Effect of SOCS1 overexpression on RPE cell activation by proinflammatory cytokines.
The purpose of this study was to investigate the in vitro effect of Suppressor Of Cytokine Signaling 1 (SOCS1) overexpression in retinal pigment epithelium (RPE) cells on their activation by pro-inflammatory cytokines IFNγ, TNFα and IL-17. Retinal pigment epithelium cells (ARPE-19) were stably transfected with the control plasmid pIRES2-AcGFP1 or the plasmid pSOCS1-IRES2-AcGFP1. They were stimulated by IFNγ (150ng/ml), TNFα (30ng/ml) or IL-17 (100ng/ml). The levels of SOCS1 mRNA were measured by real-time PCR. Signal Transducer and Activator of Transcription 1 (STAT1) phosphorylation and IκBα expression were analysed by western Blot (WB). IL-8 secretion was analysed by ELISA and expression of MHCII molecules and ICAM-1/CD54 by flow cytometry. Our data show that SOCS1 mRNA overexpression in RPE cells prevents IFNγ-induced SOCS1 mRNA increase and IFNγ-mediated STAT1 phosphorylation. Moreover, SOCS1 overexpression in RPE cells inhibits IFNγ-induced decrease of IL-8 secretion and prevents IFNγ-induced MHC II and ICAM1/CD54 upregulation. However, SOCS1 overexpression does not affect TNFα-induced IκBα degradation nor block TNFα-induced or IL-17-induced IL-8 secretion. On the contrary, IL-17-induced secretion is increased by SOCS1 overexpression. In conclusion, SOCS1 overexpression in RPE cells inhibits some IFNγ-mediated responses that lead to uveitis development. This notion raises the possibility that SOCS1 overexpression could be a novel target for treating non-infectious uveitis. However, some proinflammatory effects of TNFα and IL-17 stimulation on RPE are not blocked by SOCS1 overexpression.


The effect of buccal-lingual slot dimension size on third-order torque response.
The focus of the presented study was to investigate the effect of buccal-lingual (B-L) orthodontic bracket slot dimension on third-order torque mechanics. Three types of orthodontic brackets and two archwire sizes were considered. Ortho Classic H4 (0.026″ B-L slot, passive), Ormco Damon Q (0.028″ B-L slot, passive), and In-Ovation R (0.028″ slot, active) brackets were tested using 0.017″ × 0.025″ and 0.019″ × 0.025″ beta-titanium archwires. An in vitro orthodontic torque simulator (OTS) was used to rotate archwires relative to a single bracket while recording forces and moments in three directions. For each bracket-archwire combination, a total of n = 47 samples were tested. Repeated measures analysis of variance between brackets was conducted for third-order torque values at 3° increments between 9° and 30° during loading and unloading for each archwire size. Statistically significant differences between H4 and Q brackets were only found for 0.017″ × 0.025″ archwires during loading, and 0.019″ × 0.025″ archwires during unloading. Conversely, differences between H4 and R brackets were found for both archwires during loading and unloading phases. Finally, when using a 0.017″ × 0.025″ archwire the H4 brackets reached the 5 Nmm threshold before R and Q brackets; however, there was little difference found when using a 0.019″ × 0.025″ archwire. The concept of using a smaller B-L bracket slot dimension in orthodontic treatment showed it may theoretically allow for more options, primarily using smaller archwires to correct third-order rotational misalignments. However, it is suspected that bracket material limitations and added loading on the door currently prevent this from being clinically applicable.


Two key arginine residues in the coat protein of Bamboo mosaic virus differentially affect the accumulation of viral genomic and subgenomic RNAs.
The interactions between viral RNAs and coat proteins (CPs) are critical for the efficient completion of infection cycles of RNA viruses. However, the specificity of the interactions between CPs and genomic or subgenomic RNAs remains poorly understood. In this study, Bamboo mosaic virus (BaMV) was used to analyse such interactions. Using reversible formaldehyde cross-linking and mass spectrometry, two regions in CP, each containing a basic amino acid (R99 and R227, respectively), were identified to bind directly to the 5' untranslated region of BaMV genomic RNA. Analyses of the alanine mutations of R99 and R227 revealed that the secondary structures of CP were not affected significantly, whereas the accumulation of BaMV genomic, but not subgenomic, RNA was severely decreased at 24 h post-inoculation in the inoculated protoplasts. In the absence of CP, the accumulation levels of genomic and subgenomic RNAs were decreased to 1.1%-1.5% and 33%-40% of that of the wild-type (wt), respectively, in inoculated leaves at 5 days post-inoculation (dpi). In contrast, in the presence of mutant CPs, the genomic RNAs remained about 1% of that of wt, whereas the subgenomic RNAs accumulated to at least 87%, suggesting that CP might increase the accumulation of subgenomic RNAs. The mutations also restricted viral movement and virion formation in Nicotiana benthamiana leaves at 5 dpi. These results demonstrate that R99 and R227 of CP play crucial roles in the accumulation, movement and virion formation of BaMV RNAs, and indicate that genomic and subgenomic RNAs interact differently with BaMV CP.


Systemic sclerosis in children: a national retrospective survey in Japan.
A retrospective questionnaire survey of pediatric departments, for childhood collagen disease from 1985 to 1994 was used to clarify the clinical features of scleroderma in Japan. In the primary survey, 0.9% of the children with a rheumatic condition and scleroderma. Answers to this questionnaire were received on 18 (localized 9; systemic 9) patients from 15 institutions. In order to examine systemic sclerosis (SSc), seven cases of SSc in Japanese articles during the same period as the questionnaire were added to these answers and compared to the Japanese epidemic study investigated by Fukuyama in 1974. There were 16 children, seven boys and nine girls, with SSc during the 10-year period in Japan. The mean age of onset of symptoms was 8.0 +/- 2.8 years and the age at diagnosis 10.1 +/- 3.0 years. Eighty percent of children had Raynaud's phenomenon at the onset of SSc, and skin and musculoskeletal involvement was highly recognized during the course of the disease. Atrophy of the frenulum linguae and lung fibrosis were commonly seen in SSc. In serological studies, 80% of children have antinuclear antibodies and approximately 50% of patients have anti-Scl-70 (topoisomelase I) antibodies at the onset and during the course of childhood SSc. The prognosis is poor, as remission occurred in only one child. The clinical symptoms and examination of serological autoimmune antibodies were supportive of an early diagnosis of SSc. When compared to the previous national survey of children with SSc, the present results showed that the male-to-female ratio was reduced, the age at onset was low, the positive incidence of serological autoimmune antibodies elevated, and the usage of vasodilators and nonsteroid anti-inflammatory drugs (NSAID) increased, with corticosteroids decreased. But, the positive percentage of clinical symptoms were not changed in both studies. For a complete retrospective nationwide epidemic survey carried out on children with scleroderma, especially SSc, it is important to include dermatology departments.


Enhancement of avian mandibular chondrogenesis in vitro in the absence of epithelium.
The roles of mandibular epithelium in chondrogenesis and growth of mandibular mesenchyme were examined in organ cultures. Epithelium and mesenchyme were separated from the mandibular arches of chick embryos at stages before and after the onset of chondrogenesis in vivo (stages 18-28). Isochronic and heterochronic tissue recombinations were prepared. Removal of the mandibular epithelium resulted in reduced growth of the explants and enhanced chondrogenesis, resulting in increased levels of mRNAs for type II collagen and aggrecan. The presence of mandibular epithelium promoted cell division in loosely arranged undifferentiated tissue from the mandibular mesenchyme and resulted in increased levels of type I collagen mRNA. Enhanced chondrogenesis was also observed in the mesenchyme isolated with basement membrane and isolated mesenchyme grown within Matrigel. These findings suggest that mandibular epithelium has mitogenic and chondrogenic-inhibitory effects on the underlying mesenchyme that are stage independent. Furthermore, the chondrogenic-inhibitory effect of mandibular epithelium on the underlying mesenchymal cells is not mediated by basement membrane.


Autoimmune Heparin-Induced Thrombocytopenia after Transcatheter Aortic Valve Implantation: Successful Treatment with Adjunct High-Dose Intravenous Immunoglobulin.
We describe a rare case of autoimmune heparin-induced thrombocytopenia after transcatheter aortic valve implantation in which antibodies against platelet factor 4/heparin have led to platelet activation even after heparin cessation, causing a delayed drop in platelet count to below 20 × 10 9 /L. Most interestingly, platelet count rapidly improved after intravenous immunoglobulin treatment and no new thromboembolic complications were observed with further anticoagulation with rivaroxaban.


Tolerating the "doubting Thomas": how centrality of religious beliefs vs. practices influences prejudice against atheists.
Past research has found a robust effect of prejudice against atheists in largely Christian-dominated (belief-oriented) samples. We propose that religious centrality of beliefs vs. practices influences attitudes toward atheists, such that religious groups emphasizing beliefs perceive non-believers more negatively than believers, while groups emphasizing practices perceive non-practicing individuals more negatively than practicing individuals. Studies 1-2, in surveys of 41 countries, found that Muslims and Protestants (belief-oriented) had more negative attitudes toward atheists than did Jews and Hindus (practice-oriented). Study 3 experimentally manipulated a target individual's beliefs and practices. Protestants had more negative attitudes toward a non-believer (vs. a believer), whereas Jews had more negative attitudes toward a non-practicing individual (vs. a practicing individual, particularly when they had a Jewish background). This research has implications for the psychology of religion, anti-atheist prejudice, and cross-cultural attitudes regarding where dissent in beliefs or practices may be tolerated or censured within religious groups.


Dextran-induced anaphylactoid reaction in man: altered reactivity of high molecular weight kininogen.
Normal levels of factor XII and of high and low molecular weight kininogens (HMWK and LMWK) were registered in plasma specimens from 5 individuals who had developed anaphylactoid reactions upon injection of dextran during surgery (dextran reactors, DR). Factor XII was assayed as prekallikrein activator (PKA) activated with kaolin at 0 degrees, and kininogen fractions were estimated through the release of kinin caused by plasma kallikrein or hog pancreas kallikrein (HPK). Subnormal levels of factor XII apparently present in plasma from one DR, and after affinity chromatography on a lysine-Sepharose column also in plasma from another DR, were normalized by addition of plasma deficient in factor XII or by addition of purified HMWK. Treatment of plasma from DR with acetone (25% v/v) induced a conversion of HMWK into a state which was non-functional as a cofactor in the surface-dependent activation of factor XII, and the passage of plasma from DR through a lysine-Sepharose column altered the HMWK present to a substance that released kinin only very slowly by incubation with HPK. It is concluded that the treatments mentioned will favour the activation in plasma from DR of a factor that will cause the conversion of HMWK. Previous experiments with rat plasma demonstrated that plasmin and also a plasmin-like factor without affinity for lysine-Sepharose were able to destroy the capacity of HMWK to function as a cofactor in the surface-dependent activation of factor XII, without a corresponding release of kinin.


Dynamical localization in quasiperiodic driven systems.
We investigate how the time dependence of the Hamiltonian determines the occurrence of dynamical localization (DL) in driven quantum systems with two incommensurate frequencies. If both frequencies are associated to impulsive terms, DL is permanently destroyed. In this case, we show that the evolution is similar to a decoherent case. On the other hand, if both frequencies are associated to smooth driving functions, DL persists although on a time scale longer than in the periodic case. When the driving function consists of a series of pulses of duration sigma, we show that the localization time increases as sigma(-2) as the impulsive limit, sigma-->0, is approached. In the intermediate case, in which only one of the frequencies is associated to an impulsive term in the Hamiltonian, a transition from a localized to a delocalized dynamics takes place at a certain critical value of the strength parameter. We provide an estimate for this critical value, based on analytical considerations. We show how, in all cases, the frequency spectrum of the dynamical response can be used to understand the global features of the motion. All results are numerically checked.


A review of traditional and contemporary assays for direct and indirect detection of Equid herpesvirus 1 in clinical samples.
Equid herpesvirus 1 (EHV-1) is one of the most economically important equine viral pathogens. Its clinical manifestations in horses vary from acute upper respiratory tract disease, abortion, or neonatal death, to neurological disease termed equine herpesviral myeloencephalopathy, which may lead to paralysis and a fatal outcome. Successful identification of EHV-1 infection in horses depends on a variety of factors such as suitable case selection with emphasis on timing of sample collection, selection of appropriate sample(s) based on the clinical manifestations, application of relevant diagnostic technique(s) and/or test(s), and careful evaluation and interpretation of laboratory results. Several traditional serologic and virus isolation assays have been described; however, these assays have inherent limitations that prevent rapid and reliable detection of EHV-1. The advent of molecular biologic techniques has revolutionized the diagnosis of infectious diseases in humans and animal species. Specifically, polymerase chain reaction (PCR)-based assays have allowed detection of nucleic acid in clinical specimens precisely and rapidly as compared to the traditional methods that detect the agent or antigen, or agent-specific antibodies in serum. The new molecular methods, especially real-time PCR, can be a very useful means of EHV-1 detection and identification. Veterinarians involved in equine practice must be aware of the advantages and disadvantages of various real-time PCR assays, interpretation of viral genetic marker(s), and latency in order to provide the best standard of care for their equine patients.


Two closely related kappa variable region pseudogenes pose an evolutionary paradox.
Two pseudogenes belonging to the Igk-V1 variable region group have been isolated from BALB/c mice. The genes share greater than 96.5% identity of nucleotide sequence in a 1800 base pair (bp) region surrounding the coding region, but deletions of 221 bp and 84 bp have removed essential sequences from the two genes. As the deletions are different in the two pseudogenes, they must have occurred independently in each gene during or subsequent to the duplication event which gave rise to the genes from a common ancestral gene. Polymerase chain reaction analysis was used to identify the pseudogenes in inbred strains of mice. BALB/c (Igkc) and AKR (Igka), prototype strains representative of the predominant kappa haplotypes, possess both pseudogenes but no intact copy. Only one of the pseudogenes was present in SJL (Igka). Strains C58, c.C58 (Igkd) and NZB (Igkb) possessed an intact version of the gene. This distribution of haplotypes is consistent with a close linkage of the pseudogenes with other Igk-V1 genes on chromosome 6. The translated amino acid sequence of the pseudogenes indicates that prior to their acquiring deletions they encoded typical Igk-V1 variable regions except for an unusual FR2 region, in which the conserved proline at position 44 is replaced by leucine and the normally hydrophobic position 36 was occupied by histidine. Possible mechanisms to explain the occurrence of deletions in both of the pseudogenes in the recent evolution of BALB/c are discussed. One explanation would be that the two genes were already nonfunctional at the time of the duplication so that the subsequent deletions represent neutral events which became fixed in the inbred strains by a process of genetic drift. Alternatively, if the genes were functional at the time of duplication, their rapid loss due to deletion events suggests that negative selection may have acted to eliminate the genes from the V-region repertoire.


Recommendations for the management of biofilm: a consensus document.
The potential impact of biofilm on healing in acute and chronic wounds is one of the most controversial current issues in wound care. A significant amount of laboratory-based research has been carried out on this topic, however, in 2013 the European Wound Management Association (EWMA) pointed out the lack of guidance for managing biofilms in clinical practice and solicited the need for guidelines and further clinical research. In response to this challenge, the Italian Nursing Wound Healing Society (AISLeC) initiated a project which aimed to achieve consensus among a multidisciplinary and multiprofessional international panel of experts to identify what could be considered part of 'good clinical practice' with respect to the recognition and management of biofilms in acute and chronic wounds. The group followed a systematic approach, developed by the GRADE working group, to define relevant questions and clinical recommendations raised in clinical practice. An independent librarian retrieved and screened approximately 2000 pertinent published papers to produce tables of levels of evidence. After a smaller focus group had a multistep structured discussion, and a formal voting process had been completed, ten therapeutic interventions were identified as being strongly recommendable for clinical practice, while another four recommendations were graded as being 'weak'. The panel subsequently formulated a preliminary statement (although with a weak grade of agreement): 'provided that other causes that prevent optimal wound healing have been ruled out, chronic wounds are chronically infected'. All members of the panel agreed that there is a paucity of reliable, well-conducted clinical trials which have produced clear evidence related to the effects of biofilm presence. In the meantime it was agreed that expert-based guidelines were needed to be developed for the recognition and management of biofilms in wounds and for the best design of future clinical trials. This is a fundamental and urgent task for both laboratory-based scientists and clinicians.


Maternal Obesity Programming of Perivascular Adipose Tissue and Associated Immune Cells: An Understudied Area With Few Answers and Many Questions.
At present, the worldwide prevalence of obesity has become alarmingly high with estimates foreshadowing a continued escalation in the future. Furthermore, there is growing evidence attributing an individual's predisposition for developing obesity to maternal health during gestation. Currently, 60% of pregnancies in the US are to either overweight or obese mothers which in turn contributes to the persistent rise in obesity rates. While obesity itself is problematic, it conveys an increased risk for several diseases such as diabetes, inflammatory disorders, cancer and cardiovascular disease (CVD). Additionally, as we are learning more about the mechanisms underlying CVD, much attention has been brought to the role of perivascular adipose tissue (PVAT) in maintaining cardiovascular health. PVAT regulates vascular tone and for a significant number of individuals, obesity elicits PVAT disruption and dysregulation of vascular function. Obesity elicits changes in adipocyte and leukocyte populations within PVAT leading to an inflammatory state which promotes vasoconstriction thereby aiding the onset/progression of CVD. Our current understanding of obesity, PVAT and CVD has only been examined at the individual level without consideration for a maternal programming effect. It is unknown if maternal obesity affects the propensity for PVAT remodeling in the offspring, thereby enhancing the obesity/CVD link, and what role PVAT leukocytes play in this process. This perspective will focus on the maternal contribution of the interplay between obesity, PVAT disruption and CVD and will highlight the leukocyte/PVAT interaction as a novel target to stem the tide of the current obesity epidemic and its secondary health consequences.


Molecular markers for leaf rust resistance genes in wheat.
Over 100 genes of resistance to rust fungi: Puccinia recondita f. sp. tritici, (47 Lr - leaf rust genes), P. striiformis (18 Yr - yellow rust genes) and P. graminis f. sp. tritici (41 Sr - stripe rust genes) have been identified in wheat (Triticum aestivum L.) and its wild relatives according to recent papers. Sixteen Lr resistance genes have been mapped using restriction fragments length polymorphism (RFLP) markers on wheat chromosomes. More than ten Lr genes can be identified in breeding materials by sequence tagged site (STS) specific markers. Gene Lrk 10, closely linked to gene Lr 10, has been cloned and its function recognized. Available markers are presented in this review. The STS, cleaved amplified polymorphic sequence (CAPS) and sequence characterized amplified regions (SCAR) markers found in the literature should be verified using Triticum spp. with different genetic background. Simple sequence repeats (SSR) markers for Lr resistance genes are now also available.


Cloning, purification, crystallization and preliminary X-ray crystallographic analysis of the N-terminal domain of DEAD-box RNA helicase from Staphylococcus aureus strain Mu50.
DEAD-box helicases are enzymes with an ATP-dependent RNA-unwinding function that are involved in a variety of cellular processes including RNA splicing, ribosome biogenesis and RNA degradation. In this study, the N-terminal domain of DEAD-box RNA helicase from Staphylococcus aureus strain Mu50 was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to 2.60 Å resolution using a synchrotron-radiation source. The crystal belonged to space group P1, with unit-cell parameters a=70.81, b=80.23, c=86.25 Å, α=69.54, β=66.54, γ=87.32°. The unit cell contained six molecules, with a corresponding VM of 2.91 Å3 Da(-1) and a solvent content of 56.1%.


A community-based single fall prevention exercise intervention for older adults (STEADY FEET): Study protocol for a randomised controlled trial.
Falls and fall-related injuries in older adults are a leading cause of disability and death. Evidence has shown the benefits of exercises in improving functional outcomes and reducing fall rates among community-dwelling older adults. However, there is lack of effective community-based single exercise intervention for a broad population of older adults who are at high risk for falls. We aim to evaluate the effectiveness of Steady Feet (SF), a 6-month tailored community fall prevention exercise programme for improving functional outcomes. SF classes are facilitated by community fitness instructors and an exercise video. The main outcome is between-group changes in short physical performance battery (SPPB) scores. Secondary outcomes include balance confidence, fear of falling, quality of life, fall rates, and cost effectiveness. We present the design of a 6-month randomised controlled trial of 260 older adults (≥ 60 years old). Individuals will be randomised in a 1:1 allocation ratio to the SF group or usual care group. Participants will be assessed at baseline, 3-month, and 6-month. Data on socio-demographics, co-morbidities, balance confidence, fear of falling, quality of life, physical activity level, rate of perceived exertion, fall(s) history, healthcare utilisation and cost, and satisfaction levels will be collected. Participants will also undergo functional assessments such as SPPB. Moreover, providers' satisfaction and feedback will be obtained at 3-month. An effective community fall prevention programme may lead to improved functional outcomes and reduced fall rates. Findings will also help inform the implementation and scaling of SF nation-wide. Clinicaltrials.gov registration: NCT04801316. Registered on 15th March 2021.


Armed conflicts and national trends in reproductive, maternal, newborn and child health in sub-Saharan Africa: what can national health surveys tell us?
Armed conflicts are widespread in sub-Saharan Africa and considered to be an important factor in slowing down national progress in reproductive, maternal, newborn and child health (RMNCH). The measurement of the impact of conflicts on national levels and trends in RMNCH is difficult. National surveys conducted before and sometimes during and after conflicts are a major source of information on the national and local effects of conflicts on RMNCH. We examined data from national surveys in 13 countries in sub-Saharan Africa with major conflicts during 1990-2016 to assess the levels and trends in RMNCH intervention coverage, nutritional status and mortality in children under 5 years in comparison with subregional trends. The surveys provide substantive evidence of a negative association between levels and trends in national indicators of RMNCH service coverage, child growth and under-5 mortality with armed conflict, with some notable exceptions. National surveys are an important source of data to assess the longer term national consequences of conflicts for RMNCH in most countries, despite limitations due to sampling and timing of the surveys.


Genome and cuticular hydrocarbon-based species delimitation shed light on potential drivers of speciation in a Neotropical ant species complex.
Geographic separation that leads to the evolution of reproductive isolation between populations generally is considered the most common form of speciation. However, speciation may also occur in the absence of geographic barriers due to phenotypic and genotypic factors such as chemical cue divergence, mating signal divergence, and mitonuclear conflict. Here, we performed an integrative study based on two genome-wide techniques (3RAD and ultraconserved elements) coupled with cuticular hydrocarbon (CHC) and mitochondrial (mt) DNA sequence data, to assess the species limits within the Ectatomma ruidum species complex, a widespread and conspicuous group of Neotropical ants for which heteroplasmy (i.e., presence of multiple mtDNA variants in an individual) has been recently discovered in some populations from southeast Mexico. Our analyses indicate the existence of at least five distinct species in this complex: two widely distributed across the Neotropics, and three that are restricted to southeast Mexico and that apparently have high levels of heteroplasmy. We found that species boundaries in the complex did not coincide with geographic barriers. We therefore consider possible roles of alternative drivers that may have promoted the observed patterns of speciation, including mitonuclear incompatibility, CHC differentiation, and colony structure. Our study highlights the importance of simultaneously assessing different sources of evidence to disentangle the species limits of taxa with complicated evolutionary histories.


Clinical Prediction of Suicide and Undetermined Death: A Pseudo-Prospective Clinical and Medico-Legal Study of Substance Abusers.
This study examines aspects of prediction of suicide and death of undetermined intent. We investigated all consecutive, autopsied patients between 1993 and 1997 who had been in contact with the Addiction Centre in Malmö from 1968 onwards. The staff was asked, shortly after autopsy but before they knew of the manner of death, if they thought the patient had committed suicide. The case records were blindly evaluated, and toxicological autopsy findings for alcohol in blood samples investigated. The specificity of prediction was 83% and significantly more often correct than the sensitivity, which was only 45% for suicide and for suicide/death of undetermined intent (93% versus 39%). Suicidal communication was more often considered non-serious before death of undetermined intent than before suicide. The former could be predicted by ideation but not by suicide attempt reported in case records, unlike suicide, which was predicted by both. The undetermined group also showed higher levels of alcohol in the blood at autopsy. We concluded that more serious clinical investigation of suicidal feelings, which may be hidden and not taken seriously, and treatment of alcohol use disorders with active follow-up appear urgent in the efforts to prevent suicide.


Microscopic validation of whole mouse micro-metastatic tumor imaging agents using cryo-imaging and sliding organ image registration.
We created a metastasis imaging, analysis platform consisting of software and multi-spectral cryo-imaging system suitable for evaluating emerging imaging agents targeting micro-metastatic tumor. We analyzed CREKA-Gd in MRI, followed by cryo-imaging which repeatedly sectioned and tiled microscope images of the tissue block face, providing anatomical bright field and molecular fluorescence, enabling 3D microscopic imaging of the entire mouse with single metastatic cell sensitivity. To register MRI volumes to the cryo bright field reference, we used our standard mutual information, non-rigid registration which proceeded: preprocess → affine → B-spline non-rigid 3D registration. In this report, we created two modified approaches: mask where we registered locally over a smaller rectangular solid, and sliding organ. Briefly, in sliding organ, we segmented the organ, registered the organ and body volumes separately and combined results. Though sliding organ required manual annotation, it provided the best result as a standard to measure other registration methods. Regularization parameters for standard and mask methods were optimized in a grid search. Evaluations consisted of DICE, and visual scoring of a checkerboard display. Standard had accuracy of 2 voxels in all regions except near the kidney, where there were 5 voxels sliding. After mask and sliding organ correction, kidneys sliding were within 2 voxels, and Dice overlap increased 4%-10% in mask compared to standard. Mask generated comparable results with sliding organ and allowed a semi-automatic process.


Functional segregation of the TCR and antigen-MHC complexes on the surface of CTL.
As CTL adhere to and lyze their targets, they extract cognate Ag-MHC and represent this on their own cell surface. Whether such self-presented cognate Ag stimulate the TCR of a CTL is uncertain. To analyze this, we examined TCR capping in response to self-presented Ag. We found that OVA peptide-specific OT-1 CTL that were pulsed with cognate peptide Ag did not cap their TCR, implying that the autologously presented MHC-Ag complex does not normally stimulate the TCR. However, this functional separation of the TCR and its ligand on the cell surface was not absolute. Treatment of Ag-pulsed OT-1 CTL with agents that alter cell surface charge, including trypsin, papain, tunicamycin, neuraminidase, and polybrene, allowed Ag-specific TCR capping. The TCR capped together with the restricting MHC molecule on the surface of the cell, implying an interaction between the TCR and cell-associated Ag. Further, the treated CTL underwent a time- and dose-dependent suicidal death that was both Fas- and perforin-dependent. Therefore, our results indicate that the association of the TCR with its MHC-peptide ligand on the surface of a CTL is normally proscribed by biophysical properties of the plasma membrane. Overcoming this restriction allows TCR stimulation and induces CTL effector functions and cell suicide.


Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome.
Polycystic ovary syndrome (PCOS) is an endocrinopathy with complex pathophysiology that is a common cause of anovulatory infertility in women. Although the disruption of circadian rhythms is indicated in PCOS, the role of the clock in the etiology of these pathologies has yet to be appreciated. The nuclear receptors REV-ERBα and REV-ERBβ are core modulators of the circadian clock and participate in the regulation of a diverse set of biological functions. However, in PCOS, the expression of REV-ERBs and their effects remain unclear. Here, we demonstrate that the levels of REV-ERBα and REV-ERBβ expression were lower in the granulosa cells of PCOS patients than in control subjects. In vitro, we found that the overexpression of REV-ERBα and REV-ERBβ, and their agonist SR9009, promoted the expression of mitochondrial biosynthesis genes PGC-1α, NRF1, and TFAM and inhibited autophagy in KGN cells. Our results also indicate that REV-ERBα and REV-ERBβ can inhibit apoptosis in granulosa cells and promote proliferation. Importantly, the REV-ERB agonist SR9009 ameliorates abnormal follicular development by promoting mitochondrial biosynthesis and inhibiting autophagy in a mouse PCOS model. This allows us to speculate that SR9009 has potential as a therapeutic agent for the treatment of PCOS.


Cardiovascular Outcomes in Sleep-Disordered Breathing: Are We Under-estimating?
Obstructive sleep apnea is a growing health concern, affecting nearly one billion people worldwide; increasingly recognized as an independent cardiovascular risk factor associated with incident obesity, insulin resistance, hypertension, arrhythmias, stroke, coronary artery disease, and heart failure. The prevalence of obstructive sleep apnea could be underestimated in the previous studies, leading to only modest predictions of cardiovascular outcomes. Using more physiologic data will increase sensitivity for the diagnosis of obstructive sleep apnea. Individuals at high risk of obstructive sleep apnea should be identified so that treatment efforts can be focused on them. This review will assess the evidence for the relationship between obstructive sleep apnea and cardiovascular consequences in the past, present, and future. We will also explore the role of adding physiological data obtained from sleep studies and its ability to enhance the cardiovascular outcome's predictability. Finally, we will discuss future directions and gaps that need further research.


[Study on aspiration and swallowing exercise in stroke patients].
We investigated factors for aspiration by videofluoroscopy (VF) and swallowing exercises in stroke patients. Subjects were 102 stroke patients aged 34-101 years (mean 72.8+/-13.8 years) including 72 males and 30 females and for whom VF was performed because of suspected swallowing difficulty. They consisted of 64 patients with cerebral infarction, 33 patients with cerebral hemorrhage, and 5 patients with subarachnoid hemorrhage. Aspiration was classified into aspiration with choking and silent aspiration (SA) by the presence of a cough reflex. Eating instructions such as foodstuffs and intake methods and outcome were investigated. On VF, aspiration with foodstuffs was found in 59 of 102 (57.8%) patients and SA was found in 44 of them (44.1%). Some patients ate food on the ward in spite of SA in VF. Such patients were given eating instructions by the judgment of the attending physician, but foodstuffs and intake methods based on the results of VF could be changed in most cases. As for swallowing training, direct training was conducted only in a few patients in the group that presented overt aspiration in this study. On the other hand direct training was possible in the majority of patients if foodstuffs and intake methods were handled appropriately in SA. If these strok patients were approached with attention paid to the forms of foodstuffs and intake method on the basis of detailed evaluation on VF using mimic foodstuffs, eating was possible without aspiration in many cases.


Mechanisms of LiF Interlayer Enhancements of Perovskite Light-Emitting Diodes.
The use of LiF as a thin interlayer between the electron transport layer and cathode has played a pivotal role in remarkable advances in perovskite LEDs (PeLEDs); however, the mechanism behind the effect of LiF remains to be fully understood. Here, we report a combined experimental and computational study, from which we ascribe the benefits of a LiF interlayer to the migration of dissociated Li into the cathode and dissociated F into the anode. Electronic device simulations reveal that the former improves electron injection by lowering the Schottky barrier height, while the latter reduces the barrier width. These reduce turn-on voltage and improve current density and charge balance in LEDs. We fabricate PeLEDs with and without the LiF interlayer and link these materials and electronic phenomena to the device light-current-voltage characteristics. X-ray photoelectron spectroscopy obtained in sputter profiling of PeLEDs corroborates the dissociation of LiF.


[The return of diphtheria in Europe. Is the French population protected?].
Following the generalized vaccination of children, the European countries achieved the elimination of diphtheria. However the huge epidemic which rages since 1990 in the New Independent States of ex-URSS, culminating in 1994-1995 (with respectively 47,802 and 50,412 notified cases), has showed that diphtheria could be still threatening. A serosurvey was carried out in France on 1,025 adult patients attending the emergency wards of three hospitals, located in different parts of this country. This study showed the insufficient immunity of adults, for lack of a routine programme for revaccination: only half of them have antibodies assuring their protection. The antitoxic immunity decreases according to age. This decline is more marked in women than in men, most of them being reimmunized during the military service. These data confirm the alarming results of similar serosurveys performed in others industrialized countries. The present risk of importing diphtheria in these countries requires a strengthening of clinical and bacteriological surveillance of all cases of infections attributable to C. diphtheriae, and could justify a revaccination programme for adult population, including a regular booster, at 10 year-interval, of a reduced dose of diphtheria toxoid (d), and/or using the combined toxoid Td in the wounded, instead of tetanus toxoid alone.


[Plasma amino acid levels in alcoholics].
Plasma aromatic amino acid (AAA) and branched-chain amino acid (BCAA) concentrations were determined in 197 alcoholics. The BCAA/AAA molar ratio in patients with alcohol withdrawal symptoms was compared with the ratio in patients without such symptoms. The BCAA/AAA molar ratio in patients with emotional disturbance or with transient hallucination was significantly lower than that in patients without these symptoms. The BCAA/AAA molar ratio tended to be lower in patients with alcohol withdrawal convulsion or with delirium tremens as compared to patients without such symptoms. The BCAA/AAA molar ratio had a negative correlation with plasma total bilirubin and LDH and had a positive correlation with plasma choline esterase and albumin. Oral administration of amino acid preparations (Aminoleban EN) to the patients elevated the BCAA/AAA molar ratio and normalized liver function. These results indicate that abnormalities of amino acid metabolism caused by liver damage in alcohol dependence may have an important role in the pathogenesis of alcohol withdrawal syndrome.


Patterns of osteoarthritis of the hip.
The division of osteoarthritis into primary and secondary varieties implies that these are aetiologically distinct entities, the former being due to some intrinsic defect of cartilage and the latter resulting from previous articular damage. This traditional concept is questioned and the hypothesis is advanced that osteoarthritis is always secondary to some underlying abnormality of the joint. A detailed clinical, radiographic and morbid anatomical study of 327 cases of osteoarthritis of the hip is presented. In all but twenty-seven some predisposing abnormality of the joint was diagnosed: 107 (33%) were associated with major pathology such as Perthes' disease or epiphysiolysis; minor acetabular dysplasia was present in sixty-seven (20%), with a male: female ratio of 1:10; minimal femoral head tilt was demonstrated in fifty-nine (18%), the male: female ratio being 14:1; and in forty-three (13%) there were features suggesting an underlying inflammatory arthritis. On the basis of this study a new classification is proposed and osteoarthritis of the hip is divided into three pathogenetic groups: 1) failure of essentially normal cartilage subjected to abnormal or incongruous loading for long periods; 2) damaged or defective cartilage failing under normal conditions of loading; 3) break-up of articular cartilage due to defective subchondral bone.


Effects of cosmetic formulations containing hydroxyacids on sun-exposed skin: current applications and future developments.
This paper describes recent data on the effects of various skin formulations containing hydroxyacids (HAs) and related products on sun-exposed skin. The most frequently used classes of these products, such as α- and β-hydroxyacids, polyhydroxy acids, and bionic acids, are reviewed, and their application in cosmetic formulations is described. Special emphasis is devoted to the safety evaluation of these formulations, particularly on the effects of their prolonged use on sun-exposed skin. We also discuss the important contribution of cosmetic vehicles in these types of studies. Data on the effects of HAs on melanogenesis and tanning are also included. Up-to-date methods and techniques used in those explorations, as well as selected future developments in the cosmetic area, are presented.


Gestational Exposure to Sodium Valproate Disrupts Fasciculation of the Mesotelencephalic Dopaminergic Tract, With a Selective Reduction of Dopaminergic Output From the Ventral Tegmental Area.
Gestational exposure to valproic acid (VPA) is known to cause behavioral deficits of sociability, matching similar alterations in human autism spectrum disorder (ASD). Available data are scarce on the neuromorphological changes in VPA-exposed animals. Here, we focused on alterations of the dopaminergic system, which is implicated in motivation and reward, with relevance to social cohesion. Whole brains from 7-day-old mice born to mothers given a single injection of VPA (400 mg/kg b.wt.) on E13.5 were immunostained against tyrosine hydroxylase (TH). They were scanned using the iDISCO method with a laser light-sheet microscope, and the reconstructed images were analyzed in 3D for quantitative morphometry. A marked reduction of mesotelencephalic (MT) axonal fascicles together with a widening of the MT tract were observed in VPA treated mice, while other major brain tracts appeared anatomically intact. We also found a reduction in the abundance of dopaminergic ventral tegmental (VTA) neurons, accompanied by diminished tissue level of DA in ventrobasal telencephalic regions (including the nucleus accumbens (NAc), olfactory tubercle, BST, substantia innominata). Such a reduction of DA was not observed in the non-limbic caudate-putamen. Conversely, the abundance of TH+ cells in the substantia nigra (SN) was increased, presumably due to a compensatory mechanism or to an altered distribution of TH+ neurons occupying the SN and the VTA. The findings suggest that defasciculation of the MT tract and neuronal loss in VTA, followed by diminished dopaminergic input to the ventrobasal telencephalon at a critical time point of embryonic development (E13-E14) may hinder the patterning of certain brain centers underlying decision making and sociability.


Recovering the past: patient and family review of children's old mental health treatment records.
The right of access to old mental health treatment records creates unique challenges when requests are from former child patients. One agency's experience suggests that review of these records represents an attempt to understand current problems and concerns by searching for supposedly objective observations from the past.


Early glaucoma changes in patients with and without an optic disc haemorrhage.
Previous reports have shown that retinal nerve fibre layer (RNFL) observation is useful for detection of early glaucoma changes in patients with optic disc haemorrhage. Since disc haemorrhages are not a factor in all glaucoma patients this study was carried out in order to estimate the value of RNFL observation in patients whose first glaucoma damage developed without a haemorrhage. Evaluation of the retrospective data showed that RNFL defects were the first and only detectable glaucoma changes in 46% of haemorrhagic eyes and 26% of non-haemorrhagic eyes. RNFL observation is useful in the follow-up of ocular hypertensive patients for detection of very early glaucoma changes, regardless of whether the changes develop with or without an optic disc haemorrhage.


Heritability of fitness components in a wild bird population.
Consistently with the prediction that selection should deplete additive genetic variance (V(A)) in fitness, traits closely associated to fitness have been shown to exhibit low heritabilities (h(2)=V(A)/(V(A)+V(R))). However, empirical data from the wild indicate that this is in fact due to increased residual variance (V(R)), rather than due to decreased additive genetic variance, but the studies in this topic are still rare. We investigated relationships between trait heritabilities, additive genetic variances, and traits' contribution to lifetime reproductive success ( approximately fitness) in a red-billed gull (Larus novaehollandiae) population making use of animal model analyses as applied to 15 female and 13 male traits. We found that the traits closely associated with fitness tended to have lower heritabilities than traits less closely associated with fitness. However, in contrast with the results of earlier studies in the wild, the low heritability of the fitness-related traits was not only due to their high residual variance, but also due to their low additive genetic variance. Permanent environment effects--integrating environmental effects experienced in early life as well as nonadditive genetic effects--on many traits were large, but unrelated to traits' importance for fitness.


[Rapid detection of SOX2 gene by primed in situ labeling].
To rapidly detect SOX2 gene using primed in situ labeling (PRINS). Human peripheral blood samples were cultured using an optimized method. Sequence of the SOX2 gene was amplified in situ with biotin-labeled specific primers and processed with a tyramide signal amplification (TSA) biotin system. Subsequently, fluorescence-stained signal was detected by streptavidin-Texas red. For the control group, MCF-10F cells were transfected with Lentivirus hSox2. By VideoTesT-FISH software analysis, the long arm of chromosome 3 in the experimental group showed a specific red fluorescence signal, whilst the control samples showed no specific signals for SOX2. Transfected MCF-10F cells showed various efficiency of SOX2 gene integration. PRINS utilizes a highly sensitive in situ PCR technique combined with fluorescence labeled oligodeoxynucleotides can synthesize probes in situ, thus greatly reducing the cost of probe and time for detection. It can facilitate identification and classification of induced pluripotent stem cells, and has many potential applications in this prospect.


Evidence-based medicine among hospital doctors in Jordan: awareness, attitude and practice.
The aim of this cross-sectional study was to determine the awareness and attitude of hospital doctors towards evidence-based medicine (EBM) and their related educational needs. A questionnaire study was performed on a randomly selected sample of 386 hospital doctors from both a teaching hospital and the Ministry of Health general hospitals in Jordan. Attitude towards EBM, best method of moving from opinion-based medicine to EBM, accessing and interpreting evidence and perceived barriers to practise EBM among participants were the main outcome measures. Participants welcomed promotion of EBM and 91.2% agreed that research findings are helpful in daily management of patients. About one-third of respondents (32.7%) thought that the most appropriate way to move towards EBM was by seeking and applying EBM summaries. About one half of participants (47.9%) were unaware of Cochrane database and only 5% used it to help in clinical decision making. More than half (53.7%) reported that they had access to the Internet at their office. Only minority understand the technical terms used in EBM. The major barriers to practising EBM were threat to clinical freedom/judgement, limited resources and facilities, patient overload absence of library in the locally and lack of personal time. Although there is a high support among doctors for the promotion of EBM, there is a deficit in knowledge and skills of EBM. Hence, the time appears ripe for planning and implementing an effective EBM educational programme for both undergraduate and postgraduate doctors.


Spectroscopy of stripe order in La1.8Sr0.2NiO4 using resonant soft x-ray diffraction.
Strong resonant enhancements of the charge-order and spin-order superstructure-diffraction intensities in La1.8Sr0.2NiO4 are observed when x-ray energies in the vicinity of the Ni L2,3 absorption edges are used. The pronounced photon-energy and polarization dependences of these diffraction intensities allow for a critical determination of the local symmetry of the ordered spin and charge carriers. We found that not only the antiferromagnetic order but also the charge-order superstructure resides within the NiO2 layers; the holes are mainly located on in-plane oxygens surrounding a Ni2+ site with the spins coupled antiparallel in close analogy to Zhang-Rice singlets in the cuprates.


βKlotho Inhibits Cell Proliferation by Downregulating ELK4 and Predicts Favorable Prognosis in Prostate Cancer.
Prostate cancer (PCa) ranks as the second common malignancy in males worldwide. Although conspicuous progressions in diagnosis and treatment have been achieved in the past decades, the prognosis expectation of PCa remains unsatisfied yet. To improve the prognosis prediction of PCa, more specific biomarkers are needed. In this retrospective research, we focused on βKlotho and ETS-like transcription factor 4 (ELK4), aiming to identify potential prognostic biomarkers for PCa. Western blotting was used to determine the expression of βKlotho, ELK4, and PARP in C4-2B and PC3 PCa cell lines. CCK-8 assay and colony formation assay were applied to examine the roles of βKlotho and ELK4 in the proliferation of PCa cells. The expression of βKlotho and ELK4 in PCa tissue samples was determined by immunochemistry. Pearson's χ2 test and Fisher's exact test were performed to investigate the associations among βKlotho, ELK4 and various clinical factors. Kaplan-Meier curves and Cox regression model were established to reveal the correlation among βKlotho, ELK4 expression and the prognosis of patients. βKlotho overexpression down-regulated the ELK4 expression, induced apoptosis and inhibited cell proliferation in both C4-2B and PC3 cells, which were reversed by ELK4 overexpression. βKlotho expression in PCa tissue samples had negative correlation with the ELK4 expression, and higher βKlotho expression was associated with lower Gleason score, absent distant metastasis and lower prostate-specific antigen (PSA) level. On the contrast, higher ELK4 expression was correlated with distant metastasis and higher PSA level. Moreover, βKlotho and ELK4 were both recognized as independent factors for the prognosis of patients with PCa. βKlotho inhibits proliferation of prostate cancer cells by downregulating ELK4. Both βKlotho and ELK4 expressions correlate with the prognosis of PCa, which may serve as potential biomarkers for follow-up surveillance and prognostic assessments.


Methodological issues in case-control studies: II. Test statistics as measures of efficiency.
The ratio of test statistics has been used to compare the efficiency of matched and unmatched designs, and stratified and pooled analyses for case-control studies. The index has been computed for a wide range of population conditions and it is concluded that (a) pooled analysis is always more efficient than stratified analysis when such pooling leads to a valid estimate of the relative risk, (b) the loss of efficiency by matching in the classic overmatching situation can be substantial, (c) in the confounding situation either design may be more efficient but generally the difference is small. These results add support to the contention that matching is rarely justified in case-control studies.


Clinical significance of the F wave area in diabetic polyneuropathy.
To investigate the electrophysiological significance of the abnormal F wave are (Farea) and its ratio (F/Marea) (%) to the corresponding M wave area (Marea) in patients with diabetic polyneuropathy (DP). For tibial and peroneal nerves, the F/Marea and other F wave parameters (duration [Fdur], minimum latency [Fmin], amplitude [Famp]) were compared in 34 patients and age-matched controls. For controls, the Farea correlated with the Marea, but this was not found for DP patients. The peroneal F/Marea for DP patients was significantly larger than that for controls. For the both nerves, however, the F/Marea for DP patients was larger in nerves with a decreased Marea than those in nerves with a normal Marea and in the controls. An increased F/Marea was accompanied by prolonged Fdur. A decreased F/Marea was uncommon. The incidence of abnormal F/Marea was somewhat larger than that of abnormal F/Mamp, but smaller than the values for MCV and Fmin. The relationship between Farea and the Marea for DP patients differed from that of controls. An increased F/Marea was considered to reflect a denervation-reinnervation process or some central modification in firing of the anterior horn cells. Whereas amplitude of the F wave also reflect these electrophysiological conditions, the F/Marea is a little more sensitive than F/Mamp in detecting the abnormality.


Fluid milk processing costs: current state and comparisons.
An economic-engineering model is used to derive the theoretically minimum cost of processing and distributing fluid white milk for the state of Maine. This model represents a state-of-the-art milk processing facility and is used to evaluate three questions: 1) the components of total processing costs; 2) whether the cost of milk processing declines with increasing plant size; and 3) the minimum processing volume to financially justify inplant blow-molding technology. The model indicates that significant savings in per-container processing costs can be achieved by increasing plant size. However, distribution costs, related to the geographical distribution of consumer demand and plant location in the state of Maine do not favor large centralized plants. In addition, this model is compared with results published in 1993 to evaluate cost trends over a 7-yr period. The model indicates import shifts to more technologically advanced processing equipment and a dramatic increase in labor costs. Overall, processing costs have risen 2.9% annually above the rate of inflation. Dairies that are unable to respond to increased labor costs through capital investment and expansion will likely find it more difficult to remain competitive in the milk processing industry.


Sex-specific differences in cerebral arterial myogenic tone in hypertensive and normotensive rats.
Cerebral blood flow (CBF) is maintained constant despite changes in systemic blood pressure (BP) through multiple mechanisms of autoregulation such as vascular myogenic reactivity. Our aim was to determine myogenic characteristics of cannulated middle cerebral arteries (MCA) in male and female stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) at 12 wk of age under pressurised no-flow conditions. MCA pressure-diameter relationships (20-200 mmHg) were constructed in active (with calcium) and passive (without calcium) conditions, and myogenic and mechanical properties were determined. Myogenic reactivity in WKY (P < 0.05) and SHRSP (P < 0.05) males was impaired compared with their female counterparts. Comparison of SHRSP with WKY in males revealed similar myogenic reactivity, but in females SHRSP exhibited augmented myogenic reactivity (P < 0.05). In both sexes, myogenic tone yielded at lower pressure in SHRSP compared with WKY vessels (120-140 vs. 140-180 mmHg). Stress-strain relationships and elastic moduli in WKY rats showed that vessels were stiffer in females than in males. Conversely, in SHRSP, male vessels were stiffer than female vessels. Comparison of strains in males indicated that stiffness was increased in SHRSP compared with WKY vessels, whereas the converse was observed in females. These findings demonstrate that MCA myogenic and distensibility characteristics exhibit significant sex- and strain-dependent differences. Inappropriate myogenic adaptation and augmented vascular stiffness, particularly in male SHRSP, are potential limiting factors in blood flow autoregulation and may increase the predisposition for stroke-related cerebrovascular events.


Update on European adjuvant trials with irinotecan for colorectal cancer.
Recent combinations of chemotherapy have significantly improved the response rate and survival time for patients with metastatic colorectal cancer. This improvement has been initially demonstrated with the combination of fluorouracil (5-FU)/leucovorin and irinotecan (CPT-11, Camptosar), which now is considered and recommended as first-line treatment. The combination of improved efficacy with survival benefit should translate into a better cure rate in patients with resected, locally advanced, nonmetastatic colorectal cancer for whom adjuvant chemotherapy with 5-FU/leucovorin is of proven benefit. Several randomized phase III trials are ongoing in Europe or would begin shortly to assess the potential benefit of a 5-FU/leucovorin-irinotecan combination in the adjuvant setting for patients with stage II or III colorectal cancer. This article will review the inclusion criteria and goal of these European trials. An update on accrual and on tolerance will also be provided.


Omega-3 fatty acids (fish-oil) and depression-related cognition in healthy volunteers.
Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation may be beneficial in the treatment of several psychiatric disorders, including depression. A small number of studies have suggested that there may also be cognitive and mood effects in healthy samples. The purpose of the present study was to investigate the effects of n-3 PUFA on depression-relevant cognitive functioning in healthy individuals. Fifty-four healthy university students were randomized to receive either n-3 PUFA supplements or placebo for 4 weeks in a double-blind design. The test battery included measures of cognitive reactivity, attention, response inhibition, facial emotion recognition, memory and risky decision-making. Results showed few effects of n-3 PUFAs on cognition and mood states. The n-3 PUFA group made fewer risk-averse decisions than the placebo group. This difference appeared only in non-normative trials of the decision-making test, and was not accompanied by increased impulsiveness. N-3 PUFAs improved scores on the control/perfectionism scale of the cognitive reactivity measure. No effects were found on the other cognitive tasks and no consistent effects on mood were observed. The present findings indicate that n-3 PUFA supplementation may have a selective effect on risky decision making in healthy volunteers, which is unrelated to impulsiveness.


Isolation, Identification, and Sequencing of a Goose-Derived Newcastle Disease Virus and Determination of Its Pathogenicity.
In August 2010, geese in the Meihekou area of Jilin province in China were found to be infected by a pathogen that caused a disease similar to Newcastle disease. To determine the causative agent of the infections, a virus was isolated from liver tissues of infected geese, followed by a pathogenicity determination. The isolated virus was named NDV/White Goose/China/Jilin(Meihekou)/MHK-1/2010. Specific primers were designed to amplify the whole genome of the MHK-1 virus, followed by sequencing and splicing of the entire genome. Sequencing and phylogenetic analysis of MHK-1 showed that the isolate was a virulent strain of Newcastle disease virus. The MHK-1 genome is 15,192 nucleotides long, and it belongs to the class II branch of Newcastle disease viruses, as evidenced by the amino acid sequence (112R-R-Q-K-R-F117) of the F protein. The hemagglutinin titer was 1:128 to 1:512. The chicken embryo mean death time, the intracerebral pathogenicity index, and the median lethal dose of chicken embryos of MHK-1 were 43 hr, 1.63, and 10(9)/ml, respectively, which revealed that the newly isolated MHK-1 strain is strongly pathogenic to geese.


An ionic liquid-assisted sample preparation method for sensitive integral-membrane proteome analysis.
Many ion channels and receptor proteins are potential targets for new drugs. However, standard methods for profiling these integral membrane proteins (IMPs) have not been fully established, especially when applied to rare and quantity-limited biological samples. We previously demonstrated that a mixture containing 1-butyl-3-methylimidazolium cyanate, an ionic liquid (IL), and NaOH (termed i-soln) is an excellent solubilizer for insoluble aggregates. In this study, we present a combined i-soln-assisted proteomic sample preparation platform (termed pTRUST), which is compatible with starting materials in the sub-microgram range, using our previously reported i-soln-based sample preparation strategy (iBOPs) and an in-StageTip technique. This novel and straightforward approach allows for the rapid solubilization and processing of a variety of IMPs from human samples to support highly sensitive mass spectrometry analysis. We also demonstrated that the performance of this technology surpasses that of conventional methods such as filter-aided sample preparation methods, FASP and i-FASP. The convenience and availability of pTRUST technology using the IL system have great potential for proteomic identification and characterization of novel drug targets and disease biology in research and clinical settings.


A systematic analysis and future projections of the nutritional status and interpretation of its drivers among school-aged children in South-East Asian countries.
Nutrition inadequacy during childhood and adolescence can cause suboptimal growth, intergenerational effects on offspring and an increased risk of chronic diseases in adulthood. There is little information on the prevalence and drivers of malnutrition in children aged 5-19 years, in the South-East Asian setting, since most existing interventions have to date targeted undernutrition. We assessed the national prevalence of nutritional indicators, their trends, and associated risk factors among children aged 5-19 years from 11 countries of WHO South-East Asia Region (SEA Region) in order to provide evidence to guide future policy direction. We included 5,210,646 children for analysis from 345 studies and 25 survey datasets. A Newcastle-Ottawa Scale was used to assess the quality of the study. Bayesian regression models were used to estimate the prevalence of malnutrition between 2000 and 2030, and a series of subgroup analyses were performed to assess variation in pooled estimates by different socio-demographic and lifestyle factors. The protocol was registered with PROSPERO database (CRD42023400104). Overall, pooled analysis demonstrated that indicators of undernutrition in SEA is predicted to decrease between 2000 and 2030 including stunting (36.6%-27.2%), thinness (29.5%-6.2%), and underweight (29.2%-15.9%). However, a substantial increase in prevalence of overweight (6.0% in 2000-16.9% in 2030), and obesity (2.6%-9.5%) are predicted. The prevalence of micronutrient deficiencies between 2000 and 2030 is predicted to decrease-vitamin A by 84% and vitamin D by 53%. Parents' education levels and household wealth were inversely associated with malnutrition. Children's health-related behaviours, such as unhealthy dietary habits and spending more time watching TV, playing games, or using the computer, were associated with increased chance of overweight and obesity. There were no clear signs of publication bias in our study. Our analysis highlights the pattern of a double burden of malnutrition, with clear differences between different socio-demographic groups. Despite a substantial reduction in the prevalence of stunting, underweight, and anaemia since 2000, an emerging increase in overweight/obesity and micronutrient deficiencies warrants urgent attention. World Health Organization Regional Office for South-East Asia New Delhi, India.


Genome-wide Specificity of Highly Efficient TALENs and CRISPR/Cas9 for T Cell Receptor Modification.
In T cells with transgenic high-avidity T cell receptors (TCRs), endogenous and transferred TCR chains compete for surface expression and may pair inappropriately, potentially causing autoimmunity. To knock out endogenous TCR expression, we assembled 12 transcription activator-like effector nucleases (TALENs) and five guide RNAs (gRNAs) from the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas9) system. Using TALEN mRNA, TCR knockout was successful in up to 81% of T cells. Additionally, we were able to verify targeted gene addition of a GFP gene by homology-directed repair at the TALEN target site, using a donor suitable for replacement of the reporter transgene with therapeutic TCR chains. Remarkably, analysis of TALEN and CRISPR/Cas9 specificity using integrase-defective lentiviral vector capture revealed only one off-target site for one of the gRNAs and three off-target sites for both of the TALENs, indicating a high level of specificity. Collectively, our work shows highly efficient and specific nucleases for T cell engineering.


Solution structures of DEAD-box RNA chaperones reveal conformational changes and nucleic acid tethering by a basic tail.
The mitochondrial DEAD-box proteins Mss116p of Saccharomyces cerevisiae and CYT-19 of Neurospora crassa are ATP-dependent helicases that function as general RNA chaperones. The helicase core of each protein precedes a C-terminal extension and a basic tail, whose structural role is unclear. Here we used small-angle X-ray scattering to obtain solution structures of the full-length proteins and a series of deletion mutants. We find that the two core domains have a preferred relative orientation in the open state without substrates, and we visualize the transition to a compact closed state upon binding RNA and adenosine nucleotide. An analysis of complexes with large chimeric oligonucleotides shows that the basic tails of both proteins are attached flexibly, enabling them to bind rigid duplex DNA segments extending from the core in different directions. Our results indicate that the basic tails of DEAD-box proteins contribute to RNA-chaperone activity by binding nonspecifically to large RNA substrates and flexibly tethering the core for the unwinding of neighboring duplexes.


Helicobacter pylori-related risk predictors of gastric cancer: The latest models, challenges, and future prospects.
Helicobacter pylori is known as an important determinant of preneoplastic lesions or gastric cancer (GC) risk. The bacterial genotypes may determine the clinical outcomes. However, the evidence for these associations has varied between and within continents, and the actual effect of each gene and corresponding allelic variants are still debatable. In recent years, two new models have been proposed to predict the risk of GC; the phylogeographic origin of H. pylori strains and a disrupted co-evolution between H. pylori and its human host, which potentially explain the geographic differences in the risk of H. pylori-related cancer. However, these models and earlier ones based on putative virulence factors of the bacterium may not fully justify differences in the incidence of GC, reflecting that new theories should be developed and examined. Notably, the new findings also support the role of ancestry-specific germline alteration in contributing to the ethnic/population differences in cancer risk. Moreover the high and low incidence areas of GC have shown differences in transmission ecology, largely affecting the composition of H. pylori populations. As a new hypothesis, it is proposed that any high-risk population may have its own specific risk loci (or variants) as well as new H. pylori strains with national/maybe regional gene pools that should be considered. The latter is seen in the Americas where the rapid evolution of distinct H. pylori subpopulations has been occurred. It is therefore proposed that the deep sequencing of both H. pylori and its human host is simultaneously performed in GC patients and age-sex-matched controls from high-risk areas. The expression and functional activities of the identified new determinants of GC must then be assessed and matched with human and pathogen ancestry, because some of risk loci are ancestry-specific. In addition, potential study-level covariates and moderator variables (eg physical conditions, life styles, gastric microbiome, etc) linked to causal relationships, and their impact, should be recognized and controlled.


Equation-of-state-dependent surface free-energy density for wettability in lattice Boltzmann method.
In thermodynamic theory, the liquid-vapor fluids can be described by a single multiphase equation of state and the surface wettability is usually characterized by the surface free-energy density. In this work, we propose an equation-of-state-dependent surface free-energy density for the wettability of the liquid-vapor fluids on a solid surface, which can lead to a simple closed-form analytical expression for the contact angle. Meanwhile, the thermodynamically derived equilibrium condition is equivalent to the geometric formulation of the contact angle. To numerically validate the present surface free-energy density, the mesoscopic multiphase lattice Boltzmann model with self-tuning equation of state, which is strictly consistent with thermodynamic theory, is employed, and the two-dimensional wetting condition treatment is extended to the three-dimensional situation with flat and curved surfaces. Two- and three-dimensional lattice Boltzmann simulations of static droplets on flat and curved surfaces are first performed, and the obtained contact angles agree well with the closed-form analytical expression. Then, the three-dimensional lattice Boltzmann simulation of a moving droplet on an inclined wall, which is vertically and sinusoidally oscillated, is carried out. The dynamic contact angles well satisfy the Cox-Voinov law. The droplet movement regimes are consistent with previous experiments and two-dimensional simulations. The dependence of the droplet overall velocity with respect to the dimensionless oscillation strength is also discussed in detail.


Prediction of progression to cirrhosis by a glutathione S-transferase P1 polymorphism in subjects with hereditary hemochromatosis.
Oxidative stress plays an important pathogenic role in hereditary hemochromatosis (HHC) and chronic hepatitis C virus infection (CHC). Several enzymes involved in the degradation of reactive oxidants and xenobiotics, such as glutathione S-transferase P1 (GSTP1) and manganese superoxide dismutase (MnSOD), reveal polymorphisms that affect their antioxidant capacity and may therefore modulate the progression to cirrhosis. Our objective was to establish the role of the functional polymorphisms of GSTP1 (codon 105 Ile-->Val) and MnSOD (codon 16 of precursor protein Ala-->Val) on the evolution of cirrhosis in patients with HHC and CHC. One hundred seventy-two patients with HHC who were homozygous for the C282Y mutation and 285 patients with CHC underwent liver biopsy and genotyping for the GSTP1 and MnSOD polymorphisms. In HHC, the GSTP1 Val/Val genotype was more common in patients with than in those without cirrhosis (14.8% vs 2.1%, P = .009), whereas the distribution of MnSOD variants was not different. Logistic regression analysis identified GSTP1 Val/Val genotype, serum ferritin level, male sex, and age as independent predictors for the presence of cirrhosis. The odds ratio for the GSTP1 Val/Val genotype for the development of cirrhosis was 3.85 (95% confidence interval, 1.18-12.62; P = .03). However, in patients with CHC, the GSTP1 and MnSOD genotypes were not associated with cirrhosis. Cirrhosis is more likely to develop in C282Y homozygotes with the GSTP1 Val/Val genotype than in those with non-Val/Val genotypes, which in part explains the variable phenotypic expression of HHC and highlights the central role of oxidative stress in its pathogenesis.


Checklist of African Tischeriidae (Insecta: Lepidoptera) with a redescription of the formerly neglected Tischeria urticicolella from Equatorial Africa.
Tischeria urticicolella (Ghesquière, 1940)--a poorly studied species from the Democratic Republic of Congo and formerly known as a member of the Gracillariidae--is redescribed and reported as belonging to the Tischeriidae for the first time. The external features and male genitalia are figured and described. A checklist and distribution map for all 18 Tischeriidae species currently recorded from Africa (including the Canary Islands) are given.


Global volatile profile of virgin olive oils flavoured by aromatic/medicinal plants.
The global volatile profile of commercial virgin olive oils and flavoured olive oils with aromatic/medicinal plants, was established using liquid-liquid microextraction (LLME) and headspace solid-phase microextraction (HS-SPME) combined with gas chromatography-quadrupole mass spectrometry (GC-qMS). More than 60 volatile organic compounds (VOCs belonging to different groups were identified using both methods. Olive oils volatile profile was slightly influenced by maceration process, which occurred at room temperature (20±2°C) for 15days. The predominant differences were observed in terpenoids group, since some of them were only identified in the flavoured olive oils, while others showed an increase with the maceration process. VOCs mass transfer from plants to olive oils could explain the observed results. Principal components analysis (PCA) applied to LLME/GC-qMS data allowed to distinguish the olive oils. The flavoured oils would increase the use of olive oil among consumers as consequence of the improvement of its aromatic profile and healthy properties.


Inhalation of the phosphodiesterase-3 inhibitor milrinone attenuates pulmonary hypertension in a rat model of congestive heart failure.
Most patients with congestive heart failure (CHF) develop pulmonary venous hypertension, but right ventricular afterload is frequently further elevated by increased pulmonary vascular resistance. To investigate whether inhalation of a vasodilatory phosphodiesterase-3 inhibitor may reverse this potentially detrimental process, the authors studied the effects of inhaled or intravenous milrinone on pulmonary and systemic hemodynamics in a rat model of CHF. In male Sprague-Dawley rats, CHF was induced by supracoronary aortic banding, whereas sham-operated rats served as controls. Milrinone was administered as an intravenous infusion (0.2-1 microg.kg body weight.min) or by inhalation (0.2-5 mg/ml), and effects on pulmonary and systemic hemodynamics and lung water content were measured. In CHF rats, intravenous infusion of milrinone reduced both pulmonary and systemic arterial blood pressure. In contrast, inhalation of milrinone predominantly dilated pulmonary blood vessels, resulting in a reduced pulmonary-to-systemic vascular resistance ratio. Repeated milrinone inhalations in 20-min intervals caused a stable reduction of pulmonary artery pressure. No hemodynamic effects were detected when 0.9% NaCl was administered instead of milrinone or when milrinone was inhaled in sham-operated rats. No indications of potentially adverse effects of milrinone inhalation in CHF, such as left ventricular volume overload, were detected. Moreover, lung edema was significantly reduced by repeated milrinone inhalation. If these results can be confirmed in humans, inhalation of nebulized milrinone may present a novel, effective, safe, and pulmonary selective strategy for the treatment of pulmonary venous hypertension in CHF.


Mini-Laparoscopic Cholecystectomy: Review of 7200 Cases. Could it be the New Gold Standard?
Mini-Laparoscopy by reducing the instrument size and hence incision can lead to better surgical outcome. The safety and feasibility of mini-laparoscopic cholecystectomy (mini-Lch) has not been documented with a large patient sample. This observational descriptive study reports the results of 7200 cases of mini-Lch performed at Ibrahim General Hospital and Eden Multi-care hospital, Dhaka, Bangladesh by a single surgeon. From May 1998 till July 2013in total 8700 patients were offered Mini-lch and 7200 procedures were completed successfully. The operative indication, total operative time, conversion rate, hospital stay, patient satisfaction, post operative pain, complications, morbidity and mortality were reviewed. In this series conversion to open surgery was 0.39%. Average operating time was 30.22 minutes. Early acute cases (9%) did not require conversion to open. Average post operative hospital stay was 21 hours. There was no mortality in the series. Six patients developed incisional hernia at the umbilical port site and 16 patients had umbilical wound infection. Patient acceptance was excellent, postoperative analgesic requirement was less. With Mini Lch better cosmetic result was achieved, recovery was early. Minilaparoscopic cholecystectomy is an economically feasible, and more acceptable considering the cosmetic outcome and patient acceptance. Our results indicate that this procedure could be performed successfully and safely by experienced surgeons.


Motion artifacts in fast spin-echo imaging.
The purpose of this work is to obtain a better understanding of motion artifacts in fast spin-echo imaging, in order to eventually identify efficient ways of suppressing them. To do so, the point spread function of a moving point was calculated for fast spin-echo imaging, and experimental data were acquired by imaging a moving liquid sphere with a diameter of 1.5 mm. The agreement of the experimental results with the calculated point spread function is shown to be excellent. It was found that motion artifacts in fast spin-echo imaging arise from the convolution of two distinct band patterns. One of these patterns may dominate the convolution, giving its own spacing to the resulting image. For other acquisition parameters, the convolution results in an intricate pattern that may appear to lack overall structure.


[Improved diagnosis of dementia with Lewy bodies by the combination of 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy and 99mTc-ethylcysteinate dimmer (ECD) brain perfusion SPECT].
Clinical diagnostic criteria for dementia with Lewy bodies (DLB) include abnormal findings on MIBG myocardial scintigraphy and occipital hypoperfusion as supportive features. In this study, 36 patients with probable DLB underwent MIBG scintigraphy and brain perfusion SPECT. The results of SPECT were analyzed using three different cerebral blood flow (CBF)-analyzing programs, an easy Z-score imaging system (e-ZIS), 3DSRT, and FineSRT. Among these assessments, delayed heart-to-mediastinum (dH/M) ratios on MIBG scintigraphy showed superior sensitivity (92%) to detect characteristic abnormalities in DLB. The sensitivities of CBF-analyzing programs to detect occipital hypoperfusion were 67%, 74%, and 81% for e-ZIS, 3DSRT, and FineSRT, respectively. Our results demonstrate that the combination of MIBG scintigraphy and brain perfusion SPECT could increase the accuracy of the clinical diagnosis of DLB. MIBG scintigraphy could be recommended for DLB patients in the clinical setting.


[Gamma globulin as a prophylactic measure in an outbreak of hepatitis A in an institution for mentally retarded children (author's transl)].
An outbreak of hepatitis A was observed in an institution for mentally handicapped children. Within 2 months 21 cases occurred in 4 out of 7 groups. By means of gamma-globulin administration and measures of general hygiene, the outbreak, although not immediately stopped, was brought under control. The number of overt cases was reduced and further transmission to 3 other groups was prevented. The detection of IgM antibodies to hepatitis A virus proved to be very suitable for diagnostic purposes. Subsequently it turned out that the gamma-globulin used had a very low titre in comparison with other preparations. Recommendations are given to prevent similar outbreaks in the future.


Children can't wait for health care reform.
There is widespread agreement that the American health care system needs comprehensive reform. This kind of reform will take time, however, and millions of Americans have urgent health care needs that must be met now. This is especially true for the nation's poor children, for whom the health care "safety net" has greatly eroded in the past decade. New Jersey's health care reform initiatives will ultimately provide for accessible preventive and primary pediatric care, with a community-based "medical home" serving as a child's gateway to the health care system. In the meantime, New Jersey has established programs dealing with such urgent problems as infectious childhood diseases, lead poisoning, AIDS, and infant mortality. While in the spirit of the state's long-range planning effort, these programs are up and running now, their impact maximized in this period of budgetary constraints through coalition- and network-building.


Genetic Diversity of HPV 16 and HPV 18 Based on Partial Long Control Region in Iranian Women.
Human papillomavirus (HPV) 16 and HPV 18 account for 75% of all cervical cancers. The L1 gene, encoding the major surface protein (MSP), is used to classify HPV types (lineages and sublineages), genotypes, and intratypic variants. Therefore, this study aimed to investigate the lineages, sublineages, genetic variabilities, and mutation effects on transcription factor binding sites by using partial sequences of the HPV 16 and HPV 18 long control regions (LCRs) in these samples. After DNA isolation from 56 positive samples, the LCR of HPV 16 and HPV 18 were amplified using specific primers, and phylogenetic trees were drawn through MEGA X. Compared to the reference sequences, single nucleotide polymorphisms (SNPs) were identified. The transcription binding sites were also evaluated using the online PROMO database. The LCRs of 52 samples were successfully sequenced. Overall, 81.58% of all HPV 16 variants belonged to the D1 sublineage, followed by A4 (13.16%), A1 (2.63%), and C1 (2.63%) sublineages. All HPV 18 isolates belonged to A sublineage, 92.85% to A3 sublineage, and 7.15% to A4 sublineage. Out of 27 SNPs in the HPV 16 LCR, A7382T, T7384G, C7387T, C7393G, A7431G, T7448C, and C7783A were HPV 16-specific. Also, among 14 SNPs in the HPV 18 LCR, C7577A and A7943T were not previously reported. An insertion (C) between 7432 and 7433 positions was identified in all studied HPV 16 variants. Besides, most of the HPV 16 mutations were embedded in the YY1, TFIID, Oct-2, and NF-1 binding sites, while c-Fos and MBF1, as the most common binding sites, were affected by HPV 18 LCR mutations. The present results showed that D1 and A3 were the dominant sublineages of HPV 16 and HPV 18, respectively. Therefore, women infected with these variants need to be examined in further longitudinal studies to obtain more information about the oncogenic potential of these dominant variants in Iran. Besides, YY1, TFIID, Oct-2, NF-1, c-Fos, and MBF1 were the most frequent binding sites, which were influenced by the mutations.


Tomographic imaging with Compton PET modules: ideal case and first implementation.
In our previous studies, we demonstrated that the Compton PET module, a layer structure PET detector with side readout, can provide high performance in terms of spatial/energy/timing resolution, as well as high gamma ray detection efficiency. In this study, we investigate how to translate the high performance of the detector module into good quality reconstructed tomographic images. This study is performed using GATE simulation, as well as with physical experiments. Similar detector geometry is used in the simulation and experiment: two identical 4-layer detector modules are placed with face to face distance of 56 mm. In the simulation study, each layer consists of a 1-mm-pitch pixelated crystal array. In the experimental study, each layer is a monolithic crystal, which is virtually binned into 1 mm2 cells to group single events according to the gamma ray interaction locations. A customized Derenzo phantom was placed between the two detector modules. By rotating the phantom using a motorized rotary stage, data along lines of response (LORs) at different angles were collected for reconstructing the tomographic image. The same reconstruction algorithm was used for both simulation and experimental studies. The results demonstrate that the simulation study could resolve 0.8 mm rods while the experimental study was able to resolve 1.0 mm rods.


Cerenkov luminescence tomography for small-animal imaging.
Cerenkov radiation is a well-known phenomenon in which optical photons are emitted by charged particles moving faster than the speed of light in a medium. We have observed Cerenkov photons emitted from beta-emitting radiotracers such as (18)F-fluorodeoxyglucose using a sensitive CCD camera. Phantom and in vivo mouse imaging experiments have demonstrated that surface measurements of the emitted Cerenkov optical photons could be used to reconstruct the radiotracer activity distribution inside an object by modeling the optical photon propagation with the diffusion equation and reconstructing the optical emission source distribution iteratively with a preconditioned conjugate gradient method.


Increased FDG uptake of the bone marrow mimicking malignancy in a patient of eosinophilia secondary to Sparganum mansoni infection.
Secondary eosinophilia is usually associated with parasitosis in Third World countries. We present a case of eosinophilia secondary to Sparganum mansoni infection showing multifocal FDG uptake in the axial bones mimicking malignancy. Bone marrow aspirations and biopsy revealed remarkable proliferation of eosinophils which may be related to the increased FDG uptake. This case indicates that secondary eosinophilia associated with parasitosis may be one cause of diffuse FDG uptake in the bone marrow.


The Analysis for Anemia Increasing Fracture Risk.
BACKGROUND Fractures are a major public health problem for elderly people throughout the world. Anemia is also a common, important health problem among elderly populations. The aim of this article was to estimate the association between anemia and fracture incidence via a systematic review and meta-analysis. MATERIAL AND METHODS The participant, intervention, observation, and study design (PICOS) reporting guidelines were followed, and databases were searched from their inception to May 2020 to identify relevant studies. When heterogeneity was significant, and a random-effects model was used. Subgroup analysis was conducted to explore the source of heterogeneity based on sex, study design, and region. RESULTS We found that anemia significantly increased fracture risk [relative risk (RR)=1.26, 95% confidence interval (CI)=1.14-1.39, P<0.001], specifically, hip fracture (RR=1.44, 95% CI=1.29-1.61), spine fracture (RR=1.15, 95% CI=1.08-1.23), and nonspine fracture (RR=1.42, 95% CI=1.33-1.52). Males with anemia had a 1.51-fold higher fracture risk, females had a 1.09-fold higher fracture risk. And the association was stronger in Asian (RR=1.22, 95% CI=1.07-1.40), but not in American and European study populations. CONCLUSIONS In conclusion, a significantly increased fracture risk was observed, and anemia can be a predictor of fracture risk.


Pneumonia due to Legionella bozemanii: first report of a case in Europe.
Pneumonia caused by Legionella bozemanii and acquired by a 75-year-old man while on holiday in Majorca is described. This appears to be the first report of such a case from Europe. Despite artificial ventilation and intravenous erythromycin the patient died. The causative organism was isolated from part of the lung obtained post mortem. Examination of a single sample of serum by means of an indirect immunofluorescence test gave a titre of 32 in respect of L. bozemanii antigen.


[Research on effect of sleep deprivation on cognitive brain function].
Research on the effect of sleep deprivation (SD) is an approach to shedding light on the working mechanism of sleep for cognitive brain function. To explore how SD affects cognitive function, a number of measures involving psychology, brain imaging and electrophysiology, have been adopted in this area. Research groups from domestic and verseas have focused on many aspects of cognitive science and have acquired initial results, but uniform conclusion has not been made because of mixed factors. Starting from the mechanism of SD, this paper summarizes the progress in the search of effect of SD, including the neurophysiologic change by brain imaging and the use of EEG for evaluating the decline of cognitive function, and then analyzes the main influential factors and orientation of future research in this area.


The C. elegans maternal-effect gene clk-2 is essential for embryonic development, encodes a protein homologous to yeast Tel2p and affects telomere length.
The Caenorhabditis elegans maternal-effect clk genes are involved in the temporal control of development and behavior. We report the genetic and molecular characterization of clk-2. A temperature-sensitive mutation in the gene clk-2 affects embryonic and post-embryonic development, reproduction, and rhythmic behaviors. Yet, virtually all phenotypes are fully maternally rescued. Embryonic development strictly requires the activity of maternal clk-2 during a narrow time window between oocyte maturation and the two- to four-cell embryonic stage. Positional cloning of clk-2 reveals that it encodes a protein homologous to S. cerevisiae Tel2p. In yeast, the gene TEL2 regulates telomere length and participates in gene silencing at subtelomeric regions. In C. elegans, clk-2 mutants have elongated telomeres, and clk-2 overexpression can lead to telomere shortening. Tel2p has been reported to bind to telomeric DNA repeats in vitro. However, we find that a functional CLK-2::GFP fusion protein is cytoplasmic in worms. We discuss how the phenotype of clk-2 mutants could be the result of altered patterns of gene expression.


COMMD1/Murr1 reinforces HIV-1 latent infection through IκB-α stabilization.
The transcription factor NF-κB is important for HIV-1 transcription initiation in primary HIV-1 infection and reactivation in latently HIV-1-infected cells. However, comparative analysis of the regulation and function of NF-κB in latently HIV-1-infected cells has not been done. Here we show that the expression of IκB-α, an endogenous inhibitor of NF-κB, is enhanced by latent HIV-1 infection via induction of the host-derived factor COMMD1/Murr1 in myeloid cells but not in lymphoid cells by using four sets of latently HIV-1-infected cells and the respective parental cells. IκB-α protein was stabilized by COMMD1, which attenuated NF-κB signaling during Toll-like receptor ligand and tumor necrosis factor alpha treatment and enhanced HIV-1 latency in latently HIV-1-infected cells. Activation of the phosphoinositol 3-kinase (PI3K)-JAK pathway is involved in COMMD1 induction in latently HIV-1-infected cells. Our findings indicate that COMMD1 induction is the NF-κB inhibition mechanism in latently HIV-1-infected cells that contributes to innate immune deficiency and reinforces HIV-1 latency. Thus, COMMD1 might be a double-edged sword that is beneficial in primary infection but not beneficial in latent infection when HIV-1 eradication is considered. HIV-1 latency is a major barrier to viral eradication in the era of combination antiretroviral therapy. In this study, we found that COMMD1/Murr1, previously identified as an HIV-1 restriction factor, inhibits the proteasomal degradation of IκB-α by increasing the interaction with IκB-α in latently HIV-1-infected myeloid cells. IκB-α protein was stabilized by COMMD1, which attenuated NF-κB signaling during the innate immune response and enhanced HIV-1 latency in latently HIV-1-infected cells. Activation of the PI3K-JAK pathway is involved in COMMD1 induction in latently HIV-1-infected cells. Thus, the host-derived factor COMMD1 is beneficial in suppressing primary infection but enhances latent infection, indicating that it may be a double-edged sword in HIV-1 eradication.


Effect of simulated rainfall and weathering on release of preservative elements from CCA treated wood.
The release of arsenic from wood pressure-treated with chromated copper arsenate (CCA) can be decreased by application of wood finishes, but little is known about the types of finishes that are best suited for this purpose. This study evaluated the effects of finish water repellent content and ultraviolet (UV) radiation on the release of arsenic, copper, and chromium from CCA-treated wood exposed to simulated rainfall. Deck boards treated with CCA were either left unfinished or dipped in a finish prepared with 1%, 3%, or 5% water repellent. All specimens were exposed to leaching from simulated rainfall, and a subset of specimens was also exposed to UV radiation. The rainfall was collected and analyzed for total elemental arsenic, copper, and chromium. The water repellent significantly decreased the amounts of these elements in the runoff, but for the short duration of this study there was no difference among the three water repellent concentrations. It is possible that water repellent content would have a greater effect over a longer exposure period. Exposure to UV radiation caused a significant increase in leaching from both finished and unfinished specimens. This effect may be a result of increased surface area during weathering as well as loss of fibers caused by UV-induced surface erosion.


Effects of allitridi on cell cycle arrest of human gastric cancer cells.
To determine the effect of allitridi on cell cycle of human gastric cancer (HGC) cell lines MGC803 and SGC7901 and its possible mechanism. Trypan blue dye exclusion was used to evaluate the proliferation, inhibition of cells and damages of these cells were detected with electron microscope. Flow cytometry and cell mitotic index were used to analyze the change of cell cycle, immunohistochemistry, and RT-PCR was used to examine expression of the p21(WAF1) gene. MGC803 cell growth was inhibited by allitridi with 24 h IC50 being 6.4 microg/mL. SGC7901 cell growth was also inhibited by allitridi with 24 h IC50 being 7.3 microg/mL. After being treated with allitridi at the concentration of 12 microg/mL for 24 h, cells were found to have direct cytotoxic effects, including broken cellular membrane, swollen and vesiculated mitochondria and rough endoplasmic reticula, and mass lipid droplet. When cells were treated with allitridi at the concentration of 3, 6, and 9 microg/mL for 24 h, the percentage of G0/G1 phase cells was decreased and that of G2/M phase cells was significantly increased (P = 0.002) compared with those in the group. When cells were treated with allitridi at the concentration of 6 microg/mL, cell mitotic index was much higher (P = 0.003) than that of control group, indicating that allitridi could cause gastric cancer cell arrest in M phase. Besides, the expression levels of p21(WAF1) gene of MGC803 cells and p21(WAF1) gene of SGC7901 cells were remarkably upregulated after treatment. Allitridi can cause gastric cancer cell arrest in M phase, and this may be one of the mechanisms for inhibiting cell proliferation. Effect of allitridi on cells in M phase may be associated with the upregulation of p21(WAF1) genes. This study provides experimental data for clinical use of allitridi in the treatment of gastric carcinoma.


Development of malignant ventricular arrhythmias in a young male with WPW pattern.
In Wolff-Parkinson-White Syndrome (WPW), presence of accessory pathways causes various tachyarrhythmias that lead to different symptoms and clinical conditions in patients. Atrial fibrillation is observed in about 20-30% of this group of patients. Life threatening malignant ventricular arrhythmias and sudden cardiac deaths are observed in patients having rapid conduction in accessory pathways and short antegrade refractory periods (<250 msn). We present a WPW syndrome case that presented to the emergency service with narrow QRS tachycardia and later developed malignant ventricular arrhythmia.