Clonal dominance and progression in Abelson murine leukemia virus lymphomagenesis.
We examined the clonality of tumors induced by an acutely transforming retrovirus which carries a single oncogene. Contrary to our expectation, tumors induced by the Abelson murine leukemia virus (A-MuLV) showed one to four major proviral integration events. To further investigate the process by which clonality was established, we analyzed the number of cells infected and transformed by A-MuLV at various times after in vivo infection. At the midpoint of tumor latency (14 days postinfection), we found that infection of total bone marrow cells by A-MuLV was efficient and polyclonal. However, only a minority of these infected cells were transformed as assayed in cell culture, and clonal dominance had already been established in this transformed cell population. Examination of the in vitro growth properties of transformed cells recovered from preleukemic and leukemic mice indicated that preleukemic cells had lower cloning efficiencies than primary tumor cells. Our results suggest that the rate-limiting step in this system of lymphomagenesis is the initial transformation of bone marrow target cells and that these cells undergo subsequent changes in cloning ability during the course of the disease that lead to an autonomous neoplastic state.


Features Classification Forest: A Novel Development that is Adaptable to Robust Blind Watermarking Techniques.
A novel watermarking scheme is proposed that could substantially improve current watermarking techniques. This scheme exploits the features of micro images of watermarks to build association rules and embeds the rules into a host image instead of the bit stream of the watermark, which is commonly used in digital watermarking. Next, similar micro images with the same rules are collected or even created from the host image to simulate an extracted watermark. This method, called the features classification forest, can achieve blind extraction and is adaptable to any watermarking scheme using a quantization-based mechanism. Furthermore, a larger size watermark can be accepted without an adverse effect on the imperceptibility of the host image. The experiments demonstrate the successful simulation of watermarks and the application to five different watermarking schemes. One of them is slightly adjusted from a reference to especially resist JPEG compression, and the others show native advantages to resist different image processing attacks.


[Socio-demographic, clinical and criminological features of a population discharged from forensic hospital and admitted to neuropsychiatric clinic, in scheme of restriction of freedom].
Over the past twenty years, in Italy there has been an intense debate that has focused on the function, and overcoming the limits of the institution Judicial Psychiatric Hospital (ospedale psichiatrico giudiziario - OPG). Although the contribution of legislative proposals, conferences and workshops on the OPG subject has received significant, the interest focused on the development and elaboration of criminological and epidemiological research on a national scale has been proportionately less impetum. In this study a survey aimed to explore the socio-demographic, clinical and criminological features of patients discharged from the OPG and admitted to neuropsychiatric clinic, under the restriction of freedom, has been performed. The information was gathered at the time of entry in the clinical management, by means of the first clinical interview and during subsequent interviews. During hospitalization, patients were administered the Mini-Mental State Examination (MMSE) and K Axis (Axis V of Kennedy) questionaires. 23 patients from forensic hospitals of Aversa, Secondigliano and Castiglione delle Stiviere were included in the study. The main characteristics investigated delineate a profile of an individual with an average age of about 49 years, unmarried, from a low socio-economic context, unemployed at the time of internment. About the diagnosis, schizophrenic spectrum disorders prevail, there is history of substance abuse in 35% of cases, history of previous admission to psychiatric facilities in 87% of these subjects. The type of committed crimes regards crimes against the person. About 40% of individuals have exhausted the danger to society correlate at the time of admission. Despite the small sample size, the data from this study are consistent with those reported in few studies in the literature. The specificity of clinical care needs of mentally ill offenders requires greater definition that could be achieved through the development of this research area.


Dissecting the Role of SAL1 in Metabolizing the Stress Signaling Molecule 3'-Phosphoadenosine 5'-Phosphate in Different Cell Compartments.
Plants possess the most highly compartmentalized eukaryotic cells. To coordinate their intracellular functions, plastids and the mitochondria are dependent on the flow of information to and from the nuclei, known as retrograde and anterograde signals. One mobile retrograde signaling molecule is the monophosphate 3'-phosphoadenosine 5'-phosphate (PAP), which is mainly produced from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) in the cytosol and regulates the expression of a set of nuclear genes that modulate plant growth in response to biotic and abiotic stresses. The adenosine bisphosphate phosphatase enzyme SAL1 dephosphorylates PAP to AMP in plastids and the mitochondria, but can also rescue sal1 Arabidopsis phenotypes (PAP accumulation, leaf morphology, growth, etc.) when expressed in the cytosol and the nucleus. To understand better the roles of the SAL1 protein in chloroplasts, the mitochondria, nuclei, and the cytosol, we have attempted to complement the sal1 mutant by specifically cargoing the transgenic SAL1 protein to these four cell compartments. Overexpression of SAL1 protein targeted to the nucleus or the mitochondria alone, or co-targeted to chloroplasts and the mitochondria, complemented most aspects of the sal1 phenotypes. Notably, targeting SAL1 to chloroplasts or the cytosol did not effectively rescue the sal1 phenotypes as these transgenic lines accumulated very low levels of SAL1 protein despite overexpressing SAL1 mRNA, suggesting a possibly lower stability of the SAL1 protein in these compartments. The diverse transgenic SAL1 lines exhibited a range of PAP levels. The latter needs to reach certain thresholds in the cell for its impacts on different processes such as leaf growth, regulation of rosette morphology, sulfate homeostasis, and glucosinolate biosynthesis. Collectively, these findings provide an initial platform for further dissection of the role of the SAL1-PAP pathway in different cellular processes under stress conditions.


Strain differences in the spontaneous incidence of sperm morphological abnormalities in Hatano rats.
Two inbred strains of Hatano rats, which had been bred selectively on the basis for shuttlebox avoidance responses (high- and low-avoidance animals; HAA and LAA), were different in sperm motility. We have found that there are strain differences in the spontaneous incidence of sperm morphological abnormalities. The percentages of abnormalities were extraordinarily higher in the LAA rats, whose sperm motility was lesser. Since the high sperm abnormality was an exceptional case in rats, these rats may be useful models for sperm quality.


Lanthanide ions promote the hydrolysis of 2,3-bisphosphoglycerate.
The 31P NMR studies showed that lanthanide ions promote the site-specific hydrolysis of 2,3-Bisphosphoglycerate (BPG) at pH 7.4 by cleaving the 2' phosphomonoester bond. The effect of fourteen trivalent lanthanide ions and Sc3+, and Y3+ were compared by the percentage of hydrolysis obtained by determining the inorganic phosphate produced. All the trivalent lanthanide ions promote the hydrolysis, but Sc3+ not. Among them, Ce3+ affects the reaction mostly. This was mainly attributed to the autooxidation of Ce3+ to Ce4+, since the promoting effect of Ce3+ is related to the increasing Ce4+ amount in the solution and depressed by adding sulphite. Ce4+ promotes the hydrolysis more efficiently than Ce3+ do. The pseudo first-order rate constant for the hydrolysis of BPG by Ce(SO4)2 (18.7 mM) at pH 1 and pH 2, 37 degrees C is 3.1 h(-1) and 0.65 h(-1) respectively. A mechanism with a hydroxo species as reactive intermediate was proposed for the trivalent lanthanide ions. The site-specificity was explainable by this mechanism.


Potential Utility of Biased GPCR Signaling for Treatment of Psychiatric Disorders.
Tremendous advances have been made recently in the identification of genes and signaling pathways associated with the risks for psychiatric disorders such as schizophrenia and bipolar disorder. However, there has been a marked reduction in the pipeline for the development of new psychiatric drugs worldwide, mainly due to the complex causes that underlie these disorders. G-protein coupled receptors (GPCRs) are the most common targets of antipsychotics such as quetiapine and aripiprazole, and play pivotal roles in controlling brain function by regulating multiple downstream signaling pathways. Progress in our understanding of GPCR signaling has opened new possibilities for selective drug development. A key finding has been provided by the concept of biased ligands, which modulate some, but not all, of a given receptor's downstream signaling pathways. Application of this concept raises the possibility that the biased ligands can provide therapeutically desirable outcomes with fewer side effects. Instead, this application will require a detailed understanding of the mode of action of antipsychotics that drive distinct pharmacologies. We review our current understanding of the mechanistic bases for multiple signaling modes by antipsychotics and the potential of the biased modulators to treat mental disorders.


Exon skipping during splicing of albumin mRNA precursors in Nagase analbuminemic rats.
Based on the observation that albumin transcripts accumulate in the liver nuclear RNA fraction of Nagase analbuminemic rats (NAR), it was proposed [Esumi, H., Takahashi, Y., Sato, S., Nagase, S. & Sugimura, T. (1983) Proc. Natl. Acad. Sci. USA 80, 95-99] [corrected] that a 7-base-pair deletion at the splice donor site of intron H-I of the albumin gene in these animals leads to impaired processing of albumin pre-mRNA. To identify the specific splicing abnormality, we examined the primary structure of cytoplasmic albumin mRNA across the junctions of exons G-H-I by RNase protection mapping, Northern blot hybridization, Southern blot analysis of polymerase chain reaction-amplified cDNA, and DNA sequencing. The major albumin mRNA species in NAR showed precise deletion of exon H, suggesting that this exon was skipped during albumin pre-mRNA processing. Since the intron G-H splice donor and acceptor sites and exon H sequence are normal, the finding of exon H skipping in NAR has important implications regarding the mechanism of splice site selection. Moreover, the NAR model provides an excellent system to study splicing in vivo in a higher animal.


The use and effectiveness of maternal scaffolding in mother-infant games.
Maternal behaviors within mother-infant games were examined to determine the amount, type, and functional value of maternal helping behaviors. 17 mother-infant pairs were videotaped on monthly visits from 8 to 16 months as they played 5 separate games. 2 of these games, roll the ball and peekaboo, were analyzed in terms of "rounds" of each game. Results show that dyads play more rounds of both games in the first months that infants perform game-relevant behaviors (e.g., returning a ball, performing uncovering or covering-uncovering). Maternal attention-getting and physical "stage-setting" behaviors occur in the early rounds of both games. In roll the ball, maternal hands-out and reinforcement behaviors increase in the months after the child begins to return the ball, while the percentage of rounds in which dyads play nonreturn variants decreases. Infants are more likely to return a ball when mother holds out her hands than when she does not. Infants are also able to perform returning or uncovering in game contexts before they perform similar behaviors in cognitive tests. The general similarity of findings in the peekaboo and roll-the-ball games, in spite of differences in the amounts of scaffolding, attention-getting, stage-setting, and reinforcement behaviors between the 2 games, indicates that the types and functions of maternal helping behaviors may be generalizable to other contexts of mother-infant interactions.


[Association between obesity and ovarian cancer].
Obesity is a risk factor for cancer. Epidemiological evidences associate ovarian cancer with obesity. Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer and accounts for a high rate of mortality. The association between ovarian cancer and obesity could be explained by molecular factors secreted by adipose tissue such as leptin. In EOC, leptin increases cell proliferation and inhibits apoptosis. Additionally, adipose tissue synthesizes endogenous estrogens, which increase cell proliferation of epithelial ovarian cells. Also, obesity associated hyperinsulinism could increase ovarian estrogen secretion.


Breastfeeding, skin-to-skin contact, and mother-infant interactions over infants' first three months.
The effects of skin-to-skin contact (SSC) on the maintenance of mothers' decision to breastfeed, the effects of breastfeeding and SSC on mother-infant interactions, and whether maternal depressive symptoms mediate these effects were investigated over infants' first 3 months. When infants were 1 week, 1 month, 2 months, and 3 months of age, mothers in the SSC and control groups reported the type of infant feeding provided and completed the Edinburgh Postnatal Depression Scale (EPDS; J.L. Cox, J.M. Holden, & R. Sagovsky, 1987); mother-infant interactions were coded on the Nursing Child Assessment Feeding Scale (NCAFS; G. Summer & A. Spietz, 1994). Percentage of breastfeeding dyads in the SSC group was stable over the 3 months; yet, fewer dyads in the control group were breastfeeding at the 2- and 3-month visits than at the 1-week visit. Breastfeeding dyads had higher NCAFS Caregiver subscale scores, indicating more positive maternal interactions, at 1 week, 2 months, and 3 months. NCAFS scores did not differ for the SSC and control groups. EPDS scores did not mediate the effect of SSC on breastfeeding or breastfeeding on NCAFS Caregiver subscale scores.


Methodical Challenges and a Possible Resolution in the Assessment of Receptor Reserve for Adenosine, an Agonist with Short Half-Life.
The term receptor reserve, first introduced and used in the traditional receptor theory, is an integrative measure of response-inducing ability of the interaction between an agonist and a receptor system (consisting of a receptor and its downstream signaling). The underlying phenomenon, i.e., stimulation of a submaximal fraction of receptors can apparently elicit the maximal effect (in certain cases), provides an opportunity to assess the receptor reserve. However, determining receptor reserve is challenging for agonists with short half-lives, such as adenosine. Although adenosine metabolism can be inhibited several ways (in order to prevent the rapid elimination of adenosine administered to construct concentration-effect (E/c) curves for the determination), the consequent accumulation of endogenous adenosine biases the results. To address this problem, we previously proposed a method, by means of which this bias can be mathematically corrected (utilizing a traditional receptor theory-independent approach). In the present investigation, we have offered in silico validation of this method by simulating E/c curves with the use of the operational model of agonism and then by evaluating them using our method. We have found that our method is suitable to reliably assess the receptor reserve for adenosine in our recently published experimental setting, suggesting that it may be capable for a qualitative determination of receptor reserve for rapidly eliminating agonists in general. In addition, we have disclosed a possible interference between FSCPX (8-cyclopentyl-N³-[3-(4-(fluorosulfonyl)benzoyloxy)propyl]-N¹-propylxanthine), an irreversible A₁ adenosine receptor antagonist, and NBTI (S-(2-hydroxy-5-nitrobenzyl)-6-thioinosine), a nucleoside transport inhibitor, i.e., FSCPX may blunt the effect of NBTI.


Application of artificial intelligence in trauma orthopedics: Limitation and prospects.
The varieties and capabilities of artificial intelligence and machine learning in orthopedic surgery are extensively expanding. One promising method is neural networks, emphasizing big data and computer-based learning systems to develop a statistical fracture-detecting model. It derives patterns and rules from outstanding amounts of data to analyze the probabilities of different outcomes using new sets of similar data. The sensitivity and specificity of machine learning in detecting fractures vary from previous studies. AI may be most promising in the diagnosis of less-obvious fractures that are more commonly missed. Future studies are necessary to develop more accurate and effective detection models that can be used clinically.


Optimal fluorescein-to-protein ratios of bacterial direct fluorescent-antibody reagents.
A number of bacterial systems were studied with specific direct fluorescent-antibody reagents prepared from rabbit antiserum fractions and having a wide range of fluorescein-to-protein ratios. These systems included Bacteroides, Bordetella, Clostridium, Escherichia, Legionella, Listeria, Salmonella, Shigella, and Streptococcus. For all systems studied, a fluorescein-to-protein ratio of 30 was optimal for conjugates prepared from ammonium sulfate fractions (greater than 75% gamma globulin) and pure immunoglobulin G desorbed from the Sepharose-bound protein A of Staphylococcus aureus. A pepsin digestion procedure is described that yielded the F(ab')2 piece of pure immunoglobulin G; this was labeled and studied at two fluorescein-to-protein ratios.


Biochemical regulation of the inflammasome.
The extensively studied cytokine IL-1β is an important mediator of the inflammatory response. However, dysregulated release of IL-1β can be detrimental and is attributed to the progression and pathogenesis of multiple inflammatory diseases including, rhuematoid arthritis (RA), atherosclerosis, type 2 diabetes (T2D), Alzheimers disease and gout. IL-1β is encoded as a pro-protein. A multi-protein molecular scaffold termed the "Inflammasome" is responsible for the tightly controlled and coordinated processing of pro-IL-1β. The activation of several NLR (nucleotide-binding oligomerization domain (NOD)-like receptor) family members and PYHIN (pyrin and HIN domain) proteins can drive the formation of inflammasomes. However, the exact biochemical mechanisms governing their activation have been the subject of much research. Different inflammasomes have been demonstrated to respond to the same pathogen inducing a cooperative immune response accountable for the clearance of infection. Here, we review current knowledge surrounding the biochemical regulation of the NLRP1, NLRP3, NLRC4, AIM2 and IFI16 inflammasomes.


Beyond perception: the experience of risk and stigma in community contexts.
Concerns about stigmatization are an important influence on the development of risk management and communication policies for a wide range of technologies and products such as those associated with hazardous waste storage, nuclear power, and genetic engineering of plants or foods. Although much attention has been placed on the adverse economic effects of stigma, we believe that the social, psychological, and cultural impacts are often at least as significant and merit greater attention from policymakers and researchers. Evidence for these impacts of stigma is found in recent studies of resource-based communities, whose residents may be shunned by local and nonlocal publics and whose products may suffer a loss of markets, which in turn creates social and economic hardship for community residents. We examine these aspects of stigma and link descriptions of the problem and prescriptions of recommended policies to five underlying characteristics of stigma, focusing on the possible insights and contributions from trade-off analysis and narrative approaches.


A summary of surveillance, morbidity and microbiology of laboratory-confirmed cases of infant botulism in Canada, 1979-2019.
Infant botulism is a rare toxicoinfectious disease caused by colonization of the infant's intestine with botulinum neurotoxin-producing clostridia (i.e. Clostridium botulinum or neurotoxigenic strains of C. butyricum or C. baratii). Our goal was to examine data from laboratory-confirmed cases of infant botulism reported in Canada to summarize incidence over time, over geographic distribution by province or territory, and by sex, and to compare these parameters with data from the Canadian Notifiable Disease Surveillance System (CNDSS). The average age of onset, serotype of botulinum neurotoxin (BoNT), case outcomes, length of hospitalization and suitability of clinical specimens for laboratory confirmation were also determined. We examined laboratory records from the Health Canada Botulism Reference Service and the British Columbia Centre for Disease Control (BCCDC) Public Health Laboratory. The Discharge Abstract Database (DAD) and the Hospital Morbidity Database (HMDB) of the Canadian Institute of Health Information (CIHI) were queried for data on hospitalization of infant botulism cases. The CNDSS was queried for data on reported cases of infant botulism. From 1979 to 2019, 63 laboratory-confirmed cases of infant botulism were confirmed by the Health Canada Botulism Reference Service and the BCCDC Public Health Laboratory for an annual rate of 4.30 cases per million live births. From 1983 to 2018, 57 cases of infant botulism were reported to the CNDSS. Of the 63 cases confirmed by the reference laboratories, the median age of onset was 16 weeks with a range of 2 to 52 weeks. The majority of cases were type A (76%) and B (21%), with single cases of type F and type AB. Of the 23 laboratory-confirmed cases with matched hospital records, 13 were transferred to special care and eight needed ventilator support; no deaths were reported. Spores of C. botulinum are present naturally in the environment, thus diagnosis of infant botulism does not require a history of exposure to high-risk foods such as honey. Stool samples are the most useful diagnostic specimen.


One Small RNA of Fusarium graminearum Targets and Silences CEBiP Gene in Common Wheat.
The pathogenic fungus Fusarium graminearum (F. graminearum), causing Fusarium head blight (FHB) or scab, is one of the most important cereal killers worldwide, exerting great economic and agronomic losses on global grain production. To repress pathogen invasion, plants have evolved a sophisticated innate immunity system for pathogen recognition and defense activation. Simultaneously, pathogens continue to evolve more effective means of invasion to conquer plant resistance systems. In the process of co-evolution of plants and pathogens, several small RNAs (sRNAs) have been proved in regulating plant immune response and plant-microbial interaction. In this study, we report that a F. graminearum sRNA (Fg-sRNA1) can suppress wheat defense response by targeting and silencing a resistance-related gene, which codes a Chitin Elicitor Binding Protein (TaCEBiP). Transcriptional level evidence indicates that Fg-sRNA1 can target TaCEBiP mRNA and trigger silencing of TaCEBiP in vivo, and in Nicotiana benthamiana (N. benthamiana) plants, Western blotting experiments and YFP Fluorescence observation proofs show that Fg-sRNA1 can suppress the accumulation of protein coding by TaCEBiP gene in vitro. F. graminearum PH-1 strain displays a weakening ability to invasion when Barley stripe mosaic virus (BSMV) vector induces effective silencing Fg-sRNA1 in PH-1 infected wheat plants. Taken together, our results suggest that a small RNA from F. graminearum can target and silence the wheat TaCEBiP gene to enhance invasion of F. graminearum.


[Heterogeneity of bucco-facial apraxia].
The authors have studied the bucco-facial apraxia (BFA) in 20 aphasic patients, examining 10 isolated oral gesture (IOG) and 10 combined oral gesture (COG). The heterogeneity of the BFA is indicated by the qualitative analysis of the types of errors in COG in relation to IOG. It is probably that the BFA due to the posterior lesions might base on the motor programming disorders of oral gestures, and that the BFA due to the anterior lesions on the motor realization disorders of oral gestures. It remains unsolved whether there is a continuity or some varieties between two types of BFA.


Organised cervical cancer screening programme in the Belgrade municipality of Cukarica - Evaluation of process indicators.
To evaluate the process indicators for monitoring the Organized Cervical Cancer Screening Programme (OCCSP) conducted in the Belgrade municipality of Cukarica within the first three-year interval, and to compare Pap test coverage for women aged 25 to 64 before and after implementing the organised programme. We analyzed the coverage by invitation, compliance with invitation and coverage by Pap test for the first three-year interval of the OCCSP (20th Dec 2012 - 19th Dec 2015) as well as the results of opportunistic screening for the same period and coverage by Pap test for women aged 25 to 64 for the last three years prior to the implementation of the OCCSP. After the first three years of the OCCSP implementation, coverage by invitation was 42.9%, compliance to invitation 66.7% and coverage by Pap test was 28.6%. During the same period, outside of the program (opportunistic screening) coverage by Pap test was 9.4%. In the last three years prior to the implementation of the OCCSP coverage by Pap test for women aged 25 to 64 was 21.4%. After the first three-year interval of the OCCSP implementation, the overall (organised + opportunistic) Pap test coverage for women aged 25-64 has almost doubled compared to the period when we conducted exclusively opportunistic screening (38.4 vs 21.4%). However, incentive payment for the smear takers and better coordination and planning of capacity-building is needed in order to achieve the 75% Pap tests coverage recommended by the National Programme for Early Detection of Cervical Cancer.


Changes in the lipid inclusion/Sertoli cell cytoplasm area ratio during the cycle of the human seminiferous epithelium.
The area occupied by Sertoli cell lipid inclusions--electron-lucent lipid vacuoles (LLV) and electron-dense lipid droplets (DLD)--at each stage of the cycle of the seminiferous epithelium was measured on electron micrographs in young adults and elderly men, and expressed as the ratio "area occupied by lipid inclusions/area occupied by the Sertoli cell cytoplasm". For LLV this ratio increased from stage I to stage III, and decreased from stage IV to stage VI in young adults. These results suggest that the development of LLV is synchronized with the spermatogenic process: the residual bodies released in stages I and II are phagocytized by Sertoli cells and transformed into LLV; the amounts of LLV decrease in the subsequent stages of the cycle and increase again when new residual bodies appear. In elderly men the ratio LLV/Sertoli cell cytoplasm was 1.9-2.9 times higher than in young adults at each stage of the cycle. This increase may be related to the increased germ-cell degeneration observed in ageing testes, DLD were less abundant than LLV and the DLD/Sertoli cell cytoplasm ratio did not undergo cyclic changes in young adults or elderly men.


Cell surface sialylation plays a role in modulating sensitivity towards APO-1-mediated apoptotic cell death.
APO-1/Fas(CD95), a member of the tumour necrosis factor (TNF)/nerve growth factor (NGF) receptor superfamily transduces apoptotic signals into apoptosis sensitive cells. In metabolic labelling experiments using the highly APO-1 positive cell lines HUT78 (adultT cell leukemia) and SKW6.4 (Blymphoblastoid cell line) APO-1 was characterised as a long living protein with a complex glycosylation pattern involving terminal sialic acid groups which account for 8-kDa of its apparent molecular weight on SDS-PAGE. APO-1 expression and the degree of sialylation were determined in additionalT and B cell lines. On the group I Burkitt's lymphoma cell line BL60 transfected with human APO-1 (K50) low sialylated species were detected only on the cell surface, suggesting that sialylation might be functionally important. Removal of terminal sialic acid groups by treatment of B and T cell lines with Vibrio cholerae neuraminidase (VCN) augmented sensitivity towards anti-APO-1 and human APO-1 ligand induced apoptosis. Similarly, VCN-treated U937 cells were rendered more sensitive to TNFalpha-induced cell death. Thus, sialylation may be one mechanism to regulate sensitivity towards ligand-mediated cell death in this receptor family.


Overexpression of Nfe2l1 increases proteasome activity and delays vision loss in a preclinical model of human blindness.
Proteasomes are the central proteolytic machines that are critical for breaking down most of the damaged and abnormal proteins in human cells. Although universally applicable drugs are not yet available, the stimulation of proteasomal activity is being analyzed as a proof-of-principle strategy to increase cellular resistance to a broad range of proteotoxic stressors. These approaches have included the stimulation of proteasomes through the overexpression of individual proteasome subunits, phosphorylation, or conformational changes induced by small molecules or peptides. In contrast to these approaches, we evaluated a transcription-driven increase in the total proteasome pool to enhance the proteolytic capacity of degenerating retinal neurons. We show that overexpression of nuclear factor erythroid-2-like 1 (Nfe2l1) transcription factor stimulated proteasome biogenesis and activity, improved the clearance of the ubiquitin-proteasomal reporter, and delayed photoreceptor neuron loss in a preclinical mouse model of human blindness caused by misfolded proteins. The findings highlight Nfe2l1 as an emerging therapeutic target to treat neurodegenerative diseases linked to protein misfolding.


[Chronic idiopathic neutropenia improved by recombinant granulocyte colony stimulating factor].
A 55-year-old man was admitted to our hospital for the evaluation of neutropenia. On physical examination, he had apthae and splenomegaly. CBC showed 1,000/microliter WBC with 5% neutrophils, and microcytic anemia consistent with iron deficiency. Bone marrow examination revealed a marked decrease of mature neutrophils, but normal percentage of immature myeloid cells. There was no morphological abnormality in the hemopoietic cells. He had no drug or family history responsible for the neutropenia. Anti-neutrophil auto-antibody was negative. Hence, a diagnosis of chronic idiopathic neutropenia (CIN) was made. He developed frequent episodes of infection such as balanitis, peri-anal infection, gingivitis, and pharyngitis. He was treated with steroid pulse therapy, anabolic hormone, and high dose gamma-globulin infusion, but no significant improvement occurred. Then, recombinant granulocyte-colony stimulating factor (rG-CSF) was started. The neutrophil count was normalized by the 7th day of 5 micrograms/kg/day rG-CSF administration. The administration of G-CSF was discontinued after a 14-day course. Thereafter, the neutrophil count remained at near normal level (approximately 1,500/microliter) and there have been no episodes of infection in the last 5 months. However this cannot be explained simply by the direct effect of rG-CSF on the myeloid precursors; rather, it suggests some unknown effect of G-CSF on the bone marrow microenvironment regulating myeloid hemopoiesis. We consider this to be a rare case of CIN with frequent episodes of infection, which was successfully treated with G-CSF.


LipidFrag: Improving reliability of in silico fragmentation of lipids and application to the Caenorhabditis elegans lipidome.
Lipid identification is a major bottleneck in high-throughput lipidomics studies. However, tools for the analysis of lipid tandem MS spectra are rather limited. While the comparison against spectra in reference libraries is one of the preferred methods, these libraries are far from being complete. In order to improve identification rates, the in silico fragmentation tool MetFrag was combined with Lipid Maps and lipid-class specific classifiers which calculate probabilities for lipid class assignments. The resulting LipidFrag workflow was trained and evaluated on different commercially available lipid standard materials, measured with data dependent UPLC-Q-ToF-MS/MS acquisition. The automatic analysis was compared against manual MS/MS spectra interpretation. With the lipid class specific models, identification of the true positives was improved especially for cases where candidate lipids from different lipid classes had similar MetFrag scores by removing up to 56% of false positive results. This LipidFrag approach was then applied to MS/MS spectra of lipid extracts of the nematode Caenorhabditis elegans. Fragments explained by LipidFrag match known fragmentation pathways, e.g., neutral losses of lipid headgroups and fatty acid side chain fragments. Based on prediction models trained on standard lipid materials, high probabilities for correct annotations were achieved, which makes LipidFrag a good choice for automated lipid data analysis and reliability testing of lipid identifications.


Posterior Sagittal Approach for Uterovaginal Anastomosis in a Case of Congenital Cervical Atresia with Anorectal Malformation.
Cervical atresia is a rare association with anorectal malformation (ARM) which can be missed till puberty in the presence of normal vaginal orifice. A 12-year-old girl operated for ARM in neonatal age presented with primary amenorrhea. She had a normal vaginal opening, short perineal body, and prolapsed anteposed anus and was diagnosed with cervical agenesis. As the posterior sagittal approach is standard to place the rectum in correct anatomical position, reconstruction of the anus along with adequate perineal body and uterovaginal anastomosis was performed through this approach. This report highlights the utility and versatility of this approach for the management of such complex cases.


[Systemic nursing intervention in couples in which one member has cardiac insufficiency].
Chronic heart failure is a family affair since the spouse's quality of life is affected as much as that of the patient. This article deals with three clinical cases exploring the couple's perceptions of how the illness affected their marital relationship and how helpful the family systems nursing interventions have been. Three themes emerged from the analysis of the relationship between the evolution of the illness and the marital dynamics, and these are: a search for a balance between protectiveness/overprotectiveness, a reassessment of the marital relationship, and the adoption of new coping strategies. The family systems nursing interventions that were perceived as the most helpful were the systemic questionf1p4++ and the exploration of the couple's strengths and resources. These interventions allowed the couple to: 1) share their illness experience; 2) increase their understanding of the relationship between the illness and their marital dynamics, and 3) reflect on different ways to enhance their competence and resources in meeting with the challenges of this type of cardiac health problem.


Novel Benchmark Values for Open Major Anatomic Liver Resection in Non-cirrhotic Patients: A Multicentric Study of 44 International Expert Centers.
This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens.


M- and T-tropic HIVs promote apoptosis in rat neurons.
Neuronal loss, reactive astrocytes, and other abnormalities are seen in the brain of individuals with acquired immune deficiency syndrome-associated Dementia Complex (ADC). Human immunodeficiency virus-1 (HIV-1) is believed to be the main agent causing ADC. However, little is known about the molecular and cellular mechanisms of HIV-1 neurotoxicity considering that HIV-1 does not infect post-mitotic neurons and that viral load does not necessarily correlate with ADC. Various viral proteins, such as the envelope protein gp120 and the transcription activator Tat, have been shown to induce neuronal apoptosis through direct and indirect mechanisms both in vitro and in vivo. Progeny HIV-1 virions can also cause neuronal death. However, it has not been fully established yet whether HIV-1 promotes neuronal apoptosis by a direct mechanism. To explore the neurotoxic effect of HIV-1, we exposed rat cerebellar granule cells and cortical neurons in culture to two different strains of HIV-1, IIIB and BaL, T- and M-tropic strains that utilize CXCR4 and CCR5 coreceptors, respectively, to infect cells. We observed that both viruses elicit a time-dependent apoptotic cell death in these cultures without inducing a productive infection as determined by the absence of the core protein of HIV-1, p24, in cell lysates. Instead, neurons were gp120 positive, suggesting that the envelope protein is shed by the virus and then subsequently internalized by neurons. The CXCR4 receptor antagonist AMD3100 or the CCR5 receptor inhibitor D-Ala-peptide T-amide blocked HIV IIIB and HIV Bal neurotoxicity, respectively. In contrast, the N-methyl-D-aspartate receptor blocker MK801 failed to protect neurons from HIV-mediated apoptosis, suggesting that HIV-1 neurotoxicity can be initiated by the viral protein gp120 binding to neuronal chemokine receptors.


A long-term survivor with esophageal melanoma and pulmonary metastasis after single-stage esophagectomy and lobectomy: Case report and literature review.
The optimal therapeutic regimen for primary malignant melanoma of the esophagus (PMME) need to be further elucidated. Besides, the efficacy of surgery for PMME with remote metastasis is uncertain for its rarity. Herein a previously healthy patient was admitted for dysphagia and fatigue, without significant weight loss. The pathological and molecular tests revealed his diagnosis of BRAF-mutant, advanced PMME with localized pulmonary metastasis. Single-stage Ivor-Lewis esophagectomy and lobectomy were performed successfully, followed by 4 cycles of conventional chemotherapy, and concurrent high-dose interferon lasting for 1 year. The patient survived without logo-regional recurrence or remote metastasis during the follow up of two and a half years up to now. Timely resection of localized primary and metastatic lesions might deliver a chance to obtain better prognosis for selected PMME patients; however, high-quality trials with longer follow-up are needed.


Repair of femoral fractures in calves via external skeletal fixator with intramedullary pin tie-in.
To describe the success rate and associated complications of external skeletal fixator/intramedullary pin tie-in for calf femoral fracture fixation. Clinical retrospective. Ten calves, less than 30 days old, with diaphyseal/metaphyseal femoral fractures. Medical records were reviewed from the University of Wisconsin from 2000 to 2020. Fractures were repaired using open reduction and fixation. An intramedullary Steinman pin was placed, exiting near the greater trochanter, and utilized for fracture reduction. Bicortical transfixation pins were placed distal and proximal to the fracture site. Poly(methyl methacrylate) (PMMA)-filled tubing connected the transfixation pins and proximal intramedullary pin, creating a Type 1a external skeletal fixator (ESF) tie-in. Follow up was obtained via medical records and phone interviews. Short-term survival rate was 7/10 (70%). Postanesthetic death occurred once. Postoperative complications occurred in all remaining cases. The most common findings were transfixation pin tract lucency and lameness (6/9 cases), implant dysfunction (5/9 cases), and infection (4/9 cases). Three of five cases with long-term follow up survived; all went on to productive careers. Although patients were prone to postoperative complications, short-term survival was comparable to previous reports. The external skeletal fixator/intramedullary (ESF/IM) pin tie-in is less expensive and offers comparable success rates to other methods, providing a lower cost option for calf femoral fracture repair.


The effects of sensory stimulation on REM sleep duration.
Previous experiments have demonstrated that auditory (AS) and/or somatosensory (SS) stimulation can increase the duration of REM sleep periods in rats, cats and humans. The objectives of this study were to determine whether repeated AS stimulation causes habituation to the stimulus and whether any additive effects could be obtained with the simultaneous application of AS and SS. Three experimental procedures were used in this study. In experiment 1, animals were recorded for 4 consecutive days with AS, followed by a post-stimulus session. In experiment 2, they were recorded for 24 hours with AS applied at each REM period, followed by a subsequent 24-hours-post-stimulus recording. In experiment 3, animals underwent AS, SS stimulation, or simultaneous application of both in a random fashion at each REM period. The results of all experiments confirm previous findings showing that auditory or somatosensory stimuli significantly increase REM sleep period duration. In addition, AS--applied with different presentations during REM and throughout the sleep-wake cycle--are capable of increasing REM duration regardless of the manner in which they were presented. However, the effects of the stimuli were not additive. It is worth noting that although REM duration increased, REM period frequency decreased, resulting in no net change of total REM sleep through time. Furthermore, no changes were observed in other sleep-wake variables. These experiments clearly demonstrate that repeated auditory stimulation does not cause habituation, and there are no evident side effects on the sleep-wake cycle. These results confirm that the mechanisms involved in REM generation and maintenance can be modulated by sensory modalities.


Integration site selection by retroviruses and transposable elements in eukaryotes.
Transposable elements and retroviruses are found in most genomes, can be pathogenic and are widely used as gene-delivery and functional genomics tools. Exploring whether these genetic elements target specific genomic sites for integration and how this preference is achieved is crucial to our understanding of genome evolution, somatic genome plasticity in cancer and ageing, host-parasite interactions and genome engineering applications. High-throughput profiling of integration sites by next-generation sequencing, combined with large-scale genomic data mining and cellular or biochemical approaches, has revealed that the insertions are usually non-random. The DNA sequence, chromatin and nuclear context, and cellular proteins cooperate in guiding integration in eukaryotic genomes, leading to a remarkable diversity of insertion site distribution and evolutionary strategies.


Serratia myotis sp. nov. and Serratia vespertilionis sp. nov., isolated from bats hibernating in caves.
During the study of bacteria associated with bats affected by white-nose syndrome hibernating in caves in the Czech Republic, we isolated two facultatively anaerobic, Gram-stain-negative bacteria, designated strains 12(T) and 52(T). Strains 12(T) and 52(T) were motile, rod-like bacteria (0.5-0.6 µm in diameter; 1-1.3 µm long), with optimal growth at 20-35 °C and pH 6-8. On the basis of the almost complete sequence of their 16S rRNA genes they should be classified within the genus Serratia; the closest relatives to strains 12(T) and 52(T) were Serratia quinivorans DSM 4597(T) (99.5 % similarity in 16S rRNA gene sequences) and Serratia ficaria DSM 4569(T) (99.5% similarity in 16S rRNA gene sequences), respectively. DNA-DNA relatedness between strain 12(T) and S. quinivorans DSM 4597(T) was only 37.1% and between strain 52(T) and S. ficaria DSM 4569(T) was only 56.2%. Both values are far below the 70% threshold value for species delineation. In view of these data, we propose the inclusion of the two isolates in the genus Serratia as representatives of Serratia myotis sp. nov. (type strain 12(T) =CECT 8594(T) =DSM 28726(T)) and Serratia vespertilionis sp. nov. (type strain 52(T) =CECT 8595(T) =DSM 28727(T)).


Enhanced Fibrinolysis with Magnetically Powered Colloidal Microwheels.
Thrombi that occlude blood vessels can be resolved with fibrinolytic agents that degrade fibrin, the polymer that forms between and around platelets to provide mechanical stability. Fibrinolysis rates however are often constrained by transport-limited delivery to and penetration of fibrinolytics into the thrombus. Here, these limitations are overcome with colloidal microwheel (µwheel) assemblies functionalized with the fibrinolytic tissue-type plasminogen activator (tPA) that assemble, rotate, translate, and eventually disassemble via applied magnetic fields. These microwheels lead to rapid fibrinolysis by delivering a high local concentration of tPA to induce surface lysis and, by taking advantage of corkscrew motion, mechanically penetrating into fibrin gels and platelet-rich thrombi to initiate bulk degradation. Fibrinolysis of plasma-derived fibrin gels by tPA-microwheels is fivefold faster than with 1 µg mL-1 tPA. µWheels following corkscrew trajectories can also penetrate through 100 µm sized platelet-rich thrombi formed in a microfluidic model of hemostasis in ≈5 min. This unique combination of surface and bulk dissolution mechanisms with mechanical action yields a targeted fibrinolysis strategy that could be significantly faster than approaches relying on diffusion alone, making it well-suited for occlusions in small or penetrating vessels not accessible to catheter-based removal.


Robust structured-light depth mapping via recursive decomposition of binary codes.
Structured-light depth cameras rely on projecting and resolving coded patterns on a three-dimensional scene with high contrast. The front-end optics of such depth cameras impose a fundamental restriction on the depth-sensing range and accuracy: the patterns only remain sharp within the depth of field jointly determined by the camera and projector. We present here a robust method to improve the depth-sensing range and accuracy for a structured-light depth camera without changing the underlying optical design. Moreover, it shows the unique advantage in macrophotography of highly light-scattering objects. We analyze the proposed method theoretically and validate it in experiments.


Plasmid mediated antibiotic resistance in Klebsiella pneumoniae.
Klebsiella pneumoniae species (108) isolated from tertiary care hospitalized patients were investigated for antibiotic resistance patter. 74% isolates were from urine, 13.5% from pus, 4.5% from blood and 8% from sputum. The resistance pattern of the organisms to various antibiotics were as follows: ampicillin 93.3%, cefotaxime 70%, ceftazidime 81%, gentamicin 68.5%, amikacin 63.75%, netilmicin 74%, norfloxacin 55%, ofloxacin 53%, chloramphenicol 82%, tetracycline 85%, sulphamethoxazole 96%, trimethoprim 94%. 2-4 drug resistance was found in 34.5%, 5-8 drug resistance was in 25.1% and 9-12 drug resistance was found in 40.4% of strains. Out of 65 strains, 25 strains could be successfully conjugated. Common drugs which were transferred to transconjugants were sulphamethoxazole, trimethoprim, gentamicin, netilmicin, amikacin, chloramphenicol, tetracycline, ampicillin, cefotaxime and ceftazidime. A large plasmid of 98.7% kb could be demonstrated in these strains by alkali denaturation method and agarose gel electrophoresis.


[Role of whole-body diffusion weighted imaging (WB-DWI) in the diagnosis and monitoring of newly diagnosed multiple myeloma].
Objective: To explore the practical value of whole-body diffusion weighted imaging (WB-DWI) in the diagnosis and monitoring of newly diagnosed multiple myeloma (MM) patients. Methods: The clinical data of 107 newly diagnosed MM patients at hematology department of the first affiliated hospital of Soochow's University from September 2012 to January 2016 were retrospectively analyzed. The results of all the 60 patients who were performed WB-DWI before treatment were analyzed. And the role of WB-DWI in the diagnosis and monitoring MM was discussed. Results: Of 60 patients, 57 were found to have more or less abnormal foci of osteoclasia by WB-DWI with the positive rate of 95.0% (57/60) . Myeloma related bone lesions occurred predominantly in the axial skeleton, which were commonly seen in ribs, spines and pelvis. There were 96.5% (55/57) patients who had osteolytic rib lesions. And the ribs were the most vulnerable organs. Thirteen patients who had no osteoclasia by computerized tomography (CT) examination were detected abnormal limited diffuse lesions by WB-DWI. Eight patients underwent more than one follow-up WB-DWI. The mean apparent diffusion coefficient (ADC) values of the maximal lesions from all eight patients before and after treatment were 0.984×10(-3)mm(2)/s and 1.142×10(-3)mm(2)/s, respectively. They were both higher than the normal range [ (0.516±0.180) ×10(-3)mm(2)/s]. Mean ADC values of the maximal lesions after treatment were higher than that before treatment. The results of WB-DWI after the induction chemotherapy were consistent with clinical therapeutic effect. Conclusions: WB-DWI has an important value in the diagnosis and monitoring of newly diagnosed MM. It has higher sensitivity than than that of CT. The results of WB-DWI after induction therapy has a nice correlation with treatment effect and it could monitor the disease.


ISCEV Standard for full-field clinical electroretinography (2008 update).
This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV Standard for clinical electroretinography (ERG). The parameters for flash stimulation and background adaptation have been tightened, and responses renamed to indicate the flash strength (in cd x s x m(-2)). The ISCEV Standard specifies five responses: (1) Dark-adapted 0.01 ERG (rod response); (2) Dark-adapted 3.0 ERG (combined rod-cone response); (3) Dark-adapted 3.0 oscillatory potentials; (4) Light-adapted 3.0 ERG (cone response); (5) Light-adapted 3.0 flicker (30 Hz flicker). An additional Dark-adapted 10.0 ERG or Dark-adapted 30.0 ERG response is recommended.


Prevalence of Listeria species in raw milk from farm bulk tanks in Nagano prefecture.
Raw milk samples from bulk tanks of a total of 943 farms, which corresponded to approximately 60% of all dairy farms in Nagano Prefecture were examined for Listeria species between December 1990 and April 1991. Listeria spp. were isolated from 29 (3.1%) of 943 milk specimens. In the southern, central, eastern and northern areas of the prefecture, Listeria spp. were isolated from 6.1% (22/362), 1.5% (4/272), 1.4% (2/143) and 0.6% (1/166) of samples, respectively. Listeria monocytogenes was isolated from three (0.3%) bulk tanks in the southern area: two of the strains isolated from two different farm bulk tanks were serovar 4b, and the other one was 1/2a. Besides, between February 1991 and January 1992, 504 samples of raw milk from farm bulk tanks were collected nine times from 56 farms in the southern area, where the prevalence of Listeria spp. was the highest, and examined for the seasonal variation in the presence of Listeria spp. The prevalence of Listeria spp. was higher in spring (14.3%) than in autumn (4.8%). The 56 farms were divided into three groups according to the prevalence of Listeria spp., namely, three farms in Group 1 gave a high contamination rate (50% < or =), 14 farms in Group 2 a low contamination rate and the remaining 39 farms in Group 3 no recovering of Listeria spp. Sixteen strains of L. monocytogenes serovar 4b were isolated from four farms.


Combined photodynamic therapy and intravitreal triamcinolone injection for the treatment of choroidal neovascularisation secondary to pathological myopia: a pilot study.
To assess the efficacy and safety of combined intravitreal triamcinolone (IVTA) and photodynamic therapy (PDT) with verteporfin in the treatment of choroidal neovascularisation (CNV) secondary to pathological myopia. 22 eyes of 22 patients with subfoveal or juxtafoveal CNV due to pathological myopia were prospectively recruited for combined PDT with IVTA. The treatment outcomes at 1 year were compared with those in a control group of 22 eyes that received PDT monotherapy. At 1 year, the logMAR best-corrected visual acuity (BCVA) for the combined PDT with IVTA group changed from 0.62 to 0.61 (p = 0.74), whereas that for the monotherapy group changed from 0.61 to 0.67 (p = 0.33). The mean logMAR BCVA and proportions of patients without losing > or =3 lines at 1 year were similar between the two groups (p = 0.68 and 0.74, respectively). Subgroup analyses showed that eyes with baseline logMAR BCVA worse than 0.6 (Snellen equivalent 20/80) or CNV with greatest linear dimension > or =750 microm which received combined therapy had better mean logMAR BCVA at 1 year (p = 0.023 and 0.041, respectively), with a higher proportion of eyes gaining > or =2 lines of BCVA (p = 0.027 and 0.017, respectively) compared with PDT monotherapy. Combined PDT with IVTA did not seem to result in significantly better visual outcome compared with PDT monotherapy. However, combined therapy might result in better visual outcome in selected patients with worse initial visual acuity or larger myopic CNV. Further studies are warranted to investigate the role of combined PDT with IVTA in the treatment of myopic CNV, especially in patients with worse prognostic factors.


The eosinophilic granulocyte an active participant in the late phase asthmatic reaction?
The role of the eosinophilic granulocyte in immediate hypersensitivity reactions is generally believed to be a beneficial one since this cell may phagocytose mast cell granules and inactivate certain mast cell mediators. However it has become clear that the eosinophilic granulocyte also has potent secretory capacities, and by this property may contribute in a detrimental way to the allergic process. In studying the late phase allergen induced bronchoconstriction by means of bronchoalveolar lavage (BAL) an evident infiltration of eosinophilic granulocytes in the bronchioli in the beginning of the late phase asthmatic reaction was noticed. Since also eosinophil cationic protein (ECP) has been reported to be elevated in the lavage fluid an active secretory role of the eosinophil in the late phase asthmatic reaction seemed likely. Although the release of ECP and other granular proteins may contribute to epithelial damage and inflammation and thereby to an increase in bronchial hyperreactivity they do not explain the late phase bronchoconstrictive reaction. Since leukotrienes were thought possible candidates to cause this reaction it was decided to isolate eosinophils from human peripheral blood and to study their leukotriene synthesis pattern. To our surprise purified human eosinophils almost exclusively synthesize the strongly bronchoconstrictive leukotriene LTC4 in considerable quantities upon in vitro stimulation with either the calcium-ionophore A23187 or opsonized zymosan. These findings suggest that the eosinophil may play an active role in causing the late phase asthmatic reaction.


[Current advance in cerebral malaria].
Cerebral malaria (CM), a severe neurological syndrome caused by Plasmodium falciparum infection, is a serious life-threatening disease with a high mortality. Survivors' persistent brain injury is manifested as long-term neurocognitive disorders. The main neuropathological feature of CM is the sequestration of parasited red blood cells (pRBCs) in cerebral microvessels. Other neuropathological features of CM include petechial hemorrhage in the brain parenchyma, annular hemorrhage, extensive brain endothelial cell activation, and focal endothelial cell injury and necrosis. However, its pathogenesis is still not clear. Currently, some studies have suggested that the pathogenesis of cerebral malaria mainly include pRBC adhesion, inflammatory reaction cascade, vascular leakage damage and brain hypoxia. Studies have shown that the biomarkers currently used as diagnostic and prognostic markers for CM include C-X-C motif chemokine ligand 10 (CXCL10), CXC chemokine ligand 4 (CXCL4), angiopoietin (Ang). In this paper, we systematically summarize the basic and clinical research for cerebral malaria in recent years and the latest literatures for drug studies, and focused on the advance of studies on cerebral malaria and its immunologic mechanism in the recent three years in the aspects of cytokines, immune cells, regulatory factors and biomarkers, so as to provide references for relevant studies.


Effect of hesperidin dietary supplementation on hen performance, egg quality and yolk oxidative stability.
1. The purpose of this study was to evaluate the effects of dietary supplementation with hesperidin (one or 3 g/kg of feed) for 31 d on the performance, egg quality and yolk oxidative stability of brown and white laying hens (26-wk old). 2. Supplementation with hesperidin did not affect egg production, egg weight and egg quality traits. 3. No hesperidin effect on yolk and plasma cholesterol was observed. A strain effect was found with lower total and per g yolk cholesterol of brown hens in comparison to the white ones. 4. Oxidative stability of egg yolk, expressed as ng MDA/g yolk, was significantly improved in the hesperidin groups even from the first week of supplementation. At the same time, a significant improvement in the oxidative stability of egg yolk due to the incorporation of hesperidin in hens' diet was observed after 30 and 90 d of storage at 20°C and 4°C, respectively. 5. No hesperidin by strain interaction was detected for any of the traits measured. 6. In conclusion, incorporation of hesperidin to laying hens' feed did not affect productive and egg qualitative traits. On the other hand, dietary hesperidin supplementation significantly improved oxidative stability of both fresh and stored eggs. Antioxidant properties of hesperidin seem to make it a promising natural agent for improving the shelf life of eggs.


Influences of dietary restriction and age on liver enzyme activities and lipid peroxidation in mice.
Dietary restriction extends maximum life span in rodents by unknown mechanisms. We compared livers from 12- and 24-mo-old mice fed control (C, approximately 95 kcal/wk) or restricted (R, approximately 55 kcal/wk) amounts of diet since 3 wk of age. We hypothesized that dietary restriction might alter the activity levels of enzymes with possible relevance to aging processes. The enzymes included several xenobiotic metabolizers, radical scavengers (catalase, superoxide dismutase, glutathione peroxidase), superoxide sources (xanthine oxidase, peroxisomal beta-oxidation of palmitoyl-CoA) and glucose-6-phosphatase. Lipid peroxidation (LP) was also measured. Comparing 12- and 24-mo-old mice, the strongest diet or age effect was an increased catalase activity for group R (42% higher at 12 mo, 64% at 24 mo). LP was clearly lower in group R at 12 mo (a 30% decrease) and somewhat lower (13%) at 24 mo than in group C. Similarly, in 12-mo-old C and R mice injected with either the P-450 inducer beta-naphthoflavone (beta-NF in corn oil) or with corn oil alone. R mice showed higher catalase activity (40-44%) and lower LP (43-46%) in both beta-NF-injected and vehicle-injected groups. These data suggest that if free radical damage is involved in aging, it may be a particular kind of damage, that is, that in part prevented by a selective increase in catalase activity.


Clinical application of intra-aortic balloon pump in patients with cardiogenic shock during the perioperative period of cardiac surgery.
Intra-aortic balloon pumps (IABP) have saved many patients with cardiogenic shock during the perioperative period of cardiac surgery. However, the ideal insertion timing is controversial. In the present study, we aimed to optimize the insertion timing, in order to increase the survival rate of the patients. A total of 197 patients with cardiogenic shock during the perioperative period of cardiac surgery and implemented IABP from January 2011 to October 2015 were selected for the study. Patients were divided into five groups on the basis of application timing of IABP: 0-60, 61-120, 121-180, 181-240 and >240 min. The 30-day mortality, application rate of continuous renal replacement therapy (CRRT), duration of mechanical ventilation, duration of hospital stay and hospitalization charges were analyzed in the above groups. The risk factors related to mortality and the occurrence of IABP complications were also analyzed. The mortality in the 0-60, 61-120, 121-180, 181-240 and >240 min groups were 42.17, 36.6, 77.3, 72.7 and 79.3%, respectively. Earlier IABP insertion resulted in less patients receiving CRRT from acute renal failure and less daily hospitalization charges. However, the IABP application timing had no effect on indexes such as hospitalization duration, duration of mechanical ventilation and total hospitalization charges. Multifactor logistic regression analysis indicated that the independent risk factors of death in patients with cardiogenic shock during cardiac surgery were related to IABP support timing and vasoactive-inotropic score (VIS) before balloon insertion. In the first 120 min of cardiogenic shock during the perioperative period of cardiac surgery, IABP application decreased 30-day mortality. Mortality was related with VIS score of patients, which can be used to predict the prognosis of patients with cardiogenic shock.


Natural Extracts for Antibacterial Applications.
Bacteria-induced epidemics and infectious diseases are seriously threatening the health of people around the world. In addition, antibiotic therapy has been inducing increasingly more serious bacterial resistance, which makes it urgent to develop new treatment strategies to combat bacteria, including multidrug-resistant bacteria. Natural extracts displaying antibacterial activity and good biocompatibility have attracted much attention due to greater concerns about the safety of synthetic chemicals and emerging drug resistance. These antibacterial components can be isolated and utilized as antimicrobials, as well as transformed, combined, or wrapped with other substances by using modern assistive technologies to fight bacteria synergistically. This review summarizes recent advances in natural extracts from three kinds of sources-plants, animals, and microorganisms-for antibacterial applications. This work discusses the corresponding antibacterial mechanisms and the future development of natural extracts in antibacterial fields.


Polidocanol versus hypertonic glucose for sclerotherapy treatment of reticular veins of the lower limbs: study protocol for a randomized controlled trial.
The prevalence of chronic venous disease is high and occurs more frequently in females. According to the clinical, etiological, anatomical, and pathological classification (CEAP) definition, the reticular veins are included in the C1 class and are mainly associated with aesthetic complaints. Several invasive techniques are used for treatment, including mini phlebectomy, laser ablation, and radiofrequency ablation. However, a wide range of sclerosing agents may serve as minimally invasive alternatives, promoting chemical sclerosis of the vein wall. Although this technique is routinely performed around the world, there is no consensus on the most efficacious and safe chemical agent to be used. Inclusion criteria are women between 18 and 69 years old with at least 10 cm long reticular veins in the lower limbs, on the outer side of the leg/thigh. Patients with CEAP 2 to 6, or with allergies, pregnancy, performing breastfeeding, or with any dermatologic or clinical problems will be excluded. Patients with venous ultrasound mapping showing involvement of saphenous trunks and/or a deep venous system will also be excluded. Patients will be randomized into two groups, one receiving 75% pure glucose and the other group receiving 0.2% polidocanol diluted in 70% glucose. Just one limb and one session per patient will be performed. The sclerosing agent volume will not exceed 5 mL. Clinical follow-up will include visits on days 7 and 60, always with photographic documentation. This project aims to enroll 96 patients and subject them to a double-blind treatment after the randomization process. The design is intended to evaluate efficacy through a primary end point and safety through a secondary end point. Forty-eight patients have currently been enrolled. Preliminary results for these patients showed that 25 received treatment, 2 were excluded, and 22 returned after 7 days and showed no greater adverse events. To date, establishing efficacy criteria has not been possible, and no patients have reached the 60-day return point. These data may help doctors choose the best chemical agent for the treatment of reticular veins. ClinicalTrials.gov Identifier: NCT02054325, 3/02/2014.


Effects intracerebral microinjection and intraperitoneal injection of [60]fullerene on brain functions differ in rats.
Fullerenes are condensed ring aromatic compounds with extended pi systems and unique cage structures. Fullerenes are used for medical devices such as carbon nanotubes because they are very flexible and suitable for drug delivery systems. Recently, fullerene derivatives and tube-shaped materials have been used for neuroregeneration studies, and we expect that fullerenes and carbon nanotubes have potential uses as materials in novel medical devices targeting the brain. However, little information on the effects of fullerenes on brain function is available; thus, we examined the effects of [60]fullerene (C60) on the central nervous system in this study. In a V79 cell colony Asia, the IC50 of C60 was 1620 microg/ml. In an in vivo study, 0.25 mg/kg B.W. of C60 was injected into the lateral brain ventricle or abdominal cavity of rats. The intracerebral injection of C60 increased the locomotor behavior of the rats on days 1 and 30 after the injection. The intraperitoneal injection of C60 did not change the locomotor behavior of rats acutely, but it was decreased on day 30. The intracerebral injection of C60 affected monoamine concentrations in the rat brain. In particular, serotonin turnover rates were increased in the hypothalamus, cerebral cortex, striatum, and hippocampus, and dopamine turnover rates were increased in the hypothalamus, cerebral cortex, and striatum. The intraperitoneal injection of C60 decreased only the dopamine turnover rate in the hippocampus. These results suggest that intracerebral injection of C60 had different effects on the central nervous system than intraperitoneal injection. In conclusion, it was suggested that fullerene did not cross the blood-brain barrier. The intracerebral injection of C60 affected neurotransmission in the brain widely, and the monoamine dysbolism might be related to changes in locomotor activity.


Sexual Violence-Related Pregnancy Among Internally Displaced Women in an Internally Displaced Persons Camp in Northeast Nigeria.
Sexual violence is quite common in conflict situations and puts women at risk of unintended pregnancies. In the northeast region of Nigeria with the ongoing insurgency, a substantial number of women are kidnapped and subjected to forced marriages and repeated sexual assaults. This study set out to report on the disclosure and outcomes of sexual violence-related pregnancies (SVRPs) among women liberated from insurgents and relocated to one of largest Internally Displaced Persons (IDP) camps located in Borno State, northeast Nigeria. The clinic records of women with SVRP were reviewed. Forty-seven women with SVRP were identified by the health care providers using a snowball technique to reach as many of the women with SVRP as possible. The mean age of the participants was 15.3 years (SD = 3.4 years), and all the participants had spent 2 years or more in captivity. Most of the women first disclosed the pregnancy to their peers before disclosure to health care providers or family members. All the women initially requested to have the pregnancy terminated; however, abortion services are not offered in the clinic in line with the country's restrictive abortion laws. Following counseling and psychosocial support offered in the clinic, 19 (40%) of the women continued with the pregnancy and were delivered in the camp clinic while the remaining 26 women left the camp shortly after disclosure and pregnancy outcomes are not known. SVRP is not uncommon in humanitarian settings with its associated stigma and unwillingness among the survivors to keep the pregnancy. There is a need for further studies to provide more insight into the extent of this problem and help-seeking for SVRPs especially for women in such difficult circumstances to provide needed empirical information to drive advocacy efforts for more comprehensive services.


Overweight and Obesity: The Interplay of Eating Habits and Physical Activity.
The prevalence of overweight and obesity has been steadily increasing over the last 50 years, with worldwide obesity rates tripling since 1975, thus reaching pandemic proportions [...].


The family intensive care unit syndrome: A qualitative content analysis.
Hospitalization of patients in an intensive care unit (ICU) is associated with a series of psychological problems for their family members called family intensive care unit syndrome (FICUS). Nonetheless, family members of patients in ICU often receive little attention from health care providers. Exploring family members' experiences of their patients' hospitalization in ICU helps health care providers focus more clearly on their problems. This study aimed to explore FICUS-related experiences among the family members of patients in ICU. This was a qualitative content analysis study. This qualitative study was conducted in 2019. Participants were 14 family members of patients in ICU who were purposively selected from three hospitals in Tehran, Iran. Data were collected using semi-structured interviews and were analyzed using qualitative content analysis. Participants' experiences of FICUS fell into four categories, that is, threat to psychological well-being (with four subcategories), threat to physical health (with three subcategories), threat to social health (with three subcategories), and change in spiritual orientation (with two subcategories). The 12 subcategories of these categories were emotional disturbances, hopelessness, changes in sleep pattern, mood changes, physical symptoms, aggravation of the existing illnesses, negligence towards personal health, alteration in social interactions, alteration in the burden of responsibility, alternation in the life process, resort to spiritual beliefs, and spiritual conflict, respectively. FICUS symptoms are not limited to psychological problems, rather they include a wide range of psychological, physical, social, and spiritual problems, which can affect the different aspects of family members' lives. Along with care delivery to patients in ICU, health care providers should provide care and support to patients' family members. FICUS is a major threat to health among the family members of patients in ICU. Careful assessment of these family members helps identify family members who are at risk for FICUS and identify FICUS effects on their decisions and health status.


Role of small acute hyperintense lesions in long-term progression of cerebral small vessel disease and clinical outcome: a 14-year follow-up study.
Small hyperintense lesions are found on diffusion-weighted imaging (DWI) in patients with sporadic small vessel disease (SVD). Their exact role in SVD progression remains unclear due to their asymptomatic and transient nature. The main objective is to investigate the role of DWI+lesions in the radiological progression of SVD and their relationship with clinical outcomes. Participants with SVD were included from the Radboud University Nijmegen Diffusion tensor MRI Cohort. DWI+lesions were assessed on four time points over 14 years. Outcome measures included neuroimaging markers of SVD, cognitive performance and clinical outcomes, including stroke, all-cause dementia and all-cause mortality. Linear mixed-effect models and Cox regression models were used to examine the outcome measures in participants with a DWI+lesion (DWI+) and those without a DWI+lesion (DWI-). DWI+lesions were present in 45 out of 503 (8.9%) participants (mean age: 66.7 years (SD=8.3)). Participants with DWI+lesions and at least one follow-up (n=33) had higher white matter hyperintensity progression rates (β=0.36, 95% CI=0.05 to 0.68, p=0.023), more incident lacunes (incidence rate ratio=2.88, 95% CI=1.80 to 4.67, p<0.001) and greater cognitive decline (β=-0.03, 95% CI=-0.05 to -0.01, p=0.006) during a median follow-up of 13.2 (IQR: 8.8-13.8) years compared with DWI- participants. No differences were found in risk of all-cause mortality, stroke or dementia. Presence of a DWI+lesion in patients with SVD is associated with greater radiological progression of SVD and cognitive decline compared with patients without DWI+lesions.


Catalytic Site-Selective Acylation of Carbohydrates Directed by Cation-n Interaction.
Site-selective functionalization of hydroxyl groups in carbohydrates is one of the long-standing challenges in chemistry. Using a pair of chiral catalysts, we now can differentiate the most prevalent trans-1,2-diols in pyranoses systematically and predictably. Density functional theory (DFT) calculations indicate that the key determining factor for the selectivity is the presence or absence of a cation-n interaction between the cation in the acylated catalyst and an appropriate lone pair in the substrate. DFT calculations also provided a predictive model for site-selectivity and this model is validated by various substrates.


Preparation of Taraxacum kok-saghyz Rubber and Biofuel Ethanol Simultaneously by the Yeast Fermentation Process.
Taraxacum kok-saghyz(TKS) rubber is considered the most ideal alternative source of natural rubber (NR). Extracting rubber from TKS with high quality, low cost, and low pollution is the basis of commercial development. The TKS roots were subjected to morphological observation and detailed compositional analysis. Scanning electron microscopy (SEM) images confirm that rubber filaments are physically entangled with plant tissues due to differences in molecular polarity. Compared with the traditional solvent TKS rubber extraction process, a new rubber extraction process developed in this study, namely, the microbial extraction (″ME″) process, is less harmful to the environment and lower in cost. The ″ME″ process is divided into three steps: dilute acid pretreatment process, enzyme degradation process, and fermentation process. After each step is completed, the purity of TKS rubber will gradually increase from 84.8% to 93.8 to 95.5%. The TKS rubber finally obtained fully meets the requirements of the traditional rubber industry, especially the tire industry. Besides, the yield of biofuel ethanol, a by-product of cellulose fermentation, reaches 2.05 g/100 g of TKS roots (dry weight), which can effectively reduce the production cost of TKS rubber. In the rubber extraction process, microorganisms have little effect on the quality of TKS rubber. The results show that the molecular weight and chemical structure of TKS rubber is very close to NR, so the ″ME″ process can be used as a new method for large-scale extraction of TKS rubber.


Electric Destabilization of Supramolecular Lipid Vesicles Subjected to Fast Electric Pulses.
Biological membranes are weakly permeable to hydrophilic molecules and ions and electric pulses can induce their transient permeabilization, but this process is not well characterized. We directly assay the electropermeabilization process, on the minimum model of lipid vesicles, by using a highly sensitive fluorescence method based on manganese ion transport. The approach gives access, at the single-lipid self-assembly level, to the transmembrane potential needed to detect divalent ion permeabilization on supramolecular giant unilamellar lipid vesicles. The critical values are strongly dependent on the lipid composition and are observed to vary from 10 to 150 mV. These values appear to be much lower than those previously reported in the literature for cells and vesicles. The detection method appears to be a decisive parameter as it is controlled by the transport of the reporter dye. We also provide evidence that the electropermeabilization process is a transient transition of the lipid self-organization due to the loss of assembly cohesion induced by bioelectrochemical perturbations of the zwitterionic interface with the solution.


Physiological functions of presenilins; beyond γ-secretase.
Presenilin (PS) was identified in screens for mutations causing the early onset forms of familial Alzheimer's disease (FAD) in 1995. As catalytic units of the γ-secretase complex, presenilins participate in the processing of amyloid beta protein (Aβ), the main component of deposits in brain of patients with AD. The more than 90 substrates of γ-secretase isolated so far demonstrate its contribution to wide range of cellular processes and signaling events. However, recent findings have revealed numerous γ-secretase-independent presenilin functions, including involvement in calcium homeostasis, endoplasmic reticulum (ER) stress and autophagy. This mini-review attempts to summarize the multiple physiological and pathological functions of presenilin.


[Chylous mesenteric cyst].
The authors present a case report of a female patient with a recurrent mesenteric cyst. Chylous cyst is one of rare diagnoses of a cyst close to the pancreas in patients with no history of acute pancreatitis. Chylous cysts need to be managed radically; otherwise, given their nature, they are likely to recur.


Multielemental elution behavior of metal ions adsorbed on iminodiacetic acid chelating resin by using hydrogen peroxide as an eluent.
In the present work, we investigated the multielemental elution behavior of metal ions absorbed on iminodiacetic acid (IDA) chelating resin by using hydrogen peroxide (H(2)O(2)) as an eluent. As a result, V(V), Mo(VI), W(VI), Nb(V) and Ta(V) were efficiently eluted by H(2)O(2). In contrast, other metal ions were rarely recovered. The oxidation states of V(V), Mo(VI), and W(VI) were not changed through the H(2)O(2) eluting process, checked by X-ray photoelectron analysis. In addition, the UV-vis adsorption spectra and IR spectra of V(V), Mo(VI) and W(VI) in the H(2)O(2) eluent suggested the formation of metal-peroxo complexes through H(2)O(2) elution. The desorption of these metal ions from IDA functional groups is explained in term of destabilization along with the coordination of peroxo-ligands to the V(V)-, Mo(VI)- and W(VI)-IDA complexes, and a decrease in the adsorption capacity by electrostatic repulsion between dissociated carboxylic groups of IDA and the oxoanions in the neutral pH shown in 30 wt% H(2)O(2). When this method was applied to the selective separation of V(V), Mo(VI) and W(VI) from other metals in an acid soluble fraction of fly-ash, 83.4 ± 2.5% of V(V), 88.1 ± 3.3% of Mo(VI), and 69.3 ± 5.4% of W(VI) were recovered in a 30 wt% H(2)O(2) eluent.


Losartan reverses COX-2-dependent vascular dysfunction in offspring of hyperglycaemic rats.
This study examined whether chronic treatment with losartan, an angiotensin II type 1 receptor (AT1R) antagonist, might reverse COX-2-mediated vascular dysfunction in mesenteric resistance arteries (MRA) from offspring of hyperglycaemic rats. Male 12-month-old offspring of hyperglycaemic (O-DR) and normoglycaemic (O-CR) rats were treated with losartan (15mg·kg·day-1) during 2months. Third order MRA of untreated and losartan-treated O-DR and O-CR were mounted in wire myograph for isometric tension measurements. COX-2 expression was analyzed by Western blot; TxA2, PGE2 and PGF2α release was measured using commercial kits. O-DR showed increased blood pressure, impaired acetylcholine-induced vasodilation and increased noradrenaline-induced vasoconstriction than O-CR. All these parameters were normalized by losartan in O-DR. Pre-incubation of MRA with indomethacin (COX-1/2 inhibitor), NS-398 (COX-2 inhibitor) or tempol (superoxide dismutase mimetic) increased relaxation to acetylcholine and reduced contraction to noradrenaline only in O-DR. COX-2 expression, TxA2, PGE2 and PGF2α release were increased in O-DR. In losartan-treated O-DR, NS-398, indomethacin or tempol failed to produce any effect on acetylcholine or noradrenaline responses. Losartan treatment reduced COX-2 expression, TxA2, PGE2 and PGF2α release in O-DR. The present results reveal that chronic losartan administration in O-DR normalizes endothelial function in MRA by correcting the existing COX-2 overexpression and the imbalance between endothelium-derived relaxing and contracting factors. These findings not only support the beneficial effects of AT1 receptor antagonist in O-DR, but also suggest the implication of angiotensin II as a putative mediator of hyperglycemia-programmed vascular dysfunction in rats.


Fluorescence Approach for the Determination of Fluorescent Dissolved Organic Matter.
Excitation-emission matrix (EEM) fluorescence spectroscopy coupled with parallel factor (PARAFAC) analysis has been widely applied to characterize dissolved organic matter (DOM) in aquatic and terrestrial systems. However, its application in environmental samples is limited because PARAFAC is not able to handle nontrilinear EEM data, leading to the overestimated number of components and incorrect decomposition results. In this work, a new method, parallel factor framework-clustering analysis (PFFCA), is proposed to resolve this problem. First, simulated data with different signal-to-noise ratios and intensities of nontrilinear structure were tested to confirm the robustness of PFFCA. The residual sum of squares (RSS) of PARAFAC was significantly higher than that of PFFCA (p < 0.037). Second, a set of data originating from a synthetic mixture of humic acid and bovine serum albumin was applied to compare with PARAFAC with known samples. PFFCA provided an estimation (R2 > 0.92) closer to actual EEM than PARAFAC (R2 > 0.81). Finally, to confirm the feasibility of PFFCA in analyzing natural samples, DOM-containing samples collected from both a polluted lake and river were tested, indicating that PFFCA provides a more precise estimation than PARAFAC. The results clearly indicate that PFFCA offers a robust approach for the unique decomposition of complex synthetic and natural samples, which is of great significance in understanding the characteristics of DOM in aqueous systems.


Repair of membrane damage in X-irradiated E. coli.
When E. coli B/r or E. coli K12 AB1157 were X-irradiated in the presence of oxygen and incubated immediately after irradiation in broth containing penicillin in concentration that on its own was not lethal to unirradiated bacteria, substantial additional killing was caused. When treatment with penicillin was delayed for increasing times after irradiation the additional killing became progressively less. These results were interpreted as demonstrating the repair or removal of oxygen-dependent radiation-induced lesions in the bacterial membranes. Removal of these lesions was inhibited by incubation of the irradiated bacteria at low temperature before treatment with penicillin or by exposing the cells to a non-lethal concentration of toluene before irradiation. These observations suggest that an enzymatic repair process may be involved in the removal of the membrane lesions. The fatty acid mutant E. coli K 1060 proved exceptional in that some additional killing by penicillin was detectable after anaerobic as well as aerobic irradiation. This points to the importance of membrane composition in the development of those radiation lesions that are brought to light by penicillin treatment.


[Propofol infusion syndrome in children].
Propofol infusion syndrome, characterised by cardiovascular collapse, metabolic acidosis, hepatomegaly, renal failure and rhabdomyolysis, is a rare and often fatal syndrome seen in critically ill children undergoing long-term propofol sedation. Propofol may impair mitochondrial free fatty acid metabolism, resulting in an imbalance between energy demand and utilisation and thus compromising cardiac and peripheral muscle cell function. Propofol should be used with caution for sedation in critically ill children, as well as for long-term anaesthesia in otherwise healthy children, and doses exceeding 4 mg/kg/h should be avoided.


Generalized eigensystem techniques for the inverse problem of electrocardiography applied to a realistic heart-torso geometry.
We have previously proposed two novel solutions to the inverse problem of electrocardiography, the generalized eigensystem technique (GES) and the modified generalized eigensystem technique (tGES), and have compared these techniques with other numerical techniques using both homogeneous and inhomogeneous eccentric spheres model problems. In those studies we found our generalized eigensystem approaches generally gave superior performance over both truncated singular value decomposition (SVD) and zero-order Tikhonov regularization (TIK). In this paper we extend the comparison to the case of a realistic heart-torso geometry. With this model, the GES and tGES approaches again provide smaller relative errors between the true potentials and the numerically derived potentials than the other methods studied. In addition, the isopotential maps recovered using GES and tGES appear to be more accurate than the maps recovered using either SVD and TIK.


From Reductionism to Holism: Systems-oriented Approaches in Cancer Research.
Somatic mutation theory of cancer has directed cancer research during the last century. A deluge of information on cellular, molecular, and genetic behavior was uncovered, but so was a mind-numbing complexity that still challenges research and concepts, and expectations in the war on cancer have by and large not been fulfilled. A change of paradigm beyond reductionism has been called for, especially as research ubiquitously points at the importance of tissue, microenvironment, extracellular matrix, embryonic and morphogenetic fields, and fields of tissue maintenance and organization in the processes of carcinogenesis, cancer control, and cancer progression, as well as in the control of cellular and genetic behavior. Holistic, organismic systems concepts open new perspectives for cancer research and treatment, as well as general biological understanding.


A century of leishmaniasis in Alpes-Maritimes, France.
A century of publications on leishmaniasis in Alpes-Maritimes, in southern France, is here reviewed. Autochtonous human and canine leishmaniasis were first recognised in this département, which lies by the Mediterranean Sea and near the Italian border, in 1918 and 1925, respectively. The parasite responsible for the leishmaniasis, Leishmania infantum, is transmitted by Phlebotomus perniciosus and P. ariasi. The human leishmaniasis is zoonotic, with domestic dogs acting as the main 'reservoir' hosts. In prospective surveys over the last two decades, a mean of 12% of the domestic dogs checked in Alpes-Maritimes have been found seropositive for L. infantum but only about 50% of the seropositive animals showed any clinical signs of infection at the time of the surveys. During the last 30 years, 178 cases of human visceral leishmaniasis have been recorded in the area. Such cases are sporadic and often opportunistic, occurring predominantly in children (29% of the 178 cases) or HIV-positive subjects (31%). Recently, it has been demonstrated that, in Alpes-Maritimes, approximately 20% of those found seropositive in leishmanin skin tests are asymptomatic carriers, with amastigotes in their peripheral blood.


Globotriaosyl ceramide and globoside as major glycolipid components of fibroblasts in scirrhous gastric carcinoma tissues.
Scirrhous gastric cancer is characteristic in that cancer cells proliferate and invade with prominent fibrosis. To search for the expression of specific carbohydrate chains in scirrhous gastric cancer, we have examined the glycosphingolipid composition of scirrhous cancer tissues (n=10) in comparison with that of non-scirrhous cancer tissues (n=10) by means of two-dimensional thin layer chromatography, followed by fast atom bombardment mass spectrometry of the individual glycolipids and immunostaining analysis. The major neutral glycosphingolipids from scirrhous gastric cancer tissues were identified as ceramide monohexoside, ceramide dihexoside, globotriaosyl ceramide (Gb3) and globoside (Gb4), while the major acidic glycosphingolipids were II3 NeuAcalpha-LacCer, II3 NeuAcalpha2-LacCer and sulfatide. Relative concentrations of Gb3 and Gb4 in scirrhous gastric cancer tissues (Gb3 + Gb4 = 58%) were two times higher than those in non-scirrhous gastric cancer tissues (29%). Orthotopic fibroblasts cloned from scirrhous gastric cancer tissues showed similar high concentrations of Gb3 and Gb4 to scirrhous gastric cancer tissues. Furthermore, immunohistochemical study revealed that Gb3 and Gb4 were expressed intensely on the fibroblasts. On the other hand, analysis of glycosphingolipids in four scirrhous gastric cancer cell lines yielded the following results. i) The contents of Gb3 and Gb4 were low (6%), compared with orthotopic fibroblasts (62%). ii) Significant amounts of Le(a) (pentaglycosylceramide) and Le(b) (hexa- and heptaglycosylceramides), which could not be detected in scirrhous cancer tissues, were observed. The results show that the major neutral glycosphingolipids such as Gb3 and Gb4 of scirrhous gastric cancer tissues were derived from orthotopic fibroblasts and not from the cancer cells.


Early modulation of intra-cortical inhibition during the observation of action mistakes.
Errors while performing an action are fundamental for learning. During interaction others' errors must be monitored and taken into account to allow joint action coordination and imitation learning. This monitoring relies on an action observation network (AON) mainly based on parietofrontal recurrent circuits. Although different studies suggest that inappropriate actions may rapidly be inhibited during execution, little is known about the modulation of the AON when an action misstep is shown. Here we used single and paired pulse transcranial magnetic stimulation to assess corticospinal excitability, intracortical facilitation and intracortical inhibition at different time intervals (120, 180, 240 ms) after the visual presentation of a motor execution error. Results show a specific and early (120 ms) decrease of intracortical inhibition likely because of a significant mismatch between the observed erroneous action and observer's expectations. Indeed, as proposed by the top-down predictive framework, the motor system may be involved in the generation of these error signals and our data show that this mechanism could rely on the early decrease of intracortical inhibition within the corticomotor system.


Evolving trends in enteral alimentation.
Nutrition has become a cornerstone of surgical patient care. With better understanding of metabolic and compositional requirements, great advances have been made in the area of total parenteral nutrition. Recent attention to full utilization of alimentary tract function has prompted a resurgence of interest in dietary formulas and methods of delivery. Three new approaches to the alimentary tract provide better access for feeding. Needle catheter jejunostomy allows early alimentary tract utilization following operations, while percutaneous endoscopic gastrostomy and jejunostomy provide long-term solutions to the provision of enteral alimentation. Future utilization of these techniques will certainly lead to better patient care.


Transforming growth factor beta-1 in acute myocardial infarction in rats.
TGF-beta 1 has been examined in the heart during myocardial infarction caused by ligation of the left coronary artery. Infarcted and uninfarcted myocardium have been compared by immunohistochemical staining of TGF-beta 1 and by Northern blot analysis of mRNA. Normal ventricular myocytes are strongly stained by an antibody to TGF-beta 1. Progressive loss of staining of these myocytes begins within 1 hr after coronary ligation. However, by 24-48 hr after ligation, intense staining of myocytes at the margin of infarcted areas is seen. Northern blots of infarcted myocardium 48 hr after ligation show a 3- to 4-fold increase in the principal 2.4 kb TGF-beta 1 mRNA; there is also a marked increase in a minor 1.9 kb transcript. In the same tissue samples, there is a 2-fold decrease in the mRNA for the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase. The results indicate a significant role for TGF-beta in the response of the heart to injury.


Life-threatening deep fascial space infections of the head and neck.
In the preantibiotic era, deep fascial space infections were common, and physicians were well acquainted with their complex and sometimes subtle manifestations. Widespread use of antibiotics, however, not only has significantly decreased the incidence of deep neck infections but also has altered their clinical manifestations. This article is designed to emphasize the key clinical manifestations of the several life-threatening deep neck infections and relate them to critically important anatomic structures in the neck.


Identifying live bird markets with the potential to act as reservoirs of avian influenza A (H5N1) virus: a survey in northern Viet Nam and Cambodia.
Wet markets are common in many parts of the world and may promote the emergence, spread and maintenance of livestock pathogens, including zoonoses. A survey was conducted in order to assess the potential of Vietnamese and Cambodian live bird markets (LBMs) to sustain circulation of highly pathogenic avian influenza virus subtype H5N1 (HPAIV H5N1). Thirty Vietnamese and 8 Cambodian LBMs were visited, and structured interviews were conducted with the market managers and 561 Vietnamese and 84 Cambodian traders. Multivariate and cluster analysis were used to construct a typology of traders based on their poultry management practices. As a result of those practices and large poultry surplus (unsold poultry reoffered for sale the following day), some poultry traders were shown to promote conditions favorable for perpetuating HPAIV H5N1 in LBMs. More than 80% of these traders operated in LBMs located in the most densely populated areas, Ha Noi and Phnom Penh. The profiles of sellers operating at a given LBM could be reliably predicted using basic information about the location and type of market. Consequently, LBMs with the largest combination of risk factors for becoming virus reservoirs could be easily identified, potentially allowing control strategies to be appropriately targeted. These findings are of particular relevance to resource-scarce settings with extensively developed LBM systems, commonly found in South-East Asia.


Acoustic radiation force on a spherical thermoviscous particle in a thermoviscous fluid including scattering and microstreaming.
We derive general analytical expressions for the time-averaged acoustic radiation force on a small spherical particle suspended in a fluid and located in an axisymmetric incident acoustic wave. We treat the cases of the particle being either an elastic solid or a fluid particle. The effects of particle vibrations, acoustic scattering, acoustic microstreaming, heat conduction, and temperature-dependent fluid viscosity are all included in the theory. Acoustic streaming inside the particle is also taken into account for the case of a fluid particle. No restrictions are placed on the widths of the viscous and thermal boundary layers relative to the particle radius. We compare the resulting acoustic radiation force with that obtained from previous theories in the literature, and we identify limits, where the theories agree, and specific cases of particle and fluid materials, where qualitative or significant quantitative deviations between the theories arise.