Temporal analysis of non-ST segment elevation-acute coronary syndrome (NSTEACS) outcomes in 'young' patients under the age of fifty: A nationwide cohort study.
The characteristics and risk factor profile of young patients presenting with non-ST segment elevation acute coronary syndrome (NSTEACS) and how they may have changed over time is not well reported. We identified 26,708 NSTEACS patients aged under 50 presenting to United Kingdom (UK) hospitals between 2010 and 2017 from Myocardial Ischaemia National Audit Project (MINAP). We calculated incidence of NSTEACS per 100,000 UK population, using Office of National Statistics (ONS) population estimates, prevalence of comorbidities, ethnicity, and in-hospital mortality. We formed biennial groups to enable comparison, 2010-2011, 2012-2013, 2014-2015 and 2016-2017. The incidence of NSTEACS per 100,000 population showed minimal change between 2010 and 2017 (2010: 5.4 per 100,000 and 2017; 4.9 per 100,000). Rates of smoking (2010-11; 58% and 2016-17; 53%), and family history of coronary artery disease (CAD) (2010-11; 51% and 2016-17; 44%) fell, but the proportion of patients from an ethnic minority background (2010-11; 12% and 2016-17; 20%), with diabetes mellitus (DM) (2010-11; 14%, and 2016-17; 18%) and female patients (2010-11; 22% and 2016-17; 24%) increased over the study period. Mortality from NSTEACS remained unchanged (2010-11; 1% and 2016-17; 1%). The incidence of NSTEACS in patients aged under fifty has not reduced despite reduction in prevalence of risk factors such as smoking hypercholesterolaemia in those admitted to UK hospitals. Despite improved rates of early invasive coronary angiography and percutaneous coronary intervention in 'young' NSTEACS patients, in-hospital mortality remains unchanged.


Lithium fluxes indicate presence of Na-Cl cotransport (NCC) in human lens epithelial cells.
During regulatory volume decrease (RVD) of human lens epithelial cells (hLECs) by clotrimazole (CTZ)-sensitive K fluxes, Na-K-2Cl cotransport (NKCC) remains active and K-Cl cotransport (KCC) inactive. To determine whether such an abnormal behavior was caused by RVD-induced cell shrinkage, NKCC was measured in the presence of either CTZ or in high K media to prevent RVD. NKCC transports RbCl + NaCl, and LiCl + KCl; thus ouabain-insensitive, bumetanide-sensitive (BS) or Cl-dependent (ClD) Rb and Li fluxes were determined in hyposmotic high NaCl media with CTZ, or in high KCl media alone, or with sulfamate (Sf) or nitrate as Cl replacement at varying Rb, Li or Cl mol fractions (MF). Unexpectedly, NKCC was inhibited by 80% with CTZ (IC(50) = 31 microM). In isosmotic (300 mOsM) K, Li influx was approximately 1/3 of Rb influx in Na, 50% lower in Sf, and bumetanide-insensitive (BI). In hypotonic (200 mOsM) K, only the ClD but not BS Li fluxes were detected. At Li MFs from 0.1-1, Li fluxes fitted a bell-shaped curve maxing at approximately 0.6 Li MF, with the BS fluxes equaling approximately 1/4 of the ClD-Li influx. The difference, i.e. the BI/ClD Li influx, saturated with increasing Li and Cl MFs, with K(ms) for Li of 11 with, and 7 mM without K, and of approximately 46 mM for Cl. Inhibition of this K-independent Li influx by thiazides was weak whilst furosemide (<100 microM) was ineffective. Reverse transcription polymerase chain reaction and Western blots verified presence of both NKCC1 and Na-Cl cotransport (NCC). In conclusion, in hyposmotic high K media, which prevents CTZ-sensitive K flux-mediated RVD in hLECs, NKCC1, though molecularly expressed, was functionally silent. However, a K-independent and moderately thiazide-sensitive ClD-Li flux, i.e. LiCC, likely occurring through NCC was detected operationally and molecularly.


Utilizing 18F-fluoroethyl-l-tyrosine positron emission tomography in high grade glioma for radiation treatment planning in patients with contraindications to MRI.
Patients with high grade glioma (HGG) and contraindications to magnetic resonance imaging (MRI) are dependent on contrast-enhanced computerized tomography (CT) scan imaging for radiation therapy (RT) target volume delineation. This study reviews the experience with the utilization of 18F-fluoroethyl-l-tyrosine positron emission tomography (FET-PET) to define residual disease post craniotomy and optimize RT planning. Patients with HGG and a contraindication to MRI managed with radiation therapy between 2007 and 2015 were identified. RT target volumes including gross tumour volume (GTV) defined by CT-alone and the biological target volume (BTV) defined by PET-CT were recorded. Clinical target volumes (CTV) were created from the GTV and BTV respectively using standard protocol volume expansion. The expanded BTV was termed clinical target volume biological (CTV-B). Union and intersection between CTV and CTV-B, conformity index, volumetric parameters and individual patient outcomes were analysed. Six patients fit study criteria. There was a mean increase in CTV-B from CTV by 31.6% with a conformity index of 0.78. Two out of six patients had FET-PET avid disease outside the constructed PTV when delineated by CT-alone. One patient with CT-only planning had a new contrast-enhancing mass within 1 month of completing RT, suggesting potential geographical miss. Patients with contraindication to MRI the addition of FET-PET can improve target volume delineation for RT Planning.


Long term stability of HBsAg, anti-HBc and anti-HCV in dried blood spot samples and eluates.
Dried blood spots (DBS) are a useful specimen collection tool in situations where venous access is problematic, however, detection of biomarkers from this specimen type is subject to variation depending on storage conditions and storage time. The objective of this study is to assess the detection of HBsAg, anti-HBc and anti-HCV from DBS after storage. DBS specimens were stored at -70°C, -20°C, 4°C, 22 to 28°C and 37°C either with or without desiccant. Eluates were also prepared from DBS specimens and stored at -20°C and -70°C. DBS cards and eluates were tested for HBsAg, anti-HBc and anti-HCV at baseline on day 0 and thereafter at intervals of 14, 70 and 200 days. Loss of detection of both HBsAg and anti-HBc was evident by the first time point (14 days) in all storage conditions except for the samples (DBS and eluates) stored at -20°C or -70°C. Both HBsAg and anti-HBc stored under these conditions showed minimal variation up to the final time point (200 days) of storage. The detection of anti-HCV did not differ between the 22 to 28°C, 4°C, -20°C and -70°C DBS nor the -20°C or the -70°C stored eluates over the 200 day time period. We suggest that extended storage of DBS intended for downstream testing is best carried out by freezing either the DBS, or eluate, at -20°C or -70°C as soon as possible following collection for optimal detection of HBsAg, anti-HBc and anti-HCV.


An investigation of what protective individual- and community-level factors are associated with life satisfaction in middle-aged and older family carers in Ireland.
Family care plays an essential role in providing care in society. However, caring can cause stress, and mental and physical responses to caring vary widely. Different outcomes for carers may reflect different approaches or adaptability to caring and their ability to maintain or recover their mental health and wellbeing following an adverse event (psychosocial resilience). We aim to identify factors that may promote psychosocial resilience, conceptualized as maintaining or recovering subjective wellbeing and operationalized as satisfaction with life, among carers. Data were from 6 Waves (2009-2021) of The Irish Longitudinal Study on Aging (TILDA), a prospective biennial nationally representative longitudinal study of older adults aged ≥50 in Ireland. Family caregiving was assessed in Waves 3-6. Participants were asked if they cared for someone, their relationship to the recipient, and the number of hours per week that they provided care. We used growth mixture modeling to identify latent trajectories of satisfaction with life (SWL) before and after caring was initiated. Regression modeling was then used to identify protective factors (at the individual, family, and community levels) associated with resilient trajectories. Overall, 731 (12.2%) participants became carers during follow-up. We identified three trajectories in SWL in carers following initiation of caring, namely, Resilient-Stable (81%), Resilient-Recovery (12%), and Non-recovery (6%). Membership in Resilient-Stable and Resilient-Recovery trajectories was associated with fewer depressive symptoms (OR = 0.86, 95% CI 0.78, 0.94) and chronic conditions (OR = 0.21, 95% CI 0.06, 0.74), larger social networks (OR = 2.03, 95% CI 1.06, 3.86), more close friends and relatives (OR = 1.15, 95% CI 1.01, 1.32), and caring for someone other than a child (OR = 0.19, 95% CI 0.07, 0.51) compared to the Non-recovery group. Becoming a family carer was associated with a decline in SWL over time in some carers. However, most carers either did not experience a decline in SWL or recovered their SWL over time. We found that both individual and community-level supports may be protective for carers' wellbeing. These results will inform the priorities for social and community-level services and support for older carers and contribute to the design of new projects and programs to meet these needs.


Randomised clinical trial of an intensive intervention in the primary care setting of patients with high plasma fibrinogen in the primary prevention of cardiovascular disease.
We have studied the possible effects of an intensive lifestyle change program on plasma fibrinogen levels, in patients with no cardiovascular disease, with elevated levels of fibrinogen, normal cholesterol levels, and a moderate estimated risk of coronary heart disease (CHD) and we have also analysed whether the effect on fibrinogen is independent of the effect on lipids. This clinical trial was controlled, unblinded and randomized, with parallel groups, done in 13 Basic Health Areas (BHA) in l'Hospitalet de Llobregat (Barcelona) and Barcelona city. The study included 436 patients, aged between 35 and 75 years, with no cardiovascular disease, elevated levels of fibrinogen (> 300 mg/dl), cholesterol < 250 mg/dl, 218 of whom received a more intensive intervention consisting of advice on lifestyle and treatment. The follow-up frequency of the intervention group was every 2 months. The other 218 patients followed their standard care in the BHAs. Fibrinogen, plasma cholesterol and other clinical biochemistry parameters were assessed.The evaluation of the baseline characteristics of the patients showed that both groups were homogenous. Obesity and hypertension were the most prevalent risk factors. After 24 months of the study, statistically significant changes were seen between the adjusted means of the two groups, for the following parameters: fibrinogen, plasma cholesterol, systolic and diastolic blood pressure and body mass index. Intensive intervention to achieve lifestyle changes has shown to be effective in reducing some of the estimated CHD factors. However, the effect of intensive intervention on plasma fibrinogen levels did not correlate with the variations in cholesterol. ClinicalTrials.gov: NCT01089530.


Structural analysis and functional role of the carbohydrate component of somatostatin receptors.
SRIF receptors are membrane-bound glycoproteins. To structurally identify the carbohydrate components of SRIF receptors, solubilized rat brain SRIF receptors were subjected to lectin affinity chromatography. Solubilized SRIF receptors specifically bound to wheat germ agglutinin-lectin affinity columns but not to succinylated wheat germ agglutinin. This finding, as well as the ability of the solubilized receptor to interact with a Sambucus nigra L. lectin affinity column suggested that sialic acid residues are associated with SRIF receptors. The inability of the receptor to bind to concanavalin A, Dolichus biflorus agglutinin, Ulex europeaus I, and Jacalin lectin affinity columns suggests that high mannose, N-acetylgalactosamine, fucose, and O-linked carbohydrates are not associated with receptor. To investigate the functional role of the carbohydrate groups in brain SRIF receptors, specific sugars were selectively cleaved from SRIF receptors and the subsequent effect on the specific high affinity binding of the agonist [125I]MK 678 to SRIF receptors was determined. Treatment of the receptor with endoglycosidase D did not affect the specific binding of [125I] MK 678 to the solubilized SRIF receptors, consistent with the finding from lectin affinity chromatography that high mannose-type carbohydrate structures were not associated with SRIF receptors. Treatment of solubilized SRIF receptors with peptide-N-glycosidase F and endoglycosidases H and F reduced [125I]MK 678 binding to SRIF receptors indicating that either hybrid, or a combination of hybrid and complex N-linked carbohydrate structures, have a role in maintaining the receptor in a high affinity state for agonists. Treatment of solubilized SRIF receptors with neuraminidase from Vibrio cholera abolished high affinity agonist binding to the receptors, whereas treatment of the receptor with neuraminidase from Newcastle disease virus did not affect [125I]MK 678 binding to the receptor. These findings suggest that sialic acid residues in an alpha 2,6-configuration have a role in maintaining the SRIF receptor in a high affinity conformation for agonists. This is further indicated by studies on SRIF receptors in the pituitary tumor cell line, AtT-20. Treatment of AtT-20 cells in culture with neuraminidase (V. cholera) greatly reduces high affinity [125I] MK 678 binding sites, but did not alter the maximal ability of SRIF to inhibit forskolin-stimulated cAMP accumulation in intact AtT-20 cells. This finding suggests that the desialylated SRIF receptor is functionally active and remains coupled to GTP-binding proteins, but exhibits a reduced affinity for agonists. Treatment of AtT-20 cell membranes with neuraminidase from V. cholera was also able to greatly reduce the affinity of SRIF receptors for [125I]MK 678.(ABSTRACT TRUNCATED AT 400 WORDS)


Mononuclear cell-membrane "fluidity": a study in some haematological malignancies.
The polarization of fluorescence from diphenyl hexatriene embedded in the membranes of intact peripheral-blood mononuclear cells has been measured and used to assess the "microviscosity" or fluidity of the membrane. Cell preparations were examined from patients with various types of leukaemia and related conditions in which circulating primitive cells may occur. Significantly lower fluorescence polarization values were obtained in all samples from patients with chronic lymphocytic leukaemia, but normal results were obtained in cases of chronic granulocytic leukaemia, myelosclerosis, solid lymphomas and in acute leukaemias in remission. In relapsed acute leukaemia, fluorescence polarization indicated reduced "microviscosity" of the cell membrane when large numbers (greater than 10(9)/1) of primitive cells were present; normal "microviscosity" was indicated when less than 10(9)/1 primitive cells were present. However, exceptions occurred in both cases, and the technique failed to give warning of imminent relapse in one case. Our findings suggest that a reduction in "microviscosity" as indicated by this technique is not a general property of the blood leucocytes in all types of leukaemia, and that the technique cannot, at present, be regarded as an alternative method for detecting circulating primitive cells.


Impact of a primary-based telemonitoring programme in HRQOL, satisfaction and usefulness in a sample of older adults with chronic diseases in Valencia (Spain).
Chronic patients are frequent users of healthcare services and are prone to hospital admissions. In Valencia (Spain) the Valcronic programme aims to manage chronic patients through different levels of telemonitoring and telecare. This paper examines the impact of the Valcronic programme on self-perceived HRQOL in a one-year period and on perceptions of satisfaction and usefulness in a sample of older adults with chronic diseases. The sample (n=74) was randomly selected from Valcronic users and was stratified considering different variables. HRQOL was assessed using the EQ-5D questionnaire at two points in time: before the beginning of the Valcronic programme and after a one-year follow-up. Satisfaction and usefulness were evaluated one year after users' inclusion. The whole sample experienced improvement, although not significant, of its HRQOL; patients over 75 showed impairment. Patients with at least one problem in the EQ-5D dimensions decreased after one year (82.43% vs. 74.32%). Users' perceptions of satisfaction and usefulness were highly positive. Our sample benefited from the Valcronic programme, experiencing an improvement in their HRQOL, a decreased use of health resources or high satisfaction levels. Further adjustments are needed to address a comprehensive response to the needs of the global population of reference.


Bioaccessibility of carotenoids and antioxidant capacity of seed-used pumpkin byproducts powders as affected by particle size and corn oil during in vitro digestion process.
Powders made from seed-used pumpkin flesh (SUPF) are potential sources of carotenoids. In this study, unexplored effects of particle size and corn oil on bioaccessible amounts of carotenoids and antioxidant capacity of SUPF powders during in vitro digestion process were investigated. Overall, total carotenoid relative bioaccessibility (TCRB) of 100 mesh-sized powder (100 MP, 15.46%) was higher than that of 18 mesh-sized powder (18 MP, 12.94%). With the addition of 2% corn oil, TCRB increased 108.35% (18 MP) and 88.55% (100 MP), respectively. Lutein (≥27160 µg/100 g) and β-carotene (≥5192 µg/100 g) were main carotenoid monomers in SUPF and significantly correlated with DPPH radical scavenging activity of digestive supernatant (p < 0.05). Notably, DPPH radical scavenging activity of 18 MP increased 96.54% with corn oil. These results implied that smaller particle size and oil addition could improve bioaccessible amounts of carotenoids and antioxidant capacity of SUPF powders.


Local diffusion regularization method for optical tomography reconstruction by using robust statistics.
We formulate a solution to the diffuse optical tomography (DOT) inverse problem as the minimization of an energy functional of the solution and the data. For the solution prior we introduce a local diffusion regularization potential with a threshold based on robust statistics (the Hubert function). We compare results on simulated data for the Hubert function and two other standard regularization functionals, Tikhonov and total variation.


Bladder neck electrical conductivity in the treatment of detrusor instability with biofeedback.
A new method for controlling the symptoms and objective signs of detrusor instability was investigated in a pilot study. The method uses the activity of the bladder neck, monitored by a conductivity catheter, as a biofeedback signal. Voluntary closure of the bladder neck mechanism abolishes abnormal detrusor activity. Ten severely symptomatic women with detrusor instability were assessed clinically and urodynamically before and after a course of biofeedback. Statistically significant improvements in the symptoms of urgency and urge incontinence were found. Five of the seven women who agreed to have repeat cystometry had stable cystometrograms. There was a statistically significant fall in the mean maximum deflection at rest from 41.5 to 16.5 microA (P less than 0.05) measured during bladder neck electrical conductivity tests before and after treatment.


Cystic fibrosis birth rates in Canada: a decreasing trend since the onset of genetic testing.
To estimate cystic fibrosis (CF) birth rates in Canada from 1971 to 2000 and to assess the population impact of genetic testing in families with a history of CF, after identification of the CF transmembrane conductance regulator gene in 1989. Age-at-diagnosis data were obtained from the Canadian Cystic Fibrosis Foundation Patient Data Registry and Canadian births for the corresponding years from Canadian Vital Statistics. Estimates of the CF birth rate in each year were based on a nonparametric model that allows the birth rate to vary across the years and adjusts for censoring of currently undiagnosed patients. The overall CF birth rate from 1971-1987 was 1/2714 with no increasing or decreasing trend. Beginning in 1988, 1 year before identification of the CF transmembrane conductance regulator gene, estimated CF birth rates followed a linear decline to an estimated rate of 1/3608 in 2000. CF birth rates may have stabilized in the last few years, but further decline may occur with implementation of carrier screening in the general population. These results demonstrate the temporal association of genetic testing and declining CF birth rates in Canada. They may assist in decisions relating to the allocation of resources for prenatal and neonatal CF screening programs.


Heterogeneity of lower airway inflammation in patients with NSAID-exacerbated respiratory disease.
Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) asthma is characterized by chronic rhinosinusitis and intolerance of aspirin and other COX1 inhibitors. Clinical data point to a heterogeneity within the N-ERD phenotype. Our aim was to investigate immune mediator profiles in the lower airways of patients with N-ERD. Levels of cytokines (determined by using Luminex assay) and eicosanoids (determined by using mass spectrometry) were measured in bronchoalveolar lavage fluid (BALF) from patients with N-ERD (n = 22), patients with NSAID-tolerant asthma (n = 21), and control subjects (n = 11). mRNA expression in BALF cells was quantified by using TaqMan low-density arrays. Lower airway eosinophilia was more frequent in N-ERD (54.5%) than in NSAID-tolerant asthma (9.5% [P = .009]). The type-2 (T2) immune signature of BALF cells was more pronounced in the eosinophilic subphenotype of N-ERD. Similarly, BALF concentrations of periostin and CCL26 were significantly increased in eosinophilic N-ERD and correlated with T2 signature in BALF cells. Multiparameter analysis of BALF mediators of all patients with asthma revealed the presence of 2 immune endotypes: T2-like (with an elevated level of periostin in BALF) and non-T2/proinflammatory (with higher levels of matrix metalloproteinases and inflammatory cytokines). Patients with N-ERD were classified mostly as having the T2 endotype (68%). Changes in eicosanoid profile (eg, increased leukotriene E4 level) were limited to patients with N-ERD with airway eosinophilia. Blood eosinophilia appeared to be a useful predictor of airway T2 signature (area under the curve [AUC] = 0.83); however, surrogate biomarkers had moderate performance in distinguishing eosinophilic N-ERD (for blood eosinophils, AUC = 0.72; for periostin, AUC = 0.75). Lower airway immune profiles show considerable heterogeneity of N-ERD, with skewing toward T2 response and eosinophilic inflammation. Increased production of leukotriene E4 was restricted to a subgroup of patients with eosinophilia in the lower airway.


[Adverse reactions to drugs in a health center].
To study the adverse side-effects to medication and define their principle characteristics. A descriptive, crossover, observation study with no random distribution. The population cared for at a Health Centre in Toledo. Those over 15 years old during a 6-month period. 64 adverse side-effects were detected, classified as follows: definite, 10.9%; probable, 68.7%; possible, 20.3%. The rate of adverse side-effects was 2.67 per thousand prescriptions and 2.22 per thousand consultations. Distribution by gender was 62.5% women and 37.5% men. The 35-45 age group was the one with most adverse side-effects. The most affected systems were the digestive apparatus (46.50%), followed by the nervous system (27.50%) and the skin (16.22%). The most commonly involved pharmacological groups were: analgesics and non-steroid anti-inflammatories (34.37%) and drugs for the cardiovascular system (26.56%). 98.43% were trivial and none serious. Evolution was: 59.37% recovered on stopping the drug and 23.43% with the help of treatment. The number of suspected adverse side-effects in the Centre is high, but they were trivial. It was confirmed that adverse side-effects suppose a frequent medical problem in Primary Care. It is important to make health professionals aware so that, when prescribing, they bear in mind the drug risk/benefit relationship. The identification and communication of adverse side-effects, especially of medicines newly on the market, is also important.


Immunofluorescence studies on cartilage matrix synthesis. The synthesis of link protein, chondroitin sulfate proteoglycan monomer and type II collagen.
A comparison of the synthesis and deposition of fibrous type II collagen and the constituents of chondroitin sulfate proteoglycan (CSPG) aggregates, CSPG monomer and link protein, was made for chicken sternal chondrocytes in culture, using simultaneous double immunofluorescence and lectin localization. Chondrocytes deposited only CSPG constituents--and not type II collagen--into the extracellular matrix (ECM). Intracellular precursors of CSPG monomer were localized primarily in perinuclear regions, but were observed in other cytoplasmic vesicles as well. Link protein antibodies stained the same intracellular structures, but stained the perinuclear cytoplasm less intensely. In contrast, type II procollagen was distributed in vesicles throughout the cytoplasm and was clearly absent from the distinctive, CSPG precursor-containing vesicles. Fluorescence-labelled lectins were used to further identify intracellular membrane compartments. Wheat germ agglutinin (WGA) and Ricinus lectins (which recognize carbohydrates added in the Golgi) stained the perinuclear cytoplasm, while concanavalin A (conA) (which recognizes mannose-rich oligosaccharides added co-translationally) stained vesicles throughout the rest of the cytoplasm and not the perinuclear cytoplasm. The distinctive CSPG-containing vesicles were not stained with WGA or Ricinus agglutinins. Data presented elsewhere demonstrate that the vesicles do not react with monoclonal antibodies which recognize chondroitin sulfate (CS) or keratan sulfate (KS) determinants. Thus, we conclude that the vesicles accumulate CSPG precursors which have not been modified by Golgi-mediated processes. The data indicate that matrix molecules may be segregated selectively prior to transit through the Golgi complex. The co-distribution of link protein and CSPG monomer precursors in vesicles prior to further, Golgi-mediated modification may reflect an as yet undetermined function of these vesicles in the processing or assembly of CSPG.


Human Intestinal Microbiota: Role in Development and Functioning of the Nervous System.
Recent results related to investigation of the role of intestinal microbiota (IM) in development and functioning of the human nervous system are discussed. The role of the microbiota in bidirectional communication between the gastrointestinal tract and the central nervous system is considered. Special attention is paid to the primary IM of infants, which is actively involved in formation of immune and other physiological mechanisms, including the nervous system, and is responsible for the subsequent general and psychical health of a human. The results of research on ability of the commensal intestinal microflora to produce neuroactive compounds, including neurotransmitters, short- and long-chain fatty acids, γ-aminobutyric acid, etc., are summarized. These compounds may have a considerable effect on development and functioning of the central nervous system, including the brain. Research on various animal models is discussed, including investigation of IM effect on behavior, learning abilities and memory, anxiety and depression levels, reaction to emotional stimuli, and stress resistance. A special section deals with probiotic bacteria, which are presently considered as psychobiotics with preventive and therapeutic potential for treatment of neurological and neurophysiological disorders. Development of new paradigms and concepts, rejection of some classical concepts of neurobiology is presently the key condition for the future breakthrough in investigation of human nervous activity.


[Temperature dependence of neuronal activity in hypothalamic and hippocampal slices of the guinea-pig].
Unit activity in slices of the hippocampus and medial preoptic area of the hypothalamus of guinea-pigs was extracellularly recorded under conditions of temperature changes. Seven out of nineteen hypothalamic neurons showed changes in the firing rate at threshold temperatures of 36-38 degrees C. In the suprathreshold range the activity of these neurons depended on the temperature level. It is suggested that such neurons may form a sensory part of the system controlling brain temperature within a narrow (1-2 degrees C) range. The pyramidal layer cells of the control structure (hippocampus) were insensitive to the temperature level within 32-40 degrees C.


Adherence and out-of-pocket costs among Medicare beneficiaries who are prescribed oral targeted therapies for advanced prostate cancer.
Abiraterone and enzalutamide are high-cost oral therapies that increasingly are used to treat patients with advanced prostate cancer; these agents carry the potential for significant financial consequences to patients. In the current study, the authors investigated coping and material measures of the financial hardship of these therapies among patients with Medicare Part D coverage. The authors performed a retrospective cohort study on a 20% sample of Medicare Part D enrollees who underwent treatment with abiraterone or enzalutamide between July 2013 and June 2015. The authors described the variability in adherence rates and out-of-pocket payments among hospital referral regions in the first 6 months of therapy and determined whether adherence and out-of-pocket payments were associated with patient factors and the socioeconomic characteristics of where a patient was treated. There were 4153 patients who filled abiraterone or enzalutamide prescriptions through Medicare Part D in 228 hospital referral regions. The mean adherence rate was 75%. The median monthly out-of-pocket payment for abiraterone and enzalutamide was $706 (range, $0-$3505). After multilevel, multivariable adjustment for patient and regional factors, adherence was found to be lower in patients who were older (69% for patients aged ≥85 years vs 76% for patients aged <70 years; P < .01) and in those with low-income subsidies (69% in those with a subsidy vs 76% in those without a subsidy; P < .01). Both Hispanic ethnicity and living in a hospital referral region with a higher percentage of Hispanic beneficiaries were found to be independently associated with higher out-of-pocket payments for abiraterone and enzalutamide. There were substantial variations in the adherence rate and out-of-pocket payments among Medicare Part D beneficiaries who were prescribed abiraterone and enzalutamide. Sociodemographic patient and regional factors were found to be associated with both adherence and out-of-pocket payments.


Müller glia activation by VEGF-antagonizing drugs: An in vitro study on rat primary retinal cultures.
The effects of the anti-Vascular Endothelial Growth Factor (VEGF) drugs ranibizumab and aflibercept were studied in Müller glia in primary mixed cultures from rat neonatal retina. Treatment with both agents induced activation of Müller glia, demonstrated by increased levels of Glial Fibrillary Acidic Protein. In addition, phosphorylated Extracellular-Regulated Kinase 1/2 (ERK 1/2) showed enhanced immunoreactivity in activated Müller glia. Treatment with aflibercept induced an increase in K(+) channel (Kir) 4.1 levels and both drugs upregulated Aquaporin 4 (AQP4) in activated Müller glia. The results show that VEGF-antagonizing drugs influence the homeostasis of Müller cells in primary retinal cultures, inducing an activated phenotype. Upregulation of Kir4.1 and AQP4 suggests that Müller glia activation following anti-VEGF drugs may not depict a detrimental gliotic reaction. Indeed, it could represent one of the mechanisms able to contribute to the therapeutic effects of these drugs, particularly in the presence of macular edema.


Differential effects of propranolol on head and upper limb tremor in patients with essential tremor and dystonia.
Propranolol is used as the first-line treatment in essential tremor and it has also been proposed as a treatment for tremor in dystonia. However, several issues remain uncertain. For example, it is still not clear whether propranolol exerts a beneficial effect on head tremor. Moreover, no studies have investigated whether the effect of propranolol on head and upper limb tremor in essential tremor differs from that in dystonia. We aimed to assess the effects of propranolol on tremor in different body parts in essential tremor and in patients with tremor and dystonia. Twenty-nine patients with head and upper limb tremor were enrolled in the study, 14 with essential tremor, and 15 with dystonia. Participants underwent a clinical and kinematic analysis of tremor in two sessions, i.e., without (baseline) and 'on therapy' with propranolol. We found that head tremor was more severe in patients with dystonia, while upper limb tremor was more evident in patients with essential tremor (P < 0.05). Propranolol had no effect on head tremor in either group (all Ps > 0.05), but it did reduce upper limb tremor in patients with essential tremor. The present study demonstrates differential effects of propranolol on head and upper limb tremor in patients with essential tremor. The lack of effect on head and upper limb tremor in patients with dystonia suggests that the pathophysiological mechanisms underlying tremor in these two conditions and in different body parts may be distinct.


Omeprazole as a potent activator of human cytosolic aldehyde dehydrogenase ALDH1A1.
Accumulation of lipid aldehydes plays a key role in the etiology of human diseases where high levels of oxidative stress are generated. In this regard, activation of aldehyde dehydrogenases (ALDHs) prevents oxidative tissue damage during ischemia-reperfusion processes. Although omeprazole is used to reduce stomach gastric acid production, in the present work this drug is described as the most potent activator of human ALDH1A1 reported yet. Docking analysis was performed to predict the interactions of omeprazole with the enzyme. Recombinant human ALDH1A1 was used to assess the effect of omeprazole on the kinetic properties. Temperature treatment and mass spectrometry were conducted to address the nature of binding of the activator to the enzyme. Finally, the effect of omeprazole was evaluated in an in vivo model of oxidative stress, using E. coli cells expressing the human ALDH1A1. Omeprazole interacted with the aldehyde binding site, increasing 4-6 fold the activity of human ALDH1A1, modified the kinetic properties, altering the order of binding of substrates and release of products, and protected the enzyme from inactivation by lipid aldehydes. Furthermore, omeprazole protected E. coli cells over-expressing ALDH1A1 from the effects of oxidative stress generated by H2O2 exposure, reducing the levels of lipid aldehydes and preserving ALDH activity. Omeprazole can be repositioned as a potent activator of human ALDH1A1 and may be proposed for its use in therapeutic strategies, to attenuate the damage generated during oxidative stress events occurring in different human pathologies.


Production diseases of the transition cow.
Production diseases of the dairy cow are caused by a level of production inconsistent with nutrient intake, provision of an inadequate diet, an unsuitable environment, an inappropriate breeding policy or various combinations of these factors. Although the transition period of 3 weeks pre-calving until 3 weeks post-calving is associated with a peak incidence of production disease, the effects of these diseases on dairy cow health and productivity extend far into the following lactation. Recent advances in understanding of production diseases include the emergence of propylene glycol and rumen protected choline as the supplements of choice for preventing fatty liver and the absence of any preventative effect of increased energy density in the close-up dry period diet on this condition; the linear negative influence of dietary cation anion difference (DCAD) on the incidence of milk fever regardless of urinary pH or the target level of dietary DCAD achieved; the inflammatory response associated with subacute rumen acidosis and its effect on feed intake; an increased awareness of the potential for antioxidant status to improve immunity and health in the transition period; the development of more standardised diagnostic criteria and treatment protocols for uterine infection. A significant body of knowledge already exists which should allow for the optimal management and prevention of bovine production diseases. One of the important challenges facing the dairy industry is the development, implementation and economic assessment of practical, integrated, blueprints of best practice for prevention of the production diseases and other diseases of the dairy cow.


Palisading-like arrangement of immature ganglion cell in myenteric ganglia is a unique pathological feature of immaturity of ganglia.
Immaturity of ganglia (IG), an allied disorder of Hirschsprung disease (AD-HSCR), develops as neonatal ileus, but the dysmotility spontaneously resolves after several months. The diagnosis of IG using HE staining is often difficult. We herein report a new pathological finding of IG called the 'palisading-like pattern', which may be helpful for improving the diagnostic accuracy. Cases of IG that were managed over the past 28 years were retrospectively reviewed. We investigated the clinical course and pathological findings for Hematoxylin-Eosin (HE) staining. The conventional diagnostic criteria for IG were (1) a normal or slightly increased number of ganglion cells and (2) ganglion cells with small nuclei. Among the 155 cases, 28 were diagnosed with IG, and 10 were retrospectively confirmed by HE staining. A palisading-like pattern was confirmed at the time of the initial ileostomy (median age, 2.5 days), and the palisading-like pattern had completely disappeared by the time of stoma closure (median age, 215 days) in all 10 cases. A palisading-like pattern is not present in other diseases. Even if immunostaining data are not available for a further analysis, the detection of a palisading-like pattern on HE staining makes an accurate diagnosis possible. LEVEL IV.


Tailoring Poly(Styrene-co-maleic anhydride) Networks for All-Polymer Dielectrics Exhibiting Ultrahigh Energy Density and Charge-Discharge Efficiency at Elevated Temperatures.
Polymer film capacitors have been widely used in electronics and electrical power systems due to their advantages of high power densities, fast charge-discharge speed, and great stability. However, the exponential increase of electrical conduction with temperature and applied electric field substantially degrades the capacitive performance of dielectric polymers at elevated temperatures. Here, the first example of controlling the energy level of charge traps in all-organic crosslinked polymers by tailoring molecular structures that significantly inhibit high-field high-temperature conduction loss, which largely differs from current approaches based on the introduction of inorganic fillers, is reported. The polymer network with optimized crosslinking structures exhibits an ultrahigh discharged energy density of 7.02 J cm-3 with charge/discharge efficiencies of >90% at 150 °C, far outperforming current dielectric polymers and composites. The charge-trapping effects in different crosslinked structures, as the origins of the marked improvements in the high-temperature capacitive performance, are comprehensively investigated experimentally and confirmed computationally. Moreover, excellent cyclability and self-healing features are demonstrated in the polymer film capacitors. This work offers a promising pathway of molecular structure design to scalable high-energy-density polymer dielectrics capable of operating under harsh environments.


Phenolic compounds of Phellinus spp. with antibacterial and antiviral activities.
Phellinus Quél is one of the largest genera of Hymenochaetaceae; it comprises about 220 species widely distributed on Earth. Most Phellinus species are lignicolous mushrooms that accumulate bioactive compounds. This research studied the phenolic composition of Phellinus spp. and their relationship with antibacterial and antiviral capacity. Phenolics were extracted from Phellinus badius, P. fastuosus, and P. grenadensis; their antiviral and antibacterial activities were evaluated against Listeria monocytogenes, Staphylococcus aureus, Salmonella enterica, and Escherichia coli O157: H7; and the bacteriophages MS2 and Φ- × 174. Gallic acid, chlorogenic acid, caffeic acid, epicatechin, ferulic acid, catechin, 1,3-dicaffeoylquinic acid, p-coumaric acid, and rutin were found in different proportions among Phellinus spp. Total phenolic content ranged from 96 to 209 mg GAE/g, and total flavonoids from 10 to 27 QE/g. The minimum inhibitory concentrations of P. badius, P. grenadensis, and P. fastuosus against E. coli O157: H7 were 13, 20, and 27 mg/mL, against S. enterica were 20, 30, and 15 mg/mL, and against L. monocytogenes were 10, 15, and 25 mg/mL, respectively. The phenolic content was better correlated with the antibacterial effect against E. coli O157: H7 and L. monocytogenes (r = 0.8-0.9), but not against S. enterica (r = 0.05). The antiviral activity of the extracts (0.9 mg/mL) was 29 to 41% against MS2 and 27 to 38% for Φ-X174 virus (r = 0.8-0.9). In silico analysis showed binding energy values of - 7.9 and - 4.8 kcal/mol between the identified phenolic compounds and the M and G proteins of each virus. The antibacterial and antiviral properties of Phellinus species were correlated with the phenolic content.


Acquired Cardiac Dextroposition: A Step in the Right Direction?
Despite tremendous advancements in electrocardiography machine algorithms, accurately diagnosing dextrocardia, pseudodextrocardia, and limb lead reversal remains a serious challenge. We present the case of a patient with acquired cardiac dextroposition, or "pseudodextrocardia," in which the electrocardiography machine algorithm incorrectly interpreted the finding as "dextrocardia vs limb lead reversal." (Level of Difficulty: Advanced.).


CDK4/6 inhibition in early and metastatic breast cancer: A review.
Breast cancer (BC) is responsible for 14% of cancer-related deaths in women [1]. Cyclin-dependent kinase (CDK) 4/6 inhibitors are a new class of selective drugs, offering an effective and tolerable treatment. CDK4/6 inhibitors induce cell cycle arrest in the G1 phase, and may thereby prevent tumour progression. Three CDK4/6 inhibitors have been tested in clinical BC trials: palbociclib, ribociclib, and abemaciclib. The Food and Drug Administration (FDA) and European Commission (EMA) have approved palbociclib for the treatment of patients HR+ HER2- locally advanced or metastatic BC (aBC) in combination with an aromatase inhibitor as initial therapy in postmenopausal women or in combination with fulvestrant in women who have received prior endocrine therapy. Ribociclib has been approved by the FDA in combination with an aromatase inhibitor as initial therapy for postmenopausal women with HR+ HER2- aBC. Moreover, CDK4/6 inhibitors have shown promising results in the (neo)adjuvant setting. In this review, the principal completed and ongoing clinical trials in aBC are reviewed for both the metastatic as (neo)adjuvant setting. Tables will provide a complete overview of the ongoing clinical trials. At last, the future perspectives of these CDK4/6 inhibitors are discussed.


Posterior urethral valves: determinants of outcome in a developing country.
This study aims to evaluate posterior urethral valve (PUV) in a developing country with focus on the profile of the disease, determinants of outcome and the challenges of management. Analysis of data collected prospectively from 31 patients managed for PUV at the University of Nigeria Teaching Hospital, Enugu from January 2008 to December 2009. The median age at presentation was 2.5 years (range 2 weeks-15 years). Only two (6.5%) had pre-natal diagnosis. Twenty-six (83.9%) had one or more complications of the disease at presentation. The mean estimated glomerular filtration rate was 39.5 mL/min/1.73 m(2) (range 4.4-116.0). There was hydronephrosis involving 50 renal units, and vesicoureteral reflux involving 22 renal units. Eight cases required upper tract diversion and four required dialysis prior to definitive catheter ablation. After average follow-up of 12.6 months (range 3-22 months), 18 (58.1%) cases had clinical and radiological improvement, 9 (29%) had persisting poor renal function and 4 (12.9%) died from acute renal failure and end-stage renal disease. Associated pulmonary hypoplasia in neonates, presentation at adolescent age, bilateral vesicoureteral reflux and estimated glomerular filtration rate <10.0 at presentation adversely affected outcome. Delayed diagnosis, dearth of facilities and resource deficiency remain a challenge. Significant cases of PUV present late with complications in our setting and have high morbidity and mortality. The poor outcome may be related to delayed diagnosis, poor renal function at presentation and poor renal support. Improving time to diagnosis and renal support may lead to better outcome.


Maternal vitamin D and offspring fracture risk: the Vitamin D in Pregnancy study.
Vitamin D is important for bone health and strength. Previous studies report 25-hydroxyvitamin D (25(OH)D) exposure during pregnancy may impact offspring bone health later in life. In this study, maternal 25(OH)D at recruitment was associated with a lower fracture risk in boys and an increased fracture risk in girls at 28-32 weeks gestation. Maternal 25-hydroxyvitamin D (25(OH)D) in pregnancy has been shown to be associated with offspring bone measures in some studies, but few have examined fracture risk. We aimed to determine associations between maternal vitamin D status and offspring fracture risk. In total, 475 mother-child pairs participating in the Vitamin D in Pregnancy study in southeastern Australia were recruited. Maternal serum samples were taken at recruitment (< 16 weeks gestation) and/or 28-32 weeks gestation and analysed for 25(OH)D. Incident fractures in children were ascertained from date of birth (2002-2004) until December 31, 2012. Cox proportional hazard models included maternal age at recruitment, offspring sex, birth weight, gestation length and season of vitamin D sample. Complete follow-up data were available for 400 children (median age = 9.5 years). There were 68 (17.0%) children who sustained at least one fracture. Higher maternal 25(OH)D (per 10 nmol/L) in early gestation was weakly associated with a decreased fracture risk in boys (HR 0.82; 95% CI 0.68, 0.99; p = 0.048) but not girls (HR 1.10; 95% CI 0.98, 1.25; p = 0.11). At late gestation, higher maternal 25(OH)D was associated with increased fracture risk in girls (HR 1.11; 95% CI 1.01, 1.23; p = 0.038) but not boys (HR 0.94; 95% CI 0.80, 1.10; p = 0.42). No statistically significant relationships were detected in analyses investigating 25(OH)D as a categorical variable. There is some evidence that higher maternal 25(OH)D at recruitment was associated with lower fracture risk in boys, while higher maternal 25(OH)D at 28-32 weeks gestation was associated with an increased fracture risk in girls.


Laparoscopic surgery: current status, issues and future developments.
Laparoscopic surgery has come a long way since its introduction two decades ago. In essence it represents a new era of technology-dependent surgical interventions, and to some extent its future progress depends on the growth of interventional technologies and devices (facilitative, enabling and additive). Laparoscopic surgery has had a significant impact on all surgical disciplines and is now firmly embedded in routine surgical practice. There remain, however, several outstanding issues that need to be addressed. These concern mainly quality assurance, training, resource allocation, assessment of competence and tiers of laparoscopic surgical practice in line with the changing situation facing the next generation of surgeons.


Pancreas cancer -- duct cell adenocarcinoma: survival in relation to site, size, stage and type of therapy.
The records of 508 patients with cancer of the pancreas admitted to Memorial Hospital in New York from 1949 through 1972 were examined. Ten distinctive morphological types were delineated and the pathological features and response to various modes of therapy of the most common type -- duct adenocarcinoma -- were studied in 380 patients. Median survival was related to: the site of the cancer -- it was longer with tumors of the head than those of the body or tail; the size of the tumor -- cancers smaller than 3 cm were associated with over twice the survival of those with large tumors; the stage -- stage I patients had over twice the survival of those of stages II and III; and the type of therapy employed. Actuarial survival rate at one year was: with no specific therapy, 0%; with chemotherapy, 1%; after palliative by-pass surgery, 3%; following radiation therapy, 9%; and after all types of "surative" surgery, 21%. The only survivors at five years were in the "curative" surgery group, but these represented only 1% of all patients. Revolutionary changes in diagnosis and therapy will have to occur if significant increase in survival rate is to be achieved.


Decreasing antibiotic overuse in neonatal intensive care units: quality improvement research.
Overutilization of antibiotics and emergence of resistant bacteria are important problems, particularly in intensive care units. To date, reproducible interventions to improve antibiotic utilization in hospitals have not been proven to be effective or safe. Evidence-based medicine, clinical practice guidelines, and health information technology are frequently promoted as means to cross the "quality chasm" described by the Institute of Medicine. This article outlines how these approaches intersect in a strategy for quality improvement research evaluating the safety and effectiveness of clinical practice guidelines designed to improve antibiotic use in neonatal intensive care units.


Intrahepatic absorbable fine mesh packing of hepatic injuries: preliminary clinical report.
A previous report from the authors' institution reported the effectiveness of hepatic packing with absorbable fine mesh (AFMP) for the control of hemorrhage in an animal model with an otherwise lethal hepatic injury. The technique has subsequently been applied to 12 abdominal trauma patients with hemodynamic instability and actively hemorrhaging hepatic injuries. Two patients expired in the operating room owing to uncontrolled hemorrhage from hepatic and associated injuries for a mortality of 16.7%. AFMP was successful in controlling hemorrhage in the remaining 10 patients. Hepatic injuries ranged from grade II to grade V, and all were actively hemorrhaging at the time of exploration. None of the surviving 10 patients experienced early or late recurrent bleeding attributable to the hepatic injuries, and there were no intraabdominal abscesses or late deaths. Liver function studies returned to normal prior to discharge in all surviving patients. Follow-up included serial computed tomographic scans, which demonstrated fibrosis incorporating the mesh packing. Complete resolution of injury and mesh appears to proceed over approximately a 6-month period. AFMP is a safe, effective method for controlling hepatic hemorrhage. It is easy to perform in the operating room, offers an excellent matrix for hemostasis, provides tamponade of bleeding sites, and does not require reoperation for removal of packing material, as is necessary with conventional, nonabsorbable packing techniques.


[Effect of cholinergic substances on electrical processes in a ganglion of the enteric nervous system].
In the isolated in vitro segments of cat small intestine the sensitivity of myenteric neurons was studied by means of application of acetylcholine, nicotine, lobeline. The action of these drugs depended on their concentration: 10(-10)--10(-6)g/ml usually increased while larger concentrations (10(-5)g/ml) decreased the spontaneous activity. The preliminary application of d--tubocurarine (10(-6)g/ml), hexamethonium (10(-7)g/ml), and atropine (10(-6)g/ml) prevented the excitatory effects or suppressed neuronal discharges. The alteration of spontaneous activity seems to depend on the postsynaptic action of cholinergic drugs in M- and N-cholinoreceptors.


Tolerance to morphine microinjections in the periaqueductal gray (PAG) induces tolerance to systemic, but not intrathecal morphine.
The acquisition and retention of tolerance to the antinociceptive effect of supraspinal morphine on the tail withdrawal reflex was assessed in rats implanted with unilateral cannulae in the periaqueductal gray (PAG). Development of tolerance to daily microinjections of morphine was indicated by the return of the tail flick response within 4 days, followed by the recovery of analgesic sensitivity one week later. After tolerance had developed, the effect of an acute systemic (1.5-4.5 mg/kg) or intrathecal (5-15 micrograms) morphine injection was determined. 'Cross-tolerance' was observed between systemic and supraspinal morphine but not between intrathecal and supraspinal morphine. The data indicate that tolerance to chronic intracerebral morphine produces the same behavioral consequences as tolerance to systemic morphine.


Artificial intelligence-integrated smartphone-based handheld detection of fluoride ion by Al3+-triggered aggregation-induced red-emssion enhanced carbon dots.
Artificial intelligence (AI)-integrated smartphone-based handheld determination platform, based on 3D printed accessory, Al3+-triggered aggregation-induced red-emssion enhanced carbon dots (CDs) test strip, and smartphone with self-developed YOLO v3 AI algorithm-based application, proves the feasibility for intelligent real-time on-site quantitation of F- through tracking a consecutive fluorescence (FL) colour change. CDs, manifesting dual emission of moderate green emission at 512 nm and weak red one at 620 nm under 365 nm excitation, were synthesized hydrothermally from alizarin carmine and citric acid. CDs@Al3+, with distinct aggregation-induced red-emssion enhancement and green-emssion quenchment, were prepared by adding Al3+ to the CDs solution. Inspiringly, due to intrinsic ratiometric FL variation (I620/I512), CDs@Al3+ engender a successive FL colour variation from red to green in response to different concentrations of F- with low limit of detection of 7.998 μM and wide linear range of 150-1200 µM based on excellent linearity correlation between R/G value and F- concentration. Furthermore, F- content in tap water, toothpaste and milk could be intelligently, speedily, and straightforwardly analyzed through the AI-integrated smartphone-based handheld detection platform. It is fervently desired that our study will motivate a brand-new perspective for the promotion of efficacious detection strategy and the extension of practical application promise.


Microbiological composition of follicular fluid in patients undergoing IVF and its association with infertility.
In recent years, the incidence of female infertility has risen sharply, which is affected by many factors. It was recognized that female reproductive tract microbes play a role in the process of female conception. If the reproductive tract microbes could solve a certain proportion of infertility, it would certainly reduce the pain and economic burden of many patients. The objective of this study was to investigate the microbial community composition of follicular fluid in infertile patients and its potential impact on infertility. Follicular fluid from 49 primary infertility and 52 secondary infertility patients was collected by a negative pressure needle, and the microbiota was analyzed by 16S rDNA sequencing. It was found that Lactobacillus, especially L. crispatus, might have a positive effect on female pregnancy. Considering the presence or absence of male factors and different body mass indices, L. iners might inhibit female pregnancy. However, L. iners seemed to play a positive role in egg maturation, while Gardnerella and Cutibacterium acnes might have a negative effect on female pregnancy. This study suggested the potential role of Lactobacillus in follicular fluid in improving female infertility and provided a theoretical basis for the future microbiological treatment of female infertility.


FYN is required for ARHGEF16 to promote proliferation and migration in colon cancer cells.
ARHGEF16 is a recently identified Rho-family guanine nucleotide exchange factor (GEF) that has been implicated in the activation of Rho-family GTPases such as Rho G, Rac, and Cdc42. However, its functions in colon cancer cell proliferation and migration are not well understood. In this study, we showed that ARHGEF16 was highly expressed in clinical specimens of colon cancer. In colon cancer cells, ARHGEF16-stimulated proliferation and migration in vitro and in vivo. Furthermore, we identified a nonreceptor tyrosine kinase, FYN, as a novel partner of ARHGEF16. Knocking down FYN expression decreased ARHGEF16 protein level in colon cancer cells. We further demonstrated that ARHGEF16-induced colon cancer cell proliferation and migration were dependent on FYN since knockdown FYN abolished the ARHGEF16-induced proliferation and migration of colon cancer cells. The FYN-ARHGEF16 axis mediates colon cancer progression and is a potential therapeutic target for colon cancer treatment.


The effects of ethanol methotrexate and diphenylhydantoin on [14C] leucine incorporation by human trophoblast cells cultured in vitro.
The effects of alcohol, diphenylhydantoin and methotrexate on protein synthesis by human trophoblast have been studied in vitro using a cell culture technique. None of the drugs depressed protein synthesis at pharmacological levels and for diphenylhydantoin there was evidence that the cellular accumulation of this drug was negligible.


Toxinotyping and molecular characterization of antimicrobial resistance in Clostridium perfringens isolated from different sources of livestock and poultry.
The present study was designed to understand the presence of antimicrobial resistance among the prevalent toxinotypes of Clostridium perfringens recovered from different animals of Tamil Nadu, India. A total of 75 (10.76%) C. perfringens were isolated from 697 multi-species fecal and intestinal content samples. C. perfringens type A (90.67%), type C (2.67%), type D (4%) and type F (2.67%) were recovered. Maximum number of isolates were recovered from dog (n = 20, 24.10%) followed by chicken (n = 19, 5.88%). Recovered isolates were resistant to gentamicin (44.00%), erythromycin (40.00%), bacitracin (40.00%), and tetracycline (26.67%), phenotypically and most of the isolates were found to be resistant to multiple antimicrobials. Genotypic characterization revealed that tetracycline (41.33%), erythromycin (34.66%) and bacitracin (17.33%) resistant genes were present individually or in combination among the isolates. Combined results of phenotypic and genotypic characterization showed the highest percentage of erythromycin resistance (26.66%) among the isolates. None of the isolates showed amplification for lincomycin resistance genes. The correlation matrix analysis of genotypic resistance showed a weak positive relationship between the tetracycline and bacitracin resistance while a weak negative relationship between the tetracycline and erythromycin resistance. The present study thus reports the presence of multiple-resistance genes among C. perfringens isolates that may be involved in the dissemination of resistance to other bacteria present across species. Further insights into the genome can help to understand the mechanism involved in gene transfer so that measures can be taken to prevent the AMR spread.


Auditory event-related potentials (P3a, P3b) and genetic variants within the dopamine and serotonin system in healthy females.
The late positive components of the human event-related brain potential comprise electrocortical reflections of stimulus-driven attentional capture (the anteriorly distributed P3a) and top-down control detection of relevant events (the posteriorly distributed P3b). As of yet, the neuropharmacologic and neurogenetic origin of the P3a and P3b is not fully understood. In this study, we address the contribution of dopaminergic and serotoninergic mechanisms. Sixty healthy females completed an active auditory novelty oddball paradigm while EEG was recorded. In all subjects, genetic polymorphisms within the dopamine system (dopamine transporter [DAT1], catecholamine-O-methyltransferase val158met [COMT val158met]) and the serotonin system (serotonin transporter [5HTTLPR]) were assessed. Across genotypes, novels (relative to standards) elicited a fronto-centrally distributed P3a, and targets (relative to standards) a parieto-centrally distributed P3b. Genotypes effects were observed for both P3a (COMT, 5HTTPLR) and P3b (DAT1, COMT, 5HTTLPR) only at prefrontal electrode location (Fz). Specifically, the frontal P3a was enhanced in COMT met/met homozygotes, but not in DAT1 9R. The target-related P3b was enhanced in COMT met/met and DAT1 9R relative to its genetic counterparts, but only at frontal electrodes. This 'anteriorized' enhancement may reflect either an additional frontal component in the target-related P3 dependent on dopamine, or a more subtle shift in the neural ensemble that generates the target-related P3. Results for 5HTTLPR short allele homozygotes mimicked those in COMT met/met homozygotes. In all, the present findings suggest involvement of frontal-cortical dopaminergic and serotoninergic mechanisms in bottom-up attentional capture (COMT val158met, 5HTTLPR), with an additional top-down component sensitive to striatal signals (DAT1).


Chronic degeneration of aminergic nerve endings and blood-aqueous barrier.
Chemical sympathectomy of the anterior segment of the eye was performed in rabbits with 6-hydroxydopamine (6-OHDA) intravitreously injected. The response of the pupillary diameter (PD) and intraocular pressure (IOP) to NE, E and Isoproterenol was determined through instillation of the drugs in the pretreated and control eyes. The results were as follows: 1) Both PD and IOP at different intervals of time from the injection show a sharp decrease in the treated eye. 2) About four weeks after the injection, the instillation of NE and E increases the PD only in the 6-OHDA pretreated eyes, while IP administration is not effective on both control and pretreated eyes. 3) The instillation of the three drugs, while decreasing IOP in the control eyes, does not modify the already low IOP in the pretreated eyes. The authors suggest the presence of a postdenervation supersensitivity affecting only the alpha receptors, since the beta stimulant IP is inactive in both treated and untreated eyes.


Managing the phase-down of amalgam: part II. Implications for practising arrangements and lessons from Norway.
The announcement of the Minamata Convention has triggered the lead into a phase-down in the use of dental amalgam. This paper considers aspects of this development in the context of the experience of banning the use of dental amalgam in Norway. It is suggested that strong top-down leadership and joined-up working by all relevant stakeholders, including patients, may be one of the most important keys to an effective, seamless transition to the provision of preventatively orientated, patient-centred, minimally interventive operative dentistry, based on state-of-the-art selection and application of tooth-coloured restorative materials. The benefits of such a transition are considered to be an important goal for dentistry in the UK.


Modeling sustainable reuse of nitrogen-laden wastewater by poplar.
Numerical modeling was used to simulate the leaching of nitrogen (N) to groundwater as a consequence of irrigating food processing wastewater onto grass and poplar under various management scenarios. Under current management practices for a large food processor, a simulated annual N loading of 540 kg ha(-1) yielded 93 kg ha(-1) of N leaching for grass and no N leaching for poplar during the growing season. Increasing the annual growing season N loading to approximately 1,550 kg ha(-1) for poplar only, using "weekly", "daily" and "calculated" irrigation scenarios, yielded N leaching of 17 kg ha(-1), 6 kg ha(-1), and 4 kg ha(-1), respectively. Constraining the simulated irrigation schedule by the current onsite wastewater storage capacity of approximately 757 megaliters (Ml) yielded N leaching of 146 kg ha(-1) yr(-1) while storage capacity scenarios of 3,024 and 4,536 Ml yielded N leaching of 65 and 13 kg ha(-1) yr(-1), respectively, for a loading of 1,550 kg ha(-1) yr(-1). Further constraining the model by the current wastewater storage volume and the available land area (approximately 1,000 hectares) required a "diverse" irrigation schedule that was predicted to leach a weighted average of 13 kg-N ha(-1) yr(-1) when dosed with 1,063 kg-N ha(-1) yr(-1).


Risk of venous thromboembolism or hemorrhage among individuals with chronic kidney disease on prophylactic anticoagulant after hip or knee arthroplasty.
Chronic kidney disease (CKD) confers a high risk of thrombosis and bleeding. However, little evidence exists regarding the optimal choice of postoperative thromboprophylaxis in these patients. We conducted a population-based, retrospective cohort study among adults ≥66 years old with CKD undergoing hip or knee arthroplasty who had filled an outpatient prophylactic anticoagulant prescription between 2010 and 2020 in Ontario, Canada. The primary outcomes of venous thrombosis (VTE) and hemorrhage were identified by validated algorithms using relevant diagnoses and billing codes. Overlap-weighted cause-specific Cox proportional hazard models were used to examine the association of direct oral anticoagulants (DOAC) on the 90-day risk of VTE and hemorrhage compared with low-molecular-weight heparin (LMWH). A total of 27 645 patients were prescribed DOAC (N = 22 943) or LMWH (N = 4702) after arthroplasty. Rivaroxaban was the predominant DOAC (94.5%), while LMWH mainly included enoxaparin (67%) and dalteparin (31.5%). DOAC users had higher eGFRs, fewer co-morbidities, and surgery in more recent years compared to LMWH users. After weighing, DOAC (compared with LMWH) was associated with a lower risk of VTE (DOAC: 1.5% vs. LMWH: 2.1%, weighted hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.59-0.94) and a higher risk of hemorrhage (DOAC: 1.3% vs. LMWH: 1.0%, weighted HR 1.44, 95% CI 1.04-1.99). Additional analyses including a more stringent VTE defining algorithm, different eGFR cut-offs, and limiting to rivaroxaban and enoxaparin showed consistent findings. Among elderly adults with CKD, DOAC was associated with a lower VTE risk and a higher hemorrhage risk compared to LMWH following hip or knee arthroplasty.


Mitochondrial phosphoenolpyruvate carboxykinase from the chicken. Comparison of the cDNA and protein sequences with the cytosolic isozyme.
The amino acid sequence of the mitochondrial form of phosphoenolpyruvate carboxykinase (GTP) (EC 188.8.131.52) (PEPCK-M) from the chicken was deduced from the 3571 nucleotide sequence of three overlapping cDNA clones. The derived protein sequence, which includes 607 amino acids of the mature enzyme and a leader sequence, was aligned with nine tryptic peptides of PEPCK-M and the primary sequence of the cytosolic form of PEPCK from chicken. Secondary structure predictions for the two PEPCK isozymes indicated similar packing elements of conserved, hydrophobic beta strands in the central core of the primary sequence. This core protein, which contained three GTP-binding consensus elements, was 80% identical in the two chicken isozymes, although the overall level of identity was only 63% for amino acids and 60% for nucleotides. The untranslated regions of the two cDNAs were dissimilar, although both mRNAs have potential for significant secondary structure. The PEPCK-M mRNA contained several G-C-rich regions which demonstrated free energies of formation in dyad symmetry programs up to -70 kcal/mol. The 1.6-kilobase (kb) 3'-untranslated region contained several repeat elements including one of 11 base pairs, which was present 30 times; but, a signal sequence for polyadenylation was not present. Each of the three PEPCK-M cDNA clones recognized two mRNAs of 4.2 and 3.4 kb in the livers and kidneys of starved or normally fed chickens. However, the level of these two related PEPCK-M mRNAs changed in response to cAMP treatment, with the larger mRNA predominant at 20 and 160 min and the 3.4-kb mRNA present at intermediate times. In contrast, the level of the 2.8-kb PEPCK-C mRNA increased dramatically upon addition of the cyclic nucleotide, particularly in the liver where it was not detected without cAMP induction. Thus, PEPCK-M and PEPCK-C, clearly represented the products of two distinct genes, which were distinguished by altered protein sequences and non-cross-hybridizing, differentially regulated mRNAs.


Abnormal motion displacement thresholds are associated with fine scale luminance sensitivity loss in glaucoma.
This study tests the hypothesis that abnormal motion displacement thresholds coexist with scotomas on a finer spatial scale than is measurable by conventional Humphrey perimetry. Eighteen patients with primary open angle glaucoma in one eye, and 18 age matched normal controls underwent motion displacement threshold testing and high spatial resolution perimetry. The motion displacement thresholds were significantly elevated in the glaucoma eyes, in 73% this exceeded normal limits. Ten glaucoma eyes had normal Humphrey 24-2 field nearest the motion test site: of these seven had abnormally elevated motion displacement thresholds and six had fine scale threshold depressions detected with high spatial resolution perimetry. This result suggests that glaucomatous elevations of motion displacement threshold may be present in areas of normal Humphrey 24-2 field, and this may coexist with measurable scotomas beyond the resolution of conventional Humphrey perimetry in some, but not all patients.


Differential synthesis of histone H1 during early spherulation in Physarum polycephalum.
H1 and P2 (an H1 degree/HMG-like protein) accumulate during exponential growth of Physarum microplasmodia (unpublished results), indicating that these proteins may play a role in differentiation (spherulation). To test this hypothesis, pulse labelling using [14C]lysine was used to determine whether any differential histone synthesis occurs during salts-induced spherulation. A peak in the uptake of [14C]lysine into microplasmodia was detected between 12 and 24 h following salts-induction. During the same interval, incorporation of label into the CaCl2-extracted histones occurred, with H1 being synthesised at approx. 3 times the level of the core histones and P2. Densitometry of SDS-PAGE gels showed that high levels of H1 were maintained up to 40 h in salts medium, beyond the observed peak in synthesis. The synthesis and accumulation of high levels of H1 during early spherulation indicates a role for this histone in the initiation and maintenance of a transcriptionally inactive differentiated state.


Organization of anterior cingulate and frontal cortical projections to the anterior and laterodorsal thalamic nuclei in the rat.
The anterior and laterodorsal thalamic nuclei provide massive projections to the anterior cingulate and frontal cortices in the rat. However, the organization of reciprocal corticothalamic projections has not yet been studied comprehensively. In the present study, we clarified the organization of anterior cingulate and frontal cortical projections to the anterior and laterodorsal thalamic nuclei, using retrograde and anterograde axonal transport methods. The anteromedial nucleus (AM) receives mainly ipsilateral projections from the prelimbic and medial orbital cortices and bilateral projections from the anterior cingulate and secondary motor cortices. The projections from the anterior cingulate cortex are organized such that the rostrocaudal axis of the AM corresponds to the rostrocaudal axis of the cortex, whereas those from the secondary motor cortex are organized such that the rostrocaudal axis of the AM corresponds to the caudorostral axis of the cortex. The ventromedial part of the anteroventral nucleus receives ipsilateral projections from the anterior cingulate cortex and bilateral projections from the secondary motor cortex, in a topographic manner similar to the projections to the AM. The ventromedial part of the laterodorsal nucleus (LD) receives ipsilateral projections from the anterior cingulate and secondary motor cortices. The projections are roughly organized such that more dorsal and ventral regions within the ventromedial LD receive projections preferentially from the anterior cingulate cortex. The difference in anterior cingulate and frontal cortical projections to the anterior and laterodorsal nuclei may suggest that each thalamic nucleus plays a different functional role in spatial memory processing.


NMR study of whole rat bile: the biliary excretion of 4-cyano-N,N-dimethyl aniline by an isolated perfused rat liver and a liver in situ.
The structure of two biliary metabolites of 4-cyano-N,N-dimethyl aniline (CDA) contained in whole rat bile have been studied in detail by NMR at 400 MHz. A 4-cyano-N-methyl glutathione-N-aniline conjugate was identified as a biliary metabolite of CDA using relatively simple 1H NMR techniques. Isotopically 13C labelled CDA was used to generate 13C labelled xenobiotic conjugates. Our use of 1H/13C heteronuclear NMR techniques, in particular a 13C-selective HMQC-TOCSY experiment, allowed a N-beta-glucuronide conjugate, a previously unknown biliary metabolite of CDA, to be identified. Bile samples obtained from both the isolated perfused rat liver and the rat liver in situ were analysed.


Clinical outcomes after autograft reconstruction for sternoclavicular joint instability.
Instability of the sternoclavicular (SC) joint is a rare condition. However, in some cases, SC joint instability may lead to persistent pain and impairment of shoulder function that requires surgical management. This study evaluated clinical outcomes after SC joint reconstruction with hamstring tendon autograft in patients with SC joint instability. From December 2010 to January 2014, 21 reconstructions of the SC joint with hamstring tendon autograft were performed. Outcomes data were prospectively collected and retrospectively reviewed. Data analyzed included American Shoulder and Elbow Surgeons score, Quick Disability of the Arm, Shoulder and Hand, physical component of the Short Form 12, and Single Assessment Numeric Evaluation scores. Pain with activities of daily living, work, and sleep were separately analyzed along with painless use of arm for activities. Patients were also questioned regarding postoperative satisfaction. Nine women and 10 men (2 bilaterals), with a mean age of 30 years (range, 15-56 years), were monitored for a mean of 2 years (range, 12-36 months) postoperatively. Mean American Shoulder and Elbow Surgeons, Quick Disability of the Arm, Shoulder and Hand, and Single Assessment Numeric Evaluation scores significantly improved (P < .001). Pain scores also improved over preoperative baselines, including pain with activities of daily living, work, and sleep (P < .001). Median satisfaction at final follow-up was 8.5 (range, 7-10). There were no intraoperative or postoperative complications and no cases of recurrent instability. Free hamstring tendon autograft reconstruction for SC joint instability resulted in significantly improved clinical outcomes with high patient satisfaction and no intraoperative or postoperative complications.


Antibody Arrays: Barcode Technology.
Antibody microarray is a fundamental, high-content technology for analyzing biomarkers with a multiplexity even at the proteomic level. Recent advancement in this field has driven the antibody array into a new territory related with single-cell analysis. Here we describe a flow pattern-based method for producing a high-density barcode antibody microarray for the detection of proteins in fluidic samples and in single cells. The antibody microarray is fabricated by a perpendicularly oriented flow patterning of single-stranded barcode DNAs, which are then converted into DNA-antibody conjugates. Compared to conventional microarrays, this barcode antibody microarray features a simple and high-throughput assay while achieving both high sensitivity and specificity. This barcode technology provides new clues for developing next-generation antibody microarrays and can be widely used in protein biomarker discovery, cell signaling network analysis, and disease diagnosis and prognosis.


Magnetic colloids for the generic capture of viruses.
In molecular biology or in the diagnostic field, a strong interest has been devoted to the use of magnetic nanoparticles as an efficient tool for a fast and easy biomolecule extraction. Various methods allow the synthesis of numerous types of magnetic particles, but very few of them can be adapted to biological protocols. For biological tests based on the final detection of nucleic acids, the major difficulties in the choice of these magnetic beads are their fast magnetic separation, requiring a high magnetic oxide content and overall a good compatibility with enzymes used for nucleic acid amplification. In this study, magnetic colloids were obtained from oil in water (o/w) magnetic emulsion by a two-step polymer immobilization procedure. First, a polycation, poly(ethyleneimine), was adsorbed to ensure charge inversion of the emulsion droplets. Then poly(maleic anhydride-co-methyl vinyl ether) was either chemically grafted or adsorbed if under its hydrolyzed form. The obtained colloids were characterized in terms of colloidal stability, surface charge density, and morphology and were evaluated in a reverse transcription-PCR (RT-PCR) inhibition test. Selected colloids were used for the nonspecific capture of viruses, with RT-PCR being used as a means of detection. Particle size and charge studies allowed us to follow each step of their synthesis, showing the relevance of these methods. The prepared magnetic particles exhibit a good RT-PCR compatibility when used in the range of 5-40 microg in the 50 microl amplification mix. Finally, virus capture tests revealed a capture efficiency of 90% with an average detection sensitivity of 10(3)pfu/ml.


Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival.
The aim of this study was to comprehensively delineate iron metabolism and its implications in patients with chronic heart failure (CHF). Iron deficiency is an emerging therapeutic target in CHF. Iron and clinical indexes were quantified in 157 patients with CHF. Several observations were made. First, iron homeostasis was deranged in anemic and nonanemic subjects and characterized by diminished circulating (transferrin saturation) and functional (mean cell hemoglobin concentration) iron status in the face of seemingly adequate stores (ferritin). Second, while iron overload and elevated iron stores were rare (1%), iron deficiency (transferrin saturation <20%) was evident in 43% of patients. Third, disordered iron homeostasis related closely to worsening inflammation and disease severity and strongly predicted lower hemoglobin levels independently of age, sex, erythrocyte sedimentation rate, New York Heart Association (NYHA) functional class, and creatinine. Fourth, the etiologies of anemia varied with disease severity, with an iron-deficient substrate (anemia of chronic disease and/or iron-deficiency anemia) evident in 16%, 72%, and 100% of anemic NYHA functional class I or II, III, and IV patients, respectively. Although anemia of chronic disease was more prevalent than iron-deficiency anemia, both conditions coexisted in 17% of subjects. Fifth, iron deficiency was associated with lower peak oxygen consumption and higher ratios of ventilation to carbon dioxide production and identified those at enhanced risk for death (hazard ratio: 3.38; 95% confidence interval: 1.48 to 7.72; p = 0.004) independently of hemoglobin. Nonanemic iron-deficient patients had a 2-fold greater risk for death than anemic iron-replete subjects. Disordered iron homeostasis in patients with CHF relates to impaired exercise capacity and survival and appears prognostically more ominous than anemia.


Molecular pathology of well-differentiated thyroid carcinomas.
The newly discovered molecular features of well-differentiated thyroid carcinomas derived from follicular cells are reviewed, within the frame of the 2004 WHO classification of thyroid tumours, under the following headings: "Follicular carcinoma", "Papillary carcinoma", "Follicular variant of papillary carcinoma" and "Hürthle cell tumours". A particular emphasis is put on the meaning of PAX8-PPARgamma rearrangements, RAS and BRAF mutations, and deletions and mutations of mitochondrial genes and of nuclear genes encoding for mitochondrial enzymes, for thyroid tumorigenesis.


Designing of fluorine-substituted benzodithiophene-based small molecules with efficient photovoltaic parameters.
In this study, four hole-transporting materials (JY-M1, JY-M2, JY-M3, and JY-M4) are designed by modifying benzothiadiazole-based core with diphenylamine-based carbazole via acceptors through thiophene linkers. The designed molecules exhibited deeper HOMO energy with smaller energy gaps than the reference JY molecule which enhance their hole mobility. The absorption spectra of the JY-M1, JY-M2, JY-M3, and JY-M4 molecules are located at 380 nm to 407 nm in the gaseous phase and 397 nm to 433 nm in the solvent phase, which is red-shifted and higher than the reference molecule, demonstrating that designed molecules possess improved light absorption properties and enhanced effective hole transfer. The dipole moments of the designed molecules (14.74 D to 26.12 D) indicate a greater ability for charge separation, solubility and will be beneficial to produce multilayer films. Moreover, the results of hole reorganization energy (0.38198 eV to 0.45304 eV) and charge transfer integral (0.14315 eV to 0.14665 eV) of designing molecules show improved hole mobility and lower recombination losses compared to the JY molecule. Overall, we suggested that the structural modifications in the designed molecules contributed to their enhanced efficiency in converting light energy into electrical energy and have the potential for utilization in solar devices, paving the way for future advancements in the field of photovoltaics.


Digital echocardiography and telemedicine applications in pediatric cardiology.
Digital echocardiography offers several advantages over videotape, including easy review, comparison, storage, postprocessing, and sharing of studies, quantitative analysis, and superior resolution. Newer echocardiography systems can write digital data to computer hardware, whereas older systems require digitization of analog data. Clinical and digital data compression is required to reduce study size. Clinical compression has been validated in several adult studies and one pediatric study. JPEG and MPEG digital compression ratios of 26:1 and 200:1, respectively, approximate S-videotape quality. JPEG is the DICOM 3.0 standard and is ideal for short loops, serial comparisons, and quantitative analysis. MPEG (the motion picture standard) lends itself to digitization of video streams and may be more attractive to pediatric cardiologists. Options for data storage and transfer range from limited local review to multiple offline review stations linked by a wide-area network. Telemedicine expands the capabilities of digital echocardiography in a "store and forward" or "real-time" format. Real-time neonatal telecardiology is accurate, impacts patient care, is cost-effective, and does not increase utilization. Cost, increased reliance on sonographers' skills, lack of accepted standards, and legal, licensure, and billing issues are obstacles to widespread acceptance of digital echocardiography and telemedicine.


Thapsigargin inhibits contraction and Ca2+ transient in cardiac cells by specific inhibition of the sarcoplasmic reticulum Ca2+ pump.
Regulation of the level of ionized calcium, [Ca2+]i, is critical for its use as an important intracellular signal. In cardiac and skeletal muscle the control of fluctuations of [Ca2+]i depend on sarcolemmal and sarcoplasmic reticulum ion channels and transporters. We have investigated the sesquiterpine lactone, thapsigargin (TG), because of its reported action to alter cellular calcium regulation in diverse cell types, including striated muscle cells. We have combined biochemical and physiological methods at the cellular level to determine the site of action of this agent, its specificity, and its cellular effects. Using a patch-clamp method in whole cell configuration while measuring [Ca2+]i with Indo-1 salt, we find that TG (100 nM) largely blocks the contraction and the [Ca2+]i transient in rat ventricular myocytes. Analysis of these data indicate that no sarcolemmal current or transport system is directly altered by TG, although indirect [Ca2+]i-dependent processes are affected. In permeabilized myocytes, TG blocked oxalate-stimulated calcium uptake (half-maximal effect at 10 nM) into the SR. However, TG (100 microM) had no effect on Ca(2+)-induced Ca(2+)-release in purified muscle (ryanodine-receptor enriched) vesicles while clearly blocking Ca(2+)-ATPase activity in purified (longitudinal SR) vesicles. We conclude that in striated muscle TG markedly alters calcium metabolism and thus alters contractile function only by its direct action on the Ca(2+)-ATPase.


Impact of Endoscopic Sleeve Gastroplasty in Non-alcoholic Fatty Liver Disease: a Systematic Review and Meta-analysis.
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. Endoscopic sleeve gastroplasty (ESG) has proven to be feasible, safe, and effective in the management of obesity. We performed the first systematic review and meta-analysis evaluating NAFLD and other metabolic parameters 12 months post-ESG. Four observational studies with a total of 175 patients were included. The results showed a significant (p < 0.05) reduction of 4.85 in hepatic steatosis index (95% CI - 6.02, - 3.67), 0.5 in NAFLD fibrosis score (95% CI - 0.80, - 0.19), 6.32 U/l in ALT (95% CI - 9.52, - 3.11), 17.28% in TWL (95% CI - 18.24, - 16.31), 6.31 kg/m2 in BMI (95% CI - 8.11, - 4.52), 47.97% in EWL (95% CI - 49.10, - 46.84), and 0.51% in HbA1c (95% CI - 0.90, - 0.12). ESG improves liver parameters, provides weight loss, and reduces HbA1c levels in patients suffering from NAFLD.


Optimal activation of isopsoralen to prevent amplicon carryover.
We compared the efficiencies of activation of the photochemical isopsoralen compound 10 and its resulting amplicon neutralizations under conditions with a UV transilluminator box at room temperature (RT) and a HRI-300 UV photothermal reaction chamber at RT and at 5 degrees C. Our data suggest that use of the HRI-300 reaction chamber at 5 degrees C results in a statistically significantly higher degree of amplicon neutralization.


Physiology of the fetal and transitional circulation.
The fetal circulation is an entirely transient event, not replicated at any point in later life, and functionally distinct from the pediatric and adult circulations. Understanding of the physiology of the fetal circulation is vital for accurate interpretation of hemodynamic assessments in utero, but also for management of circulatory compromise in premature infants, who begin extrauterine life before the fetal circulation has finished its maturation. This review summarizes the key classical components of circulatory physiology, as well as some of the newer concepts of physiology that have been appreciated in recent years. The immature circulation has significantly altered function in all aspects of circulatory physiology. The mechanisms and significance of these differences are also discussed, as is the impact of these alterations on the circulatory transition of infants born prematurely.


Asymmetric Catalysis upon Helically Chiral Loratadine Analogues Unveils Enantiomer-Dependent Antihistamine Activity.
Analogues of the conformationally dynamic Claritin (loratadine) and Clarinex (desloratadine) scaffolds have been enantio- and chemoselectively N-oxidized using an aspartic acid containing peptide catalyst to afford stable, helically chiral products in up to >99:1 er. The conformational dynamics and enantiomeric stability of the N-oxide products have been investigated experimentally and computationally with the aid of crystallographic data. Furthermore, biological assays show that rigidifying the core structure of loratadine and related analogues through N-oxidation affects antihistamine activity in an enantiomer-dependent fashion. Computational docking studies illustrate the observed activity differences.


[Magic, medicine and dentistry in pharaonic Egypt. 2].
Many discoveries have been made on the existence of dentistry during the pharaonic time in Egypt. Several hypotheses have been brought, but nothing has been proven definitely. Magic and medicine have been the basis of this medical science but regarding dental artwork, a doubt still remains, concerning surgery and prosthodontics.


Magnitude and Molecular Characterization of Extended-Spectrum β-Lactamase Genes among Klebsiella pneumoniae Isolates in a Large Tertiary Hospital in Ethiopia.
Background Extended-spectrum β-lactamases (ESBLs)-producing Klebsiella pneumoniae is reported worldwide increasingly. However, studies on ESBLs are still scarce in Ethiopia. Therefore, the current study aimed to determine the magnitude and resistance patterns of ESBL-producing K. pneumoniae as well as the frequency of ESBL-encoding genes.Methods A cross-sectional study was conducted from September 2018 to February 2019 at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia among a total of 132 non-duplicate K. pneumoniae isolates. Phenotypic detection of ESBL production was done using Combined Disc Test. ESBL-encoding genes of blaCTX-M, blaTEM, and blaSHV were detected through multiplex PCR.Results The magnitude of ESBL production was 102/132 (77.3%). ESBL positive isolates were 100% resistant to ceftriaxone, cefotaxime, and cefuroxime. Co-resistance of ESBL-positive isolates to other non β-lactam antimicrobials was high to trimethoprim-sulfamethoxazole (96.1%) followed by tetracycline (75.5%) and gentamicin (73.5%). However, these isolates showed high susceptibility to amikacin (96.1%) and meropenem (89.2%). From the total ESBL-positive isolates, 82.6%, 73.5%, and 75% carried blaCTX-M, blaTEM, and blaSHV genes, respectively. The majority 78/102 (76.5%) of ESBL-positive isolates harbored all three types of ESBL genes simultaneously.Conclusions The magnitude of ESBL-producing K. pneumoniae isolates was very alarming in the study area. The co-occurrence of blaCTX-M, blaTEM, and blaSHV genes is high, demanding large-scale studies to evaluate the presence of antimicrobial resistance super-clones. ESBL-producing isolates showed high resistance to most of the antimicrobials, needing phenotypic detection of ESBL regularly for better management of patients.


Roll-to-Roll Printing of Anomalous Nernst Thermopile for Direct Sensing of Perpendicular Heat Flux.
The anomalous Nernst effect (ANE) converts heat flux perpendicular to the plane into electricity, in sharp contrast with the Seebeck effect (SE), enabling mass production, large area, and flexibility of their devices through ordinary thin-film fabrication techniques. Heat flux sensors, one of the most promising applications of ANE, are powerful devices for evaluating heat flow and can lead to energy savings through efficient thermal management. In reality, however, SE caused by the in-plane heat flux is always superimposed on the measurement signal, making it difficult to evaluate the perpendicular heat flux. Here, ANE-type heat flux sensors that selectively detect a perpendicular heat flux are fabricated by adjusting the net Seebeck coefficient in their thermopile circuit with mass-producible roll-to-roll sputtering methods. The direct sensing of perpendicular heat flux using ANE-based flexible thermopiles, as well as their simple fabrication process, paves the way for the practical application of thin-film thermoelectric devices.


Towards Alzheimer's disease-related targets: One-pot Cu(I)- mediated synthesis of new nitroindazolyltriazoles.
In this work, we have investigated the one pot strategy for the Cu(I)-mediated synthesis of new triazoles bearing nitroindazole moieties using different copper catalysts. The biological activity of newly synthesized nitroindazolyltriazoles towards Alzheimer's disease-related targets, namely cholinesterases, monoamine oxidases, and amyloid aggregation, were investigated. Predictions of target affinity, physicochemical parameters, gastrointestinal absorption and brain penetration were achieved by means of in silico tools.


Combined infrarenal aorta and carotid artery reconstruction: early and late outcome in 152 patients.
Between January 1, 1985 and December 31, 1998, we performed combined infrarenal aorta and carotid artery reconstruction in 152 consecutive patients. The mean age of these patients was 65.4 +/- 8.6 years (range, 43-88 years). Infrarenal aortic disease involved abdominal aortic aneurysm in 78 patients (44.7%) and occlusive aortoiliac lesions in 84 (55.3%). Carotid artery disease was detected by performing routine Doppler ultrasonography prior to aortic reconstruction. A total of 121 carotid lesions were asymptomatic (79.6%). A total of 32 patients (21%) had a history of contralateral carotid repair. Eighty-one patients (53.2%) presented with coronary artery disease diagnosed on the basis of clinical and/or laboratory testing. Concurrent lesions were diagnosed in the renal arteries of 43 patients (28.3%) and in the visceral arteries of 16 (10.5%). Based on the results of cardiac evaluation, eight patients underwent coronary revascularization before combined reconstruction. Renal or visceral artery reconstruction was carried out during the same procedure in 30 (19.7%) and 10 (6.6%) patients, respectively. Univariate analysis demonstrated six factors that were significantly associated with perioperative mortality and morbidity: age, coronary artery disease, chronic obstructive pulmonary disease, procedure time, intraoperative blood loss, and creatinemia over 140 micromol/L. Multivariate analysis showed that only the first four of these factors were independent. Actuarial survival in the overall population, including the patients who died during the perioperative period, was 73.9 +/- 7.1% at 5 years and 50.9 +/- 10% at 10 years. From our experience, we conclude that combined infrarenal aorta and carotid artery reconstruction can be performed with no additional operative risks and consequently is the strategy of choice. In our series neither procedure had any effect on the early or late outcome of the other. Our experience suggests that combined surgery is a safe alternative to staged surgery in patients with concurrent lesions involving the infrarenal aorta and carotid artery bifurcation.


Immune Editing: Overcoming Immune Barriers in Stem Cell Transplantation.
Human pluripotent stem cells have the potential to revolutionize the treatment of inborn and degenerative diseases, including aging and autoimmunity. A major barrier to their wider adoption in cell therapies is immune rejection. Genome editing allows for tinkering of the human genome in stem and progenitor cells and raises the prospect for overcoming the immune barriers to transplantation. Initial attempts have focused primarily on the major histocompatibility barrier that is formed by the human leukocyte antigens (HLA). More recently, immune checkpoint inhibitors, such as PD-L1, CD47, or HLA-G, are being explored both, in the presence or absence of HLA, to mitigate immune rejection by the various cellular components of the immune system. In this review, we discuss progress in surmounting immune barriers to cell transplantation, with a particular focus on genetic engineering of human pluripotent stem and progenitor cells and the therapeutic cell types derived from them.


Isolation and culture of pig epiblast stem cells.
Regulation of early development can be directly interrogated in the embryo or can be studied in cultured cells isolated in the laboratory. New understanding of the developmental stages and the signalling requirements of the pig embryo have enabled the development of improved protocols for the derivation of pluripotent cells from early epiblasts. Here, we provide a detailed step-by-step description of the critical parameters required for isolation and establishment of these cells and how they can be used to study their developmental properties.


Comparative evaluation of substantivity of two biguanides - 0.2% polyhexanide and 2% chlorhexidine on human dentin.
Substantivity is one of the desirable characteristics of root canal irrigants. Among conventional endodontic irrigants, only chlorhexidine (CHX) is known to exert significant substantivity on root canal dentin. This study explored the substantivity activity of a polymeric biguanide-poly hexamethylene biguanide (PHMB). The aim of this study was to determine the substantivity of a polymeric biguanide - 0.2% PHMB and compare it with that of 2% CHX. To evaluate and compare the substantivity of 0.2% PHMB and 2% CHX on root canal dentin, dentin disks were prepared and substantivity after 1 h, 24 h, 7 days and 21 days was measured using spectrophotometry. The data so obtained were analyzed, and the intergroup comparison was made using unpaired t-test. The results of this study indicated that 0.2%. PHMB exerts significantly greater substantivity than 2% CHX on human dentin. Within the limitations, this study supports the use of 0.2% polyhexanide as an endodontic irrigant based on its property of substantivity.