Clinicopathological findings of primary esophageal malignant melanoma: report of six cases and review of literature.
We studied images and histopathological features of primary esophageal malignant melanoma to explore the clinical pathological features, diagnosis, differential diagnoses, and treatment. Immunolabelling was conducted on six cases of esophageal malignant melanoma using histological and immunohistochemical techniques. Combined with the related literature, the clinical manifestations, imaging, histopathological and immunohistochemical features, treatment, and prognosis of primary esophageal malignant melanoma were observed and analyzed. The six patients with primary esophageal malignant melanoma were all male with an average age of 63.4 years. Poor food intake was observed in all patients, and the symptoms showed progressive aggravation. Endoscopic feed tube revealed dark brown and black nodular and polypoid lesions, 1/4-1/2 loop cavity. Tumor histopathology revealed the following characteristics: tumor cells arranged in nests, sheets and cords, round or polygonal, abundant and red-stained cytoplasm, melanin granules in the cytoplasm, heterogeneous nucleus sizes, centered or deviated nuclei, clearly identifiable nucleoli, and apparent pathological mitosis. The immune phenotype was as follows: tumor cells had diffuse expression of HMB45, Melan A, and S100. The cells were CK negative, and the Ki67-positive cell number was 40%-45%. Primary esophageal malignant melanoma is rare with high malignancy and poor prognosis. Immunohistochemical staining is helpful for diagnosing this tumor. The differential diagnosis includes low differentiated carcinoma, primitive neuroectodermal tumor, esophageal sarcomatoid carcinoma, esophageal lymphoma, and other tumors.


Phenotypic and genotypic characterization of biofilm forming capabilities in non-O157 Shiga toxin-producing Escherichia coli strains.
The biofilm life style helps bacteria resist oxidative stress, desiccation, antibiotic treatment, and starvation. Biofilm formation involves a complex regulatory gene network controlled by various environmental signals. It was previously shown that prophage insertions in mlrA and heterogeneous mutations in rpoS constituted major obstacles limiting biofilm formation and the expression of extracellular curli fibers in strains of Escherichia coli serotype O157:H7. The purpose of this study was to test strains from other important serotypes of Shiga toxin-producing E. coli (STEC) (O26, O45, O103, O111, O113, O121, and O145) for similar regulatory restrictions. In a small but diverse collection of biofilm-forming and non-forming strains, mlrA prophage insertions were identified in only 4 of the 19 strains (serotypes O103, O113, and O145). Only the STEC O103 and O113 strains could be complemented by a trans-copy of mlrA to restore curli production and Congo red (CR) dye affinity. RpoS mutations were found in 5 strains (4 serotypes), each with low CR affinity, and the defects were moderately restored by a wild-type copy of rpoS in 2 of the 3 strains attempted. Fourteen strains in this study showed no or weak biofilm formation, of which 9 could be explained by prophage insertions or rpoS mutations. However, each of the remaining five biofilm-deficient strains, as well as the two O145 strains that could not be complemented by mlrA, showed complete or nearly complete lack of motility. This study indicates that mlrA prophage insertions and rpoS mutations do limit biofilm and curli expression in the non-serotype O157:H7 STEC but prophage insertions may not be as common as in serotype O157:H7 strains. The results also suggest that lack of motility provides a third major factor limiting biofilm formation in the non-O157:H7 STEC. Understanding biofilm regulatory mechanisms will prove beneficial in reducing pathogen survival and enhancing food safety.


Enhanced recovery after surgery: Current research insights and future direction.
Since the concept of enhanced recovery after surgery (ERAS) was introduced in the late 1990s the idea of implementing specific interventions throughout the peri-operative period to improve patient recovery has been proven to be beneficial. Minimally invasive surgery is an integral component to ERAS and has dramatically improved post-operative outcomes. ERAS can be applicable to all surgical specialties with the core generic principles used together with added specialty specific interventions to allow for a comprehensive protocol, leading to improved clinical outcomes. Diffusion of ERAS into mainstream practice has been hindered due to minimal evidence to support individual facets and lack of method for monitoring and encouraging compliance. No single outcome measure fully captures recovery after surgery, rather multiple measures are necessary at each stage. More recently the pre-operative period has been the target of a number of strategies to improve clinical outcomes, described as prehabilitation. Innovation of technology in the surgical setting is also providing opportunities to overcome the challenges within ERAS, e.g., the use of wearable activity monitors to record information and provide feedback and motivation to patients peri-operatively. Both modernising ERAS and providing evidence for key strategies across specialties will ultimately lead to better, more reliable patient outcomes.


Familial Mediterranean fever associated with optic neuritis, successfully treated with anti-interleukin 1 agents.
Familial Mediterranean fever (FMF) is an inherited periodic auto-inflammatory disease characterized by recurrent attacks of fever, synovitis and serositis. Ophthalmological manifestations of FMF are extremely rare. Here we described a boy who has been followed-up for FMF and attended with a loss of vision during the course of the disease. He was diagnosed with optic neuritis. As the other etiologies were excluded his optic neuritis was attributed to the underlying auto inflammatory process. After pulse steroid therapy, his symptoms improved and a complete remission occurred. Afterwards he had two more optic neuritis attacks. Thereafter anti-interleukin 1 (IL-1) drugs were introduced and he did not develop further attacks of both optic neuritis and FMF. This case presentation highlights the possible association between FMF and optic nerve involvement.


[Single photon emission computed tomography by using N-isopropyl-p-[123I]-iodoamphetamine and 99mTc-hexamethyl propyleneamine oxime in a patient with herpes simplex encephalitis].
Single photon emission computed tomographies (SPECTs) by using N-isopropyl-p-[123I-IMP]-iodo-amphetamine (123I-IMP) and 99mTc-hexamethyl propyleneamine oxime (99mTc-HM-PAO) were serially performed in a 70 yrs. old male with herpes simplex encephalitis (HSE), and the chronological changes of accumulations were studied. Accumulations of both 123I-IMP and 99mTc-HM-PAO increased initially, and then decreased with the stage of HSE being advanced. The sequential appearance of the lesion in HSE with 123I-IMP and 99mTc-HM-PAO SPECTs was as same as that reported previously by X-CT; beginning at the temporal lobe with eventually being spread to the occipital and frontal lobe. Furthermore, it was shown that findings of both SPECTs could reflect considerably the clinical features, and the laboratory data in central spinal fluid. Thus, 123I-IMP and 99mTc-HM-PAO SPECTs seemed to be a useful tool in the diagnosis, deciding of whether the treatment was suspended or continued, and clarifying the pathophysiology in HSE.


Colchicine treatment impairs skeletal muscle mitochondrial function and insulin sensitivity in an age-specific manner.
The aim of the study was to investigate the impact of autophagy inhibition on skeletal muscle mitochondrial function and glucose homeostasis in young and aged mice. The transcriptional co-activator PGC-1α regulates muscle oxidative phenotype which has been shown to be linked with basal autophagic capacity. Therefore, young and aged inducible muscle-specific PGC-1α knockout (iMKO) mice and littermate lox/lox controls were used in three separate experiments performed after either saline or colchicine injections on two consecutive days: (1) Euthanization in the basal state obtaining skeletal muscle for mitochondrial respirometry, (2) whole body glucose tolerance test, and (3) in vivo insulin-stimulated 2-deoxyglucose (2-DG) uptake into skeletal muscle. Muscle PGC-1α was not required for maintaining basal autophagy flux, regardless of age. Colchicine-induced inhibition of autophagy was associated with impairments of skeletal muscle mitochondrial function, including reduced ADP sensitivity and altered mitochondrial redox balance in both young and aged mice. Colchicine treatment reduced the glucose tolerance in aged, but not young mice, and similarly in iMKO and lox/lox mice. Colchicine reduced insulin-stimulated 2-DG uptake in soleus muscle in aged mice, independently of PGC-1α, and without affecting insulin-regulated phosphorylation of proximal or distal mediators of insulin signaling. In conclusion, the results indicate that autophagy regulates the mitochondrial ADP sensitivity and redox balance as well as whole body glucose tolerance and skeletal muscle insulin sensitivity in aged mice, with no additional effects of inducible PGC-1α deletion.


The significance of angiotensin I converting enzyme in granulomatous inflammation. Functions of ACE in granulomas.
ACE is a carboxy-terminal peptidyl dipeptidase which can be produced by granuloma macrophages and possibly by other components of the granuloma. ACE activity is influenced by regulatory T cells. This enzyme may be important in mediating and/or modulating inflammation. One mechanism involves the generation of angiotensin II which can effect inflammatory reactions. Although unstudied, ACE may also be an important inactivator of bradykinin and various neuropeptides which in turn may participate in the immunoregulation of the granuloma. Thus, therapeutic strategies designed to alter ACE activity within granulomas may alter the size, composition and ultimate resolution of these lesions.


Beating the odds: reducing the risk of not being paid by HMOs and IPAs.
Physicians are having increasing problems getting paid by HMOs, independent practice associations and other payers. This article discusses what practices should investigate about payers, and guidelines for negotiating protections in contracts with payers. Even if certain clauses cannot be negotiated, it is important that providers be aware of potential traps in the contract. By using these guidelines, physicians will be able to negotiate better contracts or decide that no contract is better than a bad contract.


Ribosomal RNA Biogenesis and Its Response to Chilling Stress in Oryza sativa.
Ribosome biogenesis is crucial for plant growth and environmental acclimation. Processing of ribosomal RNAs (rRNAs) is an essential step in ribosome biogenesis and begins with transcription of the rDNA. The resulting precursor-rRNA (pre-rRNA) transcript undergoes systematic processing, where multiple endonucleolytic and exonucleolytic cleavages remove the external and internal transcribed spacers (ETS and ITS). The processing sites and pathways for pre-rRNA processing have been deciphered in Saccharomyces cerevisiae and, to some extent, in Xenopus laevis, mammalian cells, and Arabidopsis (Arabidopsis thaliana). However, the processing sites and pathways remain largely unknown in crops, particularly in monocots such as rice (Oryza sativa), one of the most important food resources in the world. Here, we identified the rRNA precursors produced during rRNA biogenesis and the critical endonucleolytic cleavage sites in the transcribed spacer regions of pre-rRNAs in rice. We further found that two pre-rRNA processing pathways, distinguished by the order of 5' ETS removal and ITS1 cleavage, coexist in vivo. Moreover, exposing rice to chilling stress resulted in the inhibition of rRNA biogenesis mainly at the pre-rRNA processing level, suggesting that these energy-intensive processes may be reduced to increase acclimation and survival at lower temperatures. Overall, our study identified the pre-rRNA processing pathway in rice and showed that ribosome biogenesis is quickly inhibited by low temperatures, which may shed light on the link between ribosome biogenesis and environmental acclimation in crop plants.


Karyotypic Evolution in Malagasy Flying Foxes (Pteropodidae, Chiroptera) and Their Hipposiderid Relatives as Determined by Comparative Chromosome Painting.
Pteropodidae and Hipposideridae are 2 of the 9 chiropteran families that occur on Madagascar. Despite major advancements in the systematic study of the island's bat fauna, few karyotypic data exist for endemic species. We utilized G- and C-banding in combination with chromosome painting with Myotismyotis probes to establish a genome-wide homology among Malagasy species belonging to the families Pteropodidae (Pteropus rufus 2n = 38; Rousettus madagascariensis, 2n = 36), Hipposideridae (Hipposideros commersoni s.s., 2n = 52), and a single South African representative of the Rhinolophidae (Rhinolophus clivosus, 2n = 58). Painting probes of M. myotis detected 26, 28, 28, and 29 regions of homology in R. madagascariensis, P. rufus, H. commersoni s.s, and R. clivosus, respectively. Translocations, pericentric inversions, and heterochromatin additions were responsible for karyotypic differences amongst the Malagasy pteropodids. Comparative chromosome painting revealed a novel pericentric inversion on P. rufus chromosome 4. Chromosomal characters suggest a close evolutionary relationship between Rousettus and Pteropus. H. commersoni s.s. shared several chromosomal characters with extralimital congeners but did not exhibit 2 chromosomal synapomorphies proposed for Hipposideridae. This study provides further insight into the ancestral karyotypes of pteropodid and hipposiderid bats and corroborates certain molecular phylogenetic hypotheses.


Measuring the Electrical Resistivity of Liquid Iron to 1.4 Mbar.
We determined the electrical resistivity of liquid Fe to 135 GPa and 6680 K using a four-probe method in a diamond-anvil cell combined with two novel techniques: (i) enclosing a molten Fe in a sapphire capsule, and (ii) millisecond time-resolved simultaneous measurements of the resistance, x-ray diffraction, and temperature of instantaneously melted Fe. Our results show the minimal temperature dependence of the resistivity of liquid Fe and its anomalous resistivity decrease around 50 GPa, likely associated with a gradual magnetic transition, both in agreement with previous ab initio calculations.


Dominantly transmitted congenital indifference to pain.
Two patients from a family with dominantly inherited indifference to pain were investigated. Perception of the other sensory modalities was normal as was the remainder of the neurological examination. Electrophysiological studies and morphometric evaluation of myelinated and unmyelinated fibers of nerve biopsy specimens were normal. This is the first morphometric study of peripheral nerve in dominantly inherited indifference to pain.


Characterization of the major capsid proteins of myxoma virus particles using MALDI-TOF mass spectrometry.
The protein composition of poxvirus particles remains uncertain because of their large size and structural complexity. This has complicated the characterization of even well-studied Orthopoxviruses, like vaccinia virus, and little or nothing is known about the capsid composition of viruses belonging to other poxvirus genera. This paper describes methods that address this problem and have been used to identify 17 different Leporipoxvirus capsid proteins. Myxoma virus particles were purified using sucrose and Nicodenz gradient centrifugation and subfractionated into membrane and core fractions by thiol and detergent treatment. These materials were further fractionated using reverse-phase chromatography and SDS-PAGE and the resulting proteins identified by mass spectroscopy. Most of the myxoma proteins identified in this manner were homologs of either vaccinia virus structural proteins (F17R, L4R, J1R, H3L, A3L, A10L, A27L, and A45R) or virion-associated enzymes (I7L, H4L, D11L, A7L, and A22R). However, the myxoma homolog of the vaccinia P4a/A10L protein (M099L) differs from P4a protein in being proteolytically cleaved only once. M095L and M151R were also detected in core fractions. M095L and M151R are homologs of vaccinia A6L and B13R proteins, respectively, and poxvirus proteins not previously known to be capsid components. M093L, a protein of unknown function and having no certain Orthopoxvirus homolog associates with membrane fractions. These studies illustrate the conservation of Chordopoxvirion architecture and the methods that can be used to elucidate the proteins comprising these structures.


Severe macular complications in glaucoma: high-resolution multimodal imaging characteristics and review of the literature.
To describe imaging characteristics of severe macular complications occurring in glaucoma and discuss available treatments. Retrospective case series of glaucomatous patients with macular retinoschisis (MR) and/or serous retinal detachment (SRD). Patients underwent a complete ophthalmological examination and multimodal imaging including retinography, SD-OCT, fluorescein and indocyanine green angiography (FA & ICGA) and adaptive optics (AO). Ten eyes (8 patients) were included. Initial BCVA was 1.04 ± 1.12 logMAR and IOP was 24.0 ± 9.3mmHg. All eyes presented with MR while SRD was present in 5 eyes (5 patients), with a central macular thickness of 573 ± 152 μm. FA and ICGA allowed to exclude leakage in all cases. A focal lamina cribrosa defect (LCD) was found in four eyes (4 patients) using OCT, with AO providing en-face visualization of the defect in one eye. Outer retinal hole was present in 3 eyes (3 patients). No visual improvement or resolution of the macular retinoschisis was observed in eyes with medical or surgical IOP control (N = 9). Vitrectomy with internal membrane limiting peeling and gas tamponade was performed in one eye with good visual results. Multimodal high-resolution imaging is essential to diagnose severe macular complications associated with advanced glaucoma.


Leveraging epigenetics to examine differences in developmental trajectories of social attention: A proof-of-principle study of DNA methylation in infants with older siblings with autism.
Preliminary evidence suggests that changes in DNA methylation, a widely studied epigenetic mechanism, contribute to the etiology of Autism Spectrum Disorder (ASD). However, data is primarily derived from post-mortem brain samples or peripheral tissue from adults. Deep-phenotyped longitudinal infant cohorts are essential to understand how epigenetic modifications relate to early developmental trajectories and emergence of ASD symptoms. We present a proof-of-principle study designed to evaluate the potential of prospective epigenetic studies of infant siblings of children with ASD. Illumina genome-wide 450 K DNA methylation data from buccal swabs was generated for 63 male infants at multiple time-points from 8 months to 2 years of age (total N = 107 samples). 11 of those infants received a diagnosis of ASD at 3 years. We conducted a series of analyses to characterize DNA methylation signatures associated with categorical outcome and neurocognitive measures from parent-report questionnaire, eye-tracking and electro-encephalography. Effects observed across the entire genome (epigenome-wide association analyses) suggest that collecting DNA methylation samples within infant-sibling designs allows for the detection of meaningful signals with smaller sample sizes than previously estimated. Mapping networks of co-methylated probes associated with neural correlates of social attention implicated enrichment of pathways involved in brain development. Longitudinal modelling found covariation between phenotypic traits and DNA methylation levels in the proximity of genes previously associated with cognitive development, although larger samples and more complete datasets are needed to obtain generalizable results. In conclusion, assessment of DNA methylation profiles at multiple time-points in infant-sibling designs is a promising avenue to comprehend developmental origins and mechanisms of ASD.


Effectiveness of integrated care interventions for patients with long-term conditions: a review of systematic reviews.
To examine the effectiveness of integrated care intervention (ICI) models (stand-alone or combination of self-management, discharge management, case management and multidisciplinary teams models) targeting patients with one or more chronic conditions, and to identify outcome measures/indicators of effectiveness, we conducted a systematic review of published systematic reviews and meta-analyses. Included reviews comprise ICIs targeting adult patients with one or more long-term conditions. We searched MEDLINE, CINAHL and the Cochrane Database of Systematic Reviews: 60 reviews were included in the final analysis; 28 reviews evaluated ICIs focused on self-management, 4 on case management, 10 on discharge management and 5 on multidisciplinary teams; 13 reviews assessed multiple interventions that were labelled as complex. Across all reviews, only 19 reviews included intervention with multiple ICIs. Overall, interventions with multiple components, compared with interventions with single components, were more likely to improve hospital use outcomes effectively. Clinical/lifestyle/condition-specific outcomes were more likely to be improved by self-management interventions. Outcome measures identified could be classified into three main categories: organisational, patient-centred and clinical/lifestyle/condition-specific. The findings of this review may provide inputs to future design and evaluation of ICIs.


The Incremental Prognostic Value of Cardiac Computed Tomography in Comparison with Single-Photon Emission Computed Tomography in Patients with Suspected Coronary Artery Disease.
Coronary computed tomographic angiography (CCTA) facilitates comprehensive evaluation of coronary artery disease (CAD), including plaque characterization, and can provide additive diagnostic value to single-photon emission computed tomography (SPECT). However, data regarding the incremental prognostic value of CCTA to SPECT remain sparse. We evaluated the independent and incremental prognostic value of CCTA, as compared with clinical risk factors and SPECT. A total of 1,077 patients with suspected CAD who underwent both SPECT and cardiac CT between 2004 and 2012 were enrolled retrospectively. Presence of reversible or fixed perfusion defect (PD) and summed stress score were evaluated on SPECT. Presence, extent of coronary atherosclerosis and diameter stenosis (DS) were evaluated on CCTA. Plaque composition was categorized as non-calcified, mixed, or calcified according to the volume of calcified component (>130 Hounsfield Units). Patients were followed up for the occurrence of adverse cardiac events including cardiac death, non-fatal myocardial infarction, unstable angina, and late revascularization (>90 days after imaging studies). During follow-up (median 23 months), adverse cardiac events were observed in 71 patients (6.6%). When adjusted for clinical risk factors and SPECT findings, the presence of any coronary plaque, any plaque in ≥3 segments, coronary artery calcium score (CACS) ≥400, a plaque ≥50% DS, presence of non-calcified plaque (NCP) or mixed plaque (MP), and NCP/MP in ≥2 segments were independent predictors of adverse cardiac events; however, the presence of calcified plaque (CP) was not. Conventional CCTA findings, including CACS ≥400 and a plaque ≥50% DS, demonstrated incremental prognostic value over clinical risk factors and SPECT (χ² 54.19 to 101.03; p <0.001). Addition of NCP/MP in ≥2 segments resulted in further significantly improved prediction (χ² 101.03 to 113.29; p <0.001). Comprehensive CCTA evaluation of coronary atherosclerosis provides independent and incremental prognostic value in relation to SPECT evaluation of myocardial ischemia. Specifically, segmentally-analyzed plaque composition with CCTA provides further risk stratification in addition to CACS and DS.


Unconstrained retrieval from semantic memory.
The present study was designed to examine developmental change in the processes used to retrieve lexical information from semantic memory. We asked 8-, 12-, and 21-year-olds to name as many animals and pieces of furniture as they could, in separate 7-min intervals. The principal results were the following: (1) the number of items retrieved increased with age, but at all ages retrieval declined hyperbolically over the 7-min interval; (2) analysis of the time between retrieval of successive items indicated that older individuals retrieved larger clusters of items, but that the number of clusters retrieved did not vary with age; and (3) at all ages prototypic category members were retrieved first, followed by typical (but not prototypic) and atypical category members. The results are explained in terms of a model in which the information in semantic memory changes with age, but the processes used to retrieve that information do not.


Accelerated enhanced Recovery following Minimally Invasive colorectal cancer surgery (RecoverMI): a study protocol for a novel randomised controlled trial.
Definitive treatment of localised colorectal cancer involves surgical resection of the primary tumour. Short-stay colectomies (eg, 23-hours) would have important implications for optimising the efficiency of inpatient care with reduced resource utilisation while improving the overall recovery experience with earlier return to normalcy. It could permit surgical treatment of colorectal cancer in a wider variety of settings, including hospital-based ambulatory surgery environments. While a few studies have shown that discharge within the first 24 hours after minimally invasive colectomy is possible, the safety, feasibility and patient acceptability of a protocol for short-stay colectomy for colorectal cancer have not previously been evaluated in a prospective randomised study. Moreover, given the potential for some patients to experience a delay in recovery of bowel function after colectomy, close outpatient monitoring may be necessary to ensure safe implementation. In order to address this gap, we propose a prospective randomised trial of accelerated enhanced Recovery following Minimally Invasive colorectal cancer surgery (RecoverMI) that leverages the combination of minimally invasive surgery with enhanced recovery protocols and early coordinated outpatient remote televideo conferencing technology (TeleRecovery) to improve postoperative patien-provider communication, enhance postoperative treatment navigation and optimise postdischarge care. We hypothesise that RecoverMI can be safely incorporated into multidisciplinary practice to improve patient outcomes and reduce the overall 30-day duration of hospitalisation while preserving the quality of the patient experience. ETHICS AND DISSEMINATION: RecoverMI has received institutional review board approval and funding from the American Society of Colorectal Surgeons (ASCRS; LPG103). Results from RecoverMI will be published in a peer-reviewed publication and be used to inform a multisite trial. NCT02613728; Pre-results.


Identification of an adhesion site within the syndecan-4 extracellular protein domain.
The syndecan family of cell surface proteoglycans regulates cell adhesion and growth factor signaling by binding components of the extracellular matrix and growth factors. To date, all known ligand interactions are via the covalently attached glycosaminoglycan chains. To assay for potential extracellular interactions via the core proteins directly, the recombinant extracellular domain of syndecan-4 (S4ED), one of the four syndecan family members, was tested as a substratum for the attachment of mammalian cells. Human foreskin fibroblasts bind to mouse S4ED, and both mouse and chicken S4ED can block this binding, with 50% inhibition observed between 0.1 and 1 x 10(-7) M. The extracellular domain of another syndecan family member, syndecan-1, fails to compete for cell binding to mouse S4ED. Amino acids 56-109 of the 120-amino acid mouse S4ED compete fully, suggesting that the cell binding domain is within this region. The ability of syndecan-4 to interact with molecules at the cell surface via its core protein as well as its glycosaminoglycan chains may uniquely regulate the formation of cell surface signaling complexes following engagement of this proteoglycan with its extracellular ligands.


Evaluation of the ameliorative effects of immunosuppressants on crescentic glomerulonephritis in SCG/Kj mice.
The therapeutic efficacy of immunosuppressants for treating rapidly progressive glomerulonephritis (RPGN) with crescent formation remains controversial. SCG/Kj mice spontaneously develop RPGN-like symptoms, characteristic of crescentic glomerulonephritis and systemic small vessel vasculitis, associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). We evaluated the "ameliorative", not prophylactic, effects of immunosuppressive agents, deoxyspergualin (DSG), cyclophosphamide (CYC) and prednisolone (PDN), on RPGN in these mice. DSG at intraperitoneal doses of 3 and 6 mg/kg, CYC at an oral dose of 12 mg/kg, or PDN at an intraperitoneal dose of 120 mg/kg was administered once a day for 21 days to female mice "at the onset of hematuria". A set of control SCG/Kj mice received only saline injections. DSG and CYC significantly prolonged survival, improved the proteinuria, hematuria and hyperuremia, and decreased the serum level of myeloperoxidase-ANCA. Moreover, DSG significantly suppressed the formation of crescents in glomeruli. PDN failed to affect any of the parameters. DSG might be useful for inducing remission in crescentic glomerulonephritis involved in RPGN.


Neuroscience research on aging and implications for counseling psychology.
The advances in neuroscience have led to an increase in scientific understanding of the aging process, and counseling psychologists can benefit from familiarity with the research on the neuroscience of aging. In this article, we have focused on the cognitive neuroscience of aging, and we describe the progression of healthy aging to Alzheimer's disease, given its high prevalence rate among older adults (Alzheimer's Association, 2013). Common techniques used to study the cognitive neuroscience of aging are explained in regards to measuring age-related changes in the brain and the role of biomarkers in identifying cognitive decline related to Alzheimer's disease. Using this information and in collaboration with cognitive neuroscientists, it is our hope that counseling psychologists may further pursue research areas on aging as well as design appropriate interventions for older individuals who may be experiencing cognitive impairment.


The expression of active human reticulocyte 15-lipoxygenase in bacteria.
A cloned cDNA that encodes human reticulocyte 15-lipoxygenase was characterized by Northern blot analysis and heterologous expression in bacteria. The 2.7 kb cDNA specifically hybridizes to reticulocyte RNA from anemic rabbits. The RNA levels correlate with the appearance of enzymatic activity in anemia. The cDNA was subcloned into an inducible bacterial expression vector in frame with the amino terminal ten amino acids of beta-galactosidase (pUCLOX). The soluble fraction of the cell lysate of E. coli transformed with pUCLOX contained a protein that has the same catalytic and antigenic characteristics as reticulocyte 15-lipoxygenase.


What is new in the histogenesis of granulomatous skin diseases?
A granuloma is a form of inflammation, which predominantly consists of macrophages. It typically develops when the immune system attempts to enclose substances that are usually insoluble and cannot be eliminated to prevent the spread of these substances to the other body compartments. According to the source of the substances, granulomatous diseases can be divided into two groups: infectious and non-infectious. The mechanisms of infectious granuloma formation have been widely investigated because of its easy reproducibility in experimental models, both in vivo and in vitro. On the contrary, mechanisms of non-infectious granuloma formation have not been well investigated because of the difficulty to reproduce this formation in experimental models. In this article, we review our recent understanding of the histogenesis and pathogenesis of granuloma formation, confirmed from studies of infectious granulomas, and we present potential hypotheses of the histogenesis and pathogenesis of non-infectious granulomas based on clinical investigations.


Stereoisomer-specific inhibition of superoxide anion-induced rat aortic smooth-muscle cell proliferation by 17beta-estradiol is estrogen receptor dependent.
An in vitro xanthine/xanthine oxidase reaction system was used to generate superoxide anions that significantly stimulated tritiated [3H]thymidine incorporation into endothelium-removed (denuded) male rat aortic explants. Tritiated thymidine uptake was used as an index of vascular smooth-muscle cell (VSMC) proliferation. Superoxide dismutase (SOD) significantly attenuated the oxygen free radical-induced proliferative response of these cells. 17Beta-estradiol (17beta-E) significantly inhibited superoxide anion-induced VSMC proliferation. In contrast, the growth-modifying effects of 17beta-E were not mimicked by 17alpha-estradiol (17alpha-E), progesterone, or testosterone. The pure estrogen receptor (ER) antagonist, ICI 164,384, reversed the growth-inhibitory effect of 17beta-E. 17Beta-estradiol failed directly to reduce in vitro superoxide anion production or to modify xanthine oxidase activity. Therefore, these data indicate that 17beta-E, through an ER-dependent mechanism, specifically and significantly inhibited superoxide anion-mediated SMC proliferation in denuded rat aortic explants.


[Mechanisms of microbial corrosion on petrous materials].
Present studies related to stone weathering demonstrate that the biological activity of bacteria, algae, fungi and lichens play an important role in the biodegradative processes implied in stone building decay. In natural environments is not possible to separate the damage provoked by microorganisms from damage caused by physical and chemical agents. In vitro assays carried out with microbes isolated from weathered stones are required in order to understand the biological mechanisms involved in stone deterioration. We have demonstrated, by means of different techniques as commented in the text, that filamentous fungi contribute greatly to stone biodeterioration by using different mechanisms: (a) mechanical (hyphae growth and penetration in stony substrate); and (b) biochemical (organic acid excretion, cation release, chelation and deposition of organic salts, precipitation of neoformation salts and metals oxidation).


Heartbeat perception in social anxiety before and during speech anticipation.
According to current cognitive models of social phobia, individuals with social anxiety create a distorted image of themselves in social situations, relying, at least partially, on interoceptive cues. We investigated differences in heartbeat perception as a proxy of interoception in 48 individuals high and low in social anxiety at baseline and while anticipating a public speech. Results revealed lower error scores for high fearful participants both at baseline and during speech anticipation. Speech anticipation improved heartbeat perception in both groups only marginally. Eight of nine accurate perceivers as determined using a criterion of maximum difference between actual and counted beats were high socially anxious. Higher interoceptive accuracy might increase the risk of misinterpreting physical symptoms as visible signs of anxiety which then trigger negative evaluation by others. Treatment should take into account that in socially anxious individuals perceived physical arousal is likely to be accurate rather than false alarm.


Pathogenic assays of acanthamoeba belonging to the t4 genotype.
Acanthamoeba genus is introduced as opportunistic and cosmopolitan parasite. Monkey and wistar rat are appropriate models for experimental study on Acanthamoeba infection. In this study Acanthamoeba spp. were isolated from hot spring (HS), windows dust (WD) and a corneal sample of keratitis patient (KP) and their pathogenicity surveyed by in vitro and in vivo tests. Isolates of Acanthamoeba were cultivated axenically for 12 months in PYG medium. Overall, 30 wistar rats, in 6 equal groups were used for developing experimental Acanthamoeba keratitis (AK) and Granulomatous Amoebic Encephalitis (GAE). The Keratitis and Granulomatous Encephalitis experiments were performed by intrastromal and intranasal inoculation of Acanthamoeba cysts, respectively. Pathogenicity of the three isolates was also evaluated by in vitro test using osmotolerance and temperature tolerance assays. Identification of genotypes were performed by PCR technique and sequencing. None of the isolates could perform AK and GAE in wistar rats, although all isolates were described as T4 genotype. Isolates obtained from KP and WD could grow only in 30 °C, but not in 37 °C and 40 °C. On the other hand, HS isolate grew in 30 °C and 37 °C but not in 40 °C. Moreover, all of isolate grew in 0.5 M mannitol but not in 1 M and 1.5 M. T4 isolates with a long-term axenic culture and different factors related to host and parasite may play role in pathogenicity of these free-living amoebae.


Estimating probabilities from experimental frequencies.
Estimating the probability distribution q governing the behavior of a certain variable by sampling its value a finite number of times most typically involves an error. Successive measurements allow the construction of a histogram, or frequency count f, of each of the possible outcomes. In this work, the probability that the true distribution be q, given that the frequency count f was sampled, is studied. Such a probability may be written as a Gibbs distribution. A thermodynamic potential, which allows an easy evaluation of the mean Kullback-Leibler divergence between the true and measured distribution, is defined. For a large number of samples, the expectation value of any function of q is expanded in powers of the inverse number of samples. As an example, the moments, the entropy, and the mutual information are analyzed.


Recurrent cystic lymphangioma of the neck. Case report.
Cystic lymphangioma is a rare benign tumor commonly located in the head or neck. Approximately 100 adult cases have been reported in the literature. The etiopathogenesis is unclear, though trauma has been suggested as one of the possible causes. We report a case of recurrent cystic lymphangioma arising in an adult who had been successfully treated in our department, leading us to review the literature for a critical examination of our therapeutic choices and the pathological, clinical and therapeutic aspects. We performed a dissection of the cyst respecting anatomical structures.Three days after the surgery, the patient showed a recurrence under the previous site of the excision, We then decided to place a suction drainage under local anesthesia, The suction drainage was removed 25 days later.The post-operative course of the patient showed no signs of recurrence for twenty-four months. Complete surgical excision is the treatment of choice in symptomatic patients. In our experience, postoperative suction drainage improved the outcome. Some authors have come out in favor of experimental, non-surgical methods, such as percutaneous sclerotherapy, which they claim offer the most promising results. In our experience, totally excision of the mass was the treatment of choice but, placing just one suction drainage for weeks for new recurrence resulted in a surprising outcome. In fact, recurrence usually appears within the first nine months in about 10-15% of patients.


Measuring individual differences in responses to date-rape vignettes using latent variable models.
Vignette methodology can be a flexible and powerful way to examine individual differences in response to dangerous real-life scenarios. However, most studies underutilize the usefulness of such methodology by analyzing only one outcome, which limits the ability to track event-related changes (e.g., vacillation in risk perception). The current study was designed to illustrate the dynamic influence of risk perception on exit point from a date-rape vignette. Our primary goal was to provide an illustrative example of how to use latent variable models for vignette methodology, including latent growth curve modeling with piecewise slopes, as well as latent variable measurement models. Through the combination of a step-by-step exposition in this text and corresponding model syntax available electronically, we detail an alternative statistical "blueprint" to enhance future violence research efforts using vignette methodology. Aggr. Behav. 43:60-73, 2017. © 2016 Wiley Periodicals, Inc.


Suture Anchor Versus Transosseous Tunnel Repair for Inferior Pole Patellar Fractures Treated With Partial Patellectomy and Tendon Advancement: A Biomechanical Study.
Comminuted inferior pole patellar fractures can be treated in numerous ways. To date, there have been no studies comparing the biomechanical properties of transosseous tunnels versus suture anchor fixation for partial patellectomy and tendon advancement of inferior pole patellar fractures. Suture anchor repair will result in less gapping at the repair site. We also hypothesize no difference in load to failure between the groups. Controlled laboratory study. Ten cadaveric knee extensor mechanisms (5 matched pairs; patella and patellar tendon) were used to simulate a fracture of the extra-articular distal pole of the patella. The distal simulated fracture fragment was excised, and the patellar tendon was advanced and repaired with either transosseous bone tunnels through the patella or 2 single-loaded suture anchors preloaded with 1 suture per anchor. Load to failure and elongation from cycles 1 to 250 between 20 and 100 N of force were measured, and modes of failure were recorded. Statistical analysis was performed using a paired 2-tailed Student t test. The suture anchor group had less gapping during cyclic loading as compared with the transosseous tunnel group (mean ± SD, 6.83 ± 2.23 vs 13.30 ± 5.74 mm; P = .047). There was no statistical difference in the load to failure between the groups. The most common mode of failure was at the suture-anchor interface in the suture anchor group (4 of 5) and at the knot proximally on the patella in the transosseous tunnel group (4 of 5). Suture anchors yielded similar strength profiles and less tendon gapping with cyclic loading when compared with transosseous tunnels in the treatment of comminuted distal pole of the patellar fractures managed with partial patellectomy and patellar tendon advancement. Suture anchors may offer robust repair and earlier range of motion in the treatment of fractures of the distal pole of the patella. Clinical randomized controlled trials would help clinicians better understand the difference in repair techniques and confirm the translational efficacy in clinical practice.


ESHRE basic semen analysis courses 1995-1999: immediate beneficial effects of standardized training.
Many reports have shown problems with the high variability in results of semen analyses. The Special Interest Group in Andrology (SIGA) of the European Society of Human Reproduction and Embryology (ESHRE) implemented a standardized training course which has been run in different regions of the world on more than 20 occasions since 1994. The aim of the present analysis was to investigate to what extent training resulted in any immediate effects on the variability of assessments made by different observers. The variability in participants' results from the beginning to the end of each course was analysed in eight courses given between 1995 and 1999. For assessments of sperm concentration, motility, vitality and morphology, substantial improvement was seen over the duration of the course. A comprehensive, structured training course does lead to substantial reductions in inter-observer variability in semen analysis. This supports our contention that providing a thorough theoretical background and repeated practical training, combined with daily feedback of results, is highly effective in raising the technical skills of laboratory personnel performing semen analysis.


[Expansive personal space: Distance between personal belongings reflects the interpersonal distance of their owners].
People feel uncomfortable when someone else comes spatially near and thus encroaches on their personal space (PS). Although many social psychologists have explored characteristics of PS of/between/among individuals so far, there is currently no empirical research on whether the PS of individuals expands into space surrounding their belongings (or objects) that are away from their body. This study measured the spatial distance between bags which participants and confederates left behind, and thus demonstrated that the distance between bags was modulated in response to the interpersonal relationship of their owners. The present study suggests new evidence for expansive PS, which is the concept that an individual's PS expands into space surrounding his/her belongings.


Effect of 200 mEq/L Na+ hypertonic saline resuscitation on systemic inflammatory response and oxidative stress in severely burned rats.
Excessive release of inflammatory mediators and oxidative stress play important roles in the increased vascular permeability and systemic edema during the early stage of severe burn. This study investigates the effect of 200 mEq/L Na(+) hypertonic saline (HS) on systemic inflammatory response and oxidative stress in severely burned rats. Sprague-Dawley rats were divided into three groups: sham group, burn plus lactated Ringer's group, and burn plus HS group. Lung edema was assessed in terms of wet-weight-to-dry-weight ratio. Tumor necrosis factor α and interleukin 6 concentrations in serum were examined by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells were isolated and the expression of p38 mitogen-activated protein kinase was determined by Western blot analysis. The lung and intestinal concentrations of malondialdehyde, an indicator of oxidative stress, were also measured. Resuscitation with 200 mEq/L Na(+) HS significantly decreased the lung wet-weight-to-dry-weight ratio and abolished hyponatremia induced by burn injury. HS treatment also prevented the increases of myeloperoxidase activity and malondialdehyde content in the lung and intestine of severely burned rats. However, there were no significant differences, either in serum tumor necrosis factor α and interleukin 6 concentrations or with respect to the p38 mitogen-activated protein kinase expression in peripheral blood mononuclear cells, between the burn plus lactated Ringer's group and burn plus HS group (P > 0.05). Initial resuscitation with 200 mEq/L Na(+) HS after severe burn injury decreases pulmonary edema, prevents hyponatremia, and attenuates oxidative stress, but is not capable of inhibiting the systemic inflammatory response.


Economic evaluation of a JAK inhibitor compared to a monoclonal antibody for treatment of moderate-to-severe atopic dermatitis from a UK perspective.
Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by severe itching, erythema and scaling, causing pain, stigmatization and social isolation. Despite the growing availability of treatment options, unmet care needs remain. This research aimed to assess the cost-effectiveness of a novel JAK inhibitor (JAKi) compared to a monoclonal antibody and to identify key drivers of cost-effectiveness. A de novo economic model was developed to assess the cost-effectiveness of a novel JAKi compared to an established monoclonal antibody for the treatment of moderate-to-severe AD patients from a UK perspective. A targeted literature review was conducted to inform the development of the economic model with an advanced model structure. Various scenario and sensitivity analyses were performed to account for parameter- and structural uncertainty and to identify key drivers of cost-effectiveness. The JAKi was not cost-effective compared to the monoclonal antibody (£219,733.88 per quality-adjusted life year (QALY) gained) at selected price levels when applying the UK willingness-to-pay threshold of £30,000 per QALY gained. Key drivers of cost-effectiveness were utility values, intervention efficacy and drug acquisition costs. A decrease in JAKi's dose costs, as well as a lower dose, lead to cost-effectiveness. Assumptions regarding parameter inputs were necessary, therefore a considerable level of uncertainty regarding efficacy and cost data is to be accounted for in the interpretation of the results. In particular, the efficacy data were based on single clinical studies. This research revealed the cost-effectiveness of a JAKi compared to a monoclonal antibody for the treatment of moderate-to-severe AD to be highly sensitive to the costs and effectiveness inputs and identified further cost-effectiveness drivers. It demonstrated that the JAKi could be cost-effective compared to an established monoclonal antibody with a lower dose or a reduced price.


Dworkin and Casey on abortion.
This article responds to two important recent treatments of abortion rights. I will mainly discuss Ronald Dworkin's recent writings concerning abortion: his article "Unenumerated rights: whether and how Roe should be overruled," and his book Life's Dominion. In these writings Dworkin presents a novel view of what the constitutional and moral argument surronding abortion is really about. Both debates actually turn, he argues, on the question of how to interpret the widely shared idea that human life is sacred. At the heart of the abortion debate is the essentially religious notion that human life has value which transcends its value to any particular person; abortion is therefore at bottom a religious issue. Dworkin hopes to use this analysis to show that the religion clauses of the First Amendment provide a "textual home" for a woman's right to choose abortion. I wish to scrutinize this suggestion here; I want to probe the precise consequences for abortion rights of such an understanding of their basis. I will argue that the consequences are more radical than Dworkin seems to realize. The other work I will examine here is the important 1992 Supreme Court decision on abortion, Planned Parenthood v. Casey. The controlling opinion in that case, written jointly by Justices Kennedy, O'Connor, and Souter, strongly reaffirmed Roe v. Wade, but also upheld most of the provisions of a Pennsylvania statute that had mandated various restrictions on abortion. The justices' basis for upholding these restictions was their introduction of a new constitutional standard for abortion regulations, an apparently weaker standard than those that had governed previous Supreme Court abortion decisions. I think there is a flaw in Casey's new constitutional test for abortion regulations, and I will explain, when we turn to Casey, what it is and why it bears a close relation to Dworkin's reluctance to carry his argument as far as it seems to go.


Viral-bacterial pneumonia in calves: effects on plasma eicosanoids and long chain fatty acids.
In the pathogenesis of bovine pneumonic pasteurellosis, immunodepression induced by stress or respiratory viral infection permits superinfection of the lungs with Pasteurella hemolytica, which results in exudative fibrinous pneumonia. Therefore, bovine pneumonic pasteurellosis was induced by sequential inoculations of calves with bovine herpes virus-1 (BHV-1, 3 X 10(7) tissue culture infectious dose 50 (TCID50)/nostril), followed 3 days later by challenge with P. hemolytica (15 X 10(9) colony-forming units (cfu) intratracheally). To study the pathogenic mechanisms of the disease, we examined the alterations in plasma prostaglandins (PG), thromboxane B2 (TxB2), histamine, serotonin and long-chain fatty acids (LCFA) during BHV-1 infection alone and after challenge exposure to P. hemolytica (i.e. during BHV-1-pneumonic pasteurellosis). BHV-1 infection alone markedly increased plasma PGE but modestly elevated PGF2 alpha, TxB2 and arachidonic, oleic and palmitic acids. After challenge with P. hemolytica, the levels of plasma arachidonic, oleic, and palmitic acids, together with PGE and 6-keto-PGF1 alpha, were elevated markedly, in association with clinical signs of bovine pneumonic pasteurellosis. However, PGF2 alpha and stearic acid increased only transiently whereas TxB2 was unchanged from the control. On the other hand, plasma linoleic acid, histamine and serotonin remained unaltered. These results indicate enhanced eicosanoid biosynthesis and disproportionate rises in LCFA during BHV-1 pneumonic pasteurellosis. While LCFA are needed for energy metabolism, eicosanoids may mediate the immunologic, inflammatory and pulmonary vascular reactions leading to the clinico-pathologic features of BHV-1 pneumonic pasteurellosis.


Tuning the Surface Composition of Ni/meso-CeO2 with Iridium as an Efficient Catalyst for Hydrogen Generation from Hydrous Hydrazine.
Selective decomposition of hydrous hydrazine (N2 H4 ⋅H2 O) over metal catalysts provides a promising means for onboard or portable hydrogen source applications. Studies on N2 H4 ⋅H2 O decomposition catalysts mainly focus on the effects of bulk composition and structure on their performances, instead of the surface-composition-dependent properties. Herein, the synthesis of an Ir-modified Ni/meso-CeO2 catalyst is reported by using a combination of colloidal solution combustion synthesis and galvanic replacement methods. A combination of structural characterization, control experiments, and DFT calculations reveals that the Ni-Ir alloy resulting from calcination treatment exerts a profound effect on the catalytic properties. The resulting Ni@Ni-Ir/meso-CeO2 catalyst shows excellent catalytic performance towards hydrogen generation from N2 H4 ⋅H2 O, which compares favorably with the Ni-Ir bimetallic catalysts reported to date.


A comparison of the ball rebound characteristics of wooden and composite cricket bats at three approach speeds.
The primary aim of this study was to compare the rebound characteristics of wooden and composite cricket bats. The rebound characteristics of two 'experimental' bats manufactured from composite material were compared with three English willow bats and one Kashmir willow bat. The bats were tested using a specially designed testing rig, which propelled a 156 g Kookaburra cricket ball at three impact speeds: fast-medium, 67 km x h(-1); fast, 101 km x h(-1); and express, 131 km x h(-1) on to the bats mounted in position so that the ball impacts occurred at the position where the blade of the bats was the thickest. The rebound characteristics of the bats were calculated by measuring the approach and rebound speeds of the ball as it passed through a light beam positioned a short distance away from the point of impact. The statistical software package SAS was used to test for significant differences (p < 0.05) between the average rebound characteristics of the bats. Further, Scheffé's method was used as a post hoc comparison to determine whether differences existed between the composite and willow bats. When the composite and traditional willow bats were compared, the results showed no significant differences between the three average approach speeds, while the composite bats showed significantly smaller rebound speeds and coefficient of restitution at all three approach speeds. Thus, the rebound characteristics of the composite bats were significantly less than the traditionally designed English willow wooden bats and would not enhance performance by allowing the batsman to hit the ball harder, assuming all other factors, such as bat speed, mass distribution and the impact point, were the same for the bats. Further study is required to determine the physical properties of composite and wooden bats to enhance their impact characteristics.


Elderly suicides: a need for prevention.
Every 18 minutes a life is lost to suicide. Approximately every hour and a half, an elderly adult age 65 and over takes his/her life by suicide. Despite a decline in the rate of suicides over the past several years, suicides by elderly white males remains high. This paper provides a descriptive epidemiology of elderly suicides in a southern rural population and discusses implications for preventive health services that must be implemented to decrease the number of successful elderly suicides.


Noninvasive prenatal diagnosis of fetal trisomy 21 by allelic ratio analysis using targeted massively parallel sequencing of maternal plasma DNA.
Plasma DNA obtained from a pregnant woman contains a mixture of maternal and fetal DNA. The fetal DNA proportion in maternal plasma is relatively consistent as determined using polymorphic genetic markers across different chromosomes in euploid pregnancies. For aneuploid pregnancies, the observed fetal DNA proportion measured using polymorphic genetic markers for the aneuploid chromosome would be perturbed. In this study, we investigated the feasibility of analyzing single nucleotide polymorphisms using targeted massively parallel sequencing to detect such perturbations in mothers carrying trisomy 21 fetuses. DNA was extracted from plasma samples collected from fourteen pregnant women carrying singleton fetuses. Hybridization-based targeted sequencing was used to enrich 2 906 single nucleotide polymorphism loci on chr7, chr13, chr18 and chr21. Plasma DNA libraries with and without target enrichment were analyzed by massively parallel sequencing. Genomic DNA samples of both the mother and fetus for each case were genotyped by single nucleotide polymorphism microarray analysis. For the targeted regions, the mean sequencing depth of the enriched samples was 225-fold higher than that of the non-enriched samples. From the targeted sequencing data, the ratio between fetus-specific and shared alleles increased by approximately 2-fold on chr21 in the paternally-derived trisomy 21 case. In comparison, the ratio is decreased by approximately 11% on chr21 in the maternally-derived trisomy 21 cases but with much overlap with the ratio of the euploid cases. Computer simulation revealed the relationship between the fetal DNA proportion, the number of informative alleles and the depth of sequencing. Targeted massively parallel sequencing of single nucleotide polymorphism loci in maternal plasma DNA is a potential approach for trisomy 21 detection. However, the method appears to be less robust than approaches using non-polymorphism-based counting of sequence tags in plasma.


Cytological DNA methylation for cervical cancer screening: a validation set.
In a previous training set with a case-controlled design, cutoff values for host EPB41L3 and JAM3 gene methylation were obtained for the detection of cervical intraepithelial neoplasia (CIN) 2 or more severe lesions (CIN2+). This validation trial was conducted to evaluate the role of DNA methylation in screening for CIN2+ by cervical cytology among unselected participants. From June 1, 2019, to September 1, 2019, in our study center, we collected liquid-based samples from cervical swabs for methylation assays and hrHPV testing in eligible patients. The primary endpoint was the diagnostic accuracy of DNA methylation and hrHPV genotyping for CIN2+ according to confirmed histology results. Among 307 participants, compared with hrHPV testing, the methylation assay for CIN2+ had lower sensitivity (68.7% versus 86.1%, p=0.002) but higher specificity (96.7% versus 0.696, p<0.001). The methylation assay also had favorable sensitivity and specificity in patients with negative hrHPV testing (56.3% and 96.9%) and in patients with cervical adenocarcinoma (73.7% and 92.7%). DNA methylation had higher specificity than the hrHPV assay (100.0% versus 44.4%, p<0.001) for identifying residual CIN2+ in patients without residual lesions. Positive cervical DNA methylation was associated with a diagnostic probability of endometrial carcinoma (odds ratio 15.5 [95% confidence interval 4.1-58.6]) but not of ovarian epithelial carcinoma (1.4 [0.3-6.5]). The host EPB41L3 and JAM3 gene methylation assay in cervical cytology had favorable diagnostic accuracy for CIN2+ and was highly specific for residual CIN2+ lesions The methylation assay is a promising triage tool in hrHPV+ women, or even an independent tool for cervical cancer screening. The methylation status in cervical cytology could also serve as a prognostic biomarker. Its role in detecting endometrial carcinomas is worthy of further exploration.


Contribution of airway eosinophils in airway wall remodeling in asthma: Role of MMP-10 and MET.
Eosinophils play an important role in the pathophysiology of asthma being implicated in airway epithelial damage and airway wall remodeling. We determined the genes associated with airway remodeling and eosinophilic inflammation in patients with asthma. We analyzed the transcriptomic data from bronchial biopsies of 81 patients with moderate-to-severe asthma of the U-BIOPRED cohort. Expression profiling was performed using Affymetrix arrays on total RNA. Transcription binding site analysis used the PRIMA algorithm. Localization of proteins was by immunohistochemistry. Using stringent false discovery rate analysis, MMP-10 and MET were significantly overexpressed in biopsies with high mucosal eosinophils (HE) compared to low mucosal eosinophil (LE) numbers. Immunohistochemical analysis confirmed increased expression of MMP-10 and MET in bronchial epithelial cells and in subepithelial inflammatory and resident cells in asthmatic biopsies. Using less-stringent conditions (raw P-value < 0.05, log2 fold change > 0.5), we defined a 73-gene set characteristic of the HE compared to the LE group. Thirty-three of 73 genes drove the pathway annotation that included extracellular matrix (ECM) organization, mast cell activation, CC-chemokine receptor binding, circulating immunoglobulin complex, serine protease inhibitors, and microtubule bundle formation pathways. Genes including MET and MMP10 involved in ECM organization correlated positively with submucosal thickness. Transcription factor binding site analysis identified two transcription factors, ETS-1 and SOX family proteins, that showed positive correlation with MMP10 and MET expression. Pathways of airway remodeling and cellular inflammation are associated with submucosal eosinophilia. MET and MMP-10 likely play an important role in these processes.


DAD1, the defender against apoptotic cell death, is a subunit of the mammalian oligosaccharyltransferase.
DAD1, the defender against apoptotic cell death, was initially identified as a negative regulator of programmed cell death in the BHK21-derived tsBN7 cell line. Of interest, the 12.5-kDa DAD1 protein is 40% identical in sequence to Ost2p, the 16-kDa subunit of the yeast oligosaccharyltransferase (OST). Although the latter observation suggests that DAD1 may be a mammalian OST subunit, biochemical evidence to support this hypothesis has not been reported. Previously, we showed that canine OST activity is associated with an oligomeric complex of ribophorin I, ribophorin II, and OST48. Here, we demonstrate that DAD1 is a tightly associated subunit of the OST both in the intact membrane and in the purified enzyme. Sedimentation velocity analyses of detergent-solubilized WI38 cells and canine rough microsomes show that DAD1 cosediments precisely with OST activity and with the ribophorins and OST48. Radioiodination of the purified OST reveals that DAD1 is present in roughly equimolar amounts relative to the other subunits. DAD1 can be crosslinked to OST48 in intact microsomes with dithiobis(succinimidylpropionate). Crosslinked ribophorin II-OST48 heterodimers, DAD1-ribophorin II-OST48 heterotrimers and DAD1-ribophorin I-ribophorin II-OST48 heterotetramers also were detected. The demonstration that DAD1 is a subunit of the OST suggests that induction of a cell death pathway upon loss of DAD1 in the tsBN7 cell line reflects the essential nature of N-linked glycosylation in eukaryotes.


Identification of a buried cadaver based on finger ridge characteristics of a hand protected by a latex glove.
This paper presents the case of a cadaver buried in a pine grove, in loamy soil at a depth of about 1.8 m. The case is quite interesting due to the fact that one hand of the victim was bare and the other one was clad in a latex glove. In the laboratory, the severed hands were gently washed with water. The left palm exhibited signs of advanced decomposition. The ridges were visible only on the thumb. The gloved hand was found to be in much better condition. There were signs of saponification on the palm. Ridges on both the palm and all fingers were visible. The fingers of the right hand, palm prints, and the thumb of the left hand were successfully matched against a ten-print card. The match provided the police with a positive identification of the missing person.


[Research advances on associated genes and pathogenesis of hydrocephalus].
Hydrocephalus is a common medical condition characterized by abnormalities in the secretion,circulation or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. The pathogenetic mechanism for the hydrocephalus is attributed to: the overproduction of CSF by the choroid plexus; the defect in CSF absorption and obstruction of CSF flow in the cerebral ventricles. However, the underlying etiology is poorly understood. With the development of genetic engineering, a growing body of evidence indicates that genetic factors play an essential role in the pathogenesis of hydrocephalus. It is the aim of this review to summarize these findings.


Intravenous isradipine in the management of severe hypertension in pregnant and nonpregnant patients. A pilot study.
To determine the appropriate dosage regimen of isradipine in black patients with severe hypertension of pregnancy, 10 patients (gestational age, 30 to 38 weeks; diastolic blood pressure [DBP], 110 to 148 mm Hg; no hypertensive crises; and normal central venous pressure) were given an isradipine infusion while the fetal heart rate was continuously recorded using a cardiotocograph. The infusion rate of isradipine was adjusted at regular intervals until control (DBP < 95 mm Hg) was achieved. The optimal dosage regimen in black patients was found to be an initial dose of 0.15 micrograms/kg/min, with increments of 0.0025 micrograms/kg/min every 15 min until control is achieved. Thereafter, a maintenance infusion of 0.15 micrograms/kg/min can be commenced. This dosage regimen is associated with neither maternal hypotension nor fetal heart rate deceleration. A second group of 10 patients (9 men and 1 woman) with DBP > 115 mm Hg (range, 117 to 135 mm Hg) and no features of hypertensive crises were also studied. The optimal dosage regimen in this patient group differed from the other in two respects: dosage increments could be made more rapidly (at 10-min intervals); and the dosage that produced blood pressure control needed to be continued for 30 min before the maintenance infusion was commenced. This regimen was not associated with hypotension.


Proteases and oxidants in experimental pulmonary inflammatory injury.
We have examined various biochemical parameters of pulmonary inflammation in experimental animals. Intrabronchial instillation of glucose oxidase-glucose (GO/G) to produce oxidants or formylated norleu-leu-phe (FNLP) or phorbol myristate acetate (PMA) as leukocytic stimuli induced severe acute pulmonary injury in New Zealand white rabbits. PMA also induced inflammation when administered intravenously. Each stimulus induced transudation of protein from the vascular space into the pulmonary tissues, and an influx of leukocytes during the 4-6 h period of the experiment. Pathophysiologic changes were measured by edema formation (transudation of 125I-bovine serum albumin), and histologic examination. Biochemical analysis was performed by measuring concentrations of potentially injurious agents in bronchoalveolar lavage (BAL) fluid. Increased acid protease and myeloperoxidase levels were found in the BAL fluid after administration of either of the stimuli. Evidence of oxidant generation in vivo was obtained in two different ways. In the first, specific activities for catalase were measured in the BAL fluid in the presence or absence of 3-amino, 1,2,4 triazole (AT), injected at intervals before obtaining BAL fluid. In the presence of AT, specific activities for catalase dropped to 0.22 after a double instillation of FNLP and to 0.15 in the presence of GO/G. In neutrophil-depleted FNLP animals, catalase was not greatly inhibited by AT (sp act 0.90). In the second, intracellular levels of total glutathione (GSH + GSSG) in whole lung tissue and alveolar macrophages decreased when stimuli of neutrophils were administered. Intrabronchially instilled PMA, e.g., caused a drop of glutathione in whole lung tissue from the control value of 2.3 mumol GSH equivalent/100 mg dry wt to 0.54 mumol GSH equivalent/100 mg dry wt at 4 h. Neutrophil depletion and superoxide dismutase protected from this effect. From these results, we conclude that O-2 or its metabolites can initiate severe pulmonary injury as shown by the effect of GO/G and that, during development of pulmonary injury, stimulated neutrophils generate oxidants and release proteolytic enzymes into the surrounding tissues.


Humanin Exerts Neuroprotection During Cardiac Ischemia-Reperfusion Injury.
Cardiac ischemia-reperfusion (I/R) injury has been shown to impair brain function. Humanin analogue (HNG) given prior to cardiac ischemia has been shown to attenuate both heart and brain mitochondrial dysfunction caused by cardiac I/R injury. In a clinical setting, patients received medical treatment for acute myocardial infarction either during or after the onset of myocardial ischemia; thus, in this study, we tested the hypothesis that the administration of HNG during cardiac I/R injury has therapeutic potential for brain protection. Thirty-six male Wistar rats were divided into two groups: a cardiac I/R group (n = 30), and a sham group (n = 6). The I/R rats were then divided into five subgroups to receive: 1) vehicle; 2) HNG (84 μg/kg); 3) HNG (168 μg/kg); 4) HNG (252 μg/kg) intravenously administered during the cardiac-ischemia; and 5) HNG at 252 μg/kg given at the onset of reperfusion. At the end of treatment, brains were removed for determination of blood-brain barrier (BBB) breakdown, oxidative stress, brain mitochondrial function, brain mitochondrial dynamics, p-tau, amyloid-β (Aβ) and apoptosis. HNG at a dose of 168 and 252 μg/kg administered during ischemia, and 252 μg/kg given at the onset of reperfusion effectively attenuated the brain mitochondrial dysfunction, tau hyperphosphorylation and Aβ accumulation, and apoptosis, without reducing BBB breakdown, brain oxidative stress, or mitochondrial dynamic, caused by cardiac I/R injury. In conclusion, humanin exerted neuroprotection during induced cardiac I/R injury via improvement in brain mitochondrial function, and the reduction of Alzheimer's disease pathology and apoptosis.


[Sexuality of neurological patients: the place of intracavernous injections].
The first stages of management consist in explaining the particularities of the treatments for erectile dysfunction, treating the urinary and faecal incontinence, spastic problems, neuropathological pain the neuro-orthopaedic complications. Rehabilitation of the patients consists in teaching them techniques to provoke reflex erections, through the reappropriation of the spared sensitive areas, and how to administer the intracavernous injections themselves.


Modeling and Experimental Analysis on the Temperature Response of AlN-Film Based SAWRs.
The temperature responses of aluminum nitride (AlN) based surface acoustic wave resonator (SAWR) are modeled and tested. The modeling of the electrical performance is based on a modified equivalent circuit model introduced in this work. For SAWR consisting of piezoelectric film and semiconducting substrate, parasitic parameters from the substrate is taken into consideration for the modeling. By utilizing the modified model, the high temperature electrical performance of the AlN/Si and AlN/6H-SiC based SAWRs can be predicted, indicating that a substrate with a wider band gap will lead to a more stable high temperature behavior, which is further confirmed experimentally by high temperature testing from 300 K to 725 K with SAWRs having a wavelength of 12 μm. Temperature responses of SAWR's center frequency are also calculated and tested, with experimental temperature coefficient factors (TCF) of center frequency being -29 ppm/K and -26 ppm/K for the AlN/Si and AlN/6H-SiC based SAWRs, which are close to the predicted values.


Influence of autonomic nerves and drugs on myoepithelial cells in parotid glands of cat.
When a single electrical shock is applied to either the parasympathetic or to the sympathetic nerves a pressure rise is seen in the parotid duct of the cat, probably due to myoepithelial cell activation. No secretion occurred on single impulse stimulation. When repetitive stimulation was used both divisions of the autonomic nervous system could evoke secretion. The motor response to sympathetic stimulation was mediated via alpha-receptors while secretion mainly was mediated via beta-receptors.


Comparison of carbon dioxide laser and scalpel for breast lumpectomy: a randomized controlled trial.
To investigate whether the CO2 laser is superior to conventional surgical techniques for minor breast surgery in a randomized clinical trial. It has been suggested in the literature that application of CO2 laser in breast surgery might be superior to conventional surgery in some aspects. Sixty women whose breast masses were suitable for excisional biopsy were randomly allocated to laser and control (conventional surgical technique with scalpel) groups. Perioperative and postoperative variables were recorded and analyzed. The patients' ages ranged from 16-63 y. There were no significant differences between the two groups in total operative time (17.4 min with laser and 17.5 min with scalpel). There was a significant decrease in the required dose of lidocaine in the laser group (9.3 mL) compared to the scalpel group (12.4 mL; p = 0.01). In addition, hemorrhage was significantly lower in the laser group (6.6 mL) compared to the control group (11.9 mL; p = 0.006). There was no difference in the grade of the scar or postoperative pain between the two groups. Use of the CO2 laser in breast mass biopsy has some advantages, including a lower requirement for local anesthetic and a lower rate of intraoperative bleeding. Furthermore, using the laser does not prolong the operative time.


Tea tree oil, a vibrant source of neuroprotection via neuroinflammation inhibition: a critical insight into repurposing Melaleuca alternifolia by unfolding its characteristics.
Over the past few decades, complementary and alternative treatments have become increasingly popular worldwide. The purported therapeutic characteristics of natural products have come under increased scrutiny both in vitro and in vivo as part of efforts to legitimize their usage. One such product is tea tree oil (TTO), a volatile essential oil primarily obtained from the native Australian plant, Melaleuca alternifolia, which has diverse traditional and industrial applications such as topical preparations for the treatment of skin infections. Its anti-inflammatory-linked immunomodulatory actions have also been reported. This systematic review focuses on the anti-inflammatory effects of TTO and its main components that have shown strong immunomodulatory potential. An extensive literature search was performed electronically for data curation on worldwide accepted scientific databases, such as Web of Science, Google Scholar, PubMed, ScienceDirect, Scopus, and esteemed publishers such as Elsevier, Springer, Frontiers, and Taylor & Francis. Considering that the majority of pharmacological studies were conducted on crude oils only, the extracted data were critically analyzed to gain further insight into the prospects of TTO being used as a neuroprotective agent by drug formulation or dietary supplement. In addition, the active constituents contributing to the activity of TTO have not been well justified, and the core mechanisms need to be unveiled especially for anti-inflammatory and immunomodulatory effects leading to neuroprotection. Therefore, this review attempts to correlate the anti-inflammatory and immunomodulatory activity of TTO with its neuroprotective mechanisms.


Clustering of lipids driven by integrin.
Integrin is an important transmembrane receptor protein which remodels the actin network and anchors the cell membrane towards the extracellular matrix via mechanochemical pathways. The clustering of specific lipids and lipid-anchored proteins, which is essential for a certain type of endocytosis process, is facilitated at integrin-mediated active regions. To study this, we propose a minimal exactly solvable model which includes the interplay of stochastic shuttling between integrin on and off states with the intrinsic dynamics of the membrane. We propose a two-step mechanism in which the integrin induces an aster-like arrangement in the actin network, followed by clustering of lipids in that region. We obtain an analytic expression for the deformation and local membrane velocity, and thereby the evolution of clustering mediated by a single integrin. The deformation evolves nonmonotonically and its dependence on the stochastic shuttling timescales and membrane properties is elucidated. Our estimates of the area of the deformed region and the number of lipids in it indicate strong clustering.


Protective effect of administration of skim milk on exogenous and endogenous infection in mice.
In order to minimize the denaturation of proteins in milk, normal cow's milk was pasteurized at 61 C for 20 min. The protective effects of the thus prepared skim milk (low-heat skim milk) on exogenous and endogenous infection were examined as compared with conventional skim milk which was pasteurized at 121 C for 2 sec. The antibody titers to Listeria monocytogenes and Escherichia coli of low-heat skim milk were almost equal to that of raw milk, while no antibody was detected in the conventional skim milk. When mice were given low-heat skim milk or conventional skim milk, the incidence of the translocation of orally inoculated Listeria monocytogenes to the spleen was lower in the low-heat skim milk group than that in the conventional skim milk group. The life span of 7 Gy X-ray irradiated mice given low-heat skim milk was significantly prolonged in comparison to that of mice given conventional skim milk. However, there were no differences in the number of bacteria in the feces or IgA production by Peyer's patch cells between the two groups. These results suggest that antibodies in low-heat skim milk, which still have reactivity to exogenous or indigenous bacteria, may contribute to the protective effects against bacterial infection.


Organotypic co-cultures allow for immortalized human gingival keratinocytes to reconstitute a gingival epithelial phenotype in vitro.
We report here that the organotypic co-culture (OCC) system allows for significant preservation of the tissue-specific phenotype of human gingival keratinocytes (IHGK) immortalized with the E6/E7 gene of the human papillomavirus type 16 (HPV16). The approach adopted is based on the OCC system facilitating spatially separated cell growth and cell-to-cell interactions via diffusible growth factors. Generally, IHGK reveal transcription of the HPV16 E6/E7 gene at rising passages. Fluorescence in situ hybridization performed for chromosomes 1, 8, 10, and 18 demonstrates that disomic fractions differ between the tested chromosomes but otherwise remain fairly constant. Monosomies of chromosome 18 are more prominent in late passages 81 and 83, while polysomies of chromosome 10 and 18 are detected in early passages 25 and 27. In comparison with corresponding monolayer cultures (MCs), IHGK in OCCs form stratified epithelia, proliferate, and express gingival-specific gene products in vitro. Moreover, mRNA gene transcription for growth factors interleukin 1beta, granulocyte-macrophage colony stimulating factor, fibroblast growth factor 7, and EGF in OCCs is different from that in MCs. When grafted onto nude mice, IHGK develop hyperplastic, differentiated surface epithelia devoid of malignant growth. We are not aware of any other OCC system comprising of IHGK, which allows for site-specific expression of gingival epithelial markers. This substantiates reconstitution of a gingival epithelial phenotype in vitro.


How to induce multiple delays in coupled chaotic oscillators?
Lag synchronization is a basic phenomenon in mismatched coupled systems, delay coupled systems, and time-delayed systems. It is characterized by a lag configuration that identifies a unique time shift between all pairs of similar state variables of the coupled systems. In this report, an attempt is made how to induce multiple lag configurations in coupled systems when different pairs of state variables attain different time shift. A design of coupling is presented to realize this multiple lag synchronization. Numerical illustration is given using examples of the Rössler system and the slow-fast Hindmarsh-Rose neuron model. The multiple lag scenario is physically realized in an electronic circuit of two Sprott systems.


A radioimmunoassay system for human myoglobin: method development and applications.
double antibody radioimmunoassay (RIA) system for human myoglobin (hMb) was developed using our own reagents. The antigen (hMb) was isolated from human muscle, purified and stored frozen until needed for immunization, radiolabeling or reference preparation. The anti-hMb serum raised in rabbits was used at 1:2.10(4) dilution (initial). The Chloramine-T method was used for the hMb labeling obtaining at 10-15 muCi/micrograms (370-550 KBq/micrograms) specific activity. Working standards were prepared having concentrations in the range of 2.0 to 500 ng/ml. The reagents were incubated at +4 degrees C for 48 plus 24 hrs. The specificity and accuracy of our hMb-RIA system were validated using for parallel assays an already validated immunochemical system, the hemagglutination inhibition (HI) technique and the parallelism test using serum dilutions from patients with acute myocardial infarction (AMI). The serum hMb concentration in normal subjects (no = 23) was 54.14 +/- 15.08 ng/ml (X +/- SD), being higher in short-term hypothyroidism (no = 13), 87.95 +/- 20.90 ng/ml (p less than 0.0005) or in treated hyperthyroidism (no = 5), 80.03 +/- 21.81 ng/ml. In AMI (no = 6) the serum hMb concentration varied in the range of 123 to 1510 ng/ml. The sensitivity of our hMb-RIA system is 2 ng/ml and the intraassay average error (coefficient of variability % in %B) is 2.26%. Trials to shorten the incubation time showed that adequate binding of labelled Mb may be obtained with 2 plus 4 hr intervals at room temperature. It is necessary to establish, in our conditions, the variation limits for serum hMb in normal subjects according to sex and age as a comparison basis for the study of its physiological and pathological variations.


CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment.
The G1-S checkpoint of the cell cycle is frequently dysregulated in breast cancer. Palbociclib (PD0332991) is an oral inhibitor of CDK4/6. Based upon preclinical/phase I activity, we performed a phase II, single-arm trial of palbociclib in advanced breast cancer. Eligible patients had histologically confirmed, metastatic breast cancer positive for retinoblastoma (Rb) protein and measureable disease. Palbociclib was given at 125 mg orally on days 1 to 21 of a 28-day cycle. Primary objectives were tumor response and tolerability. Secondary objectives included progression-free survival (PFS) and assessment of Rb expression/localization, KI-67, p16 loss, and CCND1 amplification. Thirty-seven patients were enrolled; 84% hormone-receptor (HR)(+)/Her2(-), 5% HR(+)/Her2(+), and 11% HR(-)/Her2(-), with a median of 2 prior cytotoxic regimens. Two patients had partial response (PR) and 5 had stable disease ≥ 6 months for a clinical benefit rate (CBR = PR + 6moSD) of 19% overall, 21% in HR(+), and 29% in HR(+)/Her2(-) who had progressed through ≥2 prior lines of hormonal therapy. Median PFS overall was 3.7 months [95% confidence interval (CI), 1.9-5.1], but significantly longer for those with HR(+) versus HR(-) disease (P = 0.03) and those who had previously progressed through endocrine therapy for advanced disease (P = 0.02). Grade 3/4 toxicities included neutropenia (51%), anemia (5%), and thrombocytopenia (22%). Twenty-four percent had treatment interruption and 51% had dose reduction, all for cytopenias. No biomarker identified a sensitive tumor population. Single-agent palbociclib is well tolerated and active in patients with endocrine-resistant, HR(+), Rb-positive breast cancer. Cytopenias were uncomplicated and easily managed with dose reduction.


Evaluation of a public-private certified nurse-midwife maternity program for indigent women.
This study assessed the impact of a public-private certified nurse-midwife program on prenatal and delivery outcomes among medically indigent women. A population-based quasi-experimental design was used to compare 1 intervention county with 2 nonintervention counties. The program significantly reduced the number of women who received no prenatal care and the risk of acquiring less than adequate prenatal care. Reductions in the proportion of infants born premature or with low birth-weights were of borderline significance. The use of induction and/or stimulation of labor was statistically elevated. These results suggest that the intervention program was instrumental in reducing some, but not all, negative prenatal and delivery outcomes.


Effects of deep inspiration breath hold on prone photon or proton irradiation of breast and regional lymph nodes.
We report on a comparative dosimetrical study between deep inspiration breath hold (DIBH) and shallow breathing (SB) in prone crawl position for photon and proton radiotherapy of whole breast (WB) and locoregional lymph node regions, including the internal mammary chain (LN_MI). We investigate the dosimetrical effects of DIBH in prone crawl position on organs-at-risk for both photon and proton plans. For each modality, we further estimate the effects of lung and heart doses on the mortality risks of different risk profiles of patients. Thirty-one patients with invasive carcinoma of the left breast and pathologically confirmed positive lymph node status were included in this study. DIBH significantly decreased dose to heart for photon and proton radiotherapy. DIBH also decreased lung doses for photons, while increased lung doses were observed using protons because the retracting heart is displaced by low-density lung tissue. For other organs-at-risk, DIBH resulted in significant dose reductions using photons while minor differences in dose deposition between DIBH and SB were observed using protons. In patients with high risks for cardiac and lung cancer mortality, average thirty-year mortality rates from radiotherapy-related cardiac injury and lung cancer were estimated at 3.12% (photon DIBH), 4.03% (photon SB), 1.80% (proton DIBH) and 1.66% (proton SB). The radiation-related mortality risk could not outweigh the ~ 8% disease-specific survival benefit of WB + LN_MI radiotherapy in any of the assessed treatments.


[Design and development of a teleimaging diagnosis system based on b/S mode].
This paper introduces the design and development of a teleimaging diagnosis system by using B/S mode. A detailed design on the telediagnosis process and telediagnosis management is presented, focusing on resolving medical image transmission, management and display in the internet, and is trying to integrate the teleimaging diagnosis system with PACS.


Are CDI Systems Multicolored, Facultative, Helping Greenbeards?
Competitive and cooperative interactions between organisms, including bacteria, can significantly impact the composition of a community and the fitness of its members, as well as the fitness of their hosts when communities are living on or within other organisms. Understanding the underlying mechanisms is critical to the development of strategies to control microbiological communities that impact animal and plant health and also for understanding the evolution of social behaviors, which has been challenging for evolutionary biologists. Contact-dependent growth inhibition (CDI) is a phenomenon defined by the delivery of a protein toxin to the cytoplasm of neighboring bacteria upon cell-cell contact, resulting in growth inhibition or death unless a specific immunity protein is present. CDI was first described based on observations of interbacterial killing and has been assumed to function primarily as a means of eliminating competitor cells. However, recent molecular evidence indicates that multiple levels of specificity restrict CDI toxin delivery and activity to the same bacterial strain, and that CDI system proteins can mediate cooperative behaviors among 'self' cells, a phenomenon called contact-dependent signaling (CDS). Here we review these recent findings and discuss potential biological and evolutionary implications of CDI system-mediated interbacterial competition and cooperation.


The binding of ( 3 H)thyrotropin and an 3 H-labeled exophthalmogenic factor by plasma membranes of retro-orbital tissue.
Plasma membranes of cells from retroorbital tissue have been prepared from the Harderian glands of guinea pigs and have been characterized as being reasonably free of other subcellular structures by electron microscopy and by enzyme-marker analyses. Both bovine thyrotropin and a proteolytic derivative of bovine thyrotropin with exophthalmogenic activity but without thyroid-stimulating activity specifically bind to these membranes. Gammaglobulin from the sera of patients with malignant exophthalmos increases the binding of both pituitary factors, whereas binding is not similarly increased by gammaglobulin from the sera of individuals who are not exophthalmic. The increased binding caused by the gammaglobulin from exophthalmic patients is the same whether the sera are positive or negative for the long-acting thyroid stimulator. Present binding experiments do not indicate a direct interaction between the gammaglobulin and the plasma membranes of the cells from Harderian glands. A mechanism for the pathogenesis of human exophthalmos is proposed on the basis of these data.


Ovarian Cancers with Low CIP2A Tumor Expression Constitute an APR-246-Sensitive Disease Subtype.
Identification of ovarian cancer patient subpopulations with increased sensitivity to targeted therapies could offer significant clinical benefit. We report that 22% of the high-grade ovarian cancer tumors at diagnosis express CIP2A oncoprotein at low levels. Furthermore, regardless of their significantly lower likelihood of disease relapse after standard chemotherapy, a portion of relapsed tumors retain their CIP2A-deficient phenotype. Through a screen for therapeutics that would preferentially kill CIP2A-deficient ovarian cancer cells, we identified reactive oxygen species inducer APR-246, tested previously in ovarian cancer clinical trials. Consistent with CIP2A-deficient ovarian cancer subtype in humans, CIP2A is dispensable for development of MISIIR-Tag-driven mouse ovarian cancer tumors. Nevertheless, CIP2A-null ovarian cancer tumor cells from MISIIR-Tag mice displayed APR-246 hypersensitivity both in vitro and in vivo. Mechanistically, the lack of CIP2A expression hypersensitizes the ovarian cancer cells to APR-246 by inhibition of NF-κB activity. Accordingly, combination of APR-246 and NF-κB inhibitor compounds strongly synergized in killing of CIP2A-positive ovarian cancer cells. Collectively, the results warrant consideration of clinical testing of APR-246 for CIP2A-deficient ovarian cancer tumor subtype patients. Results also reveal CIP2A as a candidate APR-246 combination therapy target for ovarian cancer.


Chronic sclerosing osteomyelitis: treatment considerations in an atypical case.
Chronic sclerosing osteomyelitis has been frequently described in the literature but little has been recommended for the management of the resistant cases that fail to respond to conservative treatment. This report describes the long term management of a particularly aggressive case of CSO and indicates maxillary sinus disease as a possible etiologic factor in CSO of the maxillary alveolus. Treatment required in more extensive cases must be as aggressive as dictated by the entire disease process and the total medical evaluation.


Persistent Symblepharon in an Infant Following Epidemic Keratoconjunctivitis.
Epidemic keratoconjunctivitis (EKC), caused by certain species D human adenoviruses (Ads), is a highly contagious severe disease involving both the conjunctiva and cornea. The hallmark of this disease is the subepithelial infiltration of leukocytes, which results in corneal opacities that may persist for months or even years. In this case, of a 6-month-old infant, we report a symblepharon formation, a relatively rare outcome of EKC. In this condition, the palpebral conjunctiva adheres tightly to the bulbar conjunctiva of the eyeball. Our report is the first documentation of a symblepharon formation in an infant. Only two similar cases have been reported to date; therefore, a detailed description is of considerable interest to ophthalmologists. This is particularly interesting since a previous publication has associated symblepharon formation with an adenovirus infection, which is not usually involved in EKC. The development of a symblepharon following EKC is rare in infants. Since topical treatment cannot be applied due to severe eyelid edema, oral steroid therapy can be administered with pediatric consultation and meticulous monitoring.


Substitutional and positional disorder in Sr(2.88)Cu(3.12)(PO4)4.
The title compound, a hydrothermally synthesized strontium copper(II) phosphate(V) (2.88/3.12/4), is isotypic with Sr(3)Cu(3)(PO(4))(4), obtained previously by solid-state reaction, but not with Sr(3)Cu(3)(PO(4))(4), obtained previously by the hydrothermal method. A surplus of copper was observed by both structural and chemical analysis, and the formula obtained by the structural analysis is in full agreement with results of the EDX (energy-dispersive X-ray diffraction) analysis. The structure consists of layers of Cu(3)O(12) groups which are linked via the PO(4) tetrahedra. The Cu(3)O(12) groups are formed by one Cu1O(4) and two Cu2O(5) coordination polyhedra sharing corners. The central Cu1 atom of the Cu(3)O(12) group is located at an inversion centre (special position 2a). The unique structural feature of the title compound is the presence of 12% Cu in the Sr1 site (special position 2b, site symmetry 1). Moreover, disordered Sr2 atoms were observed: a main site (Sr2a, 90%) and a less occupied site (Sr2b, 10%) are displaced by 0.48 (3) A along the b axis. Such substitutional and positional disorder was not observed previously in similar compounds.


Diagnosing the miR-141 prostate cancer biomarker using nucleic acid-functionalized CdSe/ZnS QDs and telomerase.
The microRNA, miR-141, is a promising biomarker for prostate cancer. We implement here a two-step sensing platform for the sensitive detection of miR-141. The first step involves the use of semiconductor CdSe/ZnS quantum dots (QDs) modified by FRET quencher-functionalized nucleic acids, that include the recognition sequence for miR-141 and a telomerase primer sequence for the second step of the analytical platform. Subjecting the probe-modified QDs to miR-141, in the presence of duplex specific nuclease, DSN, leads to the formation of a miR-141/probe duplex and to its DSN-mediated cleavage, while regenerating the miR-141. The DSN-induced cleavage of the quencher units leads to the activation of the fluorescence of the QDs, thus allowing the optical detection of miR-141 with a sensitivity corresponding to 1.0 × 10-12 M. The nucleic acid residues associated with the QDs after cleavage of the probe nucleic acids by DSN act as primers for telomerase. The subsequent telomerase/dNTPs-stimulated elongation of the primer units forms G-quadruplex telomer chains. Incorporation of hemin in the resulting G-quadruplex telomer chains yields horseradish peroxidase-mimicking DNAzyme units, that catalyze the generation of chemiluminescence in the presence of luminol/H2O2. The resulting chemiluminescence intensities provide a readout signal for miR-141, DL = 2.8 × 10-13 M. The first step of the sensing platform is non-selective toward miR-141 and the resulting fluorescence may be considered only as an indicator for the existence of miR-141. The second step in the sensing protocol, involving telomerase, provides a selective chemiluminescence signal for the existence of miR-141. The two-step sensing platform is implemented for the analysis of miR-141 in serum samples from healthy individuals and prostate cancer carriers. Impressive discrimination between healthy individuals and prostate cancer carriers is demonstrated.


[Biotechnological potential of methylotrophic bacteria: a review of current status and future prospects].
Major results of the authors' findings on the implementation of biotechnological potential of aerobic methylobacteria and methanotrophs for obtaining forage proteins, biopolymers (polybutyrate and polysaccharides), enzymes (oxidoreductases), and bioprotectors (ectoin), as well as for degrading toxic C1 and Cn compounds have been reviewed. Unique features of the structural and functional organization of the metabolism of extremophilic (tolerant) methylotrophs are discussed, with a view for their prospective use in various fields of modern biotechnology, including biocatalysis and nanotechnology.


Presumed intraocular nocardiosis in a cardiac-transplant patient.
A 44-year-old cardiac-transplant patient receiving immunosuppressive therapy developed a chorioretinal mass OS. The lesion was consistent with an ocular nocardial infection. The patient also developed a testicular abscess that was shown to contain N. asteroides after orchiectomy. Despite appropriate systemic treatment, the patient developed extensive subretinal scarring OS. This case report is the first to describe an opportunistic ocular infection with N. asteroides after cardiac transplantation.