Validation by isoelectric focusing of the anion-exchange isotransferrin fractionation step involved in determination of carbohydrate-deficient transferrin by the CDTect assay.
Serum concentration of carbohydrate-deficient transferrin (CDT) is used for laboratory diagnosis of chronic alcohol abuse. Using isoelectric focusing for validation of the initial isotransferrin fractionation step involved in the determination of CDT by the CDTect assay, we found a complete in vitro iron saturation of transferrin and sufficient stability of the transferrin iron load during column passage; effective separation of non-CDT-isotransferrins and CDT-isotransferrins at the microcolumns; partial coelution of trisialo-Fe2-transferrin, which did not significantly affect CDT measurement; partial retention of CDT-isotransferrins, especially disialo-Fe2-transferrin, which may cause falsely negative results for CDT at the upper reference limits; good precision of the isotransferrin fractionation step; and no significant effects of low concentrations of serum protein and transferrin. We strongly urge standardization of CDT analysis and suggest isoelectric focusing for validation of CDT analysis methods and verification of odd results.


Growth of gold on a pinwheel TiO(∼1.2) encapsulation film prepared on rhodium nanocrystallites.
Rh nanoparticles of 50-100 nm diameter and 20-40 atomic layer thickness with a (111) flat top facet parallel to the support surface were grown on a TiO2(110) surface via physical vapor deposition (PVD) at room temperature (RT) followed by annealing at 1050 K. These nanoparticles were completely encapsulated by an ordered hexagonal pinwheel TiO∼1.2 ultrathin oxide (w-TiO-UTO) film. STM, XPS, and low energy ion scattering (LEIS) methods were used to characterize the postdeposition of gold and the effects of annealing on the Au/w-TiO-UTO/Rh-particle system. The adlayer exhibits 3D growth and Rh-Au bond formation at 500 K. The 3D Au nanoparticles of 2-3 nm diameter and ∼1 nm height are partially covered by TiOx species at RT and sinter via an Ostwald-ripening in the range of 500-800 K. The adparticles are gradually getting free of TiOx decoration, and at around 900 K they exhibit a double layer height with 2D character. Two different arrangements were found for these Au particles: (i) a compressed Au(111)-(1 × 1) and (ii) a reconstructed Au(111)-(2 × 1), both of them pseudomorphic with the Rh lattice underneath. Above 900 K, the thickness of these 2D particles tends to become a single layer, while they spread out and form a continuous gold layer on the Rh nanoparticles. This behavior indicates a thermally activated replacement of the w-TiO-UTO film by an Au ultrathin layer. The gold layer is stable up to 1000 K, where extended 1D interfaces are formed between gold and w-TiO-UTO layers.


Copper benzene tricarboxylate metal-organic framework with wide permanent mesopores stabilized by Keggin polyoxometallate ions.
Porous solids with organized multiple porosity are of scientific and technological importance for broadening the application range from traditional areas of catalysis and adsorption/separation to drug release and biomedical imaging. Synthesis of crystalline porous materials offering a network of uniform micro- and mesopores remains a major scientific challenge. One strategy is based on variation of synthesis parameters of microporous networks, such as, for example, zeolites or metal-organic frameworks (MOFs). Here, we show the rational development of an hierarchical variant of the microporous cubic Cu(3)(BTC)(2) (BTC = 1,3,5-benzenetricarboxylate) HKUST-1 MOF having strictly repetitive 5 nm wide mesopores separated by uniform microporous walls in a single crystal structure. This new material coined COK-15 (COK = Centrum voor Oppervlaktechemie en Katalyse) was synthesized via a dual-templating approach. Stability was enhanced by Keggin type phosphotungstate (HPW) systematically occluded in the cavities constituting the walls between the mesopores.


Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain.
Our objective was to evaluate the brain regions showing increased and decreased metabolism in patients at the time of generalized bursts of epileptic discharges in order to understand their mechanism of generation and effect on brain function. By recording the electroencephalogram during the functional MRI, changes in the blood oxygenation level-dependent signal were obtained in response to epileptic discharges observed in the electroencephalogram of 15 patients with idiopathic generalized epilepsy. A group analysis was performed to determine the regions of positive (activation) and negative (deactivation) blood oxygenation level-dependent responses that were common to the patients. Activations were found bilaterally and symmetrically in the thalamus, mesial midfrontal region, insulae, and midline and bilateral cerebellum and on the borders of the lateral ventricles. Deactivations were bilateral and symmetrical in the anterior frontal and parietal regions and in the posterior cingulate gyri and were seen in the left posterior temporal region. Activations in thalamus and midfrontal regions confirm known involvement of these regions in the generation or spread of generalized epileptic discharges. Involvement of the insulae in generalized discharges had not previously been described. Cerebellar activation is not believed to reflect the generation of discharges. Deactivations in frontal and parietal regions remarkably followed the pattern of the default state of brain function. Thalamocortical activation and suspension of the default state may combine to cause the actual state of reduced responsiveness observed in patients during spike-and-wave discharges. This brief lapse of responsiveness may therefore not result only from the epileptic discharge but also from its effect on normal brain function.


Metastatic Infiltrating Lobular Breast Cancer to the Colon Diagnosed Through Routine Bowel Screening in a 67-Year-Old Female.
Breast cancer most commonly metastasizes to the bone, lung, liver, and brain. The colon is an uncommon site for metastases and its symptoms are variable. A 67-year-old female with a history of breast cancer was referred for colonoscopy following a positive fecal occult blood test (FOBT); there were no discrete lesions concerning for primary colonic cancers or metastasis; however, a random biopsy revealed metastatic breast cancer. The possibility of colonic metastases must be considered when assessing positive FOBT in a patient with previous breast cancer.


Amyotrophic lateral sclerosis and multiple sclerosis overlap: a case report.
The concurrence of amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) is extremely rare. We reported the case of a 33-year-old woman with a past history of paresthesias at the right hand, who developed progressive quadriparesis with muscular atrophy of limbs and, finally, bulbar signs and dyspnea. Clinical and neurophysiologic investigations revealed upper and lower motor neuron signs in the bulbar region and extremities, suggesting the diagnosis of ALS. Moreover, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis demonstrated 3 periventricular and juxtacortical lesions, hyperintense in T2 and FLAIR sequences, and 3 liquoral immunoglobulin G (IgG) oligoclonal bands, consistent with diagnosis of primary progressive MS (PPMS). This unusual overlap of ALS and MS leads to the discussion of a hypothetical common pathological process of immunological dysfunction in these two disorders, although the role of immune response in ALS remains ambivalent and unclear.


The microRNA-130/301 family controls vasoconstriction in pulmonary hypertension.
Pulmonary hypertension (PH) is a complex disorder, spanning several known vascular cell types. Recently, we identified the microRNA-130/301 (miR-130/301) family as a regulator of multiple pro-proliferative pathways in PH, but the true breadth of influence of the miR-130/301 family across cell types in PH may be even more extensive. Here, we employed targeted network theory to identify additional pathogenic pathways regulated by miR-130/301, including those involving vasomotor tone. Guided by these predictions, we demonstrated, via gain- and loss-of-function experimentation in vitro and in vivo, that miR-130/301-specific control of the peroxisome proliferator-activated receptor γ regulates a panel of vasoactive factors communicating between diseased pulmonary vascular endothelial and smooth muscle cells. Of these, the vasoconstrictive factor endothelin-1 serves as an integral point of communication between the miR-130/301-peroxisome proliferator-activated receptor γ axis in endothelial cells and contractile function in smooth muscle cells. Thus, resulting from an in silico analysis of the architecture of the PH disease gene network coupled with molecular experimentation in vivo, these findings clarify the expanded role of the miR-130/301 family in the global regulation of PH. They further emphasize the importance of molecular cross-talk among the diverse cellular populations involved in PH.


Initiation of Noninvasive Ventilation for Sleep Related Hypoventilation Disorders: Advanced Modes and Devices.
Although noninvasive ventilation (NIV) has been used since the 1950s in the polio epidemic, the development of modern bilevel positive airway pressure (BPAP) devices did not become a reality until the 1990s. Over the past 25 years, BPAP technology options have increased exponentially. The number of patients receiving this treatment both in the acute setting and at home is growing steadily. However, a knowledge gap exists in the way the settings on these devices are adjusted to achieve synchrony and match the patient's unique physiology of respiratory failure. This issue is further complicated by differences in pressure and flow dynamic settings among different types of NIV devices available for inpatient and home care.


Measuring spiritual well-being in people with cancer: the functional assessment of chronic illness therapy--Spiritual Well-being Scale (FACIT-Sp).
A significant relation between religion and better health has been demonstrated in a variety of healthy and patient populations. In the past several years, there has been a focus on the role of spirituality, as distinctfrom religion, in health promotion and coping with illness. Despite the growing interest, there remains a dearth of well-validated, psychometrically sound instruments to measure aspects of spirituality. In this article we report on the development and testing of a measure of spiritual well-being, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp), within two samples of cancer patients. The instrument comprises two subscales--one measuring a sense of meaning and peace and the other assessing the role offaith in illness. A total score for spiritual well-being is also produced. Study 1 demonstrates good internal consistency reliability and a significant relation with quality of life in a large, multiethnic sample. Study 2 examines convergent validity with 5 other measures of religion and spirituality in a sample of individuals with mixed early stage and metastatic cancer diagnoses. Results of the two studies demonstrate that the FACIT-Sp is a psychometrically sound measure of spiritual well-being for people with cancer and other chronic illnesses.


Long-Term Study Of Health And Quality Of Life After Burn Injury.
The aim of the present study was to examine burn patient health status, quality of life and work status 16.2 (1.7) [mean (SD)] years after burn injury, and to compare the findings with similar questionnaire data from the same people obtained 11.5 years earlier. Data on burn-specific health (BSHS-N), generic health (SF-36), overall quality of life (QOLS), injury characteristics, socio-demography and work were obtained in 2001 from 95 adult burn patients. In 2013, 78 participants were still eligible, and 34 of them (age: 53.4 [9.4] [mean (SD)], total body surface burn: 17.8% [12.7%]; full thickness injury: 4.4% [5.1%]) answered a follow up study. In 2001, the burn patients reported impaired health status, but an overall quality of life comparable to the Norwegian general population. In particular, the participants were satisfied with their close relationships. At follow up 11.5 years later, the perceived burn-specific and generic health remained unchanged, whereas overall quality of life had improved significantly (QOLS score 77.2 (10.2) vs. 73.1 (12.1), p=0.003), with the largest improvements in the items related to satisfaction with helping others, work, physical active pastimes and independence. The results indicate that self-perceived functioning and wellbeing expressed by burn-specific and generic health status remain stable after the first years post injury. The improvement in overall quality of life 16.2 years post injury suggests long-term processes of growth.


Transient ischaemic attack: is routine use of computerised cerebral tomography worthwhile?
To evaluate the role of routine computerised cerebral tomography (CCT) in patients undergoing carotid endarterectomy (CEA) following transient ischaemic attach (TIA). A retrospective review was carried out of data collected on patients with TIA who were managed at the Durban Metropolitan Vascular Service over an 11-year period. All patients underwent carotid duplex scanning and CCT, followed by carotid endarterectomy (CEA) under general anaesthesia. The records of 140 patients were reviewed. There were 85 (61%) men and 55 (39%) women (F:M = 1:1.6). The mean age was 63 years (range 40-95 years). The presenting symptoms were amaurosis fugax, syncope and speech deficit. Risk factors for arterial disease were smoking (73%), hypertension (55%), diabetes mellitus (28%) and hyperlipidaemia (6%). Duplex ultrasonography showed significant internal carotid artery stenosis in 138 patients and occlusion in two. Arch angiography of the latter two patients showed pre-occlusive carotid stenosis. CCT scans showed abnormalities in 34 (24%) patients. These were lacunar infarcts (56%), old infarcts involving grey and white matter (32%), and cortical infarcts (12%). The findings did not influence management. All patients underwent routine CEA with selective shunting in 51 (36%) patients. Postoperative stroke rate was 2.9%. Routine CCT scanning in patients with TIA did not influence patient management and outcome. It is not cost effective and its routine use is questioned.


Sample Preparation and Imaging of Exosomes by Transmission Electron Microscopy.
Exosomes are nano-sized extracellular vesicles secreted by body fluids and are known to represent the characteristics of cells that secrete them. The contents and morphology of the secreted vesicles reflect cell behavior or physiological status, for example cell growth, migration, cleavage, and death. The exosomes' role may depend highly on size, and the size of exosomes varies from 30 to 300 nm. The most widely used method for exosome imaging is negative staining, while other results are based on Cryo-Transmission Electron Microscopy, Scanning Electron Microscopy, and Atomic Force Microscopy. The typical exosome's morphology assessed through negative staining is a cup-shape, but further details are not yet clear. An exosome well-characterized through structural study is necessary particular in medical and pharmaceutical fields. Therefore, function-dependent morphology should be verified by electron microscopy techniques such as labeling a specific protein in the detailed structure of exosome. To observe detailed structure, ultrathin sectioned images and negative stained images of exosomes were compared. In this protocol, we suggest transmission electron microscopy for the imaging of exosomes including negative staining, whole mount immuno-staining, block preparation, thin section, and immuno-gold labelling.


The future of biologics in the treatment of rheumatoid arthritis.
The development of highly effective biological therapies directed against T cells in several animal models of autoimmune disease has prompted trials of similar approaches in rheumatoid arthritis (RA). However, it is unlikely that these approaches will abrogate long-standing disease. Indeed, considerable evidence indicates that although T cells likely play a critical role in induction of RA, non-T-cell-dependent pathways become increasingly dominant as the disease progresses. According to this model, specific T-cell therapies are likely to be most effective in early disease, whereas individualized combinations of biologics targeted against pathways dominating in the recipient's synovium are more likely to be efficacious in established disease.


Molecular phenotyping and functional assessment of smooth muscle-like cells with pathogenic variants in aneurysm genes ACTA2, MYH11, SMAD3 and FBN1.
Aortic aneurysms (AAs) are pathological dilatations of the aorta. Pathogenic variants in genes encoding for proteins of the contractile machinery of vascular smooth muscle cells (VSMCs), genes encoding proteins of the transforming growth factor beta signaling pathway and extracellular matrix (ECM) homeostasis play a role in the weakening of the aortic wall. These variants affect the functioning of VSMC, the predominant cell type in the aorta. Many variants have unknown clinical significance, with unknown consequences on VSMC function and AA development. Our goal was to develop functional assays that show the effects of pathogenic variants in aneurysm-related genes. We used a previously developed fibroblast transdifferentiation protocol to induce VSMC-like cells, which are used for all assays. We compared transdifferentiated VSMC-like cells of patients with a pathogenic variant in genes encoding for components of VSMC contraction (ACTA2, MYH11), transforming growth factor beta (TGFβ) signaling (SMAD3) and a dominant negative (DN) and two haploinsufficient variants in the ECM elastic laminae (FBN1) to those of healthy controls. The transdifferentiation efficiency, structural integrity of the cytoskeleton, TGFβ signaling profile, migration velocity and maximum contraction were measured. Transdifferentiation efficiency was strongly reduced in SMAD3 and FBN1 DN patients. ACTA2 and FBN1 DN cells showed a decrease in SMAD2 phosphorylation. Migration velocity was impaired for ACTA2 and MYH11 cells. ACTA2 cells showed reduced contractility. In conclusion, these assays for showing effects of pathogenic variants may be promising tools to help reclassification of variants of unknown clinical significance in AA-related genes.


A Simple and Low-cost Assay for Measuring Ambulation in Mouse Models of Muscular Dystrophy.
Measuring functional outcomes in the treatment of muscular dystrophy is an essential aspect of preclinical testing. The assessment of voluntary ambulation in mouse models is a non-invasive and reproducible activity assay that is directly analogous to measures of patient ambulation such as the 6-minute walk test and related mobility scores. Many common methods for testing mouse ambulation speed and distance are based on the open field test, where an animal's free movement within an arena is measured over time. One major downside to this approach is that commercial software and equipment for high-resolution motion tracking is expensive and may require transferring mice to specialized facilities for testing. Here, we describe a low-cost, video-based system for measuring mouse ambulation that utilizes free and open-source software. Using this protocol, we demonstrate that voluntary ambulation in the dystrophin-null mdx mouse model for Duchenne muscular dystrophy (DMD) is decreased relative to wild-type mouse activity. In mdx mice expressing the utrophin transgene, these activity deficits are not observed and the total distance traveled is indistinguishable from wild-type mice. This method is effective for measuring changes in voluntary ambulation associated with dystrophic pathology, and provides a versatile platform that can be readily adapted to diverse research settings.


Clinicopathologic correlation of localized retinal pigment epithelium debridement.
To characterize changes in the retina, retinal pigment epithelium (RPE), and choriocapillaris with fluorescein angiography (FA) and histology after hydraulic or abrasive RPE debridement in 26 domestic short-haired cats. Hydraulic debridement was produced by injecting balanced salt solution forcefully into the subretinal space. For abrasive debridement, RPE were removed with a silicone-tipped cannula after creating a localized retinal detachment. The FAs were performed after surgery, and tissue was prepared for light microscopy (LM) and scanning electron microscopy (SEM). Sixty-seven blebs were examined by FA 1 hour after surgery, and RPE debridement was confirmed by SEM or LM in 15 blebs from 10 animals. Hyperfluorescence and variable central fluorescein leakage were seen 1 week after surgery in 52 of 53 blebs (which includes all 27 blebs from the 1-week timepoint and 26 of 29 blebs from the 4-week timepoint that were studied by FA 1 week after surgery). Choriocapillary filling delays were seen in no hydraulic debridements, but in 11 of 14 abrasive blebs, especially in areas showing leakage late in the angiogram. In 1 of 13 hydraulic and 12 of 14 abrasive debridements, areas of late dye leakage had no RPE with outer retinal degeneration. At the 4-week timepoint, 1 of 17 hydraulic and 10 of 12 abrasive debridements had foci of delayed or absent choriocapillary perfusion by FA, with degenerated outer retina, no RPE, and choriocapillary atrophy by histologic analysis. Abrasive debridement is more commonly associated with abnormal FAs and with incomplete RPE repopulation, choriocapillaris atrophy, and outer retinal degeneration than is hydraulic debridement. This clinicopathologic study may give insight into FA interpretation after choroidal neovascular membrane removal in human patients.


Proteomic profiling identifies cyclooxygenase-2-independent global proteomic changes by celecoxib in colorectal cancer cells.
Celecoxib, a selective inhibitor of the enzyme cyclooxygenase-2 (COX-2), has been shown to be a promising chemoprevention agent. The chemopreventive efficacy of celecoxib is believed to be a consequence of its COX-2-dependent and COX-2-independent effects on a variety of cellular processes including proliferation, apoptosis, angiogenesis, and immunosurveillance. In an attempt to identify proteomic markers modulated by celecoxib that are independent of its inhibitory effect on COX-2, the colorectal cancer cell line HCT-116, a nonexpresser of COX-2, was treated with celecoxib. We used the powerful, state-of-the-art two-dimensional difference gel electrophoresis technology coupled with mass spectrometric sequencing to compare global proteomic profiles of HCT-116 cells before and after treatment with celecoxib. Among the differentially expressed proteins identified following celecoxib treatment were proteins involved in diverse cellular functions including glycolysis, protein biosynthesis, DNA synthesis, mRNA processing, protein folding, phosphorylation, redox regulation, and molecular chaperon activities. Our study presents a comprehensive analysis of large-scale celecoxib-modulated proteomic alterations, at least some of which may be mechanistically related to the COX-2-independent chemopreventive effect of celecoxib.


Gene silencing of cathepsins B and L using CTV-based, plant-mediated RNAi interferes with ovarial development in Asian citrus psyllid (ACP), Diaphorina citri.
Diaphorina citri Kuwayama (Hemiptera: Liviidae) is a vector of the bacteria Candidatus Liberibacter americanus (CLam) and Candidatus Liberibacter asiaticus (CLas), which are phloem-restricted and associated with the most important and destructive worldwide citrus disease, Huanglongbing (HLB). Currently, no cure for HLB has been described. Therefore, measures have focused on reducing D. citri populations. In these insects, cathepsin B (DCcathB) and L (DCcathL) enzymes play an important role in digestion, and are involved in embryogenesis, immune defense, and ecdysis. In this study, we used a CTV-based vector to deliver dsRNA (CTV-dsRNA) into Citrus macrophylla plants targeting DCcathB and DCcathL genes in D. citri that fed on the phloem of these CTV-RNAi infected plants. Subsequently, we evaluated expression of DCcathB and DCcathL genes as well as the Vitellogenin (Vg) gene by RT-qPCR in D. citri fed on CTV-dsRNA occurring in plant phloem. It was found that a defective phenotype in D. citri females as a result of knockdown of DCcathB and DCcathL genes mediated by CTV dsRNA. These results showed that Psyllids fed on plants treated with the CTV-dsRNA exhibited downregulation of the Vg gene, one of the most important genes associated with embryogenic and female development, which was associated with dsRNA-mediated silencing of the two cathepsin genes. Based on our findings, a CTV-based strategy for delivering RNAi via plants that targets DCcathB and DCcathL genes may represent a suitable avenue for development of dsRNA-based tools to manage D. citri that limits the spread of HLB.


Host preferences of the sand fly Lutzomyia longipalpis at an endemic focus of American visceral leishmaniasis in Colombia.
Blood meals from 579 Lutzomyia longipalpis (Diptera:Psychodidae), collected in an endemic focus of American visceral leishmaniasis in Colombia, were identified by precipitin test. Sand fly collections were made during a 16-month period from the inside walls of two houses, a pigpen, and rock crevices in a small community (El Callejon) within the endemic area. Feeding patterns of the sand flies varied with locality and date of collection. Overall, bovine feedings predominated, but feedings were also recorded on pigs, equines, humans, dogs, opossums, birds, and reptiles. Calculation of the forage ratios for each host species indicated that cows and pigs were the preferred hosts of Lu. longipalpis in El Callejon. Results of this study suggest that Lu. longipalpis is an opportunistic feeder and is not highly anthropophilic nor strongly attracted to dogs.


Plasmid-associated Bacteriocin Production by and Immunity of Lactobacillus acidophilus TK8912.
Lactobacillus acidophilus TK8912 produces an antibacterial substance, designated acidocin 8912, which is active against strains of Lactobacillus and Lactococcus. Of all conditions tested, the production of acidocin 8912 was maximum at 30°C in MRS broth. Acidocin 8912 was stable to heat treatment (120°C for 20min), but completely inactivated by protease treatment. Curing a plasmid pLA103 resulted in the loss of both acidocin 8912 production (Acd(+)) and host immunity (Acd(r)). A plasmid-cured strain, TK1-4 (Acd(-) Acd(8)), was transformed to Acd(+)Acd(r) with the pLA103 plasmid. These results provided the first direct evidence in lactobacilli for involvement of this plasmid in bacteriocin production and immunity.


Continuous production of L-phenylalanine by transamination.
L-Phenylalanine was produced continuously from L-as-partate and phenylpyruvate by transaminase from a newly screened Pseudomonas putida strain. The process was carried out with an isolated enzyme in homogeneous phase in an enzyme membrane reactor and with immobilized whole cells in a stirred tank reactor, respectively. Due to the difference in transport resistance, the productivity of the free enzyme in homogeneous phase (72 mmol/L h) was about 3 times higher than the productivity achieved using immobilized cells. However, a better stability of the biocatalyst was observed with immobilized cells.


Independent Association of Serum Aldosterone Level with Metabolic Syndrome and Insulin Resistance in Korean Adults.
A relationship between renin-angiotensin system (RAS) components and metabolic syndrome (MetS) has been suggested, but not elucidated clearly. We examined the levels of RAS components in patients with and without MetS and their association with MetS in Korean population. This study was approved by the review boards of the participating institutions and endorsed by the Korean Society of Lipid and Atherosclerosis. We screened 892 Koreans aged ≥20 years who underwent evaluation of hypertension, diabetes, or dyslipidemia at 6 tertiary hospitals in 2015-2016. After excluding patients who were taking diuretics, β-blockers, or RAS blockers, or suspected of primary aldosteronism, 829 individuals were enrolled. Anthropometric and biochemical parameters including aldosterone, plasma renin activity (PRA), and aldosterone-to-PRA ratio were evaluated. The homeostasis model assessment for insulin resistance (HOMA-IR) were used for evaluating insulin resistance. The mean age of the participants was 52.8±12.8 years, 56.3% were male, and their mean systolic and diastolic blood pressures were 133.9±20.0 and 81.2±14.6 mmHg, respectively. The levels of serum aldosterone, but not PRA, were significantly higher in subjects with MetS than in those without (20.6±33.6 vs. 15.3±12.2 ng/dL, p<0.05), and positively correlated with waist circumference, blood pressure, triglycerides, and glycated hemoglobin. The levels of aldosterone were independently associated with the number of MetS components and HOMA-IR after adjusting for conventional risk factors. Serum aldosterone levels were higher in Korean adults with MetS than in those without. This finding suggests that increased aldosterone level might be closely associated with insulin resistance.


Mitochondrial cytochrome c release is a key event in hyperoxia-induced lung injury: protection by cyclosporin A.
Hyperoxia is known to induce extensive alveolar cell death by still poorly defined mechanisms. In this study, the mitochondria-dependent cell death pathway was explored during hyperoxia-induced lung injury in mice. We observed a progressive release of cytochrome c from the mitochondria into the cytosol of alveolar cells. This release was accompanied by the translocation of the proapoptotic protein Bax from cytosol to mitochondria without detectable activation of caspase-3. As cytochrome c release can be induced by mitochondrial membrane alteration and permeability transition (MPT), mice were treated with cyclosporin A, which specifically inhibits MPT. Cyclosporin A treatment prevented mitochondrial release of cytochrome c during hyperoxia and concomitantly preserved mitochondria from extensive swelling and crista disorganization, as assessed by electron microscopy analysis of alveolar epithelial cells. These morphological and biochemical observations correlated with decreased lung tissue damage, as evaluated by morphological score and lung weight. In conclusion, mitochondrial damage and cytochrome c release are important linked events in hyperoxia-induced lung injury and can be efficiently blocked by cyclosporin A.


Bidirectional axonal transport of 16S acetylcholinesterase in rat sciatic nerve.
Axonal transport of the 16S Molecular form of acetylcholinesterase (16S-AChE) in doubly ligated rat sciatic nerves was studied by means of velocity sedimentation analysis on sucrose gradients. This form of AChE was selectively confined to motor, and not to sensory, fibers in the sciatic nerve, where it represented 3--4% of total AChE. Its activity increased linearly with time (4--20 hr) in nerve segments (7 mm) proximal to the central ligature (4.5 mU/24hr) and distal to the peripheral ligature (2.0 mU/24 hr). From the linear rates of accumulation of 16S-AChE, we conclude that the enzyme is conveyed by anterograde and retrograde axonal transport at velocities close to those previously defined for the movement of total AChE (410 mm/day, anterograde; 220 mm/day, retrograde). The transport of AChE molecular forms, other than the 16S form, could not be resolved presumably due to their presence in blood as well as at extraaxonal sites. The present findings are consistent with the view that in rat sciatic nerve most, if not all, of the small portion of total AChE (approximately 3%) which is transported may be accounted for by 16S-AChE.


Effect of having and switching multiple avatars on the operator's right to talk and receive social support.
People with communication difficulties encounter several challenges in their daily online interactions, such as a limited right to talk (RoT), insufficient social support (SS), and a low sense of being attended to (SoBA). Computer-mediated technologies are limited in addressing such problems owing to their limited capacity in transferring verbal and nonverbal cues between users. In this study, to address the limited RoT, low SS, and low SoBA challenges, we proposed a robotic video conference system with two teleoperated robot avatars. The proposed system was compared with another robotic video conference system that adopts only one teleoperated robot avatar. In the field experiment, 37 participants took part in two discussion sessions using each system type, where RoT, SS, and SoBA were adopted as the measured indices. The proposed system significantly increased the users' RoT and SS compared with other robotic video conference systems. This study contributes to the literature by demonstrating the effect exerted by the type of robotic video conference adopted on users' feelings about RoT, SS, and SoBA.


Suitability of endoscopic submucosal dissection for treatment of submucosal gastric cancers.
Endoscopic submucosal dissection (ESD) is not considered appropriate for all submucosal cancers owing to the risk of lymph node metastasis and difficulty estimating the deep margin status. This study aimed to determine predictive factors for lymph node metastases in submucosal cancer and to explore in which patients ESD might be feasible. Details of patients who had curative gastrectomy for submucosal gastric cancer at Asan Medical Centre from 2007 to 2011 were reviewed retrospectively to determine the relationship between lymph node metastasis and clinicopathological characteristics, including age, sex, tumour location, size, gross appearance, depth of invasion, histological type/differentiation, presence of lymphovascular/perineural invasion, and immunohistochemical staining results for p53, human epidermal growth factor receptor (HER) 1 and HER2. A total of 1773 patients were analysed. The presence of lymphovascular invasion was related most strongly to lymph node metastasis. Multivariable analysis revealed that depth of invasion, tumour size, differentiation, gross appearance and perineural invasion were also related. Metastatic lymph nodes were found in four of 105 patients who met the classical criteria for ESD; all showed a moderately differentiated histological appearance. No lymph node metastases were observed in well differentiated SM1 tumours of any size (infiltration into upper third of submucosa), or in well differentiated SM2 (infiltration into middle third of submucosa) tumours of 2 cm or less without lymphovascular invasion. Patients with well differentiated SM1 cancer of any size and those with well differentiated SM2 cancer of 2 cm or less without lymphovascular invasion may be suitable candidates for ESD.


[Optimize conditions and activities for neutrophil lipase immobilized by nano-silica dioxide].
We used adsorption method to immobilize the lipase by using nano-silica dioxide as the carrier. And we also studied different immobilization conditions effects on the catalytic activity. We got optimize immobilization conditions which were as follow the lipase quantity of 28,300 U/g, temperature of 45 degrees C, pH of 7.5 and treated for 10 h. Under these conditions the immobilized lipase activity yield 3867 U/g carrier. The best reactive temperature for immobilized lipase was 45 degrees C and higher than 5 degrees C for free enzyme, and the optimal pH dropped to 5.5 compared that of free enzyme (pH 7.0). The immobilized lipase stability for thermal and pH are improved than free lipase. When temperature was below 70 degrees C the immobilized enzyme activity was over 70% than initial activity. The free lipase activity just kept original 30% at 50 degrees C. When pH was 5-8, the immobilized lipase activity was still more than 50% and the free lipase only remained 20%. When we used the immobilized neutrophil lipase catalyzing different oil to produce biodiesel such as soybean oil, rapeseed oil and waste oil, the esterification rate of rapeseed oil was the highest.


Outcomes of re-treatment with first-line trastuzumab plus a taxane in HER2 positive metastatic breast cancer patients after (neo)adjuvant trastuzumab: A prospective multicenter study.
Trastuzumab is the backbone of HER2-positive early breast cancer (eBC) and metastatic breast cancer (mBC) treatment, but limited data exist as to re-treatment in relapsed patients. In this prospective, single arm, multicenter trial, we assessed efficacy and safety of trastuzumab and taxane combination in Chinese patients with HER2-positive mBC relapsed after prior (neo)adjuvant trastuzumab. Patients with previous (neo)adjuvant trastuzumab treatment for≥9 weeks and a relapse-free interval ≥6 months were assigned to trastuzumab treatment with paclitaxel or docetaxel. The primary endpoint was progression free survival (PFS). Secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), time to progression (TTP), overall survival (OS) and safety profile. Thirty-two patients were enrolled and treated for a median duration of 33.5 weeks. The median PFS was 9.9 months (95% CI, 6.28 - 13.63 months). The ORR was 81.3% (95% CI, 63.6% - 92.8%) and CBR (CR+PR+SD≥6months) was 81.3% (95% CI, 63.6% - 92.8%). The median DOR was 9.8 months (95% CI, 5.82 - 11.60 months) and median TTP was 9.9 months (95% CI, 6.28-13.63 months). OS median follow-up time was 20.1 months and 25% OS time was 25.5 months. The safety profile was acceptable with common adverse events including leukopenia (59.4%), neutropenia (56.3%), hypoaesthesia (34.4%) and granulocytopenia (31.3%). In conclusion, re-treatment with trastuzumab plus a taxane as first-line therapy is an effective regimen for patients with HER2-positive mBC relapsed after (neo)adjuvant trastuzumab. The safety profile was good and the adverse reactions were tolerable and manageable.


Arginase activity of Leishmania isolated from patients with cutaneous leishmaniasis.
Cutaneous leishmaniasis (CL) is one of the most important vector-borne parasitic diseases, highly endemic in Iran, and its prevalence is increasing all over the country. Arginase (ARG) activity in isolated Leishmania parasites from CL patients is yet to be explored. This study aimed to compare the ARG activity of isolated Leishmania promastigotes from CL patients with a standard strain of Leishmania major and its influences on the disease pathogenesis. We recruited 16 confirmed CL patients from Qom Province, in central Iran; after detection of Leishmania species using PCR-RFLP, we assessed the levels of ARG in the isolated promastigotes and determined the parasites' growth rate. Only L. major was identified from CL patients. The level of ARG activity in the isolated Leishmania promastigotes from CL patients was significantly higher than that obtained from the standard strain of L. major. No significant correlations between ARG activity and lesion size, number or duration were observed; in contrast, a significant negative correlation was seen between ARG level and Leishmania' growth rate. The obtained results suggest that increased ARG expression and activity in the isolated Leishmania promastigotes might contribute to the higher parasite infectivity and play a major role in the pathogenicity of the CL.


Kraepelin's views on obsessive neurosis: a comparison with DSM-5 criteria for obsessive-compulsive disorder.
Emil Kraepelin (1856-1926) is considered one of the founders of modern psychiatric nosology. However, his conceptualization of obsessive-compulsive phenomena is relatively understudied. In this article, we compare and contrast excerpts from the eighth edition (1909-1915) of Kraepelin's Textbook of Clinical Psychiatry focusing on what Kraepelin called "obsessive neurosis" and related "original pathological conditions" with the current DSM-5 criteria for obsessive-compulsive disorder (OCD). Consistently with DSM-5 OCD, Kraepelin described obsessive neurosis as characterized by obsessive ideas, compulsive acts, or both together. His detailed descriptions of these symptoms are broadly coherent with their characterization in DSM-5, which is also true for the differential diagnoses he provided. He also mentioned cases illustrating decreased insight into symptoms and association with tic disorders. In conclusion, Kraepelin's experience, which reflects decades of consistent clinical work, may help validate current ideas and explain how the current conceptualization has emerged and developed. Even though one can hardly say that the classification laid out in DSM-5 goes back to Kraepelin's views directly, it still is true that Kraepelin played an outstanding role in systematizing psychiatric diagnostic criteria in general, and provided a major contribution to the conceptual history of OCD.


[Zhu Lian's contribution to international communication of acupuncture-moxibustion].
ZHU Lian is the founder of international communication of acupuncture-moxibustion after establishment of New China. This article discussed ZHU Lian's great deal of pioneering work and historic contributions from the aspects of acupuncture-moxibustion treatments for foreign people, international training and communication, and the international influence of Xin Zhenjiu Xue. Our research showed that ZHU Lian's early work didn't only enlarge acupuncture's worldwide influence and spreading pace, especially in Soviet Union, India and Korea, but also accumulated precious experiences for each subject of Chinese medicine attending into international medical care and academic communication in the future.


The Medawar Lecture 2004 the truth about science.
The attitudes of scientists towards the philosophy of science is mixed and includes considerable indifference and some hostility. This may be due in part to unrealistic expectation and to misunderstanding. Philosophy is unlikely directly to improve scientific practices, but scientists may find the attempt to explain how science works and what it achieves of considerable interest nevertheless. The present state of the philosophy of science is illustrated by recent work on the 'truth hypothesis', according to which, science is generating increasingly accurate representations of a mind-independent and largely unobservable world. According to Karl Popper, although truth is the aim of science, it is impossible to justify the truth hypothesis. According to Thomas Kuhn, the truth hypothesis is false, because scientists can only describe a world that is partially constituted by their own theories and hence not mind-independent. The failure of past scientific theories has been used to argue against the truth hypothesis; the success of the best current theories has been used to argue for it. Neither argument is sound.


Analysis of imprinted gene expression and implantation in haploid androgenetic mouse embryos.
The successful development of mammalian embryos requires both parental genomes. Nuclear transfer techniques have been adapted to generate uniparental embryos, which possess two sets of paternal or maternal genomes. These embryos fail to develop to term because of abnormal imprinted gene expression, which is not regulated by Mendelian inheritance. Uniparental embryos provide us with an important model to investigate imprinted gene function and ontogenesis. To evaluate the pre- and post-developmental ability of haploid androgenetic mouse embryos, and to analyse the expression of imprinted genes Igf2r, Asb4 and Mest in haploid androgenetic/gynogenetic blastocysts, we produced the haploid mouse embryos using the enucleation technique, examined their development at 6.5 dpc and quantified gene expression by quantitative real-time PCR. The results demonstrated that the developmental potential of haploid embryos was severely impaired and revealed that the haploid androgenones could induce the deciduas reaction, but failed to retain a live foetus at 6.5 dpc. Expression of imprinted genes Igf2r and Asb4 was unregulated in haploid androgenetic/gynogenetic blastocysts.


Targeting the gut to treat obesity and its metabolic consequences: view from the Chair.
The neurohumoral signaling systems of the gastrointestinal (GI) tract are considered the most significant of the peripheral inputs controlling both food intake in the short term and energy balance over a longer time course. The importance of the GI tract in the control of energy balance is underscored by the marked beneficial effects of bariatric surgeries for the treatment of obesity. Despite their effectiveness, the mechanisms of bariatric surgery remain to be fully elucidated. Considerable new evidence points to the importance of gut-brain communication, gut barrier function and microbial signaling as three of the most important mechanisms of bariatric surgery-induced weight loss. These mechanisms are reviewed in the present article and the accompanying four papers.


When Social Networks Meet D2D Communications: A Survey.
In the last few years, one of the main characteristics of the current technological development is the constantly increasing need for data exchange among various types of devices, both mobile and fixed. Within this context, the direct communications between devices has the potential to create new, location-based peer-to-peer applications and services, as well as to help offload traffic from the congested traditional cellular networks. The main hurdles for this kind of Device to Device (D2D) communications are throughput, spectral efficiency, latency and fairness. Most of these hurdles can be overcome by the use of the new Social IoT (SIoT) paradigm, of things and people involved together in the network, guided autonomously by social relationships following the rules set by their owners. This paper aims to investigate the state of the art of socially-driven D2D communications. Upon an initial analysis, we perform an in-deep literature investigation of the main directions in which social ties can improve D2D communication, draw conclusions and identify the research topics left open.


Two haplotypes of the P2X(7) receptor containing the Ala-348 to Thr polymorphism exhibit a gain-of-function effect and enhanced interleukin-1beta secretion.
The P2X(7) receptor is an ATP-gated cation channel expressed in immune cells and plays a role in proinflammatory cytokine release from monocytes and macrophages. This study investigated the coinheritance of 12 functionally relevant single nucleotide polymorphisms (SNPs) in the human P2X(7) gene (P2RX7), and the functional effect of each singly and in combination was assessed by measurements of ATP-induced currents and ethidium(+) uptake. Genotyping of 3430 Caucasian subjects identified 4 common haplotypes in addition to the common (wild-type) P2X(7)-1. Two haplotypes (denoted P2X(7)-2 and P2X(7)-4) contained various combinations of gain-of-function SNPs. P2X(7)-4 was identified uniquely by the Gln-460 to Arg polymorphism (rs2230912). When expressed in HEK-293 cells, recombinant P2X(7)-2, and P2X(7)-4 haplotypes displayed a 3-fold and 5-fold increase, respectively, in receptor function compared to the wild-type P2X(7)-1. Both P2X(7) haplotypes contained the Ala-348>Thr polymorphism (rs1718119), and this mutation was critical for the gain-of-function effect. Peripheral blood monocytes and erythrocytes from subjects homozygous for gain-of-function P2X(7) haplotypes exhibited increased ATP-induced ethidium(+) uptake and (86)Rb(+) efflux, respectively, and this correlated with increased IL-1beta secretion from LPS-primed monocytes. Inheritance of these P2X(7) haplotypes predisposing to increased proinflammatory cytokine secretion may be important in genetic association studies of inflammatory, infectious, and psychiatric disorders.


Percutaneous drainage of pleural collections.
Pneumothorax is a frequent complication of interventional pulmonary procedures. Percutaneous catheter placement enables safe and effective drainage of pneumothoraces with rapid restoration of vital capacity, oxygenation, and lung reexpansion.


Adipose Tissue-Derived Stem Cell Therapy for Post-Surgical Breast Reconstruction--More Light than Shadows.
Breast cancer remains the most common tumor in women, and new techniques for post- surgical breast reconstruction have been recently introduced. These new procedures include autologous fat grafting with or without the enrichment with autologous stromal vascular fraction (SVF), platelet-derived growth factors and insulin. The reported improvement of fat graft viability with these techniques likely depends on the presence in the SVF of multipotent resident adipose derived-stem cells (ASCs). The clinical advantage derives from the plasticity of ASCs and their ability to generate new functional adipose tissue and vessels. However, there is an ongoing debate regarding the possible interplay between breast tumor cells and resident or transplanted ASCs for their capacity to locally secrete growth factors. Most of the data in the literature concerning ASCs is derived from in vitro models, whereas the knowledge of ASC behavior in vivo remains scarce. Recent reports concerning SVF/ASC enrichment of fat graft did not describe any significant worsening of prognosis for patients undergoing those procedures. However, further studies and longer follow-ups are needed to specifically define technical procedures and to confirm the safety of procedures of SVF/ASC enrichment during post-surgical breast reconstruction.


Lydia Marie DeWitt and Mary Butler Kirkbride: Prototypical Circa-Early-1900s Women of Pathology and an Analysis of Their Contributions to the Discovery of Insulin.
The year 2023 marks the centenary of the Nobel Prize honoring the discovery of insulin. Little-known experimental pathologists Lydia DeWitt, MD, at the University of Michigan and Mary Kirkbride, DSc [Hon], at Columbia University, both just beginning their academic careers, made independent contributions to the discovery that have never been critically examined. This happened at a time when women in pathology were exceedingly rare. To explore the facilitative roles of DeWitt and Kirkbride in the discovery and to examine their trail-breaking careers in academic pathology. Available primary and secondary historical resources were reviewed. DeWitt made and tested pancreatic extracts from duct-ligated atrophic pancreas (ie, Frederick Banting's great idea to prevent digestion of its hypothetical internal secretion) 15 years before Banting; Banting was unaware of her work. His idea came from reading a paper by pathologist Moses Barron. Prior duct-ligation studies had sometimes been viewed with skepticism because histologic identification of islets in atrophic duct-ligated pancreata was imperfect; Kirkbride addressed this with histochemical staining, convincing Barron and, therefore, indirectly influencing and motivating Banting. The lives and convoluted careers of these 2 early-20th-century women are explored and compared with those of other contemporary women in pathology. A unifying pattern becomes clear: careers in experimental pathology and bacteriology were accepted but performing clinical work in anatomic pathology was not. Both DeWitt and Kirkbride are prototypical early-20th-century women in academic pathology whose careers were constrained by gender. However, Kirkbride made a unique and unrecognized contribution to the discovery of insulin.


What Is the Effect of Body Mass Index on Subjective Outcome Following Vaginal Hysterectomy for Prolapse?
Obesity is a significant risk factor for pelvic organ prolapse (POP), but the effects of obesity on outcomes of surgery for POP are poorly understood. The aim of this study was to assess the relationship between POP symptomatology, subjective outcomes of surgery and body mass index (BMI) in women undergoing vaginal hysterectomy for POP. Pre- and postoperative data from a validated pelvic floor questionnaire (electronic Personal Assessment Questionnaire-Pelvic Floor) were collected prospectively from 60 women undergoing vaginal hysterectomy for POP. Of these, 20 were normal weight (BMI 18.5-24.9 kg/m2), 20 were overweight (BMI 25-29.9 kg/m2), and 20 were women with obesity (BMI 30-34.9 kg/m2). The relationship between BMI and symptom scores for prolapse, impact on vaginal symptoms on quality of life (VS-QoL) and 'overall change in condition' was assessed. Pre- and postoperative symptom scores were compared using repeated mixed analysis of variance test for BMI as a categorical variable (normal, overweight, and obese). Spearman rank order correlation test was carried out to evaluate BMI as a continuous variable. All women underwent vaginal hysterectomy using a standardized technique. Overall, 93% of women reported improvement in their condition. The main finding was that 'overall change in condition' was negatively correlated with increasing BMI (rs=-0.324, P=0.028). Irrespective of BMI, significant improvements were observed in symptoms of prolapse and VS-QoL at 3-month postoperation. With increasing BMI, women are likely to report lower levels of satisfaction following prolapse surgery, despite reporting equivalent improvements in symptoms. BMI is known to affect how individuals perceive their general health and well-being with obese individuals reporting poorer levels of subjective health status. Women with obesity may perceive change in their condition after prolapse surgery differently to women of normal weight. Reduction of weight prior to prolapse surgery could be considered in obese women to improve subjective outcomes of surgery.


Constitutive activity of human prostaglandin E receptor EP3 isoforms.
1. The human EP3 prostaglandin receptor is a seven transmembrane, G protein-coupled receptor that couples to inhibition of adenylyl cyclase. The receptor occurs as at least six isoforms which result from alternative splicing. The isoforms are identical over the first 359 amino acids, comprising the seven transmembrane helices, but differ in the carboxyl terminal tail which ranges in length from 6 to 65 amino acids beyond the common region. 2. We have stably expressed in CHO-K1 cells four of the isoforms (EP3I-EP3IV) and a form of the EP3 receptor (T-359) truncated at the carboxyl-terminal region defined by the alternative splicing site at amino acid number 359. 3. Isoforms EP3I and EP3II showed concentration-dependent inhibition of forskolin-stimulated adenylyl cyclase in CHO-K1 cells by the EP3 receptor agonist, sulprostone. The IC50 calculated for sulprostone inhibition was 0.2 nM for EP3I and 0.15 nM for EP3II. The maximum extent of inhibition was 80% for both isoforms. 4. Isoforms EP3III and EP3IV showed marked constitutive activity, inhibiting forskolin-stimulated adenylyl cyclase in the absence of agonist. EP3IV also displayed some agonist-dependent inhibition whereas EP3III was fully constitutively active. 5. The truncated receptor T-359 was fully constitutively active, inhibiting forskolin-stimulated adenylyl cyclase by about 70% in the absence of agonist, and showed no agonist-dependent inhibition, in agreement with a similar truncation of the mouse EP3 receptor. 6. To confirm that differences in cyclic AMP level between isoforms represent constitutive activity, we treated cells with pertussis toxin for 6 h to abolish Gi function. Pertussis toxin reversed sulprostone-mediated inhibition of cyclic AMP formation in EP3I and EP3II and abolished constitutive activity of EP3III, EP3IV and T-359 so that the level of forskolin-stimulated cyclic AMP produced was the same in all cells and similar to that obtained in mock-transfected cells. In mock-transfected cells, sulprostone had no effect on forskolin-stimulated cyclic AMP formation. 7. For these experiments we chose clones that showed similar expression levels of each isoform, as determined by binding of [3H]-prostaglandin E2 (PGE2) (EP3I, 0.71; EP3II, 1.47; EP3IV, 1.59 pmol mg-1 protein). Mock-transfected cells showed no detectable binding of [3H]-PGE2. In addition, we performed a detailed study of the effects of expression level on constitutive activity. Over a six fold range of expression there was no change in the properties of each isoform with regard to whether it was constitutively active or not. 8. The degree of constitutive activity correlated with the inverse of the length of the C-terminal tail of the isoforms. However, no correlation was found between isoforms from human and mouse: whereas EP3II shows no constitutive activity, its mouse homologue, EP3 gamma, shows almost complete constitutive activity, even though the C-terminal domains of the receptors following the splice site differ in only 7 of 29 amino acids.


Local injection of M-CH combined with i.p. hyperthermic hypo-osmolar infusion is an effective therapy in advanced gastric cancer.
Treatment failure of surgically treated gastric cancer is attributed to the spread of gastric cancer cells into the abdominal cavity and lymphatic or hematogenic canals. In the present study, local injection of mitomycin C bound to activated carbon (M-CH) combined with i.p. hyperthermic hypo-osmolar infusion (IPHHOI) was intraoperatively administered to prevent lymph node recurrence and peritoneal recurrence of gastric cancer. Between April 1998 and August 1999, 79 patients with advanced gastric cancer were allocated randomly to two groups. Forty patients underwent M-CH plus IPHHOI combined with surgery (M-CH1+IPHHOI group) and the remaining 39 underwent surgery alone (control group). Lymph node and peritoneal recurrence were significantly decreased in the M-CH1+IPHHOI group compared to that in the control group (p<0.05). The 1- and 2-year survival rates for the M-CH1+IPHHOI group were 91.2 and 72.1%, and those for the control group were 78.9 and 45.5%. The M-CH1IPHHOI group reaped a significant survival benefit (p=0.0352) compared to the control group. Although this study was conducted randomly for a small number of patients and short time, compared with the control group, the M-CH1+IPHHOI group had a beneficial effect in preventing lymph node recurrence and peritoneal recurrence after curative gastrectomy for advanced gastric cancer.


Requirement of phosphatidylglycerol for maintenance of photosynthetic machinery.
Phosphatidylglycerol (PG) is a ubiquitous component of thylakoid membranes. Experiments with the pgsA mutant of the cyanobacterium Synechocystis sp. PCC6803 defective in biosynthesis of PG have demonstrated an indispensable role of PG in photosynthesis. In the present study, we have investigated the light susceptibility of the pgsA mutant with regard to the maintenance of the photosynthetic machinery. Growth of the mutant cells without PG increased the light susceptibility of the cells and resulted in severe photoinhibition of photosynthesis upon a high-light treatment, whereas the growth in the presence of PG was protected against photoinhibition. Photoinhibition induced by PG deprivation was mainly caused by an impairment of the restoration process. The primary target of the light-induced damage in thylakoid membranes, the D1 protein of photosystem (PS) II was, however, synthesized and degraded with similar rates irrespective of whether the mutant cells were incubated with PG or not. Intriguingly, it was found that instead of the synthesis of the D1 protein, the dimerization of the PSII core monomers was impaired in the PG-deprived mutant cells. Addition of PG to photoinhibited cells restored the dimerization capacity of PSII core monomers. These results suggest that PG plays an important role in the maintenance of the photosynthetic machinery through the dimerization and reactivation of the PSII core complex.


Osteocutaneous radial forearm free flap in subtotal nasal reconstruction.
A 66-year-old man presented with a large squamous cell carcinoma of the right nasal vestibule. He underwent partial rhinectomy and medial maxillectomy followed by staged reconstruction. Reconstruction of a full-thickness nasal defect requires repair of three distinct layers: the skin-soft tissue envelope, subsurface framework and intranasal lining. We report the first use in the UK of an osteocutaneous radial forearm free flap in the reconstruction of a subtotal nasal deficit. The skin of the radial forearm free flap was tubed to recreate the nasal lining and the radial bone reconstructed the dorsal contour of the nose. A full-thickness paramedian forehead flap supplied external coverage. The osteocutaneous radial forearm free flap and forehead flap is a viable option for large nasal defects requiring reconstruction of framework, nasal lining and external covering.


Effect of whole body gamma irradiation on fatty acid composition of liver lipids of female rats and radioprotection by cystamine.
Effect of whole body gamma irradiation (1200 R) on the fatty acid composition of liver lipids and its triglycerides (TG), phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC) has been studied in female rats. Radioprotective effect of cystamine on radiation-induced alterations in fatty acid composition of above liver lipid fractions has been studied by giving crystamine 15 min before irradiation. Irradiation increased palmitic acid levels in liver total lipids, and PE and decreased in TG. Cystamine prevented these changes. Irradiation increased palmitoleic acid levels in liver total lipids, total phospholipids and PC and these were prevented by prior administration of cystamine. Linoleic acid was decreased in liver total lipids, TG, total phospholipids and increased in PE and PC of irradiated rats. Administration of cystamine before irradiation partially protected these changes. Arachidonic acid was reduced in all liver lipid fractions of irradiated rats and this was only partially protected by cystamine, which itself reduced its levels in the control animals. Irradiation increased the levels of eicosatrienoic acid and these were not prevented by cystamine.


Effect of grafting density of the side chains on spontaneous curvature and persistence length of two-dimensional comblike macromolecules.
We develop a theory that predicts the response of a two-dimensional (2D) comblike macromolecule (brush) to the bending which is accompanied by redistribution of the side chains with respect to the backbone. The brush is considered under poor solvent conditions, i.e., monomer units of the side chains and of the backbone attract each other. The line tension is explicitly taken into account. It is shown that densely grafted brushes (or brushes with long side chains) demonstrate spontaneous curvature. This curvature is induced by elasticity of the side chains: asymmetrically distributed side chains forming curved segments of the brush possess smaller elastic free energy than symmetrically distributed ones forming rectilinear segments of the brush. Sparsely grafted brushes (or brushes with short enough side chains) exhibit elastic response to the bending. In this case, a role of the elasticity of the side chains diminishes and main contributions to the elastic response of the brush come from the mixing entropy of the side chains and from the line tension. It is shown that persistence length of the sparsely grafted brushes lambda as a function of the number of segments in the side chain M can be approximated by a power function, lambda=const x M(alpha), with the exponent alpha<or=2. This persistence length is much smaller than that of the 2D brush with fixed distribution of the side chains. Our theoretical predictions are consistent with computer simulations.


Toward a Comprehensive Hypothesis of Chronic Interstitial Nephritis in Agricultural Communities.
Over the past 20 years, there has been an increase in chronic interstitial nephritis in agricultural communities (CINAC) not associated with traditional risk factors. This disease has become an important public health problem and is observed in several countries in Central America and Asia. CINAC predominantly affects young male farmers between the third and fifth decades of life with women, children, and adolescents less often affected. Clinically, CINAC behaves like a chronic tubulointerstitial nephropathy but with systemic manifestations not attributable to kidney disease. Kidney biopsy reveals chronic tubulointerstitial nephritis with variable glomerulosclerosis and mild chronic vascular damage, with the severity depending on sex, occupation, and CKD stage. The presence of toxicological, occupational, and environmental risk factors within these communities suggests a multifactorial etiology for CINAC. This may include exposure to agrochemicals, a contaminated environment, repeated episodes of dehydration with heat stress, and an underlying genetic predisposition. An understanding of these interacting factors using a multidisciplinary approach with international cooperation and the formulation of a comprehensive hypothesis are essential for the development of public health programs to prevent this devastating epidemic.


Ecological correlates of abundance in the Tana mangabey (Cercocebus galeritus).
I investigated the ecological correlates of abundance in the Tana mangabey (Cercocebus galeritus), one of the world's most endangered primates, with the goal of recommending management strategies. I systematically selected 31 forest fragments throughout the mangabey's 60-km distribution along the lower Tana River in southeastern Kenya. Within the 31 fragments, I measured vegetation structure, food abundance, and human forest product use in 107 belt transects, and conducted 370 mangabey surveys. I used a weighted multiple regression analysis to determine whether there was a dependence between the selected forest attributes and the mean number of mangabey groups per fragment. Fragment area and density of trees > or =10 cm diameter at breast height (DBH) were the only variables that significantly correlated with the variation in mangabey abundance. No additional variables were significant when the analysis was limited to forest fragments inside the Tana River Primate National Reserve (TRPNR) or to fragments outside the TRPNR. When I estimated the resources available before recent human forest product use by adding nonharvested and harvested variables, the total basal area of the top 15 food species became significant. This was only within the TRPNR, however. Management, therefore, should focus on increasing forest area, density of trees > or =10 cm DBH, and coverage of food trees throughout the mangabey's distribution. Solutions must be found for the problem of forest clearing, and forest product use must be better managed to protect the habitat of this critically endangered primate. The significance of food abundance only within the TRPNR suggests a need to collect dietary data from mangabey groups in fragments toward the southern limit of the mangabey's distribution, where plant species composition differs from that in fragments in which dietary data have been previously collected.


Phytotoxic activity against Bromus tectorum for secondary metabolites of a seed-pathogenic Fusarium strain belonging to the F. tricinctum species complex.
The winter annual grass Bromus tectorum (cheatgrass) has become highly invasive in semiarid ecosystems of western North America. In these areas, a natural phenomenon, complete cheatgrass stand failure ('die-off'), is apparently caused by a complex interaction among soilborne fungal pathogens. Several Fusarium strains belonging to the Fusarium tricinctum species complex were isolated from these soils and found to be pathogenic on B. tectorum seeds. One of these strains was produced in cheatgrass seed culture to evaluate its ability to produce phytotoxins. Six metabolites were isolated and identified by spectroscopic methods (essentially 1D and 2D NMR and ESIMS) as acuminatopyrone (1), blumenol A (2), chlamydosporol (3), isochlamydosporol (4), ergosterol (5) and 4-hydroxybenzaldehyde (6). Upon testing against B. tectorum in a seedling bioassay, (6) the coleoptile and radicle length of cheatgrass seedlings were significantly reduced. Compounds 1 and 2 showed moderate activity, while 3-5 were not significantly different from the control.


Regulatory T cell populations in sepsis and trauma.
Sepsis syndrome remains the leading cause of mortality in intensive care units. It is now believed that along with the body's hyperinflammatory response designated to eliminate the underlying pathogen, mechanisms are initiated to control this initial response, which can become deleterious and result in immune dysfunctions and death. A similar state of immune suppression has been described after numerous forms of severe trauma/injury. Although the evidence for immune dysfunctions after sepsis has grown, much remains to be understood about mechanisms underpinning its development and how it acts to increase the morbid state of the critically ill patient. In this context, although the majority of clinical and basic science conducted so far has focused on the roles of myeloid cell populations, the contribution of T lymphocytes and in particular, of regulatory T cells has been somewhat ignored. The studies presented here support the concept that regulatory T lymphocytes (CD4+CD25+ regulatory, gammadelta, and NK T cells) play a role in the control of immune responses and are affected by injury and sepsis. This may be related to their capacity to interact with components of the innate and adaptive immune responses and to their ability to be activated nonspecifically by bacterial products and/or cytokines and to regulate through direct cell-cell and/or soluble mediators. It is our hope that a better understanding of the mechanism through which those rare lymphocyte subsets exert such a profound effect on the immune response may help in improving our ability not only to diagnose but also to treat the critically ill individual.


[From gene to disease: copper-transporting P ATPases alteration].
Copper is a trace metal, essential for many biological processes. Copper is also toxic if in excessive amounts; its homeostatic balance requires a delicate regulation. Several severe hereditary human disorders of copper regulatory mechanisms have been identified; they are related to mutations in gene ATP7A and ATP7B coding for copper-transporting proteins. Those mutations result in copper deficiency for ATP7A (Menkes disease) and copper overload for ATP7B (Wilson disease). Usually, clinical and biochemical phenotypes of these diseases are disparate. This article focuses on the molecular pathogenesis of Wilson and Menkes disease, and discusses how causing mutations are correlated with molecular defects and disease phenotypes.


Frederic Chopin--the man, his music and his illness.
Frédéric Chopin's unique position in the history of music relies on a surprisingly limited and special production. However, the artistic level is invariably high and the musical language is both universal and unmistakably personal. A nearly life-long suffering from illness marked his life and influenced his artistry, as composer and pianist. Chopin's struggle with a fateful disease, and his instinctive understanding that he would loose, made imprints on some of his works that carry a sombre intensity, bordering on desperation. The emotional tension of these compositions, that appear already from youth and henceforward, goes far beyond the musical conventions of the time. The nature of Chopin's disease has been subject to numerous speculations. This is not surprising, considering the wide spectrum of symptoms and the dynamics of his illness--or illnesses. Taking into account all reported symptoms and signs since childhood and henceforth, it is postulated that Chopin suffered from cystic fibrosis by heriditariness, possibly superimposed by tuberculosis or atypical mycobacteria. This would explain all his symptoms, and to some extent also the ambivalence of contemporary physicians. By available gene technology it would be possible to investigate, for proof or dismissal, if this hypothesis is true.


[Comparative study of monolateral and circular fixator in the treatment of infectious tibial nonunion].
To compare treatment effect of monolateral and circular external fixator in infectious tibial nonunion and to explore external fixation structure with better osteogenic ability and fewer complications. A retrospective analysis was performed on 150 patients with infectious tibial nonunion admitted from January 2010 to December 2014. Patients who met the inclusion and exclusion criteria were divided into monolateral fixator group and circular fixator group according to the type of external fixation. Demographic and perioperative data of the two groups were collected. New bone quality was assessed by pixels ratio, treatment effect was assessed by complications. Notes for treatment was explored by case analysis. A total of 64 patients with infectious mid-tibial nonunion were included, 26 in monolateral fixator group and 38 in circular fixator group. There was no difference in demographic data between two groups. The pixel ratio of new bone between two groups was from 0.91 to 0.97 with an average of (0.94±0.03), and from 0.93 to 0.97 with an average of(0.95±0.02), respectively, with no statistical significance (P>0.05). The external fixation index was from 34.1 to 50.6 with an average of (42.3±8.3) days /cm in monolateral fixator group and from 44.5 to 56.1 with an average of (45.8±10.3) days/cm in the circular fixator group, and the difference was not statistically significant (P>0.05). There were 7 cases (26.9%) of complications in monolateral fixator group and 5 cases (13.2%) in circular fixator group, the difference was not statistically significant (P>0.05), but 5 cases of foot ptosis in monolateral fixator group and none in circular fixator group. The time of weight bearing in monolateral fixator group was later than that in circular fixator group, and the difference was statistically significant (P<0.05). Monolateral and circular fixators can achieve equivalent bone formation in the treatment of infected tibial nonunion. Circular fixator is recommended for patients with severe osteoporosis or concomitant medical diseases requiring early weight bearing. Hydroxyapatite coated screws are recommended if a monolateral external fixator is selected when the expected enlarged length is long and the fixation time is long and close monitoring of the ankle movement is required to avoid foot droop.


Lymph node dissection in resectable advanced gastric cancer.
The extent of surgery for gastric cancer has been debated since Billroth performed his first gastrectomy in 1881. This review gives an overview of the available literature on the extent of gastrectomy and lymphadenectomy for advanced resectable gastric cancer. Subtotal gastrectomy is associated with lower morbidity and mortality compared with total gastrectomy, without compromising long-term survival. However, a positive resection margin decreases the chance of curation. Frozen section examination may prevent this. For poorly differentiated singlet ring cell tumors, there may be an argument to perform a total gastrectomy in all cases. In 1981, the Japanese Research Society for the Study of Gastric Cancer provided guidelines for the standardization of surgical treatment and pathological evaluation of gastric cancer. Since then, D2 lymph node dissections have become the standard of care in Japan. Because of the superior stage-specific survival rates in Japan, a D2 dissection was evaluated in several Western randomized controlled trials, but no survival benefit was found for a D2 over a D1 dissection. This might be explained by the increased mortality in the D2 dissection groups which might be the result of a standard pancreaticosplenectomy and low experience with D2 dissections. Adding the removal of the para-aortic nodes to a D2 dissection does not further improve survival. The removal of lymph node stations 10 and 11 by splenectomy showed an increased morbidity, no survival benefit, and a very poor prognosis if lymph nodes were affected. Therefore, pancreaticosplenectomy should only be performed in cases of tumor invasion into these organs. A D2 dissection without routine splenectomy and pancreatic tail resection in experienced hands should be considered standard of care for advanced resectable gastric cancer, both in Asian and in Western patients. Centralization and auditing may further improve outcomes after gastrectomy.


Clinical and genomic features of Corynebacterium macginleyi-associated infectious keratitis.
Infectious keratitis is a potentially sight threatening ophthalmological emergency. Contact lens wear is a common risk factor. Diagnostic advances such as MALDI-TOF MS provides new insights into the spectrum of corneal pathogens and on microbes previously considered as commensals. Corynebacterium macginleyi was described in 1995, and in 2018, the genomic features of three isolates were reported after whole-genome sequencing. Here we describe the clinical characteristics of patients with infectious keratitis (n = 29) presumably caused by Corynebacterium macginleyi, and analyze the genomic features of C. macginleyi (n = 22) isolated from the corneal ulcers of these patients. The disease course was uneventful apart from minor interventions such as corneal cross-linking and amniotic membrane transplant. Genome sequencing and comparison revealed a highly conserved core genome of C. macginleyi. Based on the analyses of single nucleotide polymorphisms, the population could be divided into two main clades that also differed in a few clade-specific genomic islands. Patients infected with an isolate belonging to the minor clade (n = 7) presented a more severe disease. Comparisons with other corynebacterial species clearly separated C. macginleyi. C. macginleyi may be considered a corneal pathogen; genomic analysis provided insights into its population structure and disease-causing potential.


Ascogregarina taiwanensis infection in Aedes aegypti and Aedes albopictus in Santa Catarina, South Brazil.
This study registers Ascogregarina spp. infection in field populations of Aedes aegypti and Aedes albopictus in a subtropical region of Brazil. Mosquito larvae collected in tires placed in four municipalities of Santa Catarina were identified morphologically and assessed for Ascogregarina sp. infection using morphological and molecular methods. Both mosquito species harbored Ascogregarina taiwanensis, whose genomic DNA was confirmed in both the Aedes species by PCR. DNA sequences were deposited in GenBank. Conclusion: Both Ae. albopictus e Ae. aegypti harbor Ascogregarina sp.


[The periods of actual bed occupancy per year and the length of stay of surgical patients in the hospital].
Taking into account the lack of science-reasonable data about average number of days of bed capacity in year and average number of days of various patient treatment in the hospital, the attempt is undertaken to substantiate these parameters in reference to DM of RF central military medicine institutions. In result of lead research it was established, that average terms of bed capacity in central military hospitals during the last 5 years were 310 days. Average patient terms of treatment differ essentially depending on age and contingent, that is necessary to take into account to define hospital bed requirement norms.


Neonatal Transport - Experience of a Tertiary Care Hospital of Bangladesh.
Safe transportation is mostly an unnoticed neonatal health issue in Bangladesh and no documentation is available regarding the existing practices. So this study was intended to document transport status of the referred newborn to a tertiary care hospital. This observational study included 150 out born neonates over 12 months period transported from various places to NICU, Bangabandhu Sheikh Mujib Medical University (BSMMU) from May 2015 to April 2016. A structured data collection form was used to record information categorized into pre-transport, during transport and at admission. At admission detailed clinical assessment of the baby was done and recorded. Outcome was determined as discharge or death. Of 150 transported neonates, two-third were preterm 115(77%) & LBW 113(75%). Common indications for referral were prematurity and sepsis. Most of the patients were referred from private hospital 107(71%). Majority of newborns (86%) were referred from hospitals of Dhaka city while only 14% were referred from outside Dhaka. Referral notes were supplied in most of the cases 134(89%) but comprehensive information was obtainable only in 3 cases. Although main transport vehicle was ambulance 130(87%), medical personnel accompanied the sick baby only in 6(4%) of cases. The distance traveled was less than 10 kilometers (kms) in 95(63%) and more than 100 km in 10(7%) of enrolled neonates. Transport time was less than 1 hour in 72(48%), 1-6 hours in 66(44%) and more than 6 hours in 12(8%) of cases. Nearly two third of newborn were transported after office period, 107(72%). At admission 21(14%) babies had hypothermia, 8(7.62%) hypoglycemia, 16(11%), poor perfusion 28(19%), low saturation 27(18%). Hyperthermia & hyperglycemia were observed in 8(5%) & 7(5%) cases respectively. Of the total 150 babies referred, 17(11%) died. While comparing with discharged newborn, died newborn were more frequent sufferer of hypothermia (p value 0.007) and low saturation (p value 0.049) at admission. Premature, low birth weight and sick newborns are being transported despite lack of safe transport system.


Comparison of electrical velocimetry and transoesophageal Doppler echocardiography for measuring stroke volume and cardiac output.
Impedance cardiography (ICG) has been used extensively to estimate stroke volume (SV) and cardiac output (CO) from changes of thoracic electrical bioimpedance (TEB). However, studies comparing ICG with reference methods have questioned the reliability of this approach. Electrical velocimetry (EV) provides a new algorithm to calculate CO from variations in TEB. As the transoesophageal Doppler echocardiographic quantification of CO (TOE-CO) has emerged as a reliable method, the purpose of this study was to determine the limits of agreement between CO estimations using EV (EV-CO) and TOE-CO. Standard ECG electrodes were used for non-invasive EV-CO measurements. These were placed on 37 patients scheduled for coronary artery surgery necessitating transoesophageal echocardiography monitoring. Simultaneous EV-CO and TOE-CO measurements were recorded after induction of anaesthesia. EV-CO was calculated using the Bernstein-Osypka equation. TOE-CO was measured across the aortic valve using continuous-wave Doppler echocardiography and a triangular orifice model. A significant high correlation was found between the TOE-CO and the EV-CO measurements (r2=0.86). Data were related linearly. The slope of the line (1.10 (se 0.07)) was not significantly different from unity, and the point at which it intersected the ordinate (-0.46 (0.32) litre min(-1)) was not significantly different from zero. Bland-Altman analysis revealed a bias of 0.18 litre min(-1) with narrow limits of agreement (-0.99 to 1.36 litre min(-1)). The agreement between EV-CO and TOE-CO is clinically acceptable, and these two techniques can be used interchangeably.


The alpha-form of S-adenosylmethionine synthetase isozymes from liver is principally functional.
Treatment of rats with an ethionine plus adenine or a methionine diet leads not only to a marked increase of the alpha-form isozyme of S-adenosylmethionine synthetase in liver, but also to the accumulation of comparable amounts of S-adenosylethionine and S-adenosylmethionine in liver. Transplantation of ascites tumor cells into mice leads to a marked increase only of the beta-form isozyme in the host liver, but the levels of S-adenosylmethionine do not significantly change in liver.


Costa Rican consumer perceptions of gene-editing.
Costa Rica's rice production, a large determinant of the country's food security, is being negatively impacted by frequently increasing periods of intense drought. Costa Rican scientists have applied CRISPR/Cas9 to develop drought resistant rice varieties they believe the country's rice producers could benefit from. However, would Costa Ricans consume gene edited rice or products derived from this crop? A three-part, 26-question survey administered in-person to 1096 Costa Ricans uncovers their attitudes, knowledge, and perceptions of gene editing technology and crops. Multiple regressions were built where the independent variables were age, gender, education level, and subjective economic situation. No statistically significant relationships were found in the regression coefficients. Moreover, the k-means procedure (cluster analysis) was used to categorize respondents according to their attitudes on the consumption of gene-edited foods: negative, neutral, and positive. Results show that overall, Costa Rican consumers are open to the application of gene editing in agriculture and would consider consuming products derived from the application of the technology. They are also open to gene editing technology being used to address human and animal health issues. However, Costa Rican consumers are not open to gene editing being used to "design" human traits. This study adds evidence to the emerging literature on the acceptance of gene-edited food. It also highlights the importance of informing societies of just how vulnerable agriculture, and therefore food security, is to the increasingly adverse effects of climate change.


[Epidemiology of musculoskeletal disorders caused by biomechanical overload (WMSDs)].
The link between occupation and musculo-skeletal disorders has been focused on in numerous research projects, ranging from those simply observing the different pathological findings reported among workers performing particular tasks, down to the latest studies actually quantifying the "exposure" of workers to physical and psycho-social stimuli, Recently, Hagberg et al (11) carried out a critical review of the literature concerning the upper limbs. For some disorders and certain tissues, the authors reported that specific types of work-related exposure are associated with the development of musculo-skeletal pathologies, and that the relative risks for certain types of occupational exposure can be extremely high. This has been proven in relation to tendinitis of the shoulder and hand-wrist, carpal tunnel syndrome, and tense neck syndrome, as well as several localised aspecific musculo-skeletal symptoms, such as pain. For other pathologies, the study reported contradictory results. This is the case for lateral epicondylitis, narrow chest syndrome and cervical radiculopathy. Associations have moreover been observed between several groups of disorders and certain psycho-social factors (e.g. workload, degree of discretionality).


[A 41 year-old male patient with fever of unknown origin and bacteremia with actinobacillus actinomycetemcomitans].
A 41-year-old male patient presented with fever of unknown origin which had been present for 5 months. The primary diagnostic procedures did not identify an infectious focus. After a lag phase of 13 days, blood cultures became positive for Actinobacillus actinomycetemcomitans, which belongs to the HACEK group of microorganisms. According to the DUKE criteria, infective endocarditis was diagnosed despite negative transesophageal echocardiography (TEE). The sensitivity of TEE is estimated between 86 and 94%. An infected tooth was extracted as a possible focus, and the patient was treated with i.v. antibiotics for 5 weeks according to the guidelines of the AHA and ACC. The fever was permanently terminated, and the further course of the patient was uneventful. Despite negative TEE, the diagnosis "infective endocarditis" should not be rejected, and blood cultures should be grown for up to 30 days.


Roles of heterotypic CCN2/CTGF-CCN3/NOV and homotypic CCN2-CCN2 interactions in expression of the differentiated phenotype of chondrocytes.
To identify proteins that regulate CCN2 activity, we carried out GAL4-based yeast two-hybrid screening with a cDNA library derived from a chondrocytic cell line, HCS-2/8. CCN2/CTGF and CCN3/NOV polypeptides were picked up as CCN2-binding proteins, and CCN2–CCN2 and CCN2–CCN3 binding domains were identified. Direct binding between CCN2 and CCN3 was confirmed by coimmunoprecipitation in vitro and in vivo and surface plasmon resonance, and the calculated dissociation constants (K(d)) were 1.17 × 10(-9) m for CCN2 and CCN2, and 1.95 × 10(-9) m for CCN2 and CCN3. Ectopically overexpressed green fluorescent protein–CCN2 and Halo–CCN3 in COS7 cells colocalized, as determined by direct fluorescence analysis. We present evidence that CCN2–CCN3 interactions modulated CCN2 activity such as enhancement of ACAN and col2a1 expression. Curiously, CCN2 enhanced, whereas CCN3 inhibited, the expression of aggrecan and col2a1 mRNA in HCS-2/8 cells, and combined treatment with CCN2 and CCN3 abolished the inhibitory effect of CCN3. These effects were neutralized with an antibody against the von Willebrand factor type C domain of CCN2 (11H3). This antibody diminished the binding between CCN2 and CCN2, but enhanced that between CCN3 and CCN2. Our results suggest that CCN2 could form homotypic and heterotypic dimers with CCN2 and CCN3, respectively. Strengthening the binding between CCN2 and CCN3 with the 11H3 antibody had an enhancing effect on aggrecan expression in chondrocytes, suggesting that CCN2 had an antagonizing effect by binding to CCN3.


Surgical versus nonsurgical cosmetic procedures.
There has been an increase in nonsurgical interventions for facial rejuvenation since 2001, which can be attributed to an increase in the use of injectable fillers, volumizers, and biostimulators for soft tissue augmentation. The efficacy and duration of these products depend on their mode of operation, site of injection, and composition. Semipermanent devices offer a compromise between short-term and long-term results.


The effect of thermal treatment of whole soybean flour on the conversion of isoflavones and inactivation of trypsin inhibitors.
The aim of this paper was to evaluate the effect of the thermal treatment of whole soybean flour (WSF) on the conversion of isoflavones and the inactivation of trypsin inhibitors. Soybeans were ground and whole soybean flour was obtained and subjected to heat treatment in an oven for 10, 15 and 20min at 100, 150 and 200°C according to a 3(2) experimental design. The response functions were taken to be the contents of different isoflavone forms and the residual activity of trypsin inhibitors. The thermal treatment in the oven altered the content and profile of the different isoflavones forms. At 200°C for 20min, there was a higher conversion of malonylglycosides to acetylglycosides, β-glycosides and aglycones and a significant reduction in the activity of trypsin inhibitors. Mathematical models were established to estimate the process parameters in obtaining the WSF with isoflavone conversions and reductions in trypsin inhibitor activity.


Comparison of Protein-Repellent Behavior of Linear versus Dendrimer-Structured Surface-Immobilized Polymers.
For many biomedical applications, material surfaces should not only prevent unspecific protein adsorption and bacterial attachment as in many other applications in the food, health, or marine industry, but they should also promote the adhesion of tissue cells. In order to take a first step toward the challenging development of protein and bacteria-repelling and cell-adhesion-promoting materials, polyamine and poly(amido amine) surface coatings with terminal amine groups and varying structure (dendrimer, oligomer, polymer) were immobilized on model surfaces via silane chemistry. Physicochemical analysis showed that all modifications are hydrophilic (contact angles <60°) and possess similar surface free energies (SFEs, ∼46-54 mN/m), whereas their amine group densities and zeta potentials at physiological conditions (pH 7.4) varied greatly (-50 to +75 mV). In protein adsorption experiments with single proteins (human serum albumin (HSA) and lysozyme) as well as complex physiological fluids (fetal bovine serum (FBS) and human saliva), the amounts of adsorbed protein were found to correlate strongly with the zeta potential of the surface coatings. Both modifications based on linear polymers exhibited good protein repellency toward all proteins examined and are thus promising for testing in cell adhesion studies.


Levels of some acute-phase proteins in the serum of patients with cancer during radiotherapy.
The acute phase response involves changes in serum concentrations of a number of liver-synthesized proteins. Among these are C-reactive protein (CRP), ferritin (FER), transferrin (Trf) and ceruloplasmin (Cp). Determination of serum CRP, FER, Trf, and Cp was performed in 52 patients with inoperable head and neck cancer (n=11), inoperable esophageal cancer (n=10), rectal cancer (n=9; operation was performed=5, inoperable=4), and lung cancer (n=22), all of whom were treated with radical radiotherapy (RT). Post-radiotherapy CRP levels were significantly higher compared to the preradiotherapy levels (p<0.001). We found decreased serum Trf levels during the irradiation period, while acute-phase proteins such as CRP, FER, and Cp levels increased during the RT period. Further studies on the roles of other acute phase reactants and the above mentioned parameters in a large-patients-with cancer group during radiotherapy are required to understand the role of markers, which are altered during radiotherapy.


M-CSF: a novel plasmacytoid and conventional dendritic cell poietin.
The critical importance of plasmacytoid dendritic cells (pDCs) in viral infection, autoimmunity, and tolerance has focused major attention on these cells that are rare in blood and immune organs of humans and mice. The recent development of an Flt-3 ligand (FL) culture system of bone marrow cells has led to the simple generation of large numbers of pDCs that resemble their in vivo steady-state counterparts. The FL system has allowed unforeseen insight into the biology of pDCs, and it is assumed that FL is the crucial growth factor for these cells. Surprisingly we have found that a cell type with high capacity for interferon-alpha (IFN-alpha) production in response to CpG-containing oligonucleotides, a feature of pDCs, develop within macrophage-colony-stimulating factor (M-CSF)-generated bone marrow cultures. Analysis of this phenomenon revealed that M-CSF is able to drive pDCs as well as conventional DCs (cDCs) from BM precursor cells in vitro. Furthermore, application of M-CSF to mice was able to drive pDCs and cDCs development in vivo. It is noteworthy that using mice deficient in FL indicated that the M-CSF-driven generation of pDCs and cDCs in vitro and in vivo was independent of endogenous FL.


Investigating the Relatedness of Enteroinvasive Escherichia coli to Other E. coli and Shigella Isolates by Using Comparative Genomics.
Enteroinvasive Escherichia coli (EIEC) is a unique pathovar that has a pathogenic mechanism nearly indistinguishable from that of Shigella species. In contrast to isolates of the four Shigella species, which are widespread and can be frequent causes of human illness, EIEC causes far fewer reported illnesses each year. In this study, we analyzed the genome sequences of 20 EIEC isolates, including 14 first described in this study. Phylogenomic analysis of the EIEC genomes demonstrated that 17 of the isolates are present in three distinct lineages that contained only EIEC genomes, compared to reference genomes from each of the E. coli pathovars and Shigella species. Comparative genomic analysis identified genes that were unique to each of the three identified EIEC lineages. While many of the EIEC lineage-specific genes have unknown functions, those with predicted functions included a colicin and putative proteins involved in transcriptional regulation or carbohydrate metabolism. In silico detection of the Shigella virulence plasmid (pINV), which is essential for the invasion of host cells, demonstrated that a form of pINV was present in nearly all EIEC genomes, but the Mxi-Spa-Ipa region of the plasmid that encodes the invasion-associated proteins was absent from several of the EIEC isolates. The comparative genomic findings in this study support the hypothesis that multiple EIEC lineages have evolved independently from multiple distinct lineages of E. coli via the acquisition of the Shigella virulence plasmid and, in some cases, the Shigella pathogenicity islands.


Antitumor effect of transcatheter oily chemoembolization for hepatocellular carcinoma assessed by computed tomography: role of iodized oil.
The efficacy of transcatheter oily chemoembolization (TOCE) was evaluated in 82 patients with unresectable hepatocellular carcinoma (HCC) by computed tomography more than 6 months after TOCE. A doxorubicin in oil emulsion (DOE) was administered to 42 cases and an epirubicin in oil emulsion (EOE) was administered to 40 cases. No significant differences were found in the patient background characteristics between the DOE-treated group and the EOE-treated group. Tumor regression of more than 50% of the product of two dimensions was observed in 26 DOE-treated cases and in 25 EOE-treated cases at 1 year or more after TOCE. No difference in antitumor effect was observed between DOE and EOE, although a sufficient dose per tumor volume would be required to manifest an antitumor effect on hepatocellular carcinoma.


Development of a droplet digital PCR assay for quantification of the proviral load of bovine leukemia virus.
Droplet digital PCR (ddPCR) is a highly sensitive tool developed for the detection and quantification of short-sequence variants-a tool that offers unparalleled precision enabling measurement of smaller-fold changes. We describe here the use of ddPCR for the detection of Bovine leukemia virus (BLV) DNA provirus. Serum samples and whole blood from experimentally infected sheep and naturally infected cattle were analyzed through ddPCR to detect the BLV gp51 gene, and then compared with serologic and molecular tests. The ddPCR assay was significantly more accurate and sensitive than AGID, ELISA, nested PCR, and quantitative PCR. The limit of detection of ddPCR was 3.3 copies/µL, detecting positive experimentally infected sheep beginning at 6 d post-infection. The ddPCR methodology offers a promising tool for evaluating the BLV proviral load, particularly for the detection of low viral loads.