Seroprevalence of anti-SARS-CoV-2 antibodies in Colombia, 2020: A population-based study.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause very high morbidity and mortality throughout Latin American countries. However, few population-based seroprevalence surveys have been conducted to quantify attack rates and characterize drivers of transmission. We conducted a population-based cross-sectional study to assess the seroprevalence of antibodies against SARS-CoV-2 in ten cities in Colombia between September and December 2020. The study involved multi-stage cluster sampling at each city. Participants provided a serum sample and answered a demographic and risk factor questionnaire. Prior infection by SARS-CoV-2 was ascertained using the "SARS-CoV-2 Total (COV2T) Advia Centaur - Siemens" chemiluminescence assay. A total of 17863 participants from 7320 households participated in the study. Seroprevalence varied substantially between cities, ranging from 26% (95%CI 23-29 %) in Medellín to 68% (95%CI 62-74 %) in Guapi. There were no differences in seroprevalence by sex, but seropositivity was higher in certain ethnic groups. There was substantial heterogeneity in seroprevalence within cities, driven to a large extent by a strong association between socioeconomic stratum and seropositivity. Colombia has been one of the Latin American countries most affected by the COVID-19 pandemic. This study documented very high attack rates in several Colombian cities by the end of 2020 and identified key drivers of heterogeneities including ethnicity and socioeconomic stratum. Few studies of seroprevalence of SARS-CoV-2 have been conducted in Latin America, and therefore this study contributes to the fundamental understanding of the pandemic in the region. The study was sponsored by, Ministerio de Ciencia y Tecnología e Innovación -CT361/2020, Ministerio de Salud y Protección Social, Fundación Universitaria del Norte, Imperial College of London, Universidad Nacional de Colombia (Sede Medellín), Universidad de Córdoba, California University, Unidad Nacional de Gestión del Riesgo, Centro de Atención y Diagnóstico de Enfermedades Infecciosas -CDI-, Centro Internacional de Entrenamiento e Investigaciones Médicas -CIDEIM-, Departamento Administrativo Nacional de Estadística - DANE, Fondo Nacional de Turismo -FONTUR-, Secretarías de Salud Departamentales, Distritales y Municipales and Instituto Nacional de Salud.


Localized amyloidosis in relation to conjunctival haemorrhagic lymphangiectasia and occlusion of the orbital veins. A case report.
A patient with amyloidosis in the right bulbar conjunctiva and conjunctival haemorrhagic lymphangiectasia is presented. An orbitophlebography revealed occlusion of the superior and inferior ophthalmic veins in both orbits. A biopsy from the left bulbar conjunctiva obtained at the same time revealed conjunctival haemorrhagic lymphangiectasia but no amyloid. The possible relationship of the findings is discussed.


Angiographic predictors of left ventricular ejection fraction after successful angioplasty in acute myocardial infarction: an angiographic risk score for use in the catheterization laboratory.
We investigated the value of angiographic parameters in patients with successful primary angioplasty using a simple angiographic risk score. In 608 consecutive patients, we assessed the infarct-related artery, antegrade flow before treatment, presence of distal embolization, and myocardial blush grade after coronary angioplasty. LAD-related infarction (OR = 8.4; 3 points), TIMI 0-2 flow before angioplasty (OR = 2.2; 1 point), myocardial blush 0 or 1 (OR = 2.5; 1 point), and distal embolization (OR = 2.2; 1 point) were independent predictors of left ventricular ejection fraction (LVEF) < or = 40% after successful angioplasty. Patients with 0 (minimum) or 1 point have LVEF of 49.5% +/- 8.4% and 30-day mortality of 0.8%. Patients with 2-3 points have LVEF of 44.9% +/- 10.3% and 30-day mortality of 2.8%. Patients with 4 points have LVEF of 38.2% +/- 10.8% and 30-day mortality of 2.7%. Patients with 5-6 (maximum) points have LVEF of 32.0% +/- 9.4% and 30-day mortality of 6.9%. A simple angiographic score predicts LVEF and mortality in patients when leaving the catheterization laboratory after successful primary angioplasty for acute myocardial infarction.


Hematologic Malignancies in Pregnancy: Management Guidelines From an International Consensus Meeting.
The incidence of hematologic malignancies during pregnancy is 0.02%. However, this figure is increasing, as women delay conception until a later age. Systemic symptoms attributed to the development of a hematologic cancer may overlap with physiologic changes of pregnancy. A favorable prognosis is contingent upon early diagnosis and treatment. Therefore, a high index of suspicion is required by health care providers. Although timely, accurate diagnosis followed by appropriate staging is essential and should not be delayed due to pregnancy, management guidelines are lacking due to insufficient evidence-based research. Consequently, treatment is delayed, posing significant risks to maternal and fetal health, and potential pregnancy termination. This report provides guidelines for clinical management of hematologic cancers during the perinatal period, which were developed by a multidisciplinary team including an experienced hematologist/oncologist, a high-risk obstetrics specialist, a neonatologist, and experienced nurses, social workers, and psychologists. These guidelines were developed by experts in the field during the first International Consensus Meeting of Prenatal Hematologic Malignancies, which took place in Leuven, Belgium, on May 23, 2014. This consensus summary equips health care professionals with novel diagnostic and treatment methodologies that aim for optimal treatment of the mother, while protecting fetal and pediatric health.


COVID-19 and MOG-IgG-associated acquired demyelinating polyneuropathy compatible with chronic inflammatory demyelinating polyneuropathy in a previously healthy girl.
Neurological manifestations of COVID-19 in the pediatric population are not as well described as those in the adult population. We describe a case of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG)-associated disorder in a 9-year-old girl, who experienced complete recovery. This rare disorder is a demyelinating disease that often relapses and has the potential to cause severe morbidity. The case highlights the need for early recognition of asymptomatic and subacute presentations of demyelinating disorders and testing for MOG-IgG antibodies, as the management of presumed monophasic demyelinating disorders vs MOG-IgG-positive demyelinating disorder is different.


Larvicide Activity on Aedes aegypti of Essential Oil Nanoemulsion from the Protium heptaphyllum Resin.
The aim of this work was to prepare a nanoemulsion containing the essential oil of Protium heptaphyllum resin and to evaluate the larvicidal activity and the residual larvicidal effect against Aedes aegypti. The essential oil was identified by gas chromatography coupled to a mass spectrometer, and the nanoemulsions were prepared using a low-energy method and characterized by photon correlation spectroscopy. The results indicated the major constituents as p-cimene (27.70%) and α-Pinene (22.31%). Nanoemulsions had kinetic stability and a monomodal distribution in a hydrophilic-lipophilic balance of 14 with particle diameters of 115.56 ± 1.68 nn and zeta potential of -29.63 ± 3.46 mV. The nanoemulsion showed larvicidal action with LC50 = 2.91 µg∙mL-1 and residual larvicidal effect for 72 h after application to A. aegypti larvae. Consequently, the nanobiotechnological product derived from the essential oil of P. heptaphyllum resin could be used against infectious disease vectors.


Acute hemiscrotum due to inguinoscrotal Littre hernia: a case report.
Meckel diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract that is generally asymptomatic and only manifests in a specific way when complications exist. An unusual complication of MD is known as Littre hernia. It comprises less than 1% of all MD. Littre hernia is the protrusion of an MD through a potential abdominal opening. Usual sites of Littre hernia are right inguinal (50% of cases), umbilical hernia (20%), and femoral hernia (20%). We report a case of Littre hernia in a boy who presented with acute scrotal pain and swelling.


Autoradiographic and ultrastructural studies on the human fibro-atheromatous plaque.
Foam cells, either myogenic or macrophagic, are commonly detected in experimental and human fibro-atheromatous plaques. Their role in human atherosclerosis is not yet understood. This paper reports on a preliminary autoradiographic study combined with ultrastructural observations in the human fibro-atheromatous plaque. Most of the autoradiographic silver grains appeared on foam cells and monocyte-like cells, thus suggesting a local proliferation of these cells.


Insulinotrophic and hypolipidemic effects of Ecklonia cava in streptozotocin-induced diabetic mice.
To explore the anti-diabetic activity of Ecklonia cava (EC) in streptozotocin (STZ)-induced diabetic mice. Diabetes was induced by a single intraperitoneal injection of STZ (90 mg/kg). Normal and diabetic mice were treated with 0%, 3%, and 5% EC diet for 4 weeks. Serum glucose and insulin concentrations, serum lipid profile, oral glucose tolerance test, and liver and pancreatic β-cell histopathological observations were performed. In addition, in vitro glucose-induced insulin secretion was determined using pancreatic β-islet cells. EC supplementation significantly and dose-dependently decreased serum glucose concentration, and improved glucose homeostasis in diabetic mice by preventing loss of β-cell mass resulting in increase of insulin secretion. The triglyceride and total cholesterol concentrations in the serum and liver were markedly reduced by EC treatment in STZ-diabetic mice. Moreover, LDL-, and HDL-cholesterol levels were ameliorated in EC supplemented diabetic mice. Liver steatosis induced by STZ was ameliorated by EC supplementation. Furthermore, in vitro insulinotrophic effect of EC extract was observed in pancreatic β-islets. This study demonstrated that EC is a potent and efficacious hypoglycemic and hypolipidemic agent, and prevents the loss of β-cell mass resulting in increase of insulin secretary capacity.


Cortical distribution of EEG activity for component processes during mental rotation.
Alpha power (8-12 Hz) was monitored over the frontal, temporal, parietal and occipital lobes of the left and right cerebral hemispheres while participants mentally rotated three-dimensional shapes to match a specified target. By comparing the activational patterns generated during three experimental conditions, each designed to systematically isolate the involvement of the various subcomponents comprising this mental rotation task, it was suggested that the right frontal lobe mediates encoding and comparison/decision processes, while the left parietal and the left temporal region appear most involved in the generation of images and their mental rotation. A preliminary model describing the cooperative interaction of these cortical regions during mental rotation tasks is proposed.


Interrenal stress responsiveness of marbled sole, Pleuronectes yokohamae, inhabiting Tokyo Bay.
The interrenal stress responsiveness of marbled sole (Pleuronectes yokohamae) captured in the interior (Tokyo) and at the mouth (the Uraga Strait; Uraga) of Tokyo Bay, in the coastal region of Onjuku (the eastern coastal region of Chiba prefecture; Pacific) and in Ishinomaki Bay (Ishinomaki) in Japan was investigated. That is, the effects of air-exposure on plasma cortisol and glucose levels in the fish from the four different regions, and the effect of in vitro ACTH treatment on cortisol release from the head kidney tissue of the fish held under resting conditions were examined. In this study, it was found that (i) there were no significant differences in plasma cortisol and glucose levels among the fish from the four different regions under resting conditions, (ii) each air-exposed fish increased plasma cortisol and glucose levels, (iii) the cortisol response in marbled sole inhabiting Tokyo Bay, in particular the interior, was lower, delayed and prolonged, and (iv) cortisol release from the head kidney to in vitro ACTH treatment was lower in the fish from Tokyo compared with the fish from the reference (not so polluted) sites, Pacific and Ishinomaki. These results suggest that marbled sole inhabiting Tokyo Bay, in particular the interior, have been altered in their responsiveness of cortisol-producing interrenal cells to the stressor in the hypothalamus-pituitary-interrenal (HPI) axis.


People's perceptions and experience of managing life after recurrent pancreatitis: a qualitative study in eastern China.
There is a high rate of recurrent hypertriglyceridemic acute pancreatitis (HTG-RAP) and risk of developing into chronic pancreatitis among recurrent hypertriglyceridemic acute pancreatitis. The key to avoiding recurrence is home-based self-management. However, self-management has proven to be difficult. Exploring experiences and perceptions of home-based self-management among patients with HTG-RAP could inform intervention development and policy making in primary care. To explore experiences and perceptions of home-based self-management among patients with HTG-RAP. This is primarily a qualitative study involving patients from eastern China. The study was designed using semi-structured interviews combined with open interviews among individuals and focus groups. Interviews with patients (n = 25) and relatives (n = 2) were conducted from October to December, 2021. Data were analyzed using the thematic analysis approach. Five themes were identified: (1) pity, (2) sense of uncertainty, (3) contradiction, (4) the way to cope, and (5) benefits. The themes constituted a continuous process where a final coping strategy was confirmed. Patients expressed sorrow, struggle, pity, adaptation, and benefits. The disease still bothered them without attack, both mentally and physically. These key points deserve considerable attention to improve the quality of life of patients and lifestyle modification. Patients with pancreatitis were more likely to manage the disease but under a tough process, and during the struggle, they experienced a continuous and contradictory period. Ultimately, the final condition was reached.


The diagnosis and therapy of medullary thyroid carcinoma in childhood.
The influence of selective calcitonin blood level measurements and the radical surgical approach in the treatment of C-cell carcinoma of the thyroid is demonstrated using the case of an 11-year-old girl.


Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates.
N-Alkenyl ureas and N-alkenyl carbamates, like other N-acyl enamines, are typically nucleophilic at their β-carbon. However, by incorporating an α-aryl substituent, we show that they will also undergo attack at the β-carbon by organolithium nucleophiles, leading to the products of carbolithiation. The carbolithiation of E and Z N-alkenyl ureas is diastereospecific, and N-tert-butoxycarbonyl N-alkenyl carbamates give carbolithiation products that may be deprotected in situ to provide a new connective route to hindered amines.


Application of capillary electrophoresis with pH-mediated sample stacking to analysis of coumarin metabolites in microsomal incubations.
A sensitive method for the analysis of metabolites of coumarin by capillary electrophoresis (CE), incorporating pH-mediated sample stacking, was developed. The analytes were detected in phosphate buffer (pH 7.5; 25 mM), the matrix of the microsomal incubations. Detection was by direct UV absorbance. The three metabolites studied were 7-hydroxycoumarin (7-OHC), 4-hydroxycoumarin (4-OHC) and 2-hydroxyphenylacetic acid (HPAA), and the limits of detection of the analytes were 0.1, 0.5 and 0.3 microM, respectively. The developed method was then applied to microsomal incubations of coumarin. Male Cynomologus monkey microsomes were used in the study and 7-OHC was detected in the incubation mixture.


Translational Diagnostics: An In-House Pipeline to Validate Genetic Variants in Children with Undiagnosed and Rare Diseases.
Diagnosis is essential for the management and treatment of patients with rare diseases. In a group of patients, the genetic study identifies variants of uncertain significance or inconsistent with the phenotype; therefore, it is urgent to develop novel strategies to reach the definitive diagnosis. Herein, we develop the in-house Translational Diagnostics Program (TDP) to validate genetic variants as part of the diagnostic process with the close collaboration of physicians, clinical scientists, and research scientists. The first 7 of 33 consecutive patients for whom exome-based tests were not diagnostic were investigated. The TDP pipeline includes four steps: (i) phenotype assessment, (ii) literature review and prediction of in silico pathogenicity, (iii) experimental functional studies, and (iv) diagnostic decision-making. Re-evaluation of the phenotype and re-analysis of the exome allowed the diagnosis in one patient. In the remaining patients, the studies included either cDNA cloning or PCR-amplified genomic DNA, or the use of patients' fibroblasts. A comparative computational analysis of confocal microscopy images and studies related to the protein function was performed. In five of these six patients, evidence of pathogenicity of the genetic variant was found, which was validated by physicians. The current research demonstrates the feasibility of the TDP to support and resolve intramural medical problems when the clinical significance of the patient variant is unknown or inconsistent with the phenotype.


Plant tissue-based chemiluminescence flow biosensor for determination of unbound dopamine in rabbit blood with on-line microdialysis sampling.
A novel plant tissue-based chemiluminescence (CL) biosensor for dopamine combined with flow injection analysis is presented in this paper. The potato roots act as molecular recognition elements. Dopamine is oxidized by oxygen under the catalysis of polyphenol oxidase in the tissue column to produce hydrogen peroxide, which can react with luminol in the presence of peroxidase of potato tissue to generate CL signal. The CL emission intensity was linear with dopamine concentration in the range of 1x10(-5)-1x10(-7) g/ml and the detection limit was 5.3x10(-8) g/ml (3sigma) with a relative standard deviation of 1.7%. Combined with microdialysis sampling, the biosensor was applied to monitor the variation of dopamine level in the blood of rabbit after the administration of dopamine to demonstrate the favorable resolution and reliability of the system for in vivo on-line monitoring.


Spirometry for patients prescribed topical beta-blockers.
To evaluate the effects of four glaucoma medications on the cardio-respiratory system. All newly diagnosed glaucoma (primary open-angle glaucoma--POAG--or normal tension glaucoma) patients were recruited into a 12-month prospective audit. The study has resulted in glaucoma patients having a spirometry lung function test before being prescribed beta-blocker eye drops. The results of this study demonstrate a high level of both systemic and ocular side-effects caused by these topical glaucoma medications. This study confirms the findings of previous studies, which have shown topical beta-blockers to be harmful to older people with glaucoma and 'hidden' reversible airways disease. It also shows the consequences of using topical beta-blockers on patients who have previously undiagnosed respiratory and cardiac disease.


The effect of endotoxin and turpentine administration on intestinal permeability in the rat.
Intestinal permeability in 4-week-old rats has been assessed by the dual sugar (lactulose/mannitol) permeability test before and for two days after induction of systemic inflammation by various endotoxins and turpentine. Evidence of an inflammatory response to these agents was provided by marked reductions in food consumption and growth rate, hypoalbuminaemia, and a large increase in the plasma concentration of the acute-phase protein alpha-2-macroglobin. Abnormal values for intestinal permeability occurred only in animals which had been injected with E. coli 0111:B4 endotoxin. Neither turpentine nor the other endotoxins produced any detectable effect. Within 2-7h of the first exposure to a low dose, (3mg/kg) of either phenol or trichloroacetic extracts of E. coli 0111:B4 endotoxin, the lactulose:mannitol (L M ) ratio was elevated by 32% and 50% respectively (p < 0.05), but the rise was not sustained despite continued twice-daily injections of endotoxin. Administration of a higher dose, (10 mg/kg twice daily, phenol extract) resulted in diarrhoea, and a greater more persistent increase in the L M ratio; 115% (p < 0.05) 2-7h after the first injection, and 49% above control values, (p < 0.01) 24h later. The increase in L M ratio appeared to be due to a decrease in mannitol excretion. Total urinary lactulose also tended to fall, especially in rats given the high dose of endotoxin. It is concluded that a systemic inflammatory response does not necessarily lead to a change in intestinal permeability as measured by the dual sugar permeability test. The transient permeability changes observed following E. coli 0111:B4 administration may be a specific reaction to this material rather than to a more general systemic stimulus.


Cloning, molecular characterization and heterologous expression of a glutathione S-transferase gene in rice.
OsGSTL2 is one of three tandem-arranged glutathione S-transferase, lambda class genes in chromosome 3 of rice (Oryza sativa L.). It includes 9 introns and 10 exons, and encodes a protein of 244 amino acid residues with a calculated molecular mass of 27.37 kDa. The predicted three-dimensional structure of OsGSTL2 showed a typical glutathione S-transferase fold. Using semi-quantitative RT-PCR analysis, OsGSTL2 transcript was detected in the roots and leaves of seedling stage and tillering stage, and the roots, leaves and panicles of heading stage from rice plants, and the expression level of OsGSTL2 mRNA in rice roots show significant change under chlorsulfuron stress. The OsGSTL2 gene was cloned into pYTV vector and was transformed into yeast strain PEP4. Western blot analysis showed the exogenous OsGSTL2 was expressed in transformed yeast. GST activity of crude extracts of yeast showed the OsGSTL2 transgenic yeast had higher levels of GST activities than control yeasts. These findings suggested that the OsGSTL2 is a glutathione S-transferase and has potential use in detoxification.


Above-ground tree carbon storage in response to nitrogen deposition in the U.S. is heterogeneous and may have weakened.
Changes in nitrogen (N) availability affect the ability for forest ecosystems to store carbon (C). Here we extend an analysis of the growth and survival of 94 tree species and 1.2 million trees, to estimate the incremental effects of N deposition on changes in aboveground C (dC/dN) across the contiguous U.S. (CONUS). We find that although the average effect of N deposition on aboveground C is positive for the CONUS (dC/dN=+9 kg C per kg N), there is wide variation among species and regions. Furthermore, in the Northeastern U.S. where we may compare responses from 2000-2016 with those from the 1980s-90s, we find the recent estimate of dC/dN is weaker than from the 1980s-90s due to species-level changes in responses to N deposition. This suggests that the U.S. forest C-sink varies widely across forests and may be weakening overall, possibly necessitating more aggressive climate policies than originally thought.


The role of visfatin (PBEF/Nampt) in pregnancy complications.
Visfatin (PBEF/Nampt) is an adipocytokine that exerts pleiotropic effects within the human body, particularly affecting its metabolism and immunity. Visfatin was originally identified as being secreted by peripheral blood lymphocytes acting as a pre-B-cell colony-enhancing factor (PBEF). However, it was subsequently reported to be expressed in almost every tissue of the human body, with visceral fat deposits being the main source of visfatin. In addition to its secreted form, visfatin may also be found intracellularly where it functions as a nicotinamide phosphoribosyltransferase (Nampt). Visfatin maternal plasma concentrations increase during pregnancy, suggesting its important role in this complicated process. Alterations in visfatin level also take place in patients during pregnancy complications. This review focuses on the ones that most commonly occur in connection with visfatin: preterm labor, pre-eclampsia and gestational diabetes mellitus. The review aims to provide a better understanding of the role of visfatin during pregnancy and the causes of its alteration in maternal plasma, highlighting the potential use of visfatin as a diagnostic marker of pregnancy complications in the future.


A new method for lattice reduction using directional and hyperplanar shearing.
A geometric method of lattice reduction based on cycles of directional and hyperplanar shears is presented. The deviation from cubicity at each step of the reduction is evaluated by a parameter called `basis rhombicity' which is the sum of the absolute values of the elements of the metric tensor associated with the basis. The levels of reduction are quite similar to those obtained with the Lenstra-Lenstra-Lovász (LLL) algorithm, at least up to the moderate dimensions that have been tested (lower than 20). The method can be used to reduce unit cells attached to given hyperplanes.


Decreased endosteal formation during cortical bone modelling in SAM-P/6 mice with a low peak bone mass.
Inter-strain differences in bone mass and density during growth were followed in three strains of mice: SAM-P/2, SAM-R/1 and SAM-P/6 (a murine model of senile osteoporosis, Matsushita et al., Am J Pathol 1986;125:276-283). Photometrically, the inter-strain disparities first appeared in mice at about age 28 days and increased until age 60 days. During this period, tetracycline labelling revealed significant strain differences regarding rate of the appositional formation at the endosteal surface but not at the periosteal surface. The order coincided with results of the photometrical assay, that is, highest in SAM-P/2, followed by SAM-R/1 and SAM-P/6, respectively. Therefore, strain differences, especially the osteopenic state of SAM-P/6, occur, at least in part, by disparities in endosteal formation rates during cortical bone modelling.


Experimental evaluation of the deadtime phenomenon for GM detector: deadtime dependence on operating voltages.
A detailed analysis of Geiger Mueller counter deadtime dependence on operating voltage is presented in the manuscript using four pairs of radiation sources. Based on two-source method, detector deadtime is calculated for a wide range of operating voltages which revealed a peculiar relationship between the operating voltage and the detector deadtime. In the low voltage range, a distinct drop in deadtime was observed where deadtime reached a value as low as a few microseconds (22 µs for 204Tl, 26 µs for 137Cs, 9 µs for 22Na). This sharp drop in the deadtime is possibly due to reduced recombination with increasing voltage. After the lowest point, the deadtime generally increased rapidly to reach a maximum (292 µs for 204Tl, 277 µs for 137Cs, 258 µs for 22Na). This rapid increase in the deadtime is mainly due to the on-set of charge multiplication. After the maximum deadtime values, there was an exponential decrease in the deadtime reaching an asymptotic low where the manufacturer recommended voltage for operation falls. This pattern of deadtime voltage dependence was repeated for all sources tested with the exception of 54Mn. Low count rates leading to a negative deadtime suggested poor statistical nature of the data collected for 54Mn and the data while being presented here is not used for any inference.


Keratin 17: a critical player in the pathogenesis of psoriasis.
Keratin 17 (K17) is an intermediate filament protein present in the basal cells of complex epithelia, such as nails, hair follicles, sebaceous glands, and eccrine sweat glands. Studies have shown that it is expressed aberrantly in the suprabasal keratinocytes of psoriatic lesions, compared to in normal epidermis. K17 is also closely associated with the immune system and plays an important role in the pathogenesis of psoriasis. In this review, we present our experimental findings concerning the role of K17 in psoriasis, and compare them to results published in the literature. Our results show that cytokines related to Th17 and IL-22-producing (where Th17 is T helper cells, type 17 and IL is interleukin) CD4(+) T cells, including IL-17A and IL-22, upregulate the expression of K17 in keratinocytes. In addition, K17 stimulates autoreactive T cells and promotes the production of psoriasis-associated cytokines. Our findings lend support to the hypothesis that a K17/T-cell/cytokine autoimmune loop is involved in the pathogenesis of psoriasis. We therefore review the current understanding of the K17 immunoregulation, including its expression and direct/indirect effects on immune responses. Pertinent strategies for the treatment of psoriasis are also discussed.


Long-term calorie restriction decreases metabolic cost of movement and prevents decrease of physical activity during aging in rhesus monkeys.
Short-term (<1 year) calorie restriction (CR) has been reported to decrease physical activity and metabolic rate in humans and non-human primate models; however, studies examining the very long-term (>10 year) effect of CR on these parameters are lacking. The objective of this study was to examine metabolic and behavioral adaptations to long-term CR longitudinally in rhesus macaques. Eighteen (10 male, 8 female) control (C) and 24 (14 male, 10 female) age matched CR rhesus monkeys between 19.6 and 31.9 years old were examined after 13 and 18 years of moderate adult-onset CR. Energy expenditure (EE) was examined by doubly labeled water (DLW; TEE) and respiratory chamber (24 h EE). Physical activity was assessed both by metabolic equivalent (MET) in a respiratory chamber and by an accelerometer. Metabolic cost of movements during 24 h was also calculated. Age and fat-free mass were included as covariates. Adjusted total and 24 h EE were not different between C and CR. Sleeping metabolic rate was significantly lower, and physical activity level was higher in CR than in C independent from the CR-induced changes in body composition. The duration of physical activity above 1.6 METs was significantly higher in CR than in C, and CR had significantly higher accelerometer activity counts than C. Metabolic cost of movements during 24 h was significantly lower in CR than in C. The accelerometer activity counts were significantly decreased after seven years in C animals, but not in CR animals. The results suggest that long-term CR decreases basal metabolic rate, but maintains higher physical activity with lower metabolic cost of movements compared with C.


A depsipeptide fungal metabolite inhibitor of cholesteryl ester transfer protein.
The organic extract of the fermentation broth of a fungus was found to contain a depsipeptide SCH 58149 (1), containing three amino acids and a beta-hydroxy acid, by spectroscopic studies. The amino acids were phenyl alanine, alanine and leucine and the beta-hydroxy acid is 3-hydroxy-4-methyl octanoic acid. SCH 58149 exhibited weak activity against cholesterol ester transfer protein (CETP) with an IC50 of 50 microM.


Binge drinking is associated with higher cortisol and lower hippocampal and prefrontal gray matter volume: Prospective association with future alcohol intake.
Cortisol is a significant driver of the biological stress response that is potently activated by acute alcohol intake and increased with binge drinking. Binge drinking is associated with negative social and health consequences and risk of developing alcohol use disorder (AUD). Both cortisol levels and AUD are also associated with changes in hippocampal and prefrontal regions. However, no previous research has assessed structural gray matter volume (GMV) and cortisol concurrently to examine BD effects on hippocampal and prefrontal GMV and cortisol, and their prospective relationship to future alcohol intake. Individuals who reported binge drinking (BD: N = 55) and demographically matched non-binge moderate drinkers (MD: N = 58) were enrolled and scanned using high-resolution structural MRI. Whole brain voxel-based morphometry was used to quantify regional GMV. In a second phase, 65% of the sample volunteered to participate in prospective daily assessment of alcohol intake for 30 days post-scanning. Relative to MD, BD showed significantly higher cortisol and smaller GMV in regions including hippocampus, dorsal lateral prefrontal cortex (dlPFC), prefrontal and supplementary motor, primary sensory and posterior parietal cortex (FWE, p < 0.05). GMV in bilateral dlPFC and motor cortices were negatively associated with cortisol levels, and smaller GMV in multiple PFC regions was associated with more subsequent drinking days in BD. These findings indicate neuroendocrine and structural dysregulation associated with BD relative to MD. Notably, BD-associated lower GMV regions were those involved in stress, memory and cognitive control, with lower GMV in cognitive control and motor regions also predicting higher levels of future alcohol intake in BD.


Comprehension aids for on-line reading of expository text.
A chapter of expository text was presented on a CRT with optional "windowing" of definitions of selected words varying in relevance to each screen's main ideas. A test treatment was interposed to influence reading strategies. Dependent variables included text reading time, frequency of definition "calls," definition reading rates, and scores on a final comprehension test. Results indicate that a technical chapter can be read from a CRT with appreciable content retention. Subjects accessed 80% of available definitions, but those able to "call" content-relevant definitions increased their frequency of definition "calls." Definition reading rate diminished; comprehension and processing time increased only for subjects accessing the theoretically relevant definitions. The results suggest how the use of definitions enhances the comprehension of on-line training manuals, texts, and help screens. "Callable" definitions need not include all low-frequency technical concepts but only those relevant to reductive main ideas.


Palladium nanoparticle decorated carbon ionic liquid electrode for highly efficient electrocatalytic oxidation and determination of hydrazine.
In this work arrays of palladium nanoparticles were synthesized on carbon ionic liquid electrode (CILE) (Pd/CILE), and the electrocatalytic oxidation of hydrazine was investigated using this electrode. Electrochemical oxidation of hydrazine in phosphate buffer (pH 7) was performed using cyclic voltammetry and square wave voltammetric techniques (SWV). Using the proposed electrode, a highly reproducible and well-defined peak was obtained for hydrazine at a very low potential of -0.02V versus Ag/AgCl. A linear dynamic range of 5-800 microM with an experimental detection limit of 0.82 microM was obtained. These results show that the proposed electrode displays better electrocatalytic activity compared to the previously reported palladium modified electrodes towards oxidation of hydrazine.


Patterns of correlations and locomotor specialization in anuran limbs: association with phylogeny and ecology.
As anuran saltatory locomotion has specific functional requirements achieved through certain intra- and inter-limb proportions, we analyzed pattern and degree of morphological integration in limbs of ten anuran species to reveal the relationship of shared developmental programs of serially homologous structures and locomotor specialization. Our main objectives were (1) to examine if morphological and functional differences in forelimb and hindlimb were associated with reduced covariation between limbs, (2) and to reveal patterns of correlation between species and the roles played by evolutionary history (phylogeny) and ecology (lifestyle and habitat use). Species with different locomotor behaviours (walking, jumping, hopping, running, climbing, swimming and burrowing) were used. Partial correlations showed that species shared similar patterns of functionally based morphological integration, with increased correlations in elements within limbs and reduced correlations between limbs. This was mainly based on strong correlations between proximal elements, humerus-radioulna and femur-tibiofibula. To test the influence of phylogenetic relationships and ecological demands we used different matrices (correlation similarity matrix, ecological similarity matrix, matrices of phylogenetic distance and morphological distance). The changes in correlation patterns are shown to be dissociated from phylogeny. On the other hand, they are to some extent shaped by habitat use and locomotion, as the species with similar locomotor behaviour also tend to have stronger similarity in integration patterns. The results from this study provide insight into the processes underlying the evolutionary change of anuran limbs, highlighting function as the main factor that shaped morphological integration of the examined species.


Morphological and molecular characterization of the human breast epithelial cell line M13SV1 and its tumorigenic derivatives M13SV1-R2-2 and M13SV1-R2-N1.
The estrogen receptor-positive M13SV1 breast epithelial cell line was proposed to be a suitable in vitro model for breast cancer research since two derivatives with graduated tumorigenicity-M13SV1-R2-2 and M13SV1-R2-N1-are available for this cell line. In the present study, these three cell lines were comparatively examined for their morphological and their biochemical properties on the molecular level. A transcriptomic approach (gene array analysis) was chosen to unravel differences in gene expression among the three cell lines. Network analysis was conducted to identify deregulated signaling pathways. Cellular viability was determined by impedance measurements as well as by neutral red uptake assay. Apoptosis was determined by using a caspase assay. For morphological characterization, cells were grown in three-dimensional cell culture, and cellular differentiation and spheroid formation was followed by immunofluorescence staining by using confocal laser scanning microscopy. The gene array results indicated that there were only marginal differences in gene expression among the three cell lines. Network analysis predicted the R2-N1 derivative (1) to display enhanced apoptosis and (2) to have a higher migration capability compared to its parent cell line M13SV1. Enhanced apoptosis was confirmed by elevated caspase activity, and increased migration was observed in 3D culture when cells migrated out of the globular spheroids. In 3D cell culture, all three cell lines similarly formed spheroids within three days, but there was no acini formation until day 21 which is indicated by a growth arrest around day 15, cellular polarization, and the formation of hollow lumen inside the spheroids. These characteristics, however, are crucial to study, e.g., the differentiation process of breast epithelial cells in vitro. Due to the molecular and morphological features, the M13SV1 cell line and its tumorigenic derivatives seem to be less suitable as in vitro models than other cell lines such as the MCF-10A cell line which displays proper acini formation in 3D culture.


General aviation accidents related to exceedance of airplane weight/center of gravity limits.
Obesity, affects a third of the US population and its corollary occupant weight adversely impacts safe flight operations. Increased aircraft weight results in longer takeoff/landing distances, degraded climb gradients and airframe failure may occur in turbulence. In this study, the rate, temporal changes, and lethality of accidents in piston-powered, general aviation aircraft related to exceeding the maximum aircraft weight/center of gravity (CG) limits were determined. Nation-wide person body mass were from the National Health and Nutrition Examination Survey. The NTSB database was used to identify accidents related to operation of aircraft outside of their weight/CG envelope. Statistical analyses employed T-tests, proportion tests and a Poisson distribution. While the average body mass climbed steadily (p<0.001) between 1999 and 2014 the rate of accidents related to exceedance of the weight/CG limits did not change (p=0.072). However, 57% were fatal, higher (p<0.001) than the 21% for mishaps attributed to other causes/factors. The majority (77%) of accidents were due to an overloaded aircraft operating within its CG limits. As to the phase of flight, accidents during takeoff and those occurring enroute carried the lowest (50%) and highest (85%) proportion of fatal accidents respectively. While the rate of general aviation accidents related to operating an aircraft outside of its weight/CG envelope has not increased over the past 15 years, these types of accidents carry a high risk of fatality. Airmen should be educated as to such risks and to dispel the notion held by some that flights may be safely conducted with an overloaded aircraft within its CG limits.


Updated Functional Roles of NAMPT in Carcinogenesis and Therapeutic Niches.
Nicotinamide phosphoribosyltransferase (NAMPT) is notable for its regulatory roles in tumor development and progression. Emerging evidence regarding NAMPT somatic mutations in cancer patients, NAMPT expressional signatures in normal tissues and cancers, and the prognostic significance of NAMPT in many cancer types has attracted attention, and NAMPT is considered a potential biomarker of cancer. Recent discoveries have demonstrated the indirect association and direct biological functions of NAMPT in modulating cancer metastasis, proliferation, angiogenesis, cancer stemness, and chemoresistance to anticancer drugs. These findings warrant further investigation of the underlying mechanisms to provide knowledge for developing novel cancer therapeutics. In this review article, we explore recent research developments involving the oncogenic activities of NAMPT by summarizing current knowledge regarding NAMPT somatic mutations, clinical trials, transcriptome data, and clinical information and discoveries related to the NAMPT-induced signaling pathway in modulating hallmarks of cancer. Furthermore, the comprehensive representation of NAMPT RNA expression in a pancancer panel as well as in specific normal cell types at single-cell level are demonstrated. The results suggest potential sites and cell types that could facilitate NAMPT-related tumorigenesis. With this review, we aim to shed light on the regulatory roles of NAMPT in tumor development and progression, and provide information to guide future research directions in this field.


Fortifying North Carolina's Workforce for Health to Meet Current and Future Challenges.
Two new North Carolina Institute of Medicine task force reports make recommendations for bolstering the state's public health workforce through new funding and partnerships in an effort to prepare for future health crises, achieve health equity, and support the growing economy.


The use of hormonal contraceptive agents and mood disorders in women.
Mood disorders are a major cause of disability in developed countries, and contraceptive agents among the most widely used medications. The relationship between contraceptive agents and mood is unclear. The aim of this study was therefore to investigate the association between current contraception use and mood disorders in a random population-based sample of women. This study examined epidemiological data obtained from 498 women aged 20-50year participating in the Geelong Osteoporosis Study (GOS). Mood disorders were diagnosed using a clinical interview (SCID-I/NP) and information on medication use and other lifestyle factors were documented. After adjusting for age and socioeconomic status (SES), women taking progestin-only contraceptive agents had an increased likelihood of a current mood disorder (OR 3.0 95%CI: 1.1-7.8, p=0.03). In contrast, women taking combined contraceptive agents had a decreased likelihood of a current mood disorder, adjusting this for age and SES (OR 0.3 95%CI: 0.1, 0.9 p=0.03). These findings were not explained by weight, physical activity level, past depression, number of medical conditions or cigarette smoking. This study is cross-sectional, which precludes any determination regarding the direction of the relationships. These data suggest a protective effect of the combined contraceptive pill, and a deleterious effect of progestin only agents in regards to mood disorders.


A cosmopolitan fungal pathogen of dicots adopts an endophytic lifestyle on cereal crops and protects them from major fungal diseases.
Fungal pathogens are seriously threatening food security and natural ecosystems; efficient and environmentally friendly control methods are essential to help safeguard such resources for increasing human populations on a global scale. Here, we find that Sclerotinia sclerotiorum, a widespread pathogen of dicotyledons, can grow endophytically in wheat, rice, barley, maize, and oat, providing protection against Fusarium head blight, stripe rust, and rice blast. Protection is also provided by disabled S. sclerotiorum strains harboring a hypovirulence virus. The disabled strain DT-8 promoted wheat yields by 4-18% in the field and consistently reduced Fusarium disease by 40-60% across multiple field trials. We term the host-dependent trophism of S. sclerotiorum, destructively pathogenic or mutualistically endophytic, as schizotrophism. As a biotroph, S. sclerotiorum modified the expression of wheat genes involved in disease resistance and photosynthesis and increased the level of IAA. Our study shows that a broad-spectrum pathogen of one group of plants may be employed as a biocontrol agent in a different group of plants where they can be utilized as beneficial microorganisms while avoiding the risk of in-field release of pathogens. Our study also raises provocative questions about the potential role of schizotrophic endophytes in natural ecosystems.


The role of tumor microenvironment on cancer stem cell fate in solid tumors.
In the last few decades, the role of cancer stem cells in initiating tumors, metastasis, invasion, and resistance to therapies has been recognized as a potential target for tumor therapy. Understanding the mechanisms by which CSCs contribute to cancer progression can help to provide novel therapeutic approaches against solid tumors. In this line, the effects of mechanical forces on CSCs such as epithelial-mesenchymal transition, cellular plasticity, etc., the metabolism pathways of CSCs, players of the tumor microenvironment, and their influence on the regulating of CSCs can lead to cancer progression. This review focused on some of these mechanisms of CSCs, paving the way for a better understanding of their regulatory mechanisms and developing platforms for targeted therapies. While progress has been made in research, more studies will be required in the future to explore more aspects of how CSCs contribute to cancer progression. Video Abstract.


Preparation of Pickering emulsions based on soy protein isolate-tannic acid for protecting aroma compounds and their application in beverages.
In the present study, soy protein isolate was modified by tannic acid and used as a stabilizer for Pickering emulsions loaded with aroma compounds. The nanoparticles with tannic acid concentrations above 2 mg/mL were found to show great antioxidant properties. Essential oils, aroma compounds, and flavours can be stabilized by nanoparticles to form Pickering emulsions with a droplet diameter of<600 nm. E-nose analysis shows that nanoparticles provide outstanding protective functionalities for the 6 essential oils at 37 °C for 30 days. Further study of limonene and citral indicates that the nanoparticles afford nearly 60% protection against loss with a tannic acid concentration of 10 mg/mL. Furthermore, the nanoparticles also maintain the aroma of the beverages and lengthen the five-day shelf life. Overall, this research provides a sustainable, low-cost, and quickly prepared stabilizer for aroma compounds in foods.


CD5-negative phenotype of monoclonal B-lymphocytosis of undetermined significance (MLUS).
Monoclonal B lymphocytosis of undetermined significance (MLUS) is a benign condition of clonal lymphocytosis. Because of its clonal small lymphocytes and indolent clinical course, MLUS resembles and may be indistinguishable from an early stage of chronic lymphocytic leukemia (CLL). In this study we characterized the immunophenotype of MLUS. The clonal B lymphocytes from three patients of typical MLUS were shown to be CD5(-) and CD23(-) phenotype. Their immunophenotypic features remained unchanged during the clinical course. The results indicate a distinct immunophenotype of MLUS that can be useful for its diagnosis and differentiation from CLL.


Validity of the GRACE score for 6-month death or reinfarction after presentation with acute myocardial infarction in patients 80 years of age and older.
The Global Registry of Acute Coronary Events (GRACE) risk score provides a prediction of the probability of death and myocardial infarction within 6 months after acute coronary syndrome. Our aim was to detect the validity of the GRACE risk score in predicting 6-month death or reinfarction in Chinese acute myocardial infarction (AMI) inpatients 80 years of age and older between 2003 and 2012. Using the GRACE risk score to predict the combined endpoints of all-cause death or reinfarction within 6 months of AMI, we evaluated its discrimination and calibration by the C-statistic and the Hosmer-Lemeshow test, respectively. In total, 370 patients presenting with ST segment elevation myocardial infarction (STEMI) and non-STEMI were included. The GRACE risk score ranged between 181 and 325; death or reinfarction within 6 months of AMI was 49.2%. The GRACE model showed good discrimination overall (C-statistic 0.708, 95% confidence interval: 0.655-0.760, P<0.001) and in patients with non-STEMI (C-statistic 0.756, 95% confidence interval: 0.690-0.823, P<0.001). However, the discriminatory capacity was lower in patients with STEMI (C-statistic 0.645, P=0.001). The calibration was optimal overall (Hosmer-Lemeshow, P=0.398) and in the subgroups (STEMI, P=0.098; non-STEMI, P=0.822). There was a high correlation (R=0.926) between the predicted and the observed 6-month death or reinfarction after AMI. The GRACE score is accurate for determination of 6-month death or reinfarction in Chinese AMI inpatients 80 years of age and older; however, the discrimination and calibration performs less well in patients with STEMI.


Exploring individual and contextual factors contributing to tobacco cessation intervention implementation.
Previous research suggests that smoking cessation interventions are poorly implemented. This study reports the development and testing of a questionnaire including knowledge, attitude, behavioral, and organizational (KABO) factors affecting the implementation of smoking cessation practices in hospitals by health care providers and organizations. An initial pool of 44 items was developed to assess the individual knowledge, attitudes, and beliefs of health professionals towards smoking cessation practices according to the 5 A's intervention model, as well as organizational barriers and opportunities for its implementation. Items were measured in a scale from 0="Not at all/Never" to 10 = "Completely/Always". Data were collected from health workers (n = 702) in Catalonia. The validity of the instrument was measured by: (a) analyzing the items, (b) assessing the internal structure, (c) estimating the internal consistency, and (d) analyzing the relationship between this tool and the 5 A's intervention model. Seven domains were extracted: individual skills, positive organizational support, attitudes and beliefs, individual commitment, organizational resources, beliefs about patient desire/readiness to quit, and organizational endorsement. These domains explained 69.7% of the variance, and allowed for the development of a refined 26-item version of the questionnaire. Both the seven domains and the total scale showed adequate internal consistency. Psychometric testing indicates that the KABO questionnaire is a reliable and valid instrument for assessing the main barriers and facilitators to smoking cessation intervention implementation. Individual factors better explained the implementation of smoking cessation interventions in hospitals, and the seven identified domains can be used for further investigations into how the implementation of evidence-based practices impacts smoking cessation performance.


Synthesis of Cinnolin-3(2H)-one Derivatives from Rh-Catalyzed Reaction of Azobenzenes with Diazotized Meldrum's Acid.
A synthetic method of a wide range of cinnolin-3(2H)-one derivatives is developed from the reaction of symmetrical as well as unsymmetrical azobenzenes with diazotized Meldrum's acid via Rh-catalyzed C-H alkylation followed by cyclization.


Evaluation of the Norberg angle threshold: a comparison of Norberg angle and distraction index as measures of coxofemoral degenerative joint disease susceptibility in seven breeds of dogs.
To evaluate the thresholds of 2 radiographic methods used to determine coxofemoral joint laxity in 7 breeds of dogs. Three hundred and fifty clinically normal dogs. Retrospective study. Hip radiographs from 7 breeds of dogs were randomly selected from a database. None of the dogs had radiographic evidence of degenerative joint disease (DJD). Distraction index (DI) and Norberg angle (NA) were measured on these radiographs and compared with DI and NA thresholds for diagnosing DJD susceptibility derived from the literature and from evaluated Borzois. Dogs with a NA<105 degrees and a DI of < or =0.32 were considered false-positives and dogs with a NA> or =105 degrees and a DI of >0.32 were considered false-negatives. Mean age of all dogs was 22.9 months. Mean NA for all dogs was 99.37 degrees, and mean DI for all dogs was 0.44. Borzoi mean DI of was significantly less than the mean DI of the other 6 breeds. The highest (most hip laxity) Borzoi DI was 0.32, and the lowest (most hip laxity) Borzoi NA was 99 degrees. False-positive and false-negative diagnoses were identified in 6 of the 7 breeds. Using the NA threshold of 105 degrees (literature established threshold of susceptibility to DJD) resulted in a high percentage of false-negative and false-positive diagnoses. Breeds like the Labrador Retriever and Rottweiler would have large numbers of hip dysplasia susceptible dogs remain in the breeding population based on this NA threshold. False-positive diagnoses were common in breeds like the Australian Shepherd, Borzoi, and German Shepherd effectively eliminating hip dysplasia nonsusceptible dogs from the breeding population. The NA was not an accurate predictor of DJD susceptibility in these 7 breeds of dogs when using a NA threshold of 105 degrees.


Sex and sex-related differences in gamete development progression impinge on biomarker responsiveness in sentinel mussels.
In marine pollution monitoring, the biomarkers recorded in sentinel organisms are influenced by natural confounding factors that may jeopardise their interpretation. Among these confounding factors, little is known about the influence of sex along the annual reproductive cycle. The present investigation aims at contributing to understand how sex and sex-related differences in gamete development progression impinge on biomarker baseline values and on biomarker responsiveness to pollution in sentinel mussels. Mussels (Mytilus galloprovincialis) were collected from a relatively clean locality and from a chronically polluted site in the Basque Coast (Bay of Biscay) in January, April, August and November. Sex and gametogenesis stages were determined for each mussel. Tissue concentration of metals and PAHs was analysed. A battery of biomarkers was investigated: cytochrome c oxidase, pyruvate kinase and phosphoenolpyruvate carboxykinase enzyme activities; levels of protein carbonyls, malondialdehyde and 4-hydroxy-2-nonenal; lysosomal enlargement and membrane stability; intracellular neutral lipid accumulation; cell type composition and thinning of the digestive gland epithelium; and survival-in-air. Sex- and reproductive stage-related differences were found in bioaccumulation and in the values and responsiveness of most of the biomarkers. However, the patterns of sex-related differences were not consistent across all biomarkers. The differences in the biomarker responses between females and males also depended on the season, reflecting the progression of the gametogenesis cycle. Thus, selecting mussels of one specific sex does not seem to be a crucial requisite to carry out biomarker-based monitoring; yet, it is highly recommended to identify sex condition and gamete developmental stage of each mussel to test for the potentially confounding effects of sex, reproductive status and sex-related variability along the reproductive cycle.


Freeze fracture studies on the annelid septate junction.
Freeze-fractured preparations of septate junctions between epidermal cells of annelids (Lumbricus terrestris and Tubifex spec.) have been investigated. In Lumbricus the protoplasmic face (PF) of the plasma membrane is characterized by variously arranged rows of particles. Apically the rows take an undulating course and often are separated by wide distances. In the basal part of the junction the rows run closely together and more or less in parallel. The diameter of the particles measures 80--120 A, the distance between two particles (centre to centre) is 150--250 A. Additionally striking rows of large particles (long diameter 150--200 A). Are to be observed mainly near the basal part of the junction. In Tubifex both faces of the plasma membrane could be studied in detail. The protoplasmic face (PF) contains rows of distinct individual particles (mean diameter 100--150 A, centre to centre distance approx. 250 A) whereas the particles of the extracellular face (EF, mean diameter 200-250 A) usually form continuous strands in which the individual particles seem to fuse. The density of arrangement of the strands varies considerably. Additionally ladder-shaped membrane structures have been observed in plasma membranes of this species.


The impact of stent strut porosity on reducing flow in cerebral aneurysms.
Flow diversion techniques are increasingly used to treat cerebral aneurysms. The optimal stent porosity to achieve aneurysm obliteration would allow clinicians to treat aneurysms more effectively. We sought to determine the optimal porosity threshold in an in vitro flow model that would lead to stagnation of flow in an aneurysm. Using a 3-dimensional (3-D) sidewall aneurysm glass model and a 2-dimensional (2-D) cavity model, we measured the total kinetic energy (TKE) in the cavity and aneurysm using digital particle image velocimetry by adjusting for the surface area of a metal mesh across the cavity. Additionally, we assessed how a gap between the mesh and 2-D cavity impacted circulatory patterns within a cavity. In the 3-D aneurysm model, we noted a 90.4% reduction in TKE after placement of a stent. In the 2-D cavity model, we adjusted the porosity between 39.1% and 64.8% and noted a reduction in the TKE by 99.75% and 93.9%, respectively. When there was a gap between the mesh and entry into the cavity, unfavorable circulatory conditions occurred with the development of counterclockwise flow that had increased TKE within the cavity. The current model demonstrates a method to evaluate the optimal porosity threshold to achieve thrombosis of an aneurysm as a primary modality. Moreover, a gap may occur between the stent and the aneurysm that may create unfavorable circulatory conditions by increasing flow into the aneurysm.


Uncertainty principle of genetic information in a living cell.
Formal description of a cell's genetic information should provide the number of DNA molecules in that cell and their complete nucleotide sequences. We pose the formal problem: can the genome sequence forming the genotype of a given living cell be known with absolute certainty so that the cell's behaviour (phenotype) can be correlated to that genetic information? To answer this question, we propose a series of thought experiments. We show that the genome sequence of any actual living cell cannot physically be known with absolute certainty, independently of the method used. There is an associated uncertainty, in terms of base pairs, equal to or greater than micros (where micro is the mutation rate of the cell type and s is the cell's genome size). This finding establishes an "uncertainty principle" in genetics for the first time, and its analogy with the Heisenberg uncertainty principle in physics is discussed. The genetic information that makes living cells work is thus better represented by a probabilistic model rather than as a completely defined object.


A thrombotic event in a HeartMate 3 patient in the setting of secondary polycythemia.
HeartMate 3 left ventricular assist device implantation is an important treatment modality in patients with advanced heart failure. Polycythemia may predispose this population to adverse events. We present a case of a thrombotic event in a HeartMate 3 patient.


A freeze-fracture study of tubular myelin in fetal rabbit lung.
A freeze-fracture replication study was undertaken to clarify the relationship between intracellular lamellar bodies of type II alveolar epithelial cells and intra-alveolar contents in late gestation rabbit fetuses. The interior of the inclusion bodies was composed of multiple stacks and/or whorls of membranes devoid of membrane-associated particles, while the limiting membrane of intracellular lamellar inclusion bodies was studied with membrane-associated particles of 150A diameter. The intra-alveolar contents were comprised of two components; spherical bodies, and tubular elements. Spherical bodies were identical to the internal contents of the lamellar bodies and also were devoid of membrane-associated particles. Tubular elements mostly appeared rectangular on cross-fractured faces, but triangular and hexagonal forms could also be seen. These tubules rested on the surfaces of the spherical bodies and appeared to be formed of the outer lipid monolayer of spherical bodies. The present observations suggest that the tubular element of the alveolar contents is formed through the interaction between the discharged lamellar body content and the alveolar fluid.


Revealing active components, action targets and molecular mechanism of Gandi capsule for treating diabetic nephropathy based on network pharmacology strategy.
Gandi capsule is a traditional Chinese herbal formula used to promote blood circulation and removing blood stasis in clinical. Our previous study has shown that it reduces proteinuria with routine treatment in diabetic nephrophy (DN), but its pharmacological action mechanism is still unknown. To facilitate the identification of components, a component database of Gandi capsule and target database of DN were established by ourselves. The components absorbed in blood circle were identified in rat plasma after oral administration of Gandi capsule by UHPLC-QQQ-MS/MS. The potential targets were screened by using Libdock tolls in Discovery studio 3.0. Then Pathway and Network analyses were used to enrich the screened targets. The possible targets were verified by using a surface plasmon resonance (SPR) test and the molecular mechanism focusing these targets for treating DN was clarified by western blot. Six components in Gandi capsule were identified detected in rat plasma after oral administration by UHPLC-QQQ-MS/MS. After molecular docking analyses in KEGG and Discovery studio, four protein targets including HNF4A, HMGCR, JAK3, and SIRT1, were screened out, and proved as effective binding with baicalin, wogonoside by SPR. And the molecular mechanism was clarified that baicalin and wogonoside inhibit the effect of high glucose (HG)-induced decreased cell viability and podocin expression, and strengthen the activation p-AKT, p-PI3K, and p-AMPK. Baicalin and wogonoside were screened out to be the active compounds in Gandi capsule and can ameliorate HG-induced podocyte damage by influencing the AMPK and PI3K-AKT signaling pathways by binding with HNF4A, HMGCR, JAK3, and SIRT1.


The effect of sensitization of pregnant Lewis rats with encephalitogen on the subsequent susceptibility of their offspring to allergic encephalomyelitis.
In a previous report (Smith & Rumjanek, 1984), it was shown that offspring of female Lewis rats which had been sensitized with encephalitogen during the second, but not the third or first, week of pregnancy, were resistant to the induction of EAE at 10 weeks of age. These observations have been extended to show that transfer of protection, from mothers to offspring, occurs during lactation. It is shown, furthermore, that sensitization leads to decreased incidence of disease in offspring, maternal clinical status simply determining the duration of protection enjoyed by offspring. The possible source of this protection is discussed.


[Clinical and pathological analysis of 10 cases of secondary pneumothorax due to angiosarcoma of the scalp].
Angiosarcoma of the scalp is a very rare disease. Secondary pneumothorax is known as a characteristic complication in this disease due to lung metastasis. In this study, 17 patients of angiosarcoma of the scalp, diagnosed at our hospital between 1996 and 2006, were analyzed. Secondary pneumothorax was observed in 10 of these patients, among which bilateral pneumothorax occurred in 5 relapse of pneumothorax occurred in 6 and pneumothorax with bloody pleural fluid occurred in 7 patients. Characteristic findings on chest CT were multiple thin-wall cavities and ground-glass attenuation around the cavity, located in bilateral subpleural lung fields. It is suggested that the subpleural thin-wall cavities cause pneumothorax. Although pleurosclerosis were performed in 5 patients and one of them had a subsequent partial resection of the lung, pneumothorax reocurred within a short period of time in all patients. The average survival time from the first pneumothorax episode was only 4.1 months. Secondary pneumothorax caused by this disease was intractable, resulting in an unfavorable outcome. It is necessary to develop a proper treatment strategy for secondary pneumothorax to create a favorable prognosis in this disease.


Transected axons of adult hypothalamo-neurohypophysial neurons regenerate along tanycytic processes.
In the intact hypothalamo-neurohypophysial system, oxytocinergic or vasopressinergic neurons project their axons throughout the internal layer of the median eminence towards the blood vessels of the hypophysial neural lobe. When transected at the level of the median eminence, these axons undergo massive sprouting towards the external layer of the organ and the underlying perivascular region containing hypophysial portal vessels. The present study was designed to explore the possible roles of median eminence glial cells in such a reorganization of transected neurohypophysial axons. The relationships between regenerating axons and glial cells were studied by laser scanning confocal microscopy and electron microscopy on vibratome sections immunostained with specific antibodies against neurohypophysial peptides and/or against glial markers. All along the intact median eminence, two main types of glial cells were identified: (1) tanycytes immunoreactive to vimentin and slightly immunoreactive to glial fibrillary acidic protein, and (2) classical astrocytes immunoreactive to glial fibrillary acidic protein but vimentin-negative. In the intact median eminence, neurohypophysial axons were associated with astrocytic processes located in the internal layer. After a lesion of the hypophysial stalk, peptidergic regenerating axonal sprouts were found to project massively towards the external layer and to penetrate the underlying perivascular region in close association with tanycytic-like processes immunoreactive to both vimentin and to glial fibrillary acidic protein. In contrast, regenerating sprouts were absent from those regions of the lesioned median eminence containing astrocytic processes immunoreactive to glial fibrillary acidic protein but vimentin-negative. When fixed lesioned median eminences were treated by placing crystals of the lipophilic dye DiI on their ventricular surface, regenerating axons were found to be closely associated with DiI-labelled tanycytic-like end feet terminating in the external layer, and with connected thin processes projecting through the external vascular region. These data indicate that in the median eminence of the adult rat, lesioned neurohypophysial axons regenerate in close association with tanycytic processes.


Effect of short-term storage on quality parameters, DNA integrity, and oxidative stress in Russian (Acipenser gueldenstaedtii) and Siberian (Acipenser baerii) sturgeon sperm.
The sperm of Russian sturgeon (A. gueldenstaedtii) and Siberian sturgeon (A. baerii) was used to evaluate the effects of short-term (liquid) storage on functional parameters (spermatozoa motility and velocity), DNA integrity and oxidative stress indices. Spermatozoa showed >50% motility during 6 days of storage with an average velocity of 133.12±15.4 to 87.9±11.23μm s(-1) in both species. No motile spermatozoa were recorded after nine days of storage. Analysis of Russian sturgeon sperm showed no significant differences in DNA damage expressed as percent tail DNA and Olive Tail Moment for first three days of storage. In Siberian sturgeon significant differences in DNA damage were detected after two days of storage. The level of oxidative stress indices (TBARS, CP) and antioxidant activity (SOD) increased significantly with storage time in both species. Results of this study can be utilized for successful reproduction management and cryopreservation protocols of these endangered species.


Metapopulation model of rock-scissors-paper game with subpopulation-specific victory rates stabilized by heterogeneity.
Recently, metapopulation models for rock-paper-scissors games have been presented. Each subpopulation is represented by a node on a graph. An individual is either rock (R), scissors (S) or paper (P); it randomly migrates among subpopulations. In the present paper, we assume victory rates differ in different subpopulations. To investigate the dynamic state of each subpopulation (node), we numerically obtain the solutions of reaction-diffusion equations on the graphs with two and three nodes. In the case of homogeneous victory rates, we find each subpopulation has a periodic solution with neutral stability. However, when victory rates between subpopulations are heterogeneous, the solution approaches stable focuses. The heterogeneity of victory rates promotes the coexistence of species.


Complex regulatory mechanisms of telomerase activity in normal and cancer cells: how can we apply them for cancer therapy?
Telomerase activation is observed in almost 90% of human cancers but not in normal tissues of somatic origin and thus is a critical step for multistep carcinogenesis. A more thorough understanding of telomerase regulation may provide not only a molecular basis of cancer progression but also as a way to manipulate telomerase activity as a potential therapeutic modality. Recent progress in studies on telomerase regulation has shown that telomerase activation is achieved at various steps, including transcriptional and post-transcriptional levels of the telomerase reverse transcriptase (hTERT) gene. Although a number of potentially important mechanisms of telomerase activation have been proposed, none of the current models can fully explain tumor-specific activation of telomerase, suggesting a need for further extensive analysis. This review includes a summary of recent works on telomerase regulation and a discussion of how we can overcome this situation.


Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is increased in osteoarthritis and regulates chondrocyte catabolic and anabolic activities.
We determined if the epidermal growth factor receptor ligand HB-EGF is produced in cartilage and if it regulates chondrocyte anabolic or catabolic activity. HB-EGF expression was measured by quantitative PCR using RNA isolated from mouse knee joint tissues and from normal and osteoarthritis (OA) human chondrocytes. Immunohistochemistry was performed on normal and OA human cartilage and meniscus sections. Cultured chondrocytes were treated with fibronectin fragments (FN-f) as a catabolic stimulus and osteogenic protein 1 (OP-1) as an anabolic stimulus. Effects of HB-EGF on cell signaling were analyzed by immunoblotting of selected signaling proteins. MMP-13 was measured in conditioned media, proteoglycan synthesis was measured by sulfate incorporation, and matrix gene expression by quantitative PCR. HB-EGF expression was increased in 12-month old mice at 8 weeks after surgery to induce OA and increased amounts of HB-EGF were noted in human articular cartilage from OA knees. FN-f stimulated chondrocyte HB-EGF expression and HB-EGF stimulated chondrocyte MMP-13 production. However, HB-EGF was not required for FN-f stimulation of MMP-13 production. HB-EGF activated the ERK and p38 MAP kinases and stimulated phosphorylation of Smad1 at an inhibitory serine site which was associated with inhibition of OP-1 mediated proteoglycan synthesis and reduced aggrecan (ACAN) but not COL2A1 expression. HB-EGF is a new factor identified in OA cartilage that promotes chondrocyte catabolic activity while inhibiting anabolic activity suggesting it could contribute to the catabolic-anabolic imbalance seen in OA cartilage.


The Monod-Wyman-Changeux allosteric model describes haemoglobin oxygenation with only one adjustable parameter.
The Monod-Wyman-Changeux allosteric model describes the oxygen equilibrium of haemoglobin in terms of three parameters: the oxygen association constant for the T state, KT, that for the R state, KR, and the allosteric constant, L0, where Li = [Ti]/[Ri] and Ti and Ri are the T and R states, respectively, combined with i oxygen molecules (i = 0 to 4). This model predicts that heterotropic effects exerted by various non-haem ligands are due exclusively to displacement of the allosteric equilibrium (T0 in equilibrium R0) and neither the KT nor the KR values depend upon the concentration of non-haem ligands (solution conditions), whereas the experimental data indicated that not only L0, but also KT, varies significantly with changes in solution conditions. On the basis of accurate oxygen equilibrium data, which were obtained recently under a variety of solution conditions, I examined correlations between the Monod-Wyman-Changeux parameters and found the following: as long as the constraints imposed on the haemoglobin molecule are not very strong, both KR and L4 are essentially constant and, further, log L0 + 4 log KT = log L4 + 4 log KR is constant, irrespective of solution conditions. As a consequence, the haemoglobin oxygenation can virtually be described in terms of only one parameter, either KT or L0. Implications of this phenomenon are also described.


Blockade of protease-activated receptor 2 attenuates allergenmediated acute lung inflammation and leukocyte recruitment in mice.
Protease-activated receptor (PAR)2 has been implicated in mediating allergic airway inflammation.We investigate the role of PAR2 in lung inflammation and neutrophil and eosinophil recruitment into the lungs in amousemodel of shortterm acute allergic inflammation. Allergic lung inflammation was induced in sensitized BALB/c mice through intranasal instillations of ovalbumin (OVA), and mice were pretreated with the PAR2 antagonist ENMD1068 or with the PAR2-activating peptide (PAR2-AP) 1 hour before each OVA challenge. Bronchoalveolar lavage fluid (BALF) was collected, and the lungs, trachea and lymph nodes were removed after the last challenge to analyze the airway inflammation. PAR2 blockade reduced OVA-induced eosinophil and neutrophil counts, CXCL1, CCL5, amphiregulin, and interleukin (IL)-6 and 13 levels.Moreover, PAR2 blockade reduced OVA-induced PAR2 expression in cells present in BALF 2 hour after OVA challenge, and PAR2-AP acted synergistically with OVA promoting eosinophil recruitment intoBALF and increased IL-4 and IL-13 levels in lymph nodes. Conversely, PAR2 blockade increased IL- 10 levels when compared with OVA-treated mice. Our results provide evidence for a mechanism by which PAR2 meditates acute lung inflammation triggered by multiple exposures to allergen through a modulatory role on cytokine production and vascular permeability implicated in the lung diseases such as asthma.


Applications and Mechanism of 3-Hydroxybutyrate (3HB) for Prevention of Colonic Inflammation and Carcinogenesis as a Food Supplement.
Inflammatory bowel disease and colorectal carcinogenesis (CRC) are common diseases without effective prevention approach. 3-Hydroxybutyrate (3HB) reported to have multiple functions as an oral food supplement. This study observes that 3HB prevents mouse colitis and CRC. The sensitivity of wild type (WT) and GPR109a-/- mice to colitis is compared using dextran sulfate sodium salt (DSS)-induced colitis model. Flow cytometry showed that 3HB cellular surface receptor GPR109a that can decrease the percentage of M1 macrophages from 50% of the DSS-induced acute colitis mouse group to 42% DSS+3HB group mediating the inhibitory effect on inflammation. Bone marrow transplantation experiments further demonstrated that the function of 3HB depended on bone marrow cells. Subsequently, the sensitivity of WT and GPR109a-/- mice to CRC is compared using an azoxymethane-DSS-induced CRC mouse model. It is found that the activation of GPR109a inhibited CRC, depended on reduced myeloid-derived suppressor cells accumulation from 27% of the DSS group to 19% of the DSS+3HB group studied using flow cytometry. It is concluded that 3HB significantly suppresses colonic inflammation and carcinogenesis, promising to benefit colon disease prevention in form of a food supplement.


Environmental stressors differentially affect leaf ecophysiological responses in two Ipomopsis species and their hybrids.
The recombination that follows natural hybridization may produce hybrid genotypes with traits that are intermediate or extreme relative to the parental species, and these traits may influence the relative fitness of the hybrids. Here we examined leaf ecophysiological traits that may influence fitness patterns in a natural plant hybrid zone. We compared the biochemical photosynthetic capacity of Ipomopsis aggregata, I. tenuituba, and early generation hybrids, as well as their photosynthetic responses to varying light and temperature, two abiotic factors found to differ among sites along the hybrid zone. In general, ecophysiological traits expressed in these plants were consistent with their natural habitat, even when grown under common greenhouse conditions. I. tenuituba reached higher photosynthetic rates (A) at higher light levels than I. aggregata, and also had a higher optimal temperature for photosynthesis (Topt). This suite of traits may reflect adaptations to the more exposed, rocky sites where I. tenuituba is found, compared to the more vegetated, mesic I. aggregata site. Hybrids had characters that were largely intermediate or tenuituba-like, but particular individual hybrids were extreme for some traits, including light saturation level, light-saturated A, and Topt. Many of these traits are consistent with adaptations reported for plants found in warm, dry sites, so they may put certain hybrids at an advantage at the relatively xeric center of the natural hybrid zone.


New insights into the genetic basis of TAR (thrombocytopenia-absent radii) syndrome.
Thrombocytopenia with absent radii (TAR) syndrome is a rare disorder combining specific skeletal abnormalities with a reduced platelet count. Rare proximal microdeletions of 1q21.1 are found in the majority of patients but are also found in unaffected parents. Recently it was shown that TAR syndrome is caused by the compound inheritance of a low-frequency noncoding SNP and a rare null allele in RBM8A, a gene encoding the exon-junction complex subunit member Y14 located in the deleted region. This finding provides new insight into the complex inheritance pattern and new clues to the molecular mechanisms underlying TAR syndrome. We discuss TAR syndrome in the context of abnormal phenotypes associated with proximal and distal 1q21.1 microdeletion and microduplications with incomplete penetrance and variable expressivity.


Hearing parameters in noise exposed industrial workers.
This paper presents the results of a study carried out in a group of noise-exposed workers in a hydro-electric power plant. Thus, the main focus of the study is on 130 industrial workers who were exposed to high level of noise. The control group was consisted of 33 subjects with normal hearing. Hearing and acoustic reflex thresholds were obtained from all subjects and the results from age-matched subgroups were compared. The sensorineural hearing loss which were detected in 71 workers were bilateral, symmetrical and affected mainly frequencies of 4-6 kHz. In essence, the hearing losses were developed within the first 10 years of noise exposure and associated with slight progress in the following years. When acoustic reflex thresholds derived from the study and control groups were compared, statistically significant difference was determined only for the thresholds obtained at 4 kHz (p < 0.0005).


The incidence, multiple presentation and recurrence of aggressive cysts of the jaws.
The incidence, multiple presentation and recurrence rate of aggressive cysts of the jaws is discussed, based on a study of 677 cysts in 651 patients. Cysts that are considered aggressive include: cysts in which carcinoma develops, unicystic ameloblastoma, keratocysts and calcifying odontogenic cysts. Based on literature studies and on our own material, the incidence and multiplicity of these lesions is calculated. Recommendations for treatment include careful preoperative assessment and treatment of suspicious lesions with excision of the overlying mucosa and fixation of the defect with Carnoy's solution. The cyst in which carcinoma develops should be treated as a true malignancy i.e. by resection. Long term follow-up is necessary to eliminate the possibility of recurrence.


Impact of Defects for AlN Single Crystal Thin Film by Metal Nitride Vapor Phase Epitaxy.
Herein, the defect-related properties of an AlN sample prepared based on the optimal process parameters by metal nitride vapor phase epitaxy (MNVPE) were investigated. The FWHM values of the (0002)/(101̅2) planes of the sample by MNVPE are 397/422 arcsec; the advantages of similar FWHM values of (0002) and (101̅2) planes will have a huge advantage over other preparation methods such as MOCVD. From the cross-sectional TEM images of the AlN sample, it is found that the fusion of a large number of a + c type dislocations occur at the interface of the low temperature buffer layer and the epitaxial layer, which affects the growth mode of the epitaxial layer. The lower FHWM value of the E 2(high) peak of the Raman spectrum, the lower the point defect concentration, which made the sample gain higher energy defect emission bands in the PL spectra and higher transmittance in the UV-vis transmission spectrum.


Structure based design: novel spirocyclic ethers as nonpeptidal P2-ligands for HIV protease inhibitors.
A series of novel spirocyclic ethers were designed to function as nonpeptidal P2-ligands for HIV-1 protease inhibitors. Incorporation of designed ligands in the (R)-(hydroxyethylamino)sulfonamide isostere afforded potent HIV protease inhibitors.


An elutriation device to measure particle settling velocity in urban runoff.
Urban runoff is primarily treated by settling particles. One important parameter in the design of these settling basins is particle settling velocity. Yet, this parameter is rarely measured. A modified elutriation device is developed to measure particle settling velocity distribution for use in stormwater runoff treatment design and performance evaluation. The elutriation device has distinct advantages over settling column measurement, including (1) less time requirement to make measurements, and (2) flexibility to operate at various flow rates to cover wide ranges of particle settling velocity. Major modifications of the existing elutriation devices include using a variable speed pump, changing the glass column to plastic, and adding screens at the flow inlet for more uniform velocity distribution while making the column shorter. The results of the experiments showed that the particles retained in each column of the modified elutriation device could be predicted by assuming a fully-developed, laminar velocity profile across the cross-section of each column. Operation of the device under two flow rates and multiple columns increased the range of settling velocities measured. The information presented in this paper may be used to develop standard protocols for the evaluation of particle settling velocity in stormwater.


[Alkaline cultivation of bovine rotavirus in the continuous cell cultures].
Alkaline versus neutral cultivation of bovine rotavirus strain 101 in the continuous cell cultures resulted in a significant acceleration of a reproduction cycle with a very significant cytopathic effect.


Assessment of macrophage migration inhibitory factor in patients with verruca vulgaris.
Common warts are caused by human papillomaviruses (HPVs), they are among the most common cutaneous viral infections. Macrophage migration inhibitory factor (MIF) is an essential contributor in many inflammatory and immune skin diseases. Yet, its role in the pathology of common warts is unclear. To assess MIF levels in lesional and perilesional skin in patients with common warts in comparison to apparently healthy control group with matching age and sex. A case-control study performed on 60 patients with common warts (group A) and 30 age and sex matching healthy controls (group B). Two biopsies were taken from each patient in group A; one from the lesion (lesional) and the other one from the skin around the wart (perilesional), while biopsies of controls were taken from matched sites to patients. Measurement of MIF in all groups was done by quantitative ELISA kits. Significant high MIF levels were detected in lesional and perilesional skin biopsies compared to controls (P<0.001). Yet, the difference in MIF levels between lesional and perilesional skin biopsy was non-significant. No significant relations were found between lesional and perilesional MIF levels and clinical characteristics of the studied patients while both lesional and perilesional MIF levels were significantly correlated (rh=0.269, P=0.021). The significantly elevated MIF levels in lesional and perilesional skin biopsies compared to controls point to its role in wart progression from HPV infected cells.


Quantitative analysis in spontaneous canine anal sac gland adenomas and carcinomas.
Stained cytological specimens from 7 canine anal sac gland adenomas and 11 canine anal sac gland carcinomas were analyzed by computer-assisted nuclear morphometry. In each case, the nuclei of at least 100 neoplastic cells were measured, and the mean nuclear area (MNA), mean nuclear perimeter (MNP), mean nuclear diameter (MND) and nuclear roundness (NR) were calculated. The study aimed to evaluate (1) the possibility of using nuclear cytomorphometry as an auxiliary diagnostic method to differentiate between canine anal sac gland adenomas and adenocarcinomas, and (2) the prognostic value of nuclear morphometry in canine anal sac gland adenocarcinomas. The results indicated that (1) MNA, MNP, MND and NR could be used as effective auxiliary tools for differential diagnosis between canine anal sac gland adenomas and adenocarcinomas, and (2) MNA, MNP and MND are reliable prognostic indicators for canine anal sac gland adenocarcinomas.


Therapeutic options for endoscopic haemostatic failures: the place of the surgeon and radiologist in gastrointestinal tract bleeding.
The management of gastrointestinal tract bleeding has changed dramatically due to improvements of interventional endoscopy and radiology. The place of the radiologist has become very important, not only for diagnostic modalities but also for therapeutic embolisation to control the bleeding. The place of the surgeon is limited to the situation where both these less invasive techniques have failed to stop the bleeding. For arterial bleeding in the whole GI tract, angiography with subsequent embolisation is performed after failed endoscopy. For variceal bleeding the preferred treatment after endoscopic failure is transjugular intrahepatic portosystemic stent shunting (TIPS). Surgery is only needed in exceptional cases. Embolisation can be performed successfully without compromising the bowel vascularisation or inducing ischaemia, whereas surgery has a high rate of complications and mortality. For treatment of GI bleeding a multidisciplinary team including a gastroenterologist, radiologist and surgeon is mandatory.


Release of endogenous danger signals from HIFU-treated tumor cells and their stimulatory effects on APCs.
The effects of high-intensity focused ultrasound (HIFU) on the release of endogenous danger signals from tumor cells and subsequent activation of antigen-presenting cells (APCs) were evaluated in vitro. MC-38 mouse tumor cells were treated using a 1.1 MHz HIFU transducer under two different protocols (P-=6.7 MPa, 30% duty cycle, 5 s vs. P-=10.7 MPa, 3% duty cycle, 30 s) to produce either thermal necrosis or mechanical lysis of the tumor cells. Here, we report that HIFU treatment can cause the release of endogenous danger signals (ATP and hsp60) and exposure of dendritic cells (DCs) and macrophages to the supernatants of HIFU-treated tumor cells leads to an increased expression of co-stimulatory molecules (CD80 and CD86) with enhanced secretion of IL-12 by the DCs and elevated secretion of TNF-alpha by the macrophages. The potency in APC activation produced by mechanical lysis is much stronger than thermal necrosis of the tumor cells. These findings suggest that optimization of treatment strategy may help to enhance HIFU-elicited anti-tumor immunity.


Multiplexed imaging mass spectrometry of the extracellular matrix using serial enzyme digests from formalin-fixed paraffin-embedded tissue sections.
We report a multiplexed imaging mass spectrometry method which spatially localizes and selectively accesses the extracellular matrix on formalin-fixed paraffin-embedded tissue sections. The extracellular matrix (ECM) consists of (1) fibrous proteins, post-translationally modified (PTM) via N- and O-linked glycosylation, as well as hydroxylation on prolines and lysines, and (2) glycosaminoglycan-decorated proteoglycans. Accessing all these components poses a unique analytical challenge. Conventional peptide analysis via trypsin inefficiently captures ECM peptides due to their low abundance, intra- and intermolecular cross-linking, and PTMs. In previous studies, we have developed matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) techniques to capture collagen peptides via collagenase type III digestion, both alone and after N-glycan removal via PNGaseF digest. However, in fibrotic tissues, the buildup of ECM components other than collagen-type proteins, including elastin and glycosaminoglycans, limits efficacy of any single enzyme to access the complex ECM. Here, we have developed a novel serial enzyme strategy to define the extracellular matrix, including PTMs, from a single tissue section for MALDI-IMS applications. Graphical Abstract.


Reduction of leukocyte count is associated with thalidomide response in treatment of multiple myeloma.
Fifty Taiwanese patients with relapsed and/or refractory multiple myeloma (MM) were treated with thalidomide on a dose-escalation schedule, commencing with 100 mg/d nightly and incremented either to the maximally tolerated dose or 800 mg/d. Twenty-two patients (44%) responded, with 10 (45.5%) classified as partial remission and 12 (54.5%) minimal response (MR). Complete response did not occur. Of the 28 non-responders, 14 were progressive disease and 14 stable. The median time from commencement of thalidomide treatment to initial achievement of MR was 29 days (range, 8~155), and the corresponding thalidomide dose was 200 mg/d (range, 100~500). The median tolerated dose of thalidomide for the entire sample was 400 mg/d (range, 100~800), with only two (4%) able to tolerate 800 mg/d. Comparing responsive and non-responsive patients, statistically significant differences were not demonstrated for any characteristics except for CRP level and percentage cytogenetic change, which was slightly higher in the latter group relative to the former. Of particular interest, 18 of the 22 responders experienced transient reduction of leukocyte count preceding the attainment of significant reduction in M-proteins in comparison to only four of the 28 non-responders (82% vs. 14%; p<0.001). The median time from commencement of thalidomide treatment to attainment of minimal leukocyte count was 28 days (range, 7~150), with a mean of 2.19x10(9)/l (range, 0.96~3.35x10(9)/l). Leukopenia was generally transient, with rapid recovery despite subsequent continuation of thalidomide. Levels of other non-hematologically adverse effects attributed solely to thalidomide were generally acceptable. For 25 patients, thalidomide treatment was supplemented with low-dose dexamethasone (4 mg, every other day). Of these, 11 had relapsed from and 14 were primarily refractory to thalidomide treatment. Nine of the 25 dexamethasone-supplemented patients were responders (36%). Of particular note were the unusual events noted with this thalidomide-dexamethasone combination, including vascular thrombosis, acute cholecystitis, idiopathic interstitial lung disease and sudden cardiac death. Our results suggest that thalidomide is also effective for Taiwanese patients with refractory and/or relapsed MM. Importantly, the transient reduction in leukocyte count after commencement of thalidomide treatment may serve as a clinical predictor for response. Adverse effects should be carefully monitored when combining thalidomide and dexamethasone, however.


Is Meteorology a Factor to COVID-19 Spread in a Tropical Climate?
It was speculated that fewer COVID-19 infections may emerge in tropical countries due to their hot climate, but India emerged as one of the leading hotspot. There is no concrete answer on the influence of meteorological parameters on COVID-19 even after more than a year of outbreak. The present study examines the impacts of Meteorological parameters during the summer and monsoon season of 2020, in different Indian mega cities having distinct climate and geography. The results indicate the sign of association, but it varies from one climatic zone to another. The principal component analysis revealed that humidity is strongly correlated with COVID-19 infections in hillocky city Pune (R = 0.70), dry Delhi (R = 0.50) and coastal Mumbai (R = 0.46), but comparatively weak correlation is found in arid climatic city of Ahmedabad. As against the expectations, no discernible correlation is found with temperature in any of the cities. As the virus in 2020 in India largely travelled with droplets, the association with absolute humidity in the dry regions has serious implications. Clarity in understanding the impact of seasonality will greatly help epidemiological research and in making strategies to control the pandemic in India and other tropical countries around the world.


Predicting aphasia type from brain damage measured with structural MRI.
Chronic aphasia is a common consequence of a left-hemisphere stroke. Since the early insights by Broca and Wernicke, studying the relationship between the loci of cortical damage and patterns of language impairment has been one of the concerns of aphasiology. We utilized multivariate classification in a cross-validation framework to predict the type of chronic aphasia from the spatial pattern of brain damage. Our sample consisted of 98 patients with five types of aphasia (Broca's, Wernicke's, global, conduction, and anomic), classified based on scores on the Western Aphasia Battery (WAB). Binary lesion maps were obtained from structural MRI scans (obtained at least 6 months poststroke, and within 2 days of behavioural assessment); after spatial normalization, the lesions were parcellated into a disjoint set of brain areas. The proportion of damage to the brain areas was used to classify patients' aphasia type. To create this parcellation, we relied on five brain atlases; our classifier (support vector machine - SVM) could differentiate between different kinds of aphasia using any of the five parcellations. In our sample, the best classification accuracy was obtained when using a novel parcellation that combined two previously published brain atlases, with the first atlas providing the segmentation of grey matter, and the second atlas used to segment the white matter. For each aphasia type, we computed the relative importance of different brain areas for distinguishing it from other aphasia types; our findings were consistent with previously published reports of lesion locations implicated in different types of aphasia. Overall, our results revealed that automated multivariate classification could distinguish between aphasia types based on damage to atlas-defined brain areas.