The cDNA of mouse skeletal muscle transcribe for both isoforms 1 and 2 of acetylcholine receptor alpha subunit.
The mRNA isolated from mouse ocular and limb muscle and human rabdomyosarcoma cell line TE671 was subjected to reverse transcriptase polymerase chain reaction (RT-PCR) using a specific primer pair for the extracellular domain of AChR-alpha subunit that transcribes both for P3A- (isoform 1) and P3A+ (isoform 2). The cDNA synthesized from mRNA by reverse transcription, transcribed both isoforms 1 and 2 from mRNA of mouse limb and ocular muscle and human rabdomyosarcoma cell line TE671 as evidenced by agarose gel electrophoresis of polymerase chain reaction products.


Die Neustrukturierung der Notaufnahme gemäß dem G-BA-Beschluss zu einem gestuften System von Notfallstrukturen.
There is no assessment of the effects regarding the decision of the Federal Joint Committee from April 19th, 2018 which demands a central and interdisciplinary emergency room system under the control of a professionally and organizationally independent administration. The aim of this study was to solicit the current opinion of leading orthopedic surgeons regarding the above-mentioned decision. An online questionnaire was sent to all 731 members of the Verband Leitender Orthopäden und Unfallchirurgen (www.vlou.de) to compare the opinion of these leading physicians on their current and future emergency room system. The majority of the 179 responding surgeons consider emergency room systems with primary treatment of orthopedic patients by orthopedic surgeons in certain aspects to be more appropriate suitable than systems without such primary treatment. It is also not yet clear how work-related accidents should be treated according to the specifications of the German statutory accident insurance (DGUV®). The provision of training content could become more difficult if the ER rotation of orthopedic surgeons is not any longer part of these new ER concepts. The consequences of the decision of the Federal Joint Committee from April 19th, 2018 need to be reevaluated continuously and, if necessary, optimised accordingly, taking into account competing requirements, such as training regulations and the SGB VII.


Preclinical pharmacokinetics, tissue distribution and excretion studies of a novel anti-candidal agent-thiosemicarbazide derivative of isoniazid (TSC-INH) by validated UPLC-MS/MS assay.
A simple and sensitive UPLC-MS/MS assay was developed and validated for rapid determination of thiosemicarbazide derivative of isoniazid (TSC-INH), a potent anti-candidal agent in rat plasma, tissues, urine and feces. All biological samples were prepared by protein precipitation method using celecoxib as an internal standard (IS). Chromatographic separation was achieved on Acquity BEH™ C18 (50×2.1 mm, 1.7 μm) column using gradient mobile phase of acetonitrile and water (containing 0.1% formic acid) at flow rate of 0.3 mL/min. The MRM transitions were monitored at m/z 305.00→135.89 for TSC-INH and m/z 380.08→316.03 for IS in ESI negative mode. All validation parameter results were within the acceptable range described in guideline for bioanalytical method validation. The pharmacokinetic study showed that the compound TSC-INH was orally active with 66% absolute bioavailability in rats. It was rapidly absorbed with peak plasma concentration of 1985.92 ng/mL achieved within 1 h after single oral dose (10 mg/kg) administration. TSC-INH exhibited rapid distribution across the body with highest levels in liver and lungs. Penetration in brain tissues suggests that TSC-INH crossed the blood brain barrier. Only 5.23% of the orally administered drug was excreted as unconverted form in urine and feces implying that TSC-INH was metabolized extensively before excretion. With the preliminary knowledge of in vivo pharmacokinetics and disposition properties, this study will be beneficial for further development of compound TSC-INH in future studies.


Phase I/II trial of docetaxel and concurrent radiation therapy in localized high risk prostate cancer (AGUSG 03-10).
A Phase I/II trial was conducted to assess the radiosensitizer docetaxel administered weekly (20 mg/m(2)) with concurrent intensity modulated radiation therapy (72 Gy at 1.8 Gy/fraction) in high risk prostate cancer. Patients with high risk prostate cancer (clinical stage > or = T3; Gleason score 8, 9, or 10; Gleason score 7 and PSA > 10) received IMRT (Clinac 600 CD with 6 MV photons and sliding window technique) and concurrent weekly docetaxel (20 mg/m(2)) as a continuous 30 minute infusion for 8 weeks. Patients desirous of concurrent androgen suppression were not excluded. Twenty men (median age: 64 years; range, 50-78 years) were enrolled in the chemoradiation protocol. Three patients experienced treatment interruptions: dehydration requiring inpatient hydration (n = 2); NSAID induced GI bleed (n = 1). An additional patient required outpatient hydration (<24 hours) with no treatment interruption. Overall, the most frequently observed toxicities were grade 2 diarrhea (40%), grade 2 fatigue (40%), grade 2 urinary frequency (35%), taste aversion (20%), grade 2 constipation (20%), and rectal bleeding (15%). No significant hematologic toxicity (grades 2-4) was encountered among the 20 patients. Although the follow-up interval was relatively short, no significant subacute gastrointestinal toxicities have been observed. At a median follow-up duration of 11.7 months, 17 patients were free of biochemical disease recurrence, and all patients are alive. The radiosensitizer docetaxel administered weekly (20 mg/m(2)) with concurrent IMRT is well tolerated with acceptable toxicity. Early oncologic outcomes in this challenging patient cohort are encouraging.


Determination of transcortin in serum by polyethylenglycol enhanced immunonephelometry. A comparison with equilibrium dialysis and radioimmunoassay.
A method for immunonepholometric determination of transcortin has been developed. It is based upon a polyethylenglycol (PEG) enhanced immunonephelometric response using a commercial transcortin antiserum in the assay. It was found that pretreatment of the serum samples with 10% (w/v) PEG 6000 was a necessity in order to obtain satisfactory low blank values. The immunonephelometric assay showed a good correlation with transcortin concentrations as calculated from cortisol binding experiments (r = 0.9501, n = 26). The intraassay coefficient of variation for a standard serum was found to be 3.2% (n = 50) and for a pregnancy serum pool 2.6% (n = 50). The interassay coefficient of variation in ten consecutive analyses of thirteen samples was found to be 7.4%. The sensitivity allows detection of transcortin in 5 microliters of serum. The average concentration in male serum was 35 mg/l (n = 55), in female serum 36 mg/l (n = 55) and in serum from third trimester pregnant women 81 mg/l (n = 30) which agrees with the results in previously published reports.


Expression of pax6 and sox2 in adult olfactory epithelium.
The olfactory epithelium maintains stem and progenitor cells that support the neuroepithelium's life-long capacity to reconstitute after injury. However, the identity of the stem cells--and their regulation--remain poorly defined. The transcription factors Pax6 and Sox2 are characteristic of stem cells in many tissues, including the brain. Therefore, we assessed the expression of Pax6 and Sox2 in normal olfactory epithelium and during epithelial regeneration after methyl bromide lesion or olfactory bulbectomy. Sox2 is found in multiple kinds of cells in normal epithelium, including sustentacular cells, horizontal basal cells, and some globose basal cells. Pax6 is co-expressed with Sox2 in all these, but is also found in duct/gland cells as well as olfactory neurons that innervate necklace glomeruli. Most of the Sox2/Pax6-positive globose basal cells are actively cycling, but some express the cyclin-dependent kinase inhibitor p27(Kip1), and are presumably mitotically quiescent. Among globose basal cells, Sox2 and Pax6 are co-expressed by putatively multipotent progenitors (labeled by neither anti-Mash1 nor anti-Neurog1) and neuron-committed transit amplifying cells (which express Mash1). However, Sox2 and Pax6 are expressed by only a minority of immediate neuronal precursors (Neurog1- and NeuroD1-expressing). The assignment of Sox2 and Pax6 to these categories of globose basal cells is confirmed by a temporal analysis of transcription factor expression during the recovery of the epithelium from methyl bromide-induced injury. Each of the Sox2/Pax6-colabeled cell types is at a remove from the birth of neurons; thus, suppressing their differentiation may be among the roles of Sox2/Pax6 in the olfactory epithelium.


Macrophage infiltration in tumors and tumor-surrounding tissue: influence of serotonin and sensitized lymphocytes.
In a delayed-type hypersensitivity reaction serotonin released from mast cells plays an important role in the induction of a cellular infiltrate at the site of antigen challenge. In analogy, we have studied whether it is possible to enhance the number of intratumoral macrophages by injecting serotonin into a s.c. SL2 lymphosarcoma. The vessels in the tissue surrounding the tumor responded well to serotonin, as there was an influx of i.v. injected 51Cr-labeled sensitized spleen cells in this tissue during the first 4 h after intratumoral injection of serotonin. At 24 h after serotonin injection there was an influx of macrophages into this tumor-surrounding tissue. No influx of cells was detected in the tumor itself during the first hours after injection of serotonin. In the tumor, similar phenomena occurred as in the surrounding tissue, but with a delay of about 24 h. This suggests that lymphocytes leave the blood circulation in the tumor-surrounding tissue and migrate to the tumor. The influx of macrophages into the tumor after intratumoral injection of serotonin is probably due to an immunological reaction as the lymphocyte influx preceeds the macrophage influx into tumors. In addition, transfer of sensitized lymphocytes, as well as lymphocytes from a tumor-bearing host caused an enhanced influx of macrophages into the tumor. To test the specificity and serotonin dependency of the phenomenon of infiltrating cells in tumors we have used a footpad swelling assay in which the serotonin dependency and the antigen specificity of the response against syngeneic tumor cells was shown. The following picture emerged: an intratumoral serotonin injection enables lymphocytes to leave blood vessels in the tumor-surrounding tissue. These lymphocytes with specificity for tumor antigens migrate to the tumor. After contact with the antigenic tumor cells, these lymphocytes secrete chemoattractive factors for monocytes/macrophages. Also these monocytes/macrophages leave the circulation in the tumor-surrounding tissue. Subsequently the macrophages invade the tumor. We conclude that the number of intratumoral macrophages can be enhanced by serotonin.


Frey's plus versus Frey's procedure for chronic pancreatitis: Analysis of postoperative outcomes and quality of life.
Additional surgical procedures are often required in patients with chronic pancreatitis (CP) related complications. The present study aims to analyze the type of additional procedures required in patients who underwent Frey's procedure (Frey's plus) and to compare the short-term outcomes and quality of life with patients who underwent only Frey's procedure. Retrospective analysis of a prospectively maintained database of patients who underwent surgery for CP between January 2012 and February 2018 and completed at least one year of follow-up. Patients who underwent non-Frey's surgical procedures were excluded. Clinical parameters, postoperative pain relief (using Izbicki pain score) and functioning scale score (EORTC QLQ C30) of patients who underwent Frey's plus procedure and only Frey's procedure were compared. Of the 146 patients who underwent surgery for CP during the study period, 100 patients (Frey's procedure-68, Frey's plus procedure-32) were included in this study. Roux-en-Y hepaticojejunostomy was the commonly performed additional procedure (n=12). The demographic and clinical parameters were comparable, except for more patients with jaundice (28.1% vs. 2.9%, p=0.01) and prolonged operative time (374.6 mins vs. 326.3 mins, p=0.01) in Frey's plus group. However, there was no significant difference in mean intraoperative blood loss, postoperative morbidity or duration of hospital stay. At median (range) follow up of 34 (12-86) months, there was no significant difference in the pain control and quality of life between two groups. Frey's plus procedure for chronic pancreatitis can be safely performed wherever indicated without adversely affecting the postoperative outcome or quality of life.


A rabbit model with acute thrombo-embolic pulmonary hypertension created with echocardiography guidance.
A rabbit model of acute thrombo-embolic pulmonary hypertension was developed by infusing self-thrombi into the right femoral vein and simultaneously measuring the pulmonary artery pressure via a right heart catheter and echocardiography. The model was used to explore the usefulness of an ultrasound-guided protocol. In the present study, acute thrombo-embolic pulmonary hypertension was produced in 25 of 30 healthy New Zealand rabbits; the success rate was 83%. A significant and positive correlation between the right ventricle-right atrial pressure gradient, an estimate of the pulmonary artery systolic pressure derived from tricuspid regurgitation and the pulmonary artery systolic pressure measured using the right heart catheter (r=0.765, P=0.002) was noted. During the process of establishing a rabbit model of acute thrombo-embolic pulmonary hypertension, it was demonstrated that echocardiography can be used to guide the right heart catheter to obtain pulmonary artery systolic pressure measurements, to quantify the tricuspid regurgitation jet to assess the pulmonary artery systolic pressure and to observe cardiac morphologic changes so as to evaluate cardiac function. Based on the present study, it is clear that echocardiography is valuable in improving the success rate of producing the animal model of acute thrombo-embolic pulmonary hypertension. This could ultimately facilitate preclinical research and clinical research in humans.


Assessing the spatial effects of economic freedom on forest-products, grazing-land, and cropland footprints: The case of Asia-Pacific countries.
The literature has shown that economic freedom yields higher economic growth. However, the nexus between economic freedom and the environment in a world of spatial dependency is unclear. Using data from a panel of seventeen Asia-Pacific countries from 2000 to 2017, we investigate the direct and spillover effects of economic freedom (as measured by the annual indexes developed by the Heritage Foundation) and other variables on the ecological footprint of three land-cover types: cropland, forest products, and grazing land. Diagnostic tests confirm the existence of spatial-interaction effects in forest products and grazing land but reject it for cropland. Using a spatial Durbin panel model, we find that the intensity of energy use has a significant impact on the environmental footprint of all resource types. We also confirm the environmental Kuznets curve hypothesis for forest products and grazing land but not cropland. Unlike previous researchers, we find cropland footprints are unaffected by natural resource rents. We also find that the tax burden is the only economic freedom indicator with a positive and significant impact on all three environmental footprints. Our findings suggest that more investment freedom reduces environmental pressure on cropland and forest-products footprints but has a nonsignificant effect on the grazing-land footprint. Further, financial freedom reduces the forest-products footprint and increases the grazing-land footprint. Property rights, the tax burden, and business freedom increase environmental pressure while government spending lessens grazing land's ecological footprint. Our indirect and overall impact analyses suggest that all types of economic freedom reduce environmental strain in our panel. This research points to the importance of enacting environmental regulations in a way that guarantees ecological sustainability and economic development.


Virtual atom representation of hydrogen bonds in minimal off-lattice models of alpha helices: effect on stability, cooperativity and kinetics.
The most conspicuous feature of a right-handed alpha helix is the presence of hydrogen bonds between the backbone carbonyl oxygen and NH groups along the chain. A simple off-lattice model that includes hydrogen bond interactions using virtual atoms is used to examine the stability, cooperativity and kinetics of the helix-coil transition. We have studied the thermodynamics (using multiple histogram method) and kinetics (by Brownian dynamics simulations) of 16-mer minimal off-lattice models of four-turn alpha-helix sequences. The carbonyl and NH groups are represented as virtual moieties located between two alpha-carbon atoms along the polypeptide chain. The characteristics of the native conformations of the model helices, such as the helical pitch and angular correlations, coincide with those found in real proteins. The transition from coil to helix is quite broad, which is typical of these finite-sized systems. The cooperativity, as measured by a dimensionless parameter, omegac, that takes into account the width and the slope of the transition curves, is enhanced when hydrogen bonds are taken into account. The value of omegac for our model is consistent with that inferred from experiment for an alanine-based helix-forming peptide. The folding time tauF ranges from 6 to 1000 ns in the temperature range 0.7-1.9 T(F), where T(F) is the helix-coil transition temperature. These values are in excellent agreement with the results from recent fast folding experiments. The temperature dependence of tauF exhibits a nearly Arrhenius behavior. Thermally induced unfolding occurs on a time scale that is less than 40-170 ps depending on the final temperature. Our calculations also predict that, although tauF can be altered by changes in the sequence, the dynamic range over which such changes take place is not as large as that predicted for beta-turn formation. Hydrogen bonds not only affect the stability of alpha-helix formation but also have profound influence on the kinetics. The excellent agreement between our calculations and experiments suggests that these models can be used to investigate the effects of sequence, temperature and viscosity on the helix-coil transition.


Liquid metal amoeba with spontaneous pseudopodia formation and motion capability.
The unique motion of amoeba with a deformable body has long been an intriguing issue in scientific fields ranging from physics, bionics to mechanics. So far, most of the currently available artificial machines are still hard to achieve the complicated amoeba-like behaviors including stretching pseudopodia. Here through introducing a multi-materials system, we discovered a group of very unusual biomimetic amoeba-like behaviors of self-fueled liquid gallium alloy on the graphite surface immersed in alkaline solution. The underlying mechanisms were discovered to be the surface tension variations across the liquid metal droplet through its simultaneous electrochemical interactions with aluminum and graphite in the NaOH electrolyte. This finding would shed light on the packing and the structural design of future soft robots owning diverse deformation capability. Moreover, this study related the physical transformation of a non-living LM droplet to the life behavior of amoeba in nature, which is inspiring in human's pursuit of advanced biomimetic machine.


The epidemiology of Takayasu arteritis: a hospital-based study from northwestern part of Turkey.
Takayasu arteritis (TA) is a chronic, inflammatory large vessel vasculitis that affects aorta and its main branches. We aimed to evaluate the incidence and prevalence of TA in the northwestern part of Turkey. We retrospectively evaluated 23 TA patients followed by our clinic. Clinical features, treatments and responses were recorded. Our hospital is the single tertiary referral center for rheumatic diseases for a mixed rural and urban population of 620,447 people for >16 years (306,036 males, 314,411 females). Nineteen of the 23 patients were females (82.6 %) and four were males (17.4 %). The annual incidence rate for TA was 0.34/100,000. The overall prevalence of TA in our region was 3.3/100,000 (95 % CI 1.9-4.8) in individuals >16 years. The most common findings at the time of presentation were blood pressure difference (73 %) and headache (60.4 %). The most common angiographic type was type 1 (12 patients, 52.2 %). Median follow-up period was 48 months (range 10-132). Three (13 %) of the patients had stent replacements to different vascular sites. One patient had an operation for aortic aneurysm, and aortic valve replacement surgery has been made. One patient had renal artery bypass operation. Eleven patients (47.8 %) had recurrency at follow-up period and two patients (8.7 %) died. In northwestern part of Turkey, the annual incidence and prevalence of TA were higher than western population, but similar to East Asian data.


Serine protease-induced enhancement of blood-borne metastasis of rat ascites tumour cells and its prevention with deoxyribonuclease.
Serine proteases, such as alpha-chymotrypsin or elastase, caused an aggregation of rat ascites tumour cell lines, AH-130, AH-109A and YS, in a protein free medium which preserved the cell viability. This aggregation, which was monitored spectrophotometrically, was dependent upon the protease activities and was resistant to treatment with either a calcium chelating reagent (EDTA) or neuraminidase. However, the tumour cell aggregates were redispersed by treatment with deoxyribonuclease I (DNase I). This dispersal effect was dependent upon the DNase activity. A possible relationship between the tumour cell aggregation and development of blood-borne metastasis was studied. An intravenous inoculation in rats of tumour cell aggregates performed by the alpha-chymotrypsin treatment resulted in significantly higher numbers of lung metastatic foci than an injection of single cells. When the re-separated single cells, prepared in vitro by treatment with DNase I following alpha-chymotrypsin treatment, were injected instead of the aggregates, the enhancement of metastasis was reversed. These enhancement and reversal effects were mimicked in vivo by intravenous injections of protease and nuclease following inoculation of a single cell suspension. That is, the number of metastatic foci caused by single cell inoculation followed by an intravenous alpha-chymotrypsin injection, was higher than that in a control group receiving PBS instead of alpha-chymotrypsin. Again, this augmentation was reversed by an injection of DNase I following alpha-chymotrypsin injection. Furthermore, an injection of DNase I alone itself reduced the starting number of metastases resulting from injection of the single tumour cell suspension. These data suggest that the metastatic behaviour of tumour cells may be increased by protease inducible DNA dependent cell aggregation should it occur in the blood stream.


An epidemiological study of Streptococcus suis serotypes of pigs in Ontario determined by a multiplex polymerase chain reaction.
The purpose of the study was to identify the serotypes of Streptococcus suis from tonsil swabs in clinically ill and healthy pigs in Ontario using a multiplex polymerase chain reaction (PCR) method. Although 22 different serotypes were identified, most isolates were S. suis-like bacteria or untypable.


Effectiveness of hand hygiene and provision of information in preventing influenza cases requiring hospitalization.
The objective of the study was to investigate the effectiveness of non-pharmacological interventions in preventing cases of influenza requiring hospitalization. We performed a multicenter case-control study in 36 hospitals, in 2010 in Spain. Hospitalized influenza cases confirmed by reverse-transcription polymerase chain reaction and three matched controls (two hospital and one community control) per case were selected. The use of non-pharmacological measures seven days before the onset of symptoms (frequency of hand washing, use of alcohol-based hand sanitizers and handwashing after touching contaminated surfaces) was collected. We studied 813 cases hospitalized for influenza and 2274 controls. The frequency of hand washing 5-10 times (adjusted odds ratio [aOR]=0.65) and >10 times (aOR=0.59) and handwashing after contact with contaminated surfaces (aOR=0.65) were protective factors and were dose-responsive (p<0.001). Alcohol-based hand sanitizers were associated with marginal benefits (aOR=0.82). Frequent handwashing should be recommended to prevent influenza cases requiring hospitalization.


Loop-mediated isothermal amplification (LAMP): A novel rapid detection platform for pathogens.
Foodborne bacterial infections and diseases have been considered to be a major threat for public health in the worldwide. Increased incidence of human diseases caused by foodborne pathogens have been correlated with growing world population and mobility. Loop-mediated isothermal amplification (LAMP) has been regarded as an innovative gene amplification technology and emerged as an alternative to PCR-based methodologies in both clinical laboratory and food safety testing. Nowadays, LAMP has been applied to detection and identification on pathogens from microbial diseases, as it showed significant advantage in high sensitivity, specificity and rapidity. The high sensitivity of LAMP enables detection of the pathogens in sample materials even without time consuming sample preparation. An overview of LAMP mainly containing the development history, reaction principle and its application to four kind of foodborne pathogens detection are presented in this paper. As concluded, with the advantages of rapidity, simplicity, sensitivity, specificity and robustness, LAMP is capable of applications for clinical diagnosis as well as surveillance of infection diseases. Moreover, the main purpose of this paper is to provide theoretical basis for the clinical application of LAMP technology.


Pivotal role of mouse mast cell protease 4 in the conversion and pressor properties of Big-endothelin-1.
The serine protease chymase has been reported to generate intracardiac angiotensin-II (Ang-II) from Ang-I as well as an intermediate precursor of endothelin-1 (ET-1), ET-1 (1-31) from Big-ET-1. Although humans possess only one chymase, several murine isoforms are documented, each with its own specific catalytic activity. Among these, mouse mast cell protease 4 (mMCP-4) is the isoform most similar to the human chymase for its activity. The aim of this study was to characterize the capacity of mMCP-4 to convert Big-ET-1 into its bioactive metabolite, ET-1, in vitro and in vivo in the mouse model. Basal mean arterial pressure did not differ between wild-type (WT) and mMCP-4(-/-) mice. Systemic administration of Big-ET-1 triggered pressor responses and increased blood levels of immunoreactive (IR) ET-1 (1-31) and ET-1 that were reduced by more than 50% in mMCP-4 knockout (-/-) mice compared with WT controls. Residual responses to Big-ET-1 in mMCP-4(-/-) mice were insensitive to the enkephalinase/neutral endopeptidase inhibitor thiorphan and the specific chymase inhibitor TY-51469 {2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamido-3-methanesulfonylphenyl]thiazole-4-carboxylic acid}. Soluble fractions from the lungs, left cardiac ventricle, aorta, and kidneys of WT but not mMCP-4(-/-) mice generated ET-1 (1-31) from exogenous Big-ET-1 in a TY-51469-sensitive fashion as detected by high-performance liquid chromatography/ matrix-assisted laser desorption/ionization-mass spectrometry. Finally, pulmonary endogenous levels of IR-ET-1 were reduced by more than 40% in tissues derived from mMCP-4(-/-) mice compared with WT mice. Our results show that mMCP-4 plays a pivotal role in the dynamic conversion of systemic Big-ET-1 to ET-1 in the mouse model.


[Are the tools recommended by ASPEN and ESPEN comparable for assessing the nutritional status?].
[corrected] There is no "gold standard" for identification of malnutrition. The ASPEN board of directors (2002) suggest the subjective global assessment (SGA) and ESPEN (2002) recommend the nutritional risk screening-2002 (NRS-2002) to detect the prevalence of malnutrition. This cross-sectional study aims (1) to assess the prevalence of malnutrition on admission and (2) to know association between two tools used to evaluate nutritional risk. 135 patients (42.2% women and 58.8% men, 62.1 +/- 14.4 years) are studied at admission. Different parameters are assessed to evaluate nutritional state. Patient's energy requirements (Harris Benedict x Long's factor) and energy intake, calculated as 24 h-recall, are compared. The prevalence of malnutrition is assessed with two screening tools: SGA and NRS-2002. 42.2% of the patients had lost more than 5% body weight and 39.3% had an intake lower than required at admission. The prevalence of malnutrition is 40.7 and 45.1/100 patients admitted at hospital, if SGA or NRS-2002 are used, respectivility. There is strong agreement between results of two nutritional assessment methods (p = 0.000). Serum albumin and protein concentrations and linfocytes count are less in the malnourished patients. The prevalence of malnutrition is elevated. In clinical practice, both methods could be used to identify patients at nutritional risk, but the NRS-2002 is a less subjective method.


[New aspects in neurointensive and emergency medicine: the most important studies in a review and overview].
This review article summarizes the major clinical studies in neurological emergency and intensive care medicine from the end of 2020 to 2021 on the topics: recanalizing treatment in ischemic stroke, usefulness and effect of brain tissue oxygen monitoring in subarachnoid hemorrhage, efficacy of induced hypothermia in patients with cardiac arrest (CA), value of early cranial imaging after CA, relevance of rapid management and effects of different anticonvulsants in status epilepticus and incidence of critical illness polyneuropathy myopathy in intensive care unit patients with COVID-19 infections.


Ionic-exchange high-performance liquid chromatography of Escherichia coli ribosomal small-subunit proteins.
Ion-exchange high-performance liquid chromatography was applied to the separation of proteins from the 30S ribosomal subunit. The proteins present in each peak have been identified by polyacrylamide gel electrophoresis analysis. The purification has been made using either unmodified proteins or proteins specifically labeled at their SH group. The results clearly show that the method can be used to purify and identify ribosomal proteins.


Impact of computerized drug profiles and a consulting pharmacist on outpatient prescribing patterns: a clinical trial.
The effects of computerized drug profiles and clinical pharmacist consultation in the internal medicine clinics at a Veterans Administration hospital were studied. Population included patients (n = 512) and physicians (n = 35) of three internal medicine clinics during an eight-week period. The first four weeks were the preintervention period. The second four weeks were the intervention period in which a clinical pharmacist attended one clinic (A) and provided drug profiles on all patients. Two other clinics (B and C) served as controls. During the intervention, patients in clinic A experienced a significant reduction in prescribing problems as identified by the pharmacist: 49 percent of patients before the intervention versus 9.4 percent after the intervention (p less than 0.001). Patients in clinic B had no significant change in prevalence in the number of problems identified (39 versus 40 percent; NS), and patients in clinic C had a significant but less dramatic decrease (35 versus 22 percent; p less than 0.05). The proportion of patients in clinic A with net decrease in the number of prescribed medications rose from 7.1 to 34.9 percent (p less than 0.001), with a mean decrease of 0.3 medications per patient. No significant differences in number of prescribed medications were noted in clinics B or C. Accuracy of physician medication charting improved for patients in clinic A from 54 percent of charts with accurate drug lists before the intervention to 78.3 percent after the intervention (p less than 0.001). No significant improvements were noted for clinics B and C. These results suggest that computerized drug profiles together with clinical pharmacist consultation can improve prescribing practices in a hospital outpatient department.


Measuring global health inequity.
Notions of equity are fundamental to, and drive much of the current thinking about global health. Health inequity, however, is usually measured using health inequality as a proxy - implicitly conflating equity and equality. Unfortunately measures of global health inequality do not take account of the health inequity associated with the additional, and unfair, encumbrances that poor health status confers on economically deprived populations. Using global health data from the World Health Organization's 14 mortality sub-regions, a measure of global health inequality (based on a decomposition of the Pietra Ratio) is contrasted with a new measure of global health inequity. The inequity measure weights the inequality data by regional economic capacity (GNP per capita). The least healthy global sub-region is shown to be around four times worse off under a health inequity analysis than would be revealed under a straight health inequality analysis. In contrast the healthiest sub-region is shown to be about four times better off. The inequity of poor health experienced by poorer regions around the world is significantly worse than a simple analysis of health inequality reveals. By measuring the inequity and not simply the inequality, the magnitude of the disparity can be factored into future economic and health policy decision making.


Direct observation of DNA threading in flap endonuclease complexes.
Maintenance of genome integrity requires that branched nucleic acid molecules be accurately processed to produce double-helical DNA. Flap endonucleases are essential enzymes that trim such branched molecules generated by Okazaki-fragment synthesis during replication. Here, we report crystal structures of bacteriophage T5 flap endonuclease in complexes with intact DNA substrates and products, at resolutions of 1.9-2.2 Å. They reveal single-stranded DNA threading through a hole in the enzyme, which is enclosed by an inverted V-shaped helical arch straddling the active site. Residues lining the hole induce an unusual barb-like conformation in the DNA substrate, thereby juxtaposing the scissile phosphate and essential catalytic metal ions. A series of complexes and biochemical analyses show how the substrate's single-stranded branch approaches, threads through and finally emerges on the far side of the enzyme. Our studies suggest that substrate recognition involves an unusual 'fly-casting, thread, bend and barb' mechanism.


[The early development of brachytherapy of the prostate: a study on technique application in the development of urology].
Within recent years brachytherapy of the prostate has become a treatment of choice. The treatment can be dated back up to the beginning of the twentieth century. It is interesting that the urological routes have never been explored directly by authors of articles and textbooks in the field of radiology and radiooncology.


A spatial analysis of corruption, misallocation, and efficiency.
Political corruption is considered one of the major obstacles to achieving high-quality economic development in developed and developing countries. This study first calculates the ecological footprints of 29 provinces in China based on China's provincial panel data from 2006 to 2015. The provinces' ecological efficiencies were then calculated. The relationship between government corruption and ecological efficiency is researched, and the result shows that such a relationship is not linear. At different levels of ecological efficiency, government corruption has different effects on ecological efficiency. Finally, the resource misallocation index is introduced, and the spatial error model is used to further test the impact of government corruption and resource misallocation on ecological efficiency. The regression results show that high levels of government corruption and resource allocation distortion will cause a decrease in regional ecological efficiency, which adversely affects the sustainable development of the economy.


Receptor model-based source tracing and risk assessment of elements in sediment of a transboundary Himalayan River.
This study utilized surface sediments from a potentially less polluted transboundary Himalayan River (Brahmaputra: China-India-Bangladesh) to investigate the abundance of 15 geochemically and ecologically significant elements and to predict their sources and ecological consequences. INAA was applied to determine the elemental concentrations. The average abundances (μg.g-1) of Rb (94.20), Cs (4.49), Th (20.31), & U (2.73) were 1.12-2.26 folds elevated than shale. Environmental indices disclosed a pollution status ranging from "uncontaminated to moderately contaminated," with minimal Rb, U, and Th enrichment in the downstream zone. Consensus-based sediment quality guideline (SQG) threshold values suggested that only Cr (60% samples > TEL) may impose rare biological effects. Ecological risk indices suggested "minor to no" possible eco-toxicological risks for the accounted elements (Cr, Co, Mn, Zn, Sb, & As). The positive matrix factorization (PMF) model predicated the predominance of geogenic or crustal contributions (∼72.69%) for Al, K, Na, Ti, Co, Zn, Ba, Cs, As, Rb, Th, & U derived from elemental fractionations, mineral weathering, and bio-geo-chemical mobilization. The relative contributions of anthropogenic sources (∼27.31%; such as the construction of roads, settlement expansion, litter disposal, municipal waste discharge, mining activities, agricultural encroachment, etc.) on elemental distribution were significantly lower. The abundance of Cr and Mn was mainly influenced by anthropogenic sources. This study demonstrated the effectiveness of utilizing geo-environmental guidelines and receptor models in discriminating the natural & anthropogenic origins of metals in the complex riverine sediments of a less anthropogenically affected river.


Basic considerations in the treatment of obesity.
The recognition and treatment of obesity has undergone marked changes in the past two decades. Along with the abandoning of the concept of exogenous obesity, the physician has discovered a variety of developmental, psychological, pharmacologic, socioeconomic, neurological, and genetic roots for the syndrome. The clinician has also found medical treatment modalities (fasting and behavior modification) that hold much more promise than traditional supportive relationships with dietary consultation and anorexogenic medications. Surgical treatment also, ileojejunal bypass, is gradually emerging as a treatment of choice for certain well-motivated, super-obese people for whom all other treatment modalities have failed. Future research into central serotonergic mechanisms offers hope that we can begin to know what it is that turns on hunger, turns off appetite, and regulates weight in such a stable manner over such a long period of time.


In vivo hypoglycemic effects of bisphenol F exposure in high-fat diet mice.
Bisphenol F (BPF) is a widely used bisphenol A (BPA) substitute plastic additive that has attracted increasing public concerns due to its potential toxic effects on animal and human health. Although previous studies have indicated that BPF might have harmful effects on metabolic homeostasis, the systematic effects of BPF on glucose disorders remain controversial. In this study, mice fed a normal chow diet (ND) and high-fat diet (HFD) were administered BPF at a dose of 100 μg/kg of body weight, and glucose metabolism was monitored after both short- and long-term treatment. Little change in glucose metabolism was observed in BPF-treated ND mice, but improved glucose metabolism was observed in BPF-treated HFD mice. Consistently, BPF treatment led to increased insulin signalling in the skeletal muscle of HFD mice. Additionally, liver metabolite levels also revealed increased carbohydrate digestion and improved TCA cycle progression in BPF-treated HFD mice. Our results demonstrate that sustained BPF exposure at an environmentally relevant dosage may substantially improve glucose metabolism and enhance insulin sensitivity in mice fed a high-fat diet.


Correction: The thermodynamics of endosomal escape and DNA release from lipoplexes.
Correction for 'The thermodynamics of endosomal escape and DNA release from lipoplexes' by Yotam Y. Avital et al., Phys. Chem. Chem. Phys., 2016, 18, 2591-2596.


Inclusion of interleukin-6 improved performance of postoperative delirium prediction for patients undergoing coronary artery bypass graft (POD-CABG): A derivation and validation study.
Patients undergoing coronary artery bypass graft (CABG) are at high risk for developing postoperative delirium (POD). A simple prediction rule may benefit patients from early identification of POD followed by adequate preventive strategies. The purpose of the current study was to develop and validate a POD prediction rule for patients undergoing CABG (POD-CABG), by considering all possible perioperative factors. In this prospective cohort study, patients who underwent first elective isolated CABG were continuously enrolled from May 2014 to November 2015 in a tertiary hospital. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. Patients' perioperative risk factors were collected through interviews and review of medical records. The area under receiver-operating characteristic curve (AUC) was used to assess the overall performance of the predictive rule. A total of 242 and 148 patients were enrolled in the derivation and validation cohorts, respectively. Multiple logistic regression analysis identified seven variables that were independently associated with POD: age (≥65 years), gender (female), history of myocardial infarction and diabetes mellitus, postoperative atrial fibrillation, the use of intra-aortic balloon pump, and serum interleukin-6 ≥478 pg/ml at 18 hours after surgery. The AUC of the POD-CABG was 0.84 (95% CI, 0.79-0.90) in the derivation cohort, and was 0.86 (95% CI, 0.80-0.91) after bootstrap resampling. The AUC was 0.81 (95% CI, 0.73-0.88) after the POD-CABG was applied to the validation cohort. The POD-CABG with inclusion of interleukin-6 demonstrated good performance in predicting POD.


Evidence of the neuroprotective role of citicoline in glaucoma patients.
The glaucomatous disease is currently considered a disease involving ocular and visual brain structures. This new approach to glaucoma introduces the possibility of inducing an improvement by means of a pharmacological approach similar to that used in different degenerative brain disorders. In line with this hypothesis, we studied the effects of oral (1600 mg/die, Cebrolux, Tubilux Pharma, Pomezia, Rome, Italy) or intramuscular (1000 mg/die, Cebroton, Tubilux Pharma) cytidine-5'-diphosphocholine (citicoline) treatment on retinal function and neural conduction in the visual pathways of glaucoma patients with moderate visual defects. Improvement of retinal function (objectively evaluated by pattern electroretinogram recordings) and of neural conduction along visual pathways (objectively evaluated by visual evoked potential recordings) were observed in glaucoma patients after two 60-day periods of oral or intramuscular treatment with citicoline. However, partial regression of this improvement was detected after two 120-day periods of washout. This suggests that the beneficial effects observed are in part treatment-dependent. The extension of citicoline treatment up to a period of 8 years lead to the stabilization or improvement of the glaucomatous visual dysfunction. These results suggest potential neuroprotective effects of citicoline in the glaucomatous disease.


Age-related changes of body composition and abdominal adipose tissue assessed by bio-electrical impedance analysis and computed tomography.
Only scarce information is available on body composition changes with age measured simultaneously by electrical impedance and computed tomography. We aimed to describe the age-related changes of the body composition and adipose tissue distribution in Bulgarians. This cross-sectional study included 130 participants (mean age 53±9.8 years, range 35-65), divided according to their body mass index (BMI): BMI <25.0 kg/m(2) (18 women, 12 men); BMI 25.0-34.9 kg/m(2) (50 women, 50 men). Body composition was assessed by bioelectrical impedance on a Tanita TBF-215 analyzer (Tanita Corp., Tokyo, Japan). The abdominal fat was measured by computed tomography on a CT/L scanner (GE Medical Systems, USA). Increasing age was associated with a mean decrease in body weight by 268 g per year in the normal weight subjects and by 390 g in the overweight ones as well as with a fat-free mass decrease of 321 g and of 291 g per year respectively (p<0.001). One year of increasing age was associated with a mean increase of visceral adipose tissue by 2.43 cm(2) in the overweight group and by 2.68 cm(2) in the normal weight subjects and with a decrease of the subcutaneous adipose tissue by 2.30 cm(2) per year in the latter group (p<0.001). The association of fat mass and fat-free mass with age in men and women was best described by quadratic equations (both increased until the age of 45-50 and decreased thereafter). Our data showed a significant association between age and decreasing fat-free mass, increasing fat mass and abdominal fat accumulation.


Interlayer for modified cathode in highly efficient inverted ITO-free organic solar cells.
Inverted polymer solar cells with a bottom metal cathode modified by a conjugated polymer interlayer show considerable improvement of photocurrent and fill factor, which is due to hole blocking at the interlayer, and a modified surface energy which affects the nanostructure in the TQ1/[70]PCBM blend.


Plasma membrane preassociation drives β-arrestin coupling to receptors and activation.
β-arrestin plays a key role in G protein-coupled receptor (GPCR) signaling and desensitization. Despite recent structural advances, the mechanisms that govern receptor-β-arrestin interactions at the plasma membrane of living cells remain elusive. Here, we combine single-molecule microscopy with molecular dynamics simulations to dissect the complex sequence of events involved in β-arrestin interactions with both receptors and the lipid bilayer. Unexpectedly, our results reveal that β-arrestin spontaneously inserts into the lipid bilayer and transiently interacts with receptors via lateral diffusion on the plasma membrane. Moreover, they indicate that, following receptor interaction, the plasma membrane stabilizes β-arrestin in a longer-lived, membrane-bound state, allowing it to diffuse to clathrin-coated pits separately from the activating receptor. These results expand our current understanding of β-arrestin function at the plasma membrane, revealing a critical role for β-arrestin preassociation with the lipid bilayer in facilitating its interactions with receptors and subsequent activation.


Replacement of upper esophagus: results with myocutaneous flap and with gastric transposition.
The authors reviewed 25 cases of pharyngoesophageal replacement. A tubed pectoralis major myocutaneous flap was employed in ten cases where an adequate distal resection margin could be obtained above the thoracic inlet. Total gastric transposition was used in 15 cases where resection extended into the mediastinum. The overall rates of complications (52%), postoperative mortality (20%), and satisfactory deglutition (80%) were similar for both operations and were superior to those achieved with reconstructive procedures previously used by the authors. The choice of method is influenced by the length of the pharyngoesophagus to be replaced and the general condition of the patient. Gastric transposition is a more versatile operation and is adaptable to replacement of the entire esophagus if necessary, while the tubed pectoralis major myocutaneous flap has proven particularly effective for the rehabilitation of elderly and severely debilitated patients.


Appetite disorders in cancer patients: Impact on nutritional status and quality of life.
Cancer patients are at high risk of malnutrition due to several symptoms such as lack of appetite. The aim of this study was to determine the prevalence of different appetite disorders in cancer patients and their influence on dietary intake, nutritional status, and quality of life. We conducted a cross-sectional study of cancer patients at risk of malnutrition. Nutritional status was studied using Subjective Global Assessment, anthropometry, and grip strength. Dietary intake was evaluated with a 24-h recall, and patients were questioned about the presence of changes in appetite (none, anorexia, early satiety, or both). Quality of life was measured using EORTC-QLQ-C30. Multivariate analysis was performed using linear regression. 128 patients were evaluated. 61.7% experienced changes in appetite: 31% anorexia, 13.3% early satiety, and 17.2% both. Appetite disorders were more common in women and with the presence of cachexia. The combination of anorexia and satiety resulted in a lower weight and BMI. However, there were no significant effects on energy or macronutrient intake among different appetite alterations. Patients with a combination of anorexia and early satiety had worse overall health perception, role function, and fatigue. Appetite disorders are highly prevalent among cancer patients at risk of malnutrition. They have a significant impact on nutritional status and quality of life, especially when anorexia and early satiety are combined.


New miconazole-based azoles derived from eugenol show activity against Candida spp. and Cryptococcus gattii by inhibiting the fungal ergosterol biosynthesis.
This work describes the design, synthesis and antifungal activity of new imidazoles and 1,2,4-triazoles derived from eugenol and dihydroeugenol. These new compounds were fully characterized by spectroscopy/spectrometric analyses and the imidazoles 9, 10, 13 e 14 showed relevant antifungal activity against Candida sp. and Cryptococcus gattii in the range of 4.6-75.3 μM. Although no compound has shown a broad spectrum of antifungal activity against all evaluated strains, some azoles were more active than either reference drugs employed against specific strains. Eugenol-imidazole 13 was the most promising azole (MIC: 4.6 μM) against Candida albicans being 32 times more potent than miconazole (MIC: 150.2 μM) with no relevant cytotoxicity (selectivity index >28). Notably, dihydroeugenol-imidazole 14 was twice as potent (MIC: 36.4 μM) as miconazole (MIC: 74.9 μM) and more than 5 times more active than fluconazole (MIC: 209.0 μM) against alarming multi-resistant Candida auris. Furthermore, in vitro assays showed that most active compounds 10 and 13 altered the fungal ergosterol biosynthesis, reducing its content as fluconazole does, suggesting the enzyme lanosterol 14α-demethylase (CYP51) as a possible target for these new compounds. Docking studies with CYP51 revealed an interaction between the imidazole ring of the active substances with the heme group, as well as insertion of the chlorinated ring into a hydrophobic cavity at the binding site, consistent with the behavior observed with control drugs miconazole and fluconazole. The increase of azoles-resistant isolates of Candida species and the impact that C. auris has had on hospitals around the world reinforces the importance of discovery of azoles 9, 10, 13 e 14 as new bioactive compounds for further chemical optimization to afford new clinically antifungal agents.


Quality of Spine Surgery Research from the Arab Countries: A Systematic Review and Bibliometric Analysis.
Purpose. The purpose of our study is to evaluate the level of evidence (LOE) of spine surgery publications in the Arab countries and compare it with standard international literature in spine surgery and to determine the stand of the Arab nations academic production with that of the global one. Methods. An online search using "PubMed" and "Google Scholar" was carried out, using search terms related to spine surgery such as "Spine surgery," "Scoliosis," "Herniated disc." Each article was reviewed and graded by two reviewers using Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence scale. Results. We have identified 434 articles that met the inclusion criteria; 56% were level IV studies. The most common study design was case reports (42%). The number of Arab countries with publications in spine surgery was 18 countries. The country with the highest rate of publications was Egypt (26%). The quantity of the published studies increased from 151 in (2000-2008) to 283 in (2009-2015). There is statistical significance between high and low LOE articles (p = 0.0007). Conclusion. We have observed that LOE has not changed significantly over the period of 15 years and that much of the publications are of a low LOE (levels III and IV). We, herein, emphasize the need for spine surgeons in the Arab countries to conduct studies of higher LOE.


Gene Classification Based on Multi-Class SVMs with Systematic Sampling and Hierarchical Clustering (SSHC) Algorithm.
The support vector machines (SVMs) is one of the machine learning algorithms with high classification accuracy. However, the support vector machine algorithm has a very high training complexity. Thus, it is not very efficient with large datasets. In this study, we have used the multi-class support vector machines and systematic sampling with hierarchical clustering (SSHC-MCSVM) algorithm for gene expression data classification. The gene expression profiles are considered as large datasets. The gene expression datasets that are used in this study are two datasets for obese and lean individuals. In this proposed (SSHC-MCSVM) algorithm, the gene expression data are regrouped to new sets of genes based on systematic sampling with hierarchical clustering (SSHC) algorithm. The SSHC algorithm repeated n times and the k-partitions with clusters that have high adjusted Rand index (ARI) are chosen. The multi-class support vector machines are applied to the best regrouped gene expression data to classify the significant genes. The performance measures are accuracy, recall, and precision. The proposed algorithm which is SSHC-MCSVM could classify the significant genes with high accuracy, recall, and precision.


Association of osteoporosis and bone medication with the periodontal condition in elderly women.
This study investigated whether osteoporosis and its treatment may affect periodontal condition in elderly women. The findings highlighted that women with osteoporosis had a higher chance to present severe periodontitis than women with normal bone mineral density (BMD), particularly those who were not treated for osteoporosis. This study investigated whether osteoporosis increases the frequency and severity of chronic periodontitis in elderly women and evaluated the influence of vitamin D and osteoporosis treatment in the periodontal condition. In this cross-sectional study, elderly women were selected among 1266 subjects evaluated for lumbar spine and proximal femur bone mineral density (BMD) using dual energy X-ray absorptiometry. Sociodemographic, clinical characteristics, and complete periodontal examination were recorded. Serum 25-hydroxyvitamin D levels were measured by chemiluminescence. Forty-eight elderly women with normal BMD and 86 with osteoporosis were selected. Women with osteoporosis presented higher frequency of sites with clinical attachment level ≥6 mm (p = 0.003) and gingival recession ≥3 mm (p = 0.002) than those with normal BMD and were more than twice as likely to present severe periodontitis (odds ratio (OR) = 2.49, 95 % CI [1.14 to 5.43]). Osteoporotic women who were not treated for the condition had more chance to present severe periodontitis (OR = 3.16, 95 % CI [1.28 to 7.82]) than those who did use bisphosphonates (OR = 2.04, 95 % CI [0.85 to 4.89]). Among the participants who presented low levels of vitamin D, those with osteoporosis exhibited a higher chance to present severe periodontitis than those with normal BMD (p = 0.027), but the association between vitamin D levels and osteoporosis was not statistically significant after adjustment (p = 0.198). Elderly women with osteoporosis have a greater chance to present periodontitis, with higher severity than those with normal BMD. Osteoporosis treatment provides protection for periodontitis.


Myocardial blood flow and coronary flow reserve late after anatomical correction of transposition of the great arteries.
Myocardial blood flow (MBF) in children late after arterial switch operation (ASO) was investigated quantitatively by positron emission tomography (PET). In children with transposition of the great arteries (TGA), ASO is widely accepted as the management of choice. The long-term patency of coronary arteries after surgical transfer to the neo-aorta, however, remains a concern. Twenty-two normally developed, symptom-free children were investigated by PET with nitrogen-13 ammonia at rest and during adenosine vasodilation 10+/-1 years after ASO. A subgroup of 15 children (9+/-1 years; group A) had simple TGA and underwent ASO within 20 days after birth while 7 (13+/-3 years; group B) had complex TGA and underwent ASO and correction of associated anomalies later after birth. Ten young, healthy adults (26+/-6 years) served as the control group. Resting MBF was not different between groups. After correction for the rate-pressure product as an index of cardiac work, younger children of group A had significantly higher MBF at rest compared to healthy adults (102+/-29 vs. 77+/-6 ml/100 g/min; p = 0.012) while flow in group B was not different from the other groups (85+/-22 ml/100 g/min; p = NS). Hyperemic blood flows were significantly lower in both groups after ASO compared to normals (290+/-42 ml/100 g/min for group A, 240+/-28 for group B, 340+/-57 for normals; p < 0.01); thus, coronary flow reserve was significantly lower in both groups after ASO compared to healthy adults (3.0+/-0.6 for group A, 2.9+/-0.6 for group B, 4.6+/-0.9 for normals; p < 0.01). Blood flow measurements suggest decreased coronary reserve in the absence of ischemic symptoms in children late after arterial switch repair of TGA. The global impairment of stress flow dynamics may indicate altered vasoreactivity; however, the prognostic significance of these findings needs to be determined.


Mid-range left ventricular ejection fraction: Clinical profile and cause of death in ambulatory patients with chronic heart failure.
The intermediate group of patients with heart failure (HF) and mid-range left ventricular ejection fraction (HFmrEF) may constitute a specific phenotype, but a direct evidence is lacking. This study aimed to know whether this HF category is accompanied by a particular clinical phenotype and prognosis. This study includes 3446 ambulatory patients with chronic HF from two national registries. According to EF at enrollment, patients were classified as reduced (HFrEF, <40%), mid-range (HFmrEF, 40-49%) or preserved (HFpEF, ≥50%). Patients were followed-up for a median of 41months and the specific cause of death was prospectively registered. Patients with HFmrEF represented 13% of population and they exhibited a phenotype closer to HFrEF, except for a higher rate of coronary revascularization and diabetes, and a less advanced HF syndrome. The observed all-cause mortality was higher among HFrEF (33.0%), and similar between HFmrEF (27.8%) and HFpEF (28.0%) (p=0.012); however, the contribution of each cause of death differed significantly between categories (p<0.001). After propensity score matching, the risk of cardiovascular death, HF death or sudden cardiac death did not differ between HFmrEF and HFrEF in paired samples; however, patients with HFmrEF were at higher risk of cardiovascular death (sHR 1.71, 95% CI 1.13-2.57, p=0.011) and sudden cardiac death (sHR 2.73, 95% CI 1.07-6.98, p=0.036) than patients with HFpEF. Patients in the intermediate category of HFmrEF conform a phenotype closer to the clinical profile of HFrEF, and associated to higher risk of sudden cardiac death and cardiovascular death than patients with HFpEF.


Associations between circulating obesity-related biomarkers and prognosis in female breast cancer survivors: a systematic review of observational data in women enrolled in lifestyle intervention trials.
Obesity plays an important role in the development and progression of breast cancer via various oncogenic pathways. However, the biological mechanisms underlying this relationship are not fully understood. Moreover, it is unclear whether obesity-related and further associated biomarkers could be suitable targets for lifestyle interventions. This systematic review was conducted to examine relationships between obesity-related blood parameters and prognosis for breast cancer survivors enrolled in lifestyle intervention studies. A systematic, computerized literature search was conducted from inception through August 26th, 2020 in PubMed, EMBASE, and CENTRAL. The focus was on observational data from randomized controlled lifestyle intervention trials investigating associations between selected baseline biomarkers, measured in remission, and breast cancer recurrence, breast cancer mortality and/or all-cause mortality. Four studies with data from 5234 women met the inclusion criteria.Studies herein provide moderate evidence that bioavailable or serum testosterone may be positively linked to breast cancer recurrence and inversely linked to disease-free survival. Limited evidence suggests no associations with circulating estradiol or insulin levels on prognosis outcomes, whereas HDL cholesterol was inversely associated with breast cancer recurrence. For some other biomarkers, such as growth factors, adipokines, and CRP, the evidence for associations with disease prognosis was too weak to draw conclusions.Overall, despite potential candidates, there is insufficient evidence to confirm or refute that obesity-related biomarkers and sex hormones have a prognostic value for breast cancer survival. More longitudinal studies in breast cancer survivors to examine the clinical utility of obesity-related biomarkers are needed.


Primacy and recency effects in hierarchical renewal in rats.
Previous studies on hierarchical resurgence produced mixed results regarding the order and magnitude of recurrence of responses trained initially (primacy effect) or more recently (recency effect). Although changes in contextual stimuli could explain such differences, in resurgence procedures contextual stimuli are not commonly presented, thus their effects on multiple operants trained sequentially remain unclear. Renewal procedures, in contrast, have been useful to determine the effects of exteroceptive contextual stimuli on response recurrence. Thus, primacy and recency effects were studied using a renewal procedure in which three contexts were presented sequentially. Lever presses by rats were reinforced on a different lever under each training context and were then exposed to extinction in a different context. Presses on a fourth lever were never reinforced. During renewal testing, the three training contexts were presented in the same or inverse order relative to training. A strong primacy effect was found in rats exposed to the original training order. Both primacy and recency effects were found when the rats were exposed to contexts in inverse order. These results suggest that the magnitude of renewal of hierarchically trained responses is affected by training order and order of presentation of contextual stimuli during testing.


Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models.
Members of the fibroblast growth factor receptor family of kinases (FGFR1-4) are dysregulated in multiple cancers. Ponatinib (AP24534) is an oral multitargeted tyrosine kinase inhibitor being explored in a pivotal phase II trial in patients with chronic myelogenous leukemia due to its potent activity against BCR-ABL. Ponatinib has also been shown to inhibit the in vitro kinase activity of all four FGFRs, prompting us to examine its potential as an FGFR inhibitor. In Ba/F3 cells engineered to express activated FGFR1-4, ponatinib potently inhibited FGFR-mediated signaling and viability with IC(50) values <40 nmol/L, with substantial selectivity over parental Ba/F3 cells. In a panel of 14 cell lines representing multiple tumor types (endometrial, bladder, gastric, breast, lung, and colon) and containing FGFRs dysregulated by a variety of mechanisms, ponatinib inhibited FGFR-mediated signaling with IC(50) values <40 nmol/L and inhibited cell growth with GI(50) (concentration needed to reduce the growth of treated cells to half that of untreated cells) values of 7 to 181 nmol/L. Daily oral dosing of ponatinib (10-30 mg/kg) to mice reduced tumor growth and inhibited signaling in all three tumor models examined. Importantly, the potency of ponatinib in these models is similar to that previously observed in BCR-ABL-driven models and plasma levels of ponatinib that exceed the IC(50) values for FGFR1-4 inhibition can be sustained in patients. These results show that ponatinib is a potent pan-FGFR inhibitor and provide strong rationale for its evaluation in patients with FGFR-driven cancers.


Rhythmic nature of naloxone-induced aversions and nociception in rats.
Taste conditioning procedures revealed a rhythmic fluctuation in the aversiveness of naloxone in opiate-naive rats. This rhythm exhibited two peaks during each 24-hour period. One peak was evident in the light phase and the second, which was more prominent occurred in the dark phase. Analgesia produced by morphine showed an essentially similar rhythm with heat and pressure as noxious stimuli. Although control nociceptive thresholds for heat also showed this rhythm, those for pressure showed only one broad peak through most of the dark phase. With noxious heat the hyperalgesic effect of naloxone also showed two peaks of activity but, as in control responding, this was not true for pressure. Opioid systems mediating nociception of different stimuli may show differential diurnal fluctuations.


Periodate activation with manganese oxides for sulfanilamide degradation.
This study presents a novel periodate oxidation system mediated by manganese oxides for the rapid removal of aqueous contaminants. The catalytic activation of periodate on manganese oxides was demonstrated as an efficient advanced oxidation system for degradation of sulfanilamide. The reactivity of manganese oxides with different Mn valence followed the order of MnO2>Mn3O4>Mn2O3, all of which showed extraordinary reusability during repeated activation of periodate. Sulfanilamide was rapidly degraded along with stoichiometric transformation of IO4- to IO3-, and both processes exhibited good linear correlations with the dosage of manganese oxides. While the degradation of sulfanilamide in the MnO2/IO4- system was accelerated at lower solution pH, it was only slightly affected by ionic strength, water anions and humic acid. In contrast to the homogeneous system of Mn2+/IO4-, sulfanilamide degradation was not influenced in oxic and anoxic environment. It was evidenced by quenching studies and EPR tests that both singlet oxygen (1O2) and iodate radicals (IO3•) were generated when the metastable Mn(IV)-O-IO3 interacted with sulfanilamide. The XPS spectra of Mn 2p and O 1s before and after reactions indicated that the catalytic activation of periodate on MnO2 was not in company with the redox cycling of Mn(IV) species.


Preliminary study of a modified, nonflared, short, fully covered metal stent for refractory benign pancreatic duct strictures (with videos).
Fully covered self-expanding metal stents (FCSEMSs) are considered to be more effective than plastic stents for the treatment of main pancreatic duct (MPD) strictures associated with chronic pancreatitis (CP) because of their larger diameter and exertion of a radial expansion force. However, the current FCSEMSs have several limitations. To overcome these, a novel modified nonflared FCSEMS was developed. In this study we conducted a prospective long-term follow-up evaluation of the efficacy of the novel FCSEMS for the treatment of refractory benign PD strictures in patients with CP. Consecutive patients with symptomatic CP associated with refractory MPD strictures were enrolled prospectively in this single-arm study. The nonflared FCSEMS was placed intraductally or transpapillary according to the location and length of the stricture. Stent removal was performed at 3 months after placement. The primary outcome was the resolution of the pancreatic ductal stricture. Endoscopic placement of modified nonflared FCSEMSs was technically successful in all 25 patients. Intraductal FCSEMS placement was performed in 14 patients (56.0%). Stents of diameter 8 mm were used in 17 patients (68.0%). Stents of lengths 3 and 5 cm were inserted in 22 (88.0%) and 3 (12.0%) patients, respectively. In 1 patient (4.0%), stent migration developed. All other stents were removed successfully. After stent removal, resolution of the MPD stricture was confirmed in all patients, and no FCSEMS-related de novo stricture was observed. During the follow-up period (median, 34 months; interquartile range, 25-56) after the stents had been removed from the 25 patients, reintervention for recurrence of MPD stricture with abdominal pain was performed in 2 patients (8.0%). Endoscopic placement of a novel modified nonflared FCSEMS resulted in long-term stricture resolution with pain relief and reduced the rate of stent-related adverse events, particularly stent migration and stent-induced de novo MPD stricture. (Clinical trial registration number: UMIN000035681.).


Metastatic cerebral choriocarcinoma with primary neurological presentation.
Metastatic choriocarcinoma can present in bizarre fashions. Two cases with primary neurological presentations are reviewed. Cerebral metastases in choriocarcinoma generally denote a poor prognosis. However, in solitary metastases in the brain, craniotomy and excision followed by chemotherapy may be curative as illustrated by the following two cases. The first patient was diagnosed to have brain metastases 1 1/2 years after an evacuation of her molar pregnancy while the other patient developed cerebral choriocarcinoma 5 months following a spontaneous first trimester abortion. Both presented with neurological symptoms. Both patients are alive and well now, 9 and 5 years respectively after craniotomy and chemotherapy. A brief review of current considerations in the management of cerebral metastases in gestational trophoblastic disease is presented.


Southwestern blot mapping of potential regulatory proteins binding to the DNA encoding plasminogen activator inhibitor type 2.
In order to investigate the molecular basis for the regulated expression of plasminogen activator inhibitor type 2 (PAI-2), we sought to identify monocyte-derived nuclear factors which interact with the PAI-2 gene. We have explored the application of Southwestern blot mapping as an approach for identifying specific DNA-protein interactions and targeting potential regulatory DNA elements. The procedure involves an initial global screening of a crude preparation of nuclear proteins with radiolabelled DNA fragments (200-300 bp) derived from a large region (8.8 kb) of PAI-2. The bound DNA fragments are eluted and their location within PAI-2 mapped by Southern blot hybridization analysis. We have used this procedure to examine the differential binding of nuclear factors from the U937 monocytic cell in the absence and in the presence of the differentiating agent, 12-phorbol 13-myristate acetate (PMA), in order to identify proteins that bind specifically to the 5' flanking promoter region and first intron of PAI-2. Eleven DNA-binding proteins ranging in molecular mass from 27 to 92 kDa were identified, and the results define three regions of the gene which contain DNA-binding sites which may be involved in the transcriptional regulation of PAI-2. Deletion analysis using a series of 5' deletion mutants spanning PAI-2 fused to a chloramphenicol acetyltransferase-encoding reporter gene (cat) demonstrates that two of the regions identified by Southwestern blot mapping contain elements which can function to modulate PAI-2 expression in transient transfections of U937 cells.


The Use of LipidIMMS Analyzer for Lipid Identification in Ion Mobility-Mass Spectrometry-Based Untargeted Lipidomics.
Untargeted lipidomics aims to comprehensively measure and characterize all lipid species in biological systems. Ion mobility-mass spectrometry (IM-MS) has showed a great potential for untargeted lipidomic analysis. Coupling with liquid chromatography and data-independent tandem MS techniques, acquired IM-MS data set contains four-dimensional information for lipid identification, including m/z of MS1 ion, retention time (RT), collision cross section (CCS), and MS/MS spectra. In this protocol, we introduced a data processing workflow using an integrative web server, namely, LipidIMMS Analyzer, to support accurate lipid identification. The protocol demonstrated the integration of all four dimensional information to achieve unambiguous identifications of lipids in complex biological samples.


Life-cycle assessment of two sewage sludge-to-energy systems based on different sewage sludge characteristics: Energy balance and greenhouse gas-emission footprint analysis.
Anaerobic digestion and incineration are widely used sewage sludge (SS) treatment and disposal approaches to recovering energy from SS, but it is difficult to select a suitable technical process from the various technologies. In this study, life-cycle assessments were adopted to compare the energy- and greenhouse gas- (GHG) emission footprints of two sludge-to-energy systems. One system uses a combination of AD with incineration (the AI system), whereas the other was simplified by direct incineration (the DI system). Comparison between three SS feedstocks (VS/TS: 57.61 -73.1 ds.%) revealed that the AI system consistently outperformed the DI system. The results of sensitivity analyses showed that the energy and GHG emission performances were mainly affected by VS content of the SS, AD conversion efficiency, and the energy consumption of sludge drying. Furthermore, the energy and GHG emission credit of the two systems increased remarkably with the increase in the VS content of the SS. For the high-organic-content sludge (VS/TS: 55%-80%), the energy and GHG emission credit of the AI system increase with the increase of AD conversion efficiency. However, for the low organic content sludge (VS/TS: 30%-55%), it has the opposite effect. In terms of energy efficiency and GHG performance, the AI system is a good choice for the treatment of high-organic-content sludge (VS/TS>55%), but DI shows superiority over AI when dealing with low organic content sludge (VS/TS<55%).


Short-term resistance training in older adults improves muscle quality: A randomized control trial.
The purpose of this study was to evaluate whether dumbbell resistance training (DBRT) and elastic band resistance training (EBRT) are equally beneficial in the older adult. Sixty-five healthy participants (mean±SD; age=66.5±7.09 years; height=165.2±10.6 cm; body mass=74.5±14.6 kg) volunteered for this study. Participants underwent a total body dual-energy x-ray absorptiometry (DXA) scan for segmental and total body muscle and fat estimation. Functional tests included the short physical performance battery, timed up-and-go, and heel-to-toe walk. Strength was measured on dominant handgrip strength, maximal bench press, and leg press. Participants were block randomized into one of three groups: elastic band resistance training (EBRT), dumbbell resistance training (DBRT), or control (CON). EBRT and DBRT were asked to visit the laboratory twice weekly over 6-weeks while CON maintained their daily routine. Data were analyzed using a two-way repeated measures ANOVA and an alpha set at 0.05. Results indicated there was a two-way interaction for bench press, leg press, upper- and lower-body muscle quality and total arm lean mass (p<0.05). Specifically, the EBRT and DBRT improved from pre to post for total arm lean mass (p<0.021, p<0.004, respectively). Additionally, for bench press and leg press, all groups improved pre to post training (p<0.05) with DBRT superior to CON. These data suggest that EBRT provides an effective, portable, and cost-effective means to enhance lower-body function and muscle quality in an aging population, yet DBRT may be more impactful for total-body improvements.


Comparative study of 111In and 59Fe bone marrow scanning.
The aim of this work is to examine the relative merits of 59Fe and 111In scanning in estimating the functional value of the various erythropoietic areas and in appraising bone marrow distribution and extension. At first we studied a group of patients with heterogeneous distribution of bone marrow secondary to irradiation, ferrokinetics serving a reference for the comparison of 111In and 59Fe scanning. The functional value fo 59Fe scanning was thus proved, in contrast to 111In scanning which was erroneous for 13 of the 29 bone marrow areas studied. A further study of patients presenting polycythemia vera or anemia with 111In demonstrated in some cases false distribution and bone marrow extension. Furthermore, 59Fe scanning permitted evaluation of the efficiency of erythropoiesis and the existence of extramedullary erythropoiesis. Review of the literature revealed that with the activity used there was no dosimetric advantage of 111In over 59Fe.


Pediatric septorhinoplasty: Current attitudes and practices by facial plastic and reconstructive surgeons.
There is hesitation to offer pediatric patients rhinoplasty due to concerns about postoperative effect on midface growth. A cross-sectional survey of members of the American Academy of Facial Plastic and Reconstructive Surgery was conducted regarding practice information and attitudes towards pediatric septorhinoplasty. The goal of the study is to describe the current attitudes on pediatric septorhinoplasty. Cross-sectional survey. Community members of the American Academy of Facial Plastic and Reconstructive Surgery society. A 19-question survey was distributed to surgeons surveying background information and current attitudes towards pediatric septorhinoplasty practices. Fisher's exact tests were implemented using Monte Carlo methods. There were 94 total respondents. A majority believed septorhinoplasty is safe in patients <16 years of age (n = 68, 72.34 %) with most choosing either 16 years (n = 30, 31.91 %) or 14 years (n = 29, 30.85 %) as the minimum age to consider the procedure. A majority of respondents would not perform any nasal procedures in patients ≤12 years (n = 40, 43.48 %). Trends in pediatric rhinoplasty practices have evolved overtime. Despite prior beliefs and studies cautioning against performing septorhinoplasty in pediatric patients (<16 years of age), a majority of practicing facial plastic surgeons believe that pediatric septorhinoplasty can be performed in patients >14 years old. IV.


Antral follicle count (AFC) can be used in the prediction of ovarian response but cannot predict the oocyte/embryo quality or the in vitro fertilization outcome in an egg donation program.
To verify whether the antral follicle count (AFC) could predict ovarian response, oocyte/embryo quality, and IVF outcome. Prospective study. Instituto Universitario-Instituto Valenciano de Infertilidad, Valencia, Spain. One thousand seventy-four donors and 975 oocyte recipient cycles. Controlled ovarian hyperstimulation (COH), endometrial preparation, IVF/intracytoplasmic sperm injection, ET. COH and oocyte/embryo quality parameters and IVF outcome. We observed lower E(2) levels and fewer mature retrieved oocyte numbers among donors who showed an AFC that was <10. These donors also showed significantly higher cancellation and no-donation rates; poor and/or insufficient response was the principal cause (82%). However, there were no differences among the groups regarding embryo development parameters and IVF outcome. AFC is a noninvasive and simple tool that can improve the oocyte donor's selection of an egg donation program. This study suggests that AFC is a good predictor of ovarian response but cannot be used to predict oocyte/embryo quality or IVF outcome.


The treatment of normal-tension glaucoma.
Normal-tension glaucoma (NTG) is generally defined as visual field loss and optic nerve defects consistent with glaucoma and an intraocular pressure (IOP) that does not exceed 21 mmHg (Allingham, R.R., Damji, K., Freedman, S., Moroi, S., Shafranov, G., Shields, M.B. (2005). In: Pine J. and Murphy J. (Eds.), Shields' Textbook of Glaucoma, 5th edn., Lippincott Williams & Wilkins, Philadelphia, PA, pp. 197-207, Chapter 11). If a patient has an atypical presentation (unilateral disease, decreased central visual acuity or visual field loss not consistent with optic disk appearance) then the clinician should rule out medical or neurologic etiologies. IOP-dependent and IOP-independent mechanisms play a role in NTG nerve damage. The exact mechanisms of IOP-independent damage are not currently known. Research has shown that vascular etiologies, such as vascular insufficiency and vasospasm, may be possible mechanisms for IOP-independent damage. The mainstay of glaucoma treatment remains robust IOP reduction. The chief goal of ongoing glaucoma research is to more clearly identify IOP-independent mechanisms of damage and to find neuroprotective treatment strategies to prevent retinal ganglion cell death and consequent visual loss.


A lower level of reduced albumin induces serious cardiovascular incidence among peritoneal dialysis patients.
Human serum albumin is composed of human mercaptoalbumin (HMA) with cysteine residues having reducing powers and of oxidized human non-mercaptoalbumin. Previously, we reported that a lower HMA level is closely related to serious cardiovascular disease (CVD) incidence and mortality among hemodialysis patients. However, the relationship between HMA level and CVD incidence among peritoneal dialysis (PD) patients is unclear. We measured the redox state of human serum albumin using high-performance liquid chromatography in 30 continuous ambulatory PD patients. The association between HMA and incidental CVD events was evaluated. Eight patients experienced symptomatic CVD events (5 patients died) at the 5-year follow-up. The concentration and fraction of HMA (cHMA and f(HMA), respectively) showed significantly lower values in patients with CVD than those without CVD (cHMA 1.58 ± 0.39 and 2.16 ± 0.43 g/dL, f(HMA) 48.9 ± 5.4 and 56.4 ± 8.6%, respectively). Multiple forward stepwise regression analysis using cHMA and f(HMA) as the criterion variables was performed, and C-reactive protein and hemoglobin were adopted as significant explanatory variables in the former equation, whereas urea nitrogen was adopted in the latter equation. Multiple logistic regression analysis revealed that cHMA is a statistically, and f(HMA) is a marginally significant explanatory variable of CVD incidence (p = 0.0369, R = -0.260 and p = 0.0580, R = -0.214, respectively). Lower HMA level, which might be caused by chronic inflammation, anemia and accumulation of dialyzable uremic toxin(s), is closely related to serious CVD incidence among PD patients.


Cardiotoxin III induces apoptosis in K562 cells through a mitochondrial-mediated pathway.
1. Cardiotoxin (CTX) III is a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom. This is the first report on the mechanism of the anticancer effect of CTX III on human leukaemia K562 cells. 2. Cardiotoxin III was found to inhibit the growth of K562 cells in a time- and dose-dependent manner, with an IC(50) value of 1.7 mug/mL, and displayed several features of apoptosis, including apoptotic body formation, an increase in the sub-G(1) population, DNA fragmentation and poly (ADP-ribose) polymerase (PARP) cleavage. 3. Investigation of the mechanism of CTX III-induced apoptosis revealed that treatment of K562 cells with CTX III resulted in the loss of mitochondrial membrane potential, cytochrome c release from mitochondria into the cytosol and activation of caspase-9 and caspase-3 and the subsequent cleavage of the caspase-3 substrate PARP; however, CTX III did not generate reactive oxygen species (ROS). 4. Taken together, the results indicate that CTX III induces apoptosis in K562 cells through an ROS-independent mitochondrial dysfunction pathway.


Bacterial cholangitis after surgery for biliary atresia.
We retrospectively studied the incidence of bacterial cholangitis in 129 infants operated on because of biliary atresia over 5 years. Forty-six of the 101 children who underwent hepatic portoenterostomy had a total of 105 episodes of cholangitis (range one to eight episodes per child). Most episodes occurred within 3 months of the operation. Factors associated with cholangitis included good or partial restoration of bile flow, abnormal intrahepatic bile ducts or cavities at the porta hepatis, and routine postoperative use of antibiotics. External jejunostomy was not effective in preventing cholangitis. In addition to fever and decreased bile flow, increased erythrocyte sedimentation rate and signs of shock were frequently observed. The responsible organisms, most often gram-negative bacteria, were identified in 79 (75%) episodes by blood or liver cultures. Most were susceptible to trimethoprim-sulfamethoxazole and third-generation cephalosporins during the first episode, but only to cephalosporins during later episodes. The incidence of signs of portal hypertension in children with normal serum bilirubin values at age 5 years was not higher in those who had previously experienced one or more episodes of cholangitis.


Production of Bio-omega-3 eggs through the supplementation of extruded flaxseed meal in hen diet.
The full-fat flaxseed meal has obtained relatively new flourished concept as staple chicken feedstuff for the production of designer eggs. However, unprocessed flaxseed also encloses well documented anti-nutritional factors which are associated with growth depression of laying hens. The present research work was carried out to evaluate the impact of full-fat extruded flaxseed meal supplemented diets on productivity performance of hens and production of modified ω-3 fatty acids-enriched eggs. The full-fat flaxseed meal was extruded at barrel exit temperature (140 °C), screw speed (160 rpm) and feed rate (25 kg/h) for reduction of anti-nutritional compounds. One hundred and sixty, Babcock hens (age 24 weeks old) were selected at random from a large flock and ten hens were placed in each of 16 wire-mesh pens. The experimental diets prepared by supplementation of extruded flaxseed at 10%, 20% and 30% level were fed to hens along with control. The extruded flaxseed contained 86% and 76% less hydrocyanic compounds and tannin, respectively than the initial material. The hens fed with control diet consumed more feed, possessed heavy body weight and showed higher egg production as compared to hens fed on extruded flaxseed supplemented diets. The loss in body weight and egg production was recorded less for hens fed on 10% extruded flaxseed supplemented diets as compared to those fed on 30% extruded flaxseed supplemented diets. None of the experimental diets resulted in significant increase or decrease the total lipids and cholesterol content in egg yolk of hens. The extruded flaxseed supplemented diets resulted in a significant improvement of α-linolenic and docosahexaenoic acid in egg yolk with a concomitant reduction in arachidonic acid. The sensory scores were assigned higher to control eggs. Increasing level of extruded flaxseed in experimental diets decreased the scores for all sensory attributes of eggs. The present study suggested that extruded flaxseed meal up to 20% can be supplemented in the diets of hens for maximum deposition of α-linolenic acid and docosahexaenoic acid in egg yolk with acceptable detrimental effects on egg traits.


DRL performance in the weanling rat: a comparison with adult subjects.
Weanling (21-day) and adult (3-month-old) albino rats were reinforced for lever pressing on a Differential Reinforcement of Low rates 20 seconds schedule. After 2 sessions at DRL 5, 10, 15 and 20 seconds, 40 DRL 20 seconds sessions were performed, at a pace of 4 sessions a day. Adult rats emit lower response rates, higher median Inter-Response-Times (IRTs) and obtain more reinforcers than weanling rats. Furthermore, their coefficients of variation (ratio between semi-interquartile range and median of the IRT distribution) are significantly lower than those of the young subjects. Age-related differences are discussed in relationship with general activity, food motivation and timing mechanisms. It is suggested that weanling and adult timing devices do not basically differ, but that age-related differences exist at the level of the translation of time estimates into overt behavior.


Comparative macroarray analysis of morphine containing Papaver somniferum and eight morphine free Papaver species identifies an O-methyltransferase involved in benzylisoquinoline biosynthesis.
Benzylisoquinoline alkaloids constitute a group of about 2,500 structures and are mainly produced by plants of the order Ranunculales. But only the opium poppy, Papaver somniferum, and Papaver setigerum are able to produce morphine. In this study, we started to investigate by gene expression analysis the molecular basis for this exceptional biosynthetic ability. A sequencing project from P. somniferum seedlings was initiated using a method based on the amplified fragment length polymorphism technique that resulted in 849 UniGenes. These cDNAs were analysed on macroarrays for differential expression between morphine-containing P. somniferum plants and eight other Papaver species, which accumulate other benzylisoquinolines instead of morphine. Three cDNAs showing increased expression in P. somniferum compared to all the other Papaver species were identified. Whereas two showed no significant homology to any known protein, one putatively encoded an O-methyltransferase. Analysis of substrate specificity of the heterologously expressed protein and mass spectrometric identification of the enzymatic products identified this protein as S-adenosyl-L-methionine:(R,S)-3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase (EC 220.127.116.11). Unlike other O-methyltransferases of different positional specificities implicated in benzylisoquinoline metabolism, the enzyme only accepted tetrahydroxylated tetrahydrobenzylisoquinolines as substrates; methylation was tolerated only at the 6-hydroxy position.


The relationship of life-course patterns of adiposity with type 2 diabetes, depression, and their comorbidity in the Northern Finland Birth Cohort 1966.
Type 2 diabetes (T2D) and comorbid depression challenges clinical management particularly in individuals with overweight. We aim to explore the shared etiology, via lifecourse adiposity, between T2D and depression. We used data from birth until 46years from Northern Finland Birth Cohort 1966 (n = 6,372; 53.8% females). We conducted multivariate analyses on three outcomes: T2D (4.2%), depression (19.2%) and as comorbidity (1.8%). We conducted (i) Path analysis to clarify time-dependent body mass index (BMI) related pathways, including BMI polygenic risk scores (PRS); and (ii) Cox regression models to assess whether reduction of overweight between 7years and 31years influence T2D, depression and/or comorbidity. The models were tested for covariation with sex, education, smoking, physical activity, and diet score. The odd ratios (OR) of T2D in individuals with depression was 1.68 [95% confidence interval (CI): 1.34-2.11], and no change in estimate was observed when adjusted for covariates. T2D and comorbidity showed similar patterns of relationships in the path analyses (P < 0.001). The genetic risk for obesity (PRS BMI) did not show direct effect on T2D or comorbidity in adulthood but indirectly through measures of adiposity in early childhood and mid-adulthood in the path analysis (P < 0.001). Having early-onset of overweight at 7years and 31years showed highest risk of T2D (OR 3.8, 95%CI 2.4-6.1) and comorbidity (OR 5.0, 95%CI 2.7-9.5), with mild-to-moderate attenuation with adjustments. Depression showed no significant associations. We found evidence for overweight since childhood as a risk factor for T2D and co-morbidity between T2D and depression, influenced moderately by lifestyle factors in later life. However, no shared early life adiposity related risk factors were observed between T2D and depression when assessed independently in this Finnish setting.


Inlet patch: heterotopic gastric mucosa--another contributor to supraesophageal symptoms?
To determine prospectively the incidence of an inlet patch (IP) in children requiring esophagogastroduodenoscopy (EGD) and assess the prevalence of presenting symptoms between children with and without an IP. All patients undergoing EGD in a 2-year period were assessed for the presence of an IP with biopsy confirmation. IP, distal esophagus, and stomach biopsy specimens were blindly reviewed by a pathologist for the presence and degree of inflammation and intestinal metaplasia. Symptoms from children with and without an IP were compared. From 407 EGDs done by a single endoscopist, 24 patients had confirmed IP (incidence of 5.9%). The presence and degree of inflammation were always relatively greater in the columnar mucosa of the IP than in the antral/body gastric mucosa in the same patient (P = .0027) Inflammation was similar in the squamous epithelium around the IP and in the distal esophagus (P=.46). Two patients had intestinal metaplasia of the IP. The patients with IPs had a higher prevalence of respiratory symptoms than the control group (P = .03). Children with IPs may have a higher frequency of respiratory symptoms. Periodic surveillance should be performed in children with intestinal metaplasia of an IP.


Predicting the course of myasthenic weakness following double filtration plasmapheresis.
To evaluate the clinical course of patients with myasthenia gravis (MG) up to 3 months after double filtration plasmapheresis (DFP). We recorded the MG score and measured the level of acetylcholine receptor antibody (AchRAb) at baseline and day 1 (D1), week 1 (W1), 1 month (M1), 2 (M2) and 3 months (M3) after DFP in 16 MG patients. Based on the difference in score during follow-up, we divided our patients into clinical improvement (CI) and clinical worsening (CW) groups. The MG score decreased in all courses from a mean of 8.1 at baseline to 5.6 at D1, and to 4.7, 4.0, 3.8, and 3.7 at W1, M1, M2, and M3, respectively. In the CW group, AchRAb levels were significantly higher at M1 (P = 0.022). The AchRAb level at W1 correlated significantly with the MG score at M3 (P = 0.027) and the changes of MG score from W1 to M1 (P = 0.029). The ratio of AchRAb levels of M1 to W1 correlated well with MG score at W1 (P = 0.032), at M3 (P = 0.001), and the changes of MG score from W1 to M1 (P = 0.004). Excessive rebounds of AchRAb level at W1 may suggest clinical worsening and further increases in AchRAb level at M1 predict poorer outcome after DFP.


Covid-19 and adolescent acute kidney injury: Renal recovery with combined enalapril and estrogen therapy.
Covid-19 in adolescence with multisystem inflammatory injury (MIS-C) is a newly described condition sharing key features with Kawasaki disease and toxic shock syndrome. A May 2020 United Nations WHO brief covering findings from North America and Europe drew notice to this acute post-viral illness characterized by severe, diffuse hyperinflammation leading to multiorgan failure. While females diagnosed with Covid-19 generally have more favorable outcomes than males, this protection is negated by a low estrogen state. This case reports on acute kidney injury/MIS-C with amenorrhea from ovarian insufficiency in childhood, itself an uncommon presentation of idiopathic hypogonadism. Three exon variants were previously identified in a healthy, phenotypically normal 46,XX adolescent who subsequently underwent whole genome sequencing (WGS). She had only two spontaneous menses with a provisional diagnosis of premature ovarian insufficiency made by age 15. Against this background, Covid-19 infection necessitated hospital admission where progressively reduced renal function was a prime component of MIS-C. Combined angiotensin-converting enzyme inhibitor plus transdermal estrogen replacement therapy resulted in normalized estimated glomerular filtration rate (eGFR) from baseline 43 to 68 ml/min/1.73 m2, post-treatment. Serum cystatin-C also improved during this interval from 1.69 to 1.19 mg/L. Among 7 Covid-19 high risk intron variants identified was rs3131294 (6p21), near NOTCH4. Another finding at rs8068318 (17q23) was associated with creatine level and eGFR. This is the first work to explore Covid-19 and associated kidney injury as a component of MIS-C at the intersection of rare multigene variants and functional ovarian loss. The context of transition from adolescence to adulthood is also considered, where successful recovery of renal function was achieved with combined enalapril and supplemental estrogen.


The effect of continuous ambulatory peritoneal dialysis on diabetic eye complications.
Nine patients have been followed ophthalmologically since starting continuous ambulatory peritoneal dialysis (CAPD) for periods ranging from 16 to 48 months. All patients had eye disease related to their diabetes. Seven patients had proliferative diabetic retinopathy (PDR) and all these required laser treatment, six while undergoing CAPD. PDR was considered to have progressed during CAPD in four patients.