversations with its special contents were ranked by preference judgements resulting in Thurstone scalings. In terms of different health questions, the participants' judgements showed general preference structures for special health information, independent from any personal attitude towards medical information services. Great emphasis was placed on the medical conversation competence of the service provider, which is evident from recognising the specific needs and selection of information of a caller. Overall such health information was preferred that strengthened the patient's and user's autonomy and ability for decision making. Patients and persons covered by German statutory health insurance are characterised as users of information by special preferences. Identifying these preferences permits a reasonable selection of information and individual advice. Therefore, these services provide a major advantage over non-interactive health information services (print media, internet sites).


Aberrant methylation of SPARC in human lung cancers.
SPARC (secreted protein acidic and rich in cysteine) is an extracellular Ca2+-binding matricellular glycoprotein associated with the regulation of cell adhesion and growth. We investigated loss of expression of SPARC gene and promoter methylation in lung cancers and correlated the data with clinicopathological features. We observed loss of SPARC expression in 12 of 20 (60%) lung cancer cell lines. Treatment of expression-negative cell lines with a demethylating agent restored expression in all cases. Methylation frequencies of SPARC gene were 55% in 20 lung cancer cell lines. Primary tumours had methylation at a rate of 69% (119 of 173), while nonmalignant lung tissues (n=60) had very low rates (3%). In lung adenocarcinomas, SPARC methylation correlated with a negative prognosis (P=0.0021; relative risk 4.65, 95% confidence interval 1.75-12.35, multivariate Cox's proportional-hazard model). Immunostaining revealed protein expression in bronchial epithelium (weak intensity) and in juxtatumoral stromal tissues (strong intensity) accompanied by frequent loss in cancer cells that correlated with the presence of methylation (P<0.001). Our findings are of biological interest and potentially of clinical importance in human lung cancers.


Microplate reader assay for measurement of opsonized zymosan-stimulated superoxide anion production by neutrophils.
We report a microplate reader assay for the measurement of superoxide anion (O2-) production from opsonized zymosan-stimulated sheep polymorphonuclear leukocytes (PMNs). This method, for use with the particulate neutrophil activator, is a modification of the cytochrome c reduction system that measures O2- release from adherent neutrophils stimulated with soluble mediators such as phorbol-myristate-acetate (PMA). We measured O2- release from PMNs (250,000 per well) stimulated with opsonized zymosan over a dose range from 0.0625 mg/mL to 0.5 mg/mL. A dose of 0.125 mg/mL was shown to stimulate maximal superoxide production while having little effect on the optical density of the reagent blank. O2- values obtained using this method were not statistically different from values measured using cell-free supernatants. This system was useful in demonstrating PMN priming, as evidenced by the 2.7 times increase in O2- production above baseline from neutrophils isolated from sheep given a 12-hour, low-dose endotoxin infusion. This is a convenient and sensitive method for measurement of neutrophil O2- production in response to a receptor-mediated, particulate stimulus.


Motor patterns in human walking and running.
Despite distinct differences between walking and running, the two types of human locomotion are likely to be controlled by shared pattern-generating networks. However, the differences between their kinematics and kinetics imply that corresponding muscle activations may also be quite different. We examined the differences between walking and running by recording kinematics and electromyographic (EMG) activity in 32 ipsilateral limb and trunk muscles during human locomotion, and compared the effects of speed (3-12 km/h) and gait. We found that the timing of muscle activation was accounted for by five basic temporal activation components during running as we previously found for walking. Each component was loaded on similar sets of leg muscles in both gaits but generally on different sets of upper trunk and shoulder muscles. The major difference between walking and running was that one temporal component, occurring during stance, was shifted to an earlier phase in the step cycle during running. These muscle activation differences between gaits did not simply depend on locomotion speed as shown by recordings during each gait over the same range of speeds (5-9 km/h). The results are consistent with an organization of locomotion motor programs having two parts, one that organizes muscle activation during swing and another during stance and the transition to swing. The timing shift between walking and running reflects therefore the difference in the relative duration of the stance phase in the two gaits.


Investigating the link between regional oxygen metabolism and cognitive speed in multiple sclerosis: Implications for fatigue.
Most multiple sclerosis (MS) patients experience fatigue and cognitive decline but the underlying mechanisms remain unknown. Previous work has shown whole brain resting cerebral metabolic rate of oxygen (CMRO2) is associated with the extent of these symptoms. However, it is not known if the association between global CMRO2 and MS-related cognitive speed and fatigue can be localized to specific brain regions. Based upon previous research suggesting prefrontal involvement in MS-related changes in cognitive speed and fatigue, we hypothesized that oxygen metabolic changes within prefrontal cortex (PFC) might form the pathophysiologic basis of cognitive performance and fatigue in MS patients. Investigate whether PFC ΔCMRO2 is associated with cognitive speed and fatigue in MS. MS and healthy control (HC) participants were scanned using a dual--echo fMRI sequence and underwent a hypercapnia calibration experiment that permitted estimation of ΔCMRO2 while performing a scanner version of symbol-digit modalities task, a measure of information processing speed and utilized in the clinic as a reliable sentinel biomarker for global cognitive impairment in MS. Participants then completed the Modified Fatigue Impact Scale (MFIS) to measure fatigue. MS patients exhibited significant reductions in cognitive performance relative to HCs (p < 0.04). Prefrontal ΔCMRO2 explained significant variability (ΔR2 = 0.11) in cognitive speed, over and above disease and demographic variables, for the MS group only. Prefrontal ΔCMRO2 was not associated with fatigue across groups. ΔCMRO2 in visual and motor areas were not associated with cognitive performance or fatigue for either group. Prefrontal oxygen metabolism may be a sensitive measure of MS-related cognitive decline.


Identification of hydroxyropivacaine glucuronide in equine urine by ESI+/MS/MS.
Ropivacaine is a local anesthetic that has a high potential for abuse in racing horses. It can be recovered from urine collected after administration as a hydroxylated metabolite following beta-glucuronidase treatment of the urine. Based on these findings, it has been inferred that ropivacaine is present in equine urine as a glucuronide metabolite; however, these metabolites have never been directly identified. Using ESI+/MS/MS, the presence of a [M+H]+ molecular ion of m/z 467 was demonstrated in urine corresponding to the calculated mass of a hydroxyropivacaine glucuronide +1. The abundance of this ion diminished after glucuronidase treatment with concomitant appearance of a m/z 291 peak, which is consistent with its hydrolysis to hydroxyropivacaine. In further work, the m/z 467 material was fragmented in the MS/MS system, yielding fragments interpretable as hydroxyropivacaine glucuronide. These data are consistent with the presence of a hydroxyropivacaine glucuronide in equine urine and constitute the first direct demonstration of a specific glucuronide metabolite in equine urine.


Preventing youth violence: what works?
Between 1985 and 1992, serious youth violence in the United States surged to unprecedented levels. The growing use of firearms to settle disputes has contributed to this phenomenon. Youth are most often victimized by one of their peers. In response to this problem, a wide variety of programs have been implemented in an attempt to prevent youth violence or reduce its severity. Few have been adequately evaluated. In general, interventions applied between the prenatal period and age 6 appear to be more effective than interventions initiated in later childhood or adolescence. Community-based programs that target certain high-risk behaviors may be beneficial as well. A sustained commitment to evaluation research is needed to identify the most effective approaches to youth violence prevention.


The impact of working alliance in managing youth anxiety and depression: a scoping review.
A working alliance (WA) is a multidimensional construct signifying a collaborative relationship between a client and a therapist. Systematic reviews of therapies to treat depression and anxiety, almost exclusively in adults, show WA is essential across psychotherapies. However, there are critical gaps in our understanding of the importance of WA in low-intensity therapies for young people with depression and anxiety. Here, we describe an initiative to explore the effect of WA on anxiety and depression outcomes in youth aged 14-24 years through a scoping review and stakeholders' consultations (N = 32). We analysed 27 studies; most were done in high-income countries and evaluated one-on-one in-person therapies (18/27). The review shows that optimal WA is associated with improvements in: relationships, self-esteem, positive coping strategies, optimism, treatment adherence, and emotional regulation. Young people with lived experience expressed that: a favourable therapy environment, regular meetings, collaborative goal setting and confidentiality were vital in forming and maintaining a functional WA. For a clinician, setting boundaries, maintaining confidentiality, excellent communication skills, being non-judgmental, and empathy were considered essential for facilitating a functional WA. Overall, a functional WA was recognised as an active ingredient in psychotherapies targeting anxiety and depression in young people aged 14-24. Although more research is needed to understand WA's influence in managing anxiety and depression in young people, we recommend routine evaluation of WA. Furthermore, there is an urgent need to identify strategies that promote WA in psychotherapies to optimise the treatment of anxiety and depression in young people.


Toxic epidermal necrolysis and Stevens-Johnson syndrome: a review.
The aims of this review are to summarize the definitions, causes, and clinical course as well as the current understanding of the genetic background, mechanism of disease, and therapy of toxic epidermal necrolysis and Stevens-Johnson syndrome. PubMed was searched using the terms toxic epidermal necrolysis, Stevens-Johnson syndrome, drug toxicity, drug interaction, and skin diseases. Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute inflammatory skin reactions. The onset is usually triggered by infections of the upper respiratory tract or by preceding medication, among which nonsteroidal anti-inflammatory agents, antibiotics, and anticonvulsants are the most common triggers. Initially the diseases present with unspecific symptoms, followed by more or less extensive blistering and shedding of the skin. Complete death of the epidermis leads to sloughing similar to that seen in large burns. Toxic epidermal necrolysis is the most severe form of drug-induced skin reaction and includes denudation of >30% of total body surface area. Stevens-Johnson syndrome affects <10%, whereas involvement of 10%-30% of body surface area is called Stevens-Johnson syndrome/toxic epidermal necrolysis overlap. Besides the skin, mucous membranes such as oral, genital, anal, nasal, and conjunctival mucosa are frequently involved in toxic epidermal necrolysis and Stevens-Johnson syndrome. Toxic epidermal necrolysis is associated with a significant mortality of 30%-50% and long-term sequelae. Treatment includes early admission to a burn unit, where treatment with precise fluid, electrolyte, protein, and energy supplementation, moderate mechanical ventilation, and expert wound care can be provided. Specific treatment with immunosuppressive drugs or immunoglobulins did not show an improved outcome in most studies and remains controversial. The mechanism of disease is not completely understood, but immunologic mechanisms, cytotoxic reactions, and delayed hypersensitivity seem to be involved. Profound knowledge of exfoliative skin diseases is needed to improve therapy and outcome of these life-threatening illnesses.


Preservation, origin and genetic imprint of extracellular DNA in permanently anoxic deep-sea sediments.
Molecular approaches that target the total DNA pool recovered from permanently anoxic marine ecosystems have revealed an extraordinary diversity of prokaryotes and unicellular eukaryotes. However, the presence of gene sequences contained within the extracellular DNA pool is still largely neglected. We have investigated the preservation, origin and genetic imprint of extracellular DNA recovered from permanently anoxic deep-sea sediments of the Black Sea. Despite high DNase activities, huge amounts of total extracellular DNA were found in both the surface and subsurface sediment layers, suggesting reduced availability of the extracellular DNA pool to nuclease degradation. The reduced degradation of the total extracellular DNA was confirmed by its low decay rate and the high accumulation in the deeper sediment layers. The copy numbers of 16S and 18S rDNA contained within the extracellular DNA pool in both the surface and subsurface sediment layers was very high, indicating that permanently anoxic sediments of the deep Black Sea are hot spots of preserved extracellular gene sequences. The extracellular DNA recovered from these sediment layers also contained highly diversified 18S rDNA sequences. These were not only representative of the major protistan lineages, but also of new very divergent lineages, branching as independent clades at the base of the tree. Our findings indicate that the extracellular DNA pool is a major archive of present/past eukaryotic gene sequences, and they highlight the importance of integrating molecular cell-oriented approaches with molecular analyses of the extracellular DNA pool, for a better assessment of microbial diversity and temporal changes in marine benthic ecosystems.


Exploring contextual factors and patient activation: evidence from a nationally representative sample of patients with depression.
Patient activation has been considered as a "blockbuster drug of the century." Patients with mental disorders are less activated compared to patients with other chronic diseases. Low activation due to mental disorders can affect the efficiency of treatment of other comorbidities. Contextual factors are significantly associated with mental health care access and utilization. However, evidence of their association with patient activation is still lacking. Using data from the Health Tracking Household Survey 2007 and Area Health Resource File 2008, we examine the association between contextual factors and self-reported activation levels among patients with depression. We investigate two types of contextual factors--(a) site of usual source of care and (b) community characteristics, measured by mental health care resources availability, population demographics, and socioeconomic characteristics at the county level. Results show significant variation in activation levels by contextual factors. The availability of community mental health centers, lower proportion of foreign-born individuals, and higher income in the local community are associated with higher patient activation. Our results also show that depressed patients having a usual source of care at a physician's office have significantly higher patient activation levels than those with a usual source of care in the emergency department or hospital outpatient clinics. Results suggest that primary care setting is critical to having a sustained relationship between patients and physicians in order to enhance patient engagement in mental health care. Interventions in communities with low income and high immigrant populations are necessary.


Forced use as a potential cause of gastrocnemius tears during neurologic rehabilitation: a report of 2 cases.
Broadly defined, forced-use therapy uses specific techniques designed to engage the patient with brain injury in activities that disallow overcompensation with the noninvolved or less involved body segments while forcing the use of the more involved segments. Some applications may involve placing the patient's hemiparetic extremity in a closed-chain weight-bearing activity with therapist support. We describe 2 cases of gastrocnemius muscle tears that occurred during inpatient neurologic rehabilitation that may be attributed to forced use of the hemiplegic lower extremity. Each presented with signs and symptoms indicative of deep vein thrombosis of the calf but was later confirmed with magnetic resonance imaging to be muscle tears. Some closed-chain, forced-use activities may be ill advised in the early stages of rehabilitation or if force generation of the muscle is inadequate to provide a protective response to overstretching. Gastroc-soleus tears should also be considered in the differential diagnosis of unilateral or even bilateral lower-extremity swelling and pain in neurologically impaired patients who are undergoing forced-use therapy.


Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery.
Overweight and obesity represent major risk factors for diabetes and related metabolic diseases. Obesity is associated with a chronic and progressive inflammatory response leading to the development of insulin resistance and type 2 diabetes (T2D) mellitus, although the precise mechanism mediating this inflammatory process remains poorly understood. The most effective intervention for the treatment of obesity, bariatric surgery, leads to glucose normalization and remission of T2D. Recent work in both clinical studies and animal models supports bile acids (BAs) as key mediators of these effects. BAs are involved in lipid and glucose homeostasis primarily via the farnesoid X receptor (FXR) transcription factor. BAs are also involved in regulating genes involved in inflammation, obesity, and lipid metabolism. Here, we review the novel role of BAs in bariatric surgery and the intersection between BAs and immune, obesity, weight loss, and lipid metabolism genes.


Escape from shock versus escape from shock accompanied by a visual stimulus in rats.
Two groups of 15 rats each were trained in a shuttle box to escape foot-shock either unsignalled or presented in compound with a visual cue: darkness. The visual cue presented in shock compartment amplifies the behavioral tendency actually prevailing in the response repertory of the rat. During the 1st session the compound enhanced the species-specific flight resulting in shortening of the rat's escape latency. Thereafter, during subsequent sessions, darkness exaggerated resistance to enter the other compartment; thus escape latencies were longer under compounded than under unsignalled procedure. The darkness cue reduces the intertrial response rate relative to the unsignalled group. This latter finding supports the discrimination model of the effect, since the compound helps the animals to discriminate the illuminated "safe" period between trials from the aversive shock period. Our data seem to suggest that the darkness presented synchronously with escapable grid-shock acquires aversive properties.


Direct calculation of 1-octanol-water partition coefficients from adaptive biasing force molecular dynamics simulations.
The 1-octanol-water partition coefficient log K(ow) of a solute is a key parameter used in the prediction of a wide variety of complex phenomena such as drug availability and bioaccumulation potential of trace contaminants. In this work, adaptive biasing force molecular dynamics simulations are used to determine absolute free energies of hydration, solvation, and 1-octanol-water partition coefficients for n-alkanes from methane to octane. Two approaches are evaluated; the direct transfer of the solute from 1-octanol to water phase, and separate transfers of the solute from the water or 1-octanol phase to vacuum, with both methods yielding statistically indistinguishable results. Calculations performed with the TIP4P and SPC∕E water models and the TraPPE united-atom force field for n-alkanes show that the choice of water model has a negligible effect on predicted free energies of transfer and partition coefficients for n-alkanes. A comparison of calculations using wet and dry octanol phases shows that the predictions for log K(ow) using wet octanol are 0.2-0.4 log units lower than for dry octanol, although this is within the statistical uncertainty of the calculation.


Strategic response to COVID-19 in Ethiopia.
COVID-19, the novel coronavirus, has posed a major threat to low- and middle-income countries (LMICs) due to inadequate health infrastructure and human resources. Ethiopia, a low-income country with the second largest population in Africa, has coordinated a strategic response, leveraging existing infrastructure and health systems and mobilizing public health professionals and specialist expert physicians for a multifaceted, unified government approach and adaptive response. Resource limitations, particularly in critical care, have still posed challenges, but the public health and clinical interventions thus far have prevented the catastrophic toll that many predicted. As the pandemic continues, Ethiopia expects to use a triple care model integrated at all levels, consisting of COVID-19 care, isolation care for suspected cases, and essential health services, and urges intensified non-pharmaceutical interventions alongside equitable global vaccine distribution as the ultimate answers to pandemic control. This paper draws on existing data, national planning and guidelines, and expertise from health leadership to describe this response in hopes of providing an example of how future large-scale health challenges might be faced in LMICs, using Ethiopia's successes and challenges in facing the pandemic.


Nuclear factor-kappaB activation in alveolar macrophages requires IkappaB kinase-beta, but not nuclear factor-kappaB inducing kinase.
Cytokine mediated activation of alveolar macrophages (AMs) is an important event in the pathogenesis of fibrosing alveolitis (FA). Through membrane-associated antigens, cytokines (e.g., tumor necrosis-factor-alpha and interleukin-1) are believed to activate a common kinase cascade that initiates the cytoplasmic degradation of IkappaB and nuclear translocation of "nuclear factor-kappaB" (NF-kappaB). In the nucleus, NF-kappaB promotes the transcription of genes encoding chemokines and cytokines involved in chronic inflammation. Preventing cytokine-mediated NF-kappaB activation is a potential strategy for attenuating the lung injury that occurs in FA. Previously, we have demonstrated that, unlike AMs from healthy volunteers, AMs from patients with inflammatory lung diseases express the coxsackie/adenovirus receptor and the alphav integrins required for adenovirus (Adv) infection. This property allows Adv-mediated transgene delivery to diseased, but not normal, AMs and analysis of molecular pathways involved in gene transcription. In this study, AMs were infected with Adv constructs expressing a defective beta subunit of IkappaB kinase (AdvIKKbetakd) and a defective NF-kappaB inducing kinase (AdvNIKkd) to investigate the contribution of these molecules to NF-kappaB activation. We observed that IKKbeta, but not NIK, was required for NF-kappaB activation. The results of this study identify IKKbeta, but not NIK, as a potential therapeutic target in diseases that involve NF-kappaB-dependent gene transcription.


Improvement in nutrient handling in STZ induced diabetic rats treated with Ocimum gratissimum.
Alteration in digestive and absorptive enzymatic activities has been reported in diabetes mellitus (DM), but not with Ocimum gratissimum (OG) treatment. This study was, therefore, designed to indirectly assess the effect of DM and treatment with OG on nutrient digestion and absorption, through estimation of their fecal excretion. Animals were randomly assigned into three groups of six per group for control, DM and diabetic mellitus treated (DMT). Diabetes was induced by single intraperitoneal injection of 65 mg/kg streptozotocin in the test groups. OG was administered to the DMT group at dose of 1500 mg/kg once daily for 28 days. Fecal glucose, protein and cholesterol were determined. Fecal glucose was significantly (P < 0.001) lower in the DM group compared to the control and DMT groups, with the DMT groups significantly (P < 0.001) lower than the control. Fecal protein was significantly (P < 0.001) lower in the DM group than the control whereas it was significantly lower in the DMT groups than the DM. Fecal cholesterol was significantly (P < 0.001) higher in the DM than the DMT and control groups with DMT significantly (P < 0.01) higher than the control. This result indicates the propensity of OG to reverse impairment of nutrient digestion and absorption in DM.


Further studies on passive transfer of tolerance to pyrogenicity of bacterial endotoxin. The febrile and leucopenic responses.
The effect of various schedules for inducing tolerance to bacterial endotoxin in donor rabbits upon suitability for demonstration of passive transfer of tolerance to pyrogenicity in normal recipients has been investigated. Long-term treatment of donors, through 5 weeks, is no more effective than a brief series of injections, adding further evidence that tolerance is not attributable to specific antibody to the endotoxin. Qualitative differentiation of the febrile pattern of passively tolerant recipients from that seen in control animals depends upon the magnitude of the test dose of pyrogen. Passively tolerant rabbits respond to endotoxin with an acute leucopenia equivalent to that seen in controls suffering a full biphasic fever. Animals given daily injections of endotoxin continue to show the acute leucopenia, despite the early modification of the course of fever characteristic of endotoxin tolerance. The assumption that the leucopenia reflects damage to the leucocytes, with release of endogenous pyrogen, is not consistent with these findings. Rabbits rendered leucopenic by nitrogen mustard and then given endotoxin exhibit a rapidly developing fever of greater than normal intensity, the exaggeration of the febrile response being proportional to the severity of the induced leucopenia. The implications of these findings for the pathogenesis of endotoxin-induced fever are discussed. The evidence supports the hypothesis that endotoxin produces fever by direct action rather than by release of endogenous leucocytic pyrogen. It is postulated that the lesser fever, in animals having normal numbers of circulating leucocytes, reflects a limitation of available endotoxin by the known rapid sequestration in the white blood cells at the time of the acute leucopenia. It is further suggested that the biphasic febrile response of the normal rabbit results from reinoculation of the blood stream by the temporarily sequestered endotoxin, the RES of the tolerant animal clearing the released endotoxin at a rate sufficient to prevent triggering the second phase of fever.


Development of a Model to Predict Portal Vein Thrombosis in Liver Transplant Candidates: The Portal Vein Thrombosis Risk Index.
Portal vein thrombosis (PVT) is associated with inferior pretransplantation and posttransplantation outcomes. We aimed to create a predictive model to risk stratify transplant candidates for PVT. Data on adult transplants in the United States during the Model for End-Stage Liver Disease (MELD) era through September 2016 were reviewed. We constructed and validated a scoring system composed of routine, readily available clinical information to predict the development of incident PVT at 12 months from transplantation listing. A total of 66,568 liver transplant candidates were dichotomized into 2 groups to construct (n = 34,751) and validate (n = 31,817) a scoring system. In general, the derivation and validation cohorts were clinically similar. Although nonalcoholic steatohepatitis was a significant predictor of incident PVT (hazard ratio, 1.29; 95% confidence interval, 1.08-1.54; P < 0.001), age, MELD score, and moderate-to-severe ascites were also associated with increased risk. African American race was associated with decreased risk. A scoring system (PVT risk index [RI]) of these 5 variables had an area under the curve of 0.71 and 0.70 in both derivation and validation cohorts, respectively. By applying the low cutoff score of 2.6, incident PVT could be accurately excluded (negative predictive value 94%). Using the high cutoff score of 4.6 (positive predictive value 85%), PVT could be diagnosed with high accuracy. The PVT-RI predicts which candidates awaiting lifesaving liver transplantation will and will not develop future PVT. Although this scoring system will require prospective validation, it provides a powerful new tool for the clinician when risk stratifying cirrhosis patients prior to liver transplantation for future PVT development.


Palpebral conjunctival transient amplifying cells originate at the mucocutaneous junction and their progeny migrate toward the fornix.
The conjunctival epithelium performs an important role in the homeostasis and integrity of the eye. These cells need to be replaced in order to protect the integrity of the ocular surface. Epithelial cells are replaced from slow cycling stem cells which in turn produce transient amplifying cells that undergo further divisions before becoming mature conjunctival epithelial cells. The natural history of the bulbar palpebral conjunctival cells has not been previously described. A single injection of bromodeoxyuridine (brdU), a thymidine analogue, was administered intraperitoneally to adult rabbits at a concentration of 50 mg/kg body weight. The rabbits were sacrificed at 1, 3, 5, and 7 days following the injections. The orbital contents including the eyelids were exenerated en bloc, frozen in a manner that maintained the orientation and continuity between the eyelids and globe and sectioned in a parasagittal plane. The tissue was stained immunohistochemically to detect brdU labeled conjunctival epithelial cells. The brdU-positive epithelial cells were counted in a series of 0.4 mm zones starting at the mucocutaneous junction of the eyelid and progressing through the fornix and bulbar conjunctiva. Rabbit eyelids and human eyelid surgical specimens were stained for cyclin D1, a marker for cells that are in the G1 phase of the cell cycle. In both the upper and lower eyelids, the peak number of brdU labeled cells/0.4 mm zone was located at progressively greater distances from the mucocutaneous junction in the animals sacrificed at 1, 3 and 5 days respectively, and gone by 7 days. A focus of brdU-labeled conjunctival cells remained within 1-2 mm of the mucocutaneous junction at all post-injection intervals. Foci of cyclin 1-positive cells were found almost exclusively near the mucocutaneous junction, but not in the fornix. The mucocutaneous junction of the conjunctival epithelium is a source of actively dividing transient amplifying cells that migrate toward the fornix at a rate of about 1.7 mm/day as replacement conjunctiva so that at least some conjunctival epithelial stem cells must be located near the mucocutaneous junction. The presence of cyclin D1 staining cells at the mucocutaneous junction supports this view. These results are not necessarily at variance with previous studies, but they do diminish the relative importance assigned the forniceal region in palpabral conjunctival homeostasis. Moreover, the mucocutaneous junction might provide a therapeutically significant source of replacement conjunctival cells. The transit time of conjunctival epithelial cells is about 6 days.


Serum lipids: interactions between age and moderate intensity exercise.
The purpose of this study was to examine relationships between age and selected serum lipids and lipoproteins in women before and after a physical fitness programme. Twenty females 27-59 years of age who had participated in the Purdue University Physical Fitness Programme were selected and placed into one of two groups: "junior" (mean age 34, all under 40 yrs) or "senior" (mean age 50, all over 43). A two way factorial design was used to study differences in serum triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), and the risk ratios TC/HDLC and LDLC/HDLC associated with physical fitness and the eight month physical fitness programme. The ability of the biochemical variables to discriminate between the age groups was investigated using discriminant function analyses. The analyses of variance indicated that although the two age groups were matched on the basis of a multivariate physical fitness score (Ismail et al, 1965) the older group was heavier (p less than 0.05), and had higher systolic and pulse pressures (p less than 0.05). Both groups increased their physical fitness score from pre to post programme (p less than 0.01). No significant age related biochemical differences were noted in the univariate analyses; however, in the discriminant function analyses the biochemical variables significantly discriminated between the two groups before, but not after the programme. A decrease in serum triglycerides was observed in the more highly fit women in each age group. These findings suggest that moderate levels of physical activity may help to counteract some of the undesirable changes in the lipid profile associated with age.


[Congenital trypanosomiasis and leishmaniasis].
Trypanosomas and leishmanias can cross the placenta. Trypanosoma cruzi (American trypanosomiasis or Chagas' disease) may infect the placenta, with or without fetal transmission (congenital trypanosomiasis). Congenital transmission of Chagas' disease is a real problem of public health. Risk of congenital infections is less important for African trypanosomiasis and leishmaniasis. However, physicians should always think of this diagnosis in individual cases, since these diseases may occur in any part of the world, including outside the endemic areas.


Effects of aging on face identification and holistic face processing.
Several studies have shown that face identification accuracy is lower in older than younger adults. This effect of aging might be due to age differences in holistic processing, which is thought to be an important component of human face processing. Currently, however, there is conflicting evidence as to whether holistic face processing is impaired in older adults. The current study therefore re-examined this issue by measuring response accuracy in a 1-of-4 face identification task and the composite face effect (CFE), a common index of holistic processing, in older adults. Consistent with previous reports, we found that face identification accuracy was lower in older adults than in younger adults tested in the same task. We also found a significant CFE in older adults that was similar in magnitude to the CFE measured in younger subjects with the same task. Finally, we found that there was a significant positive correlation between the CFE and face identification accuracy. This last result differs from the results obtained in a previous study that used the same tasks and which found no evidence of an association between the CFE and face identification accuracy in younger adults. Furthermore, the age difference was found with subtraction-, regression-, and ratio-based estimates of the CFE. The current findings are consistent with previous claims that older adults rely more heavily on holistic processing to identify objects in conditions of limited processing resources.


An urban legend: Malignant transformation caused by radiotherapy in patients with presacral ganglioneuroma. The necessity and first-time administration of radiotherapy. Case report and literature review.
Ganglioneuromas (GNs) are well-differentiated, rare benign tumors of neural crest origin and are, for the most part, considered to be the benign equivalent of neuroblastomas. There are very few cases of GN reported to be at presacral location in the literature. The standard form of treatment is the total surgical excision. However, total resection of GN is not always possible depending on the neuron, from which it originates, and its localization. Moreover, adjuvant radiotherapy (RT) or chemotherapy is not recommended even though patients are still symptomatic after subtotal resection. This view is based on the urban legend that it undergoes a malignant transformation although it is a benign tumor. Moreover, there are no data indicating that the GN cases reported in the literature have undergone RT. Therefore, articles about the suspicion that GN may undergo spontaneous or malignant transformation after RT are absolutely controversial. Based on our case, we present here, we believe that we will explain the valid necessity of application of RT that we administered for the first time and that with the clarification of this controversial topic, a significant gap will be closed in the literature.