Risk factors for morbidity and mortality in pediatric patients with peritoneal dialysis catheters.
As peritoneal dialysis (PD) is the preferred long-term dialysis modality in the pediatric population, we sought to identify risk factors for mortality and reoperation. A retrospective review of patients undergoing PD catheter insertions at a single center from 1994-2009 was performed. The following variables were evaluated: age (<1 year), comorbidities, omentectomy, concomitant gastrostomy, and laparoscopic technique. Multivariable Cox regressions analyses were used to evaluate patient survival and reoperation-free survival of PD catheters. 207 patients with a median age of 10 years underwent PD insertion. Mortality was 7% with a median follow up of 72 months. Reoperation for malfunction and infection was required in 49% of patients with a median PD catheter survival of 11 months. Reoperation for hernias occurred in 14% of patients. Multivariate Cox regressions analyses identified age <1 year, lack of omentectomy, concomitant gastrostomy, and prematurity as variables significantly associated with higher rates of mortality or reoperation. In this large study of pediatric patients undergoing PD, higher complication rates were noted in infants less than one year of age. Concomitant gastrostomy was associated with a higher rate of reoperation for infection. Failure to perform omentectomy was associated with a higher rate of catheter failure.


The Yc and Ya subunits of rat liver glutathione S-transferases are the products of separate genes.
Rat liver glutathione S-transferases consist of binary combinations of three major classes of subunits designated as Ya (Mr = 25,600), Yb (Mr = 27,000) and Yc (Mr = 28,000). We have determined the nucleotide sequences of a cDNA insert in pGTR262 containing partial sequence of a Yc subunit. Sequence comparison with a Ya subunit cDNA clone pGTR261 revealed 70% nucleotide sequence homology and 65% amino acid sequence homology in the overlapping coding regions. Approximately 65% of the amino acid substitutions between these two subunits occur in clusters of two to eight residues. The 3' noncoding sequences of these two subunit cDNA clones are highly divergent in length and in sequences. The 3' noncoding region of pGTR262 cDNA contains open reading frames of 23, 39, and 13 amino acids which are in phase with the deduced Yc subunit sequences but interrupted by termination codons. By RNA blot hybridization analysis, we found that this Yc subunit sequence expression is tissue specific. It is expressed at a reduced level in kidney and testis as compared with liver and hardly at all in heart, lung, seminal vesicles, and spleen. We suggest that the mechanism for the tissue-specific expression of the Yc subunit of rat liver glutathione S-transferases may occur at or prior to the level of RNA processing. From the divergent DNA sequences between the Ya and Yc subunits reported in this communication and their differential induction upon acute phenobarbital administration reported by Pickett et al. (Pickett, C.B., Donohue, A. M., Lu, A. Y. H., and Hales, B. F. (1982) Arch. Biochem. Biophys. 215, 539-543) we propose that the Ya and Yc subunits of rat liver glutathione S-transferases are encoded by separate gene families or transcriptional units.


Barriers and facilitators to supporting women with postnatal depression and anxiety: A qualitative study of maternal and child health nurses' experiences.
To explore maternal and child health nurses' experiences of supporting women with postnatal depression and anxiety and the factors which impact these. Maternal and child health nurses play a key role in identifying women with postnatal depression and anxiety and facilitating their access to appropriate supports. Understanding how nurses carryout this work, and the conditions which impact their ability to do so, is critical to the development of service delivery frameworks that can facilitate optimal outcomes for women and their families. Despite this, little is known about this subject. A qualitative descriptive study. Participants were maternal and child health nurses practicing for at least six months and regularly seeing new mothers in Victoria, Australia. Twelve nurses were interviewed. Thematic analysis was conducted to identify patterns across our data. Qualitative content analysis was used to identify issues which were most emphasised by nurses. Reporting complies with the COREQ checklist. Three overarching themes were identified. Theme one pertained to steps taken by nurses following the identification of depression or anxiety symptoms and the shared challenges they encountered. Theme two concerned nurses' experiences of supporting women who required acute mental health interventions and the systemic barriers they faced. Finally, theme three related to how the existing service delivery model could be improved to better support nurses in their work. The complex system within which nurses operate presents barriers that can impede their ability to respond to women with postnatal mental health issues. There is a need for service delivery frameworks that better support nurses and facilitates equitable access to mental healthcare. Facilitating equitable access to all perinatal mental health services and interventions must be at the heart of all future policy, funding and service delivery frameworks.


The current status of resistance to organophosphorus ixodicides by the blue tick, Boophilus Decoloratus (Koch) in the Republic of South Africa and Transkei.
In a four year survey 253 isolates of Boophilus decoloratus from the Republic of South Africa and Transkei were tested in the laboratory for their susceptibility to certain organophosphorus ixodicides. Fifty-seven of these isolates were susceptible to organophosphorus compounds, 88 isolates showed a range of susceptibility between that of the susceptible laboratory strain and a strain having a resistance greater than that for the Berlin type strain. A field trial confirmed degrees of resistance shown in the laboratory to the organophosphorus ixodicides benoxophos, chlorfenvinphos, dioxathion, dicrotophos, quintiofos and chlorfenvinphos/dioxathion.


Structural characterization of a novel polysaccharide from sweet corncob that inhibits glycosylase in STZ-induced diabetic rats : Structural characterization of a novel polysaccharide.
In the current study, we extracted a polysaccharide from sweet corncob and evaluated its hypoglycemic function. After collection in water, alcohol precipitation, and purification by DEAE-52 and Sephadex G-100 columns, we obtained a polysaccharide (SCP50) that was composed primarily of mannose and glucose (9.73:190.27), with a molecular weight of 9280.33 Da. We demonstrated that SCP50 exhibited significant inhibition of α-glucosidase activity, with an IC50 of 4.866 mg/mL, Km of 1.297 × 10-3, and Vmax of 0.076 mol/L·min-1 in vitro. We also observed that SCP50 markedly attenuated disaccharidase (maltase, sucrase, and lactase) activity in a rat model of T2DM. We conclude that SCP50 exerts a hypoglycemic effect via inhibition of intestinal glycosylase. These results thus provide new insight into the hypoglycemic action underlying sweet corncob polysaccharide's effects.


Equine arteritis virus: a new isolate from the presumable first carrier stallion in Argentina and its genetic relationships among the four reported unique Argentinean strains.
Equine arteritis virus (EAV) was isolated from a testicle of the presumable first stallion infected with EAV in Argentina. This virus isolate (named LT-LP-ARG) was confirmed by GP5-specific PCR and indirect immunofluorescence assays. The PCR product was sequenced, and the phylogenetic analysis revealed that the LT-LP-ARG strain of EAV forms a monophyletic group, together with other strains previously isolated in our laboratory (LP02 group). However, all Argentinean EAV strains belong to a polyphyletic group. We believe that the virus isolate presented in this report could be the origin of EAV infection in our country.


Transmembrane signaling across the ligand-gated FhuA receptor: crystal structures of free and ferrichrome-bound states reveal allosteric changes.
FhuA protein facilitates ligand-gated transport of ferrichrome-bound iron across Escherichia coli outer membranes. X-ray analysis at 2.7 A resolution reveals two distinct conformations in the presence and absence of ferrichrome. The monomeric protein consists of a hollow, 22-stranded, antiparallel beta barrel (residues 160-714), which is obstructed by a plug (residues 19-159). The binding site of ferrichrome, an aromatic pocket near the cell surface, undergoes minor changes upon association with the ligand. These are propagated and amplified across the plug, eventually resulting in substantially different protein conformations at the periplasmic face. Our findings reveal the mechanism of signal transmission and suggest how the energy-transducing TonB complex senses ligand binding.


Moving molecular diagnostics from laboratory to clinical application: a case study using infectious pancreatic necrosis virus serotype A.
Using an RT-PCR method for detection of infectious pancreatic necrosis virus (IPNV) in Atlantic salmon as a model, this study examined the optimization and validation required to provide a method suitable for IPNV detection from fish tissue. IPNV-positive Atlantic salmon kidney samples that had been titred or kidney spiked with IPNV were used. The amount of RNA in the reverse transcription (RT), RT denaturation temperature and incubation time, PCR annealing temperature and number of cycles were optimized. The optimized RT-PCR was able to detect IPNV in Atlantic salmon kidney calculated to have a titre of ten infectious units. Extensive optimization is required to produce a PCR for detection of fish pathogens from methods designed in the laboratory. This study demonstrated some of the many variables that should be optimized before a fully validated assay can be claimed and illustrates the extensive validation required to fulfil requirements of the OIE and is of relevance to laboratories carrying out clinical testing.


A Modified Procedure to Diagnose Erectile Dysfunction Using the International Index of Erectile Function (IIEF-6) Combined With the Premature Ejaculation Diagnosis Tool (PEDT) via an Internet Survey.
The reliability of the International Index of Erectile Function (IIEF-5) in diagnosing erectile dysfunction (ED) is significantly decreased for the population with premature ejaculation (PE). We aimed to illustrate a better way of diagnosing ED among the general population through a web survey study. We collected online surveys from 2,746 men between the ages of 18 and 65. Two methods were used to determine the prevalence of ED, and these 2 methods were compared. Additionally, we divided our sample into 2 equally sized groups by median age and repeated the analyses for each group. In Method Ⅰ (M Ⅰ), men with an IIEF-5 score ≤ 21 were diagnosed with ED. In Method Ⅱ (M Ⅱ), PE was defined as a PEDT score ≥ 9, and no-PE was defined as a PEDT score ≤ 8. We used an IIEF-6 score cutoff of ≤ 24 among the PE population and a cutoff of ≤ 25 among the no-PE population to diagnose ED. We examined the results from the IIEF-5, PEDT, and IIEF-6. Of the 2,746 men, 1,540 were in a stable heterosexual relationship, and the prevalence of ED among these men was determined. The prevalence of ED, as measured by Method Ⅰ, was significantly higher than that measured by Method Ⅱ. The kappa coefficients between the 2 methods were 0.595, 0.704, and 0.430 for the overall, no-PE, and PE populations, respectively. The internal consistency of the IIEF-5 for the PE population increased if Question 5 (intercourse satisfaction) was removed. Similar trends were observed for the groups, and there were no substantial differences. Our research suggests that before using the erectile function assessment scale to evaluate erectile function, ejaculatory function should be assessed with the PEDT. This was the first study to highlight the importance of evaluating ejaculatory function using the PEDT before diagnosing ED via an internet survey. There may have been recruitment bias because our study was an internet survey. Establishing the prevalence of ED by using a combination of the IIEF-6 and PEDT was more reliable than using the IIEF-5 alone. Further validation of the modified procedure, especially regarding the effects of age on the results, in future studies is required. Wang C, Zhang H, Liu Z, et al. A Modified Procedure to Diagnose Erectile Dysfunction Using the International Index of Erectile Function (IIEF-6) Combined With the Premature Ejaculation Diagnosis Tool (PEDT) via an Internet Survey. Sex Med 2022;10:100506.


Metabolomic Signature of Angiopoietin-Like Protein 3 Deficiency in Fasting and Postprandial State.
Objective- Loss-of-function (LOF) variants in the ANGPTL3 (angiopoietin-like protein 3) have been associated with low levels of plasma lipoproteins and decreased coronary artery disease risk. We aimed to determine detailed metabolic effects of genetically induced ANGPTL3 deficiency in fasting and postprandial state. Approach and Results- We studied individuals carrying S17X LOF mutation in ANGPTL3 (6 homozygous and 32 heterozygous carriers) and 38 noncarriers. Nuclear magnetic resonance metabolomics was used to quantify 225 circulating metabolic measures. We compared metabolic differences between LOF carriers and noncarriers in fasting state and after a high-fat meal. In fasting, ANGPTL3 deficiency was characterized by similar extent of reductions in LDL (low-density lipoprotein) cholesterol (0.74 SD units lower concentration per LOF allele [95% CI, 0.42-1.06]) as observed for many TRL (triglyceride-rich lipoprotein) measures, including VLDL (very-low-density lipoprotein) cholesterol (0.75 [95% CI, 0.45-1.05]). Within most lipoprotein subclasses, absolute levels of cholesterol were decreased more than triglycerides, resulting in the relative proportion of cholesterol being reduced within TRLs and their remnants. Further, β-hydroxybutyrate was elevated (0.55 [95% CI, 0.21-0.89]). Homozygous ANGPTL3 LOF carriers showed essentially no postprandial increase in TRLs and fatty acids, without evidence for adverse compensatory metabolic effects. Conclusions- In addition to overall triglyceride- and LDL cholesterol-lowering effects, ANGPTL3 deficiency results in reduction of cholesterol proportion within TRLs and their remnants. Further, ANGPTL3 LOF carriers had elevated ketone body production, suggesting enhanced hepatic fatty acid β-oxidation. The detailed metabolic profile in human knockouts of ANGPTL3 reinforces inactivation of ANGPTL3 as a promising therapeutic target for decreasing cardiovascular risk.


Ethical aspects of blood and organ donation.
Ethics of blood and organ donation in Australia has been influenced by voluntarism and the Red Cross. The General Agreement on Trade in Services may threaten the principle of voluntary blood donation and self sufficiency of blood in Australia. However, a cooperative approach to managing the public good is more sustainable than individual self interest and the author argues that voluntary blood and organ donation should be retained.


Snap-lock bags with red band: A study of manufacturing characteristics, thermal and chemical properties.
Drug packaging is commonly submitted to the Forensic Chemistry and Physics Laboratory of the Health Sciences Authority, Singapore, for examination. The drugs seized are often packaged in plastic bags. These bags are examined for linkages to provide law enforcement with useful associations between the traffickers and drug abusers. The plastic bags submitted may include snap-lock bags, some with a red band located above the snap-lock closure and some without. Current techniques for examination involve looking at the physical characteristics (dimensions, thickness and polarising patterns) and manufacturing marks of these bags. In cases where manufacturing marks on the main body of the bags are poor or absent, the manufacturing characteristics present on the red band can be examined. A study involving approximately 1000 bags was conducted to better understand the variations in the manufacturing characteristics of the red band. This understanding is crucial in helping to determine associations/eliminations between bags. Two instrumental techniques, namely differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) were explored to evaluate the effectiveness of examining the chemical composition to discriminate the bags.


Nitric oxide involvement in the acrosome reaction triggered by leptin in pig sperm.
Nitric oxide (NO) is a signaling molecule produced by intracellular nitric oxide synthase (NOS) enzymes. This free radical appears to affect sperm capacitation, a maturation step preceding acrosome reaction. Recent studies have reported leptin ability to promote capacitation and acrosome reaction in pig male gametes. This study has investigated nitric oxide production in leptin-treated pig spermatozoa by fluorescence-activated cell sorting, while the intracellular NOS isoforms were assessed by Western blot analysis. In addition, acrosome status of treated-spermatozoa was evaluated by FITC-PNA staining. Significant increases of nitric oxide levels and acrosome reaction extent were detected in leptin-treated spermatozoa, but both the effects were reversed in presence of L-NAME. Furthermore, the immunoblots of sperm extracts have evidenced three bands of ~160 Kd(bNOS), ~130 Kd (iNOS) and ~135 Kd (eNOS). The identification of the three intracellular NOS isoforms suggests that pig spermatozoa could produce NO, while the augmented nitric oxide levels in leptin-treated male gametes indicates the capacity of the hormone to induce nitric oxide production. Furthermore, the inhibitory effect of L-NAME and of Ab-ObR on the promotion of acrosome reaction triggered by leptin suggests a possible involvement of NO in the hormone action.


Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patients.
There is controversy regarding the prognostic value of cathepsin-D in primary breast cancer. An increased level of cathepsin-D in tumour extracts has been found to be associated with a poor relapse-free and overall survival. Studies performed with immunohistochemistry or Western blotting have produced diverse results. We have analysed 2810 cytosolic extracts obtained from human primary breast tumours for cathepsin-D expression, and have correlated their levels with prognosis. The median follow-up of the patients still alive was 88 months. Patients with high cathepsin-D levels had a significantly worse relapse-free and overall survival, also in multivariate analysis (P < 0.0001). Adjuvant therapy which was associated with an improved prognosis in node-positive patients in univariate analysis, also significantly added to the multivariate models for relapse-free and overall survival. There were no statistically significant interactions between the levels of cathepsin-D and any of the classical prognostic factors in analysis for relapse-free survival, suggesting that the prognostic value of cathepsin-D is not different in the various subgroups of patients. Indeed, multivariate analyses in subgroups of node-negative and -positive patients, pre- and post-menopausal patients, and their combinations, showed that tumours with high cathepsin-D values had a significantly poor relapse-free survival, with relative hazard rates ranging from 1.3 to 1.5, compared with tumours with low cathepsin-D levels. The results presented here on 2810 patients confirm that high cytosolic cathepsin-D values are associated with poor prognosis in human primary breast cancer.


Multiple pathways of apoptosis in PC12 cells. CrmA inhibits apoptosis induced by beta-amyloid.
Stable transfectants of PC12 cells expressing bcl-2 or crmA were generated and tested for their susceptibility to various apoptotic insults. Bcl-2 expression conferred resistance to apoptosis induced by staurosporine and by oxidative insults including hydrogen peroxide and peroxynitrite, but was less effective in inhibition of activation-induced programmed cell death induced by concanavalin A. Concanavalin A-induced apoptosis was abated, however, in cells expressing very high levels of bcl-2. In contrast, cells expressing crmA were protected from concanavalin A-induced apoptosis, but were as susceptible as control cells to apoptosis induced by staurosporine and oxidative insults. Therefore, at least two apoptotic pathways in PC12 cells can be discerned by their differential sensitivity to blockade by bcl-2 and crmA. The ability of beta-amyloid (Abeta) to induce apoptosis in these cells was assessed. CrmA transfectants were protected from apoptosis induced by Abeta1-42, but only cells expressing very high levels of bcl-2 were similarly protected. These results suggest that the apoptotic pathway activated by Abeta1-42 in PC12 cells can be differentiated from the apoptotic pathway activated by oxidative insults. Gene transfer experiments also demonstrated that expression of crmA in primary cultures of hippocampal neurons is protective against cell death induced by Abeta1-42. Together these results support the hypothesis that Abeta-induced apoptosis occurs through activation-induced programmed cell death.


Neuronal regulation of immunity: why, how and where?
Neuroimmunology is one of the fastest-growing fields in the life sciences, and for good reason; it fills the gap between two principal systems of the organism, the nervous system and the immune system. Although both systems affect each other through bidirectional interactions, we focus here on one direction - the effects of the nervous system on immunity. First, we ask why is it beneficial to allow the nervous system any control over immunity? We evaluate the potential benefits to the immune system that arise by taking advantage of some of the brain's unique features, such as its capacity to integrate and synchronize physiological functions, its predictive capacity and its speed of response. Second, we explore how the brain communicates with the peripheral immune system, with a focus on the endocrine, sympathetic, parasympathetic, sensory and meningeal lymphatic systems. Finally, we examine where in the brain this immune information is processed and regulated. We chart a partial map of brain regions that may be relevant for brain-immune system communication, our goal being to introduce a conceptual framework for formulating new hypotheses to study these interactions.


Effects of windspeed on the growth and biomass allocation of white mustard Sinapis alba L.
We examined how different wind speeds and interactions between plant age and wind affect growth and biomass allocation of Sinapis alba L. (white mustard). Physiological and growth measurements were made on individuals of white mustard grown in controlled-environment wind tunnels at windspeeds of 0.3, 2.2 and 6.0 ms-1 for 42 days. Plants were harvested at four different dates. Increasing wind speed slightly increased transpiration and stomatal conductance. We did not observe a significant decline in the photosynthetic rate per unit of leaf area. Number of leaves, stem length, leaf area and dry weights of total biomass and plant parts were significantly lower in plants exposed at high wind speed conditions. There were no significant differences in the unit leaf rate nor relative growth rates, although these were always lower in plants grown at high wind speed. Allocation and architectural parameters were also examined. After 42 days of exposure to wind, plants showed higher leaf area ratio, root and leaf weight ratios and root/shoot ratio than those grown at control treatment. Only specific leaf area declined significantly with wind speed, but stem and reproductive parts also decreased. The responses of plants to each wind speed treatment depended on the age of the plant for most of the variables. It is suggested that wind operates in logarithmic manner, with relatively small or no effect at lower wind speeds and a much greater effect at higher speeds. Since there is no evidence of a significant reduction in photosynthetic rate of Sinapis with increasing wind speed it is suggested that the effect of wind on plant growth was due to mechanical effects leading to changes in allocation and developmental patterns.


New Species of the Genus Periglischrus (Acari: Spinturnicidae) from Monophyllus Bats (Chiroptera: Phyllostomidae) in the West Indies, Including a Morphometric Analysis of Its Intraspecific Variation.
The discovery of a new species, Periglischrus empheresotrichus, was determined through a review of museum collections, as well as a field survey of ectoparasites of island bats. This new species parasitizes on two bat species of the genus Monophyllus Leach, the Greater Antillean Long-tongued bat Monophyllus redmani Leach and the Lesser Antillean Long-tongued bat Monophyllus plethodon Miller. The female, male, deuthonymphs, and protonymph are described and illustrated. P. empheresotrichus n. sp. has an insular distribution, we evaluated the morphological variation of the adult populations, and concluded that intra-specific variation is correlated both with host species and locality (island) in the West Indies.


Solid sampling determination of total fluorine in baby food samples by high-resolution continuum source graphite furnace molecular absorption spectrometry.
This study describes the applicability of solid sampling technique for the determination of fluorine in various baby foods via molecular absorption of calcium monofluoride generated in a graphite furnace of high-resolution continuum source atomic absorption spectrometry. Fluorine was determined at CaF wavelength, 606.440nm in a graphite tube applying a pyrolysis temperature of 1000°C and a molecule forming temperature of 2200°C. The limit of detection and characteristic mass of the method were 0.20ng and 0.17ng of fluorine, respectively. The fluorine concentrations determined in standard reference sample (bush branches and leaves) were in good agreement with the certified values. By applying the optimized parameters, the concentration of fluorine in various baby foods were determined. The fluorine concentrations were ranged from <LOQ to 3.75μgg(-1). Owing to the ultra low sample amounts used in solid sampling analysis, micro-scale distribution of fluorine in the samples was also determined.


Early Use of Statin in Patients Treated with Alteplase for Acute Ischemic Stroke.
Studies have reported that statin usage before stroke can increase the incidence of intracerebral hemorrhage after thrombolytic treatment. However, whether the administration of statin at an early stage of ischemic stroke increases hemorrhage occurrence is unknown. The aim of this study was to assess the effect of statin on neurological imaging and functional outcomes after intravenous alteplase treatment, within 24 h of acute ischemic stroke attack. A total of 119 consecutive acute ischemic stroke patients treated by intravenous alteplase were recruited, of which 71 patients (59.7 %) were given statin therapy within 24 h of stroke onset. The physiological parameters, including demography, vascular risk factors, and clinical characteristics were recorded. The occurrence of intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), 90-day functional outcomes, and mortality in the patients were further analyzed. There were 24 occurrences of ICH after alteplase treatment (20.2 %) and there was no difference when patients were treated with statin (p = 0.280). Multivariate logistic regression analysis showed no significant correlation between the administration of statin and the occurrence of ICH (p = 0.230) or sICH (p = 0.949). There was a trend toward better neurological function with higher statin dose. The use of statin in the early stage of ischemic stroke is safe and does not increase the risk of intracerebral hemorrhage after alteplase treatment, suggesting that a clinical trial of early statin treatment on a large scale following thrombolysis is needed for further evaluation.


Our results of lower gastrointestinal endoscopy: evaluation of 700 patients.
Although radiological imaging modalities like barium enema and computed tomography provide some clues, endoscopic methods still maintain superiority in assessment and differential diagnosis of large intestinal symptoms and complaints that require biopsy. We aimed to present the results of colonoscopic procedures performed in our general surgery clinic in detail. Seven hundred patients who presented to Afyon Kocatepe University, Faculty of Medicine, Department of General Surgery Endoscopy Unit between January 2011 and July 2012 with an indication for colonoscopy were retrospectively evaluated. Out of the 700 patients enrolled in the study 356 (50.8%) were male while 344 patients (49.2%) were female. The mean age of the patients was found to be 49 years. Within the group of 700 patients who underwent colonoscopic examinations, the terminal ileum and cecum have been reached on the first attempt in 432 patients (61.7%) and colonoscopic success has been achieved. Results of colonoscopies performed on 700 patients in our clinic revealed malignancy in 42 (6%) patients, and all of these patients were treated surgically in our clinic. Mortality was not observed in this series. Procedure-related bleeding and perforation developed in 6 patients. One patient developed respiratory arrest due to sedation and patient was responsive to resuscitation. The complication rate in our series was 1%. In the study where we revised our own clinical experience, we found that our success rate was lower than the literature, and our complication rate was higher. The main reasons are accepted as our colonoscopy unit's being young and the low patient volume.


[Surgical treatment of infective endocarditis].
To summarize the experience of surgical treatment of infective endocarditis in 28 patients. Open heart surgery under cardiopulmonary bypass was performed in all patients: valve replacement (24), VSD repair and tricuspid annuloplasty (3), and Bentall (1) 17 mechanical and 7 homograft valves were placed. Two died in hospital, 4 died from infection, 1 had periprosthetic leakage and incompetence respectively. 22 survivors showed improved heart function. Combined medication and surgical treatment is superior to antibiotic treatment in long-term survival and convalescence. Infective reccurrence, reinfection and advanced heart failure are major risk factors after operation.


Bed bugs shape the indoor microbial community composition of infested homes.
Indoor pests, and the allergens they produce, adversely affect human health. Surprisingly, however, their effects on indoor microbial communities have not been assessed. Bed bug (Cimex lectularius) infestations pose severe challenges in elderly and low-income housing. They void large amounts of liquid feces into the home environment, which might alter the indoor microbial community composition. In this study, using bed bug-infested and uninfested homes, we showed a strong impact of bed bug infestations on the indoor microbial diversity. Floor dust samples were collected from uninfested and bed bug-infested homes and their microbiomes were analyzed before and after heat interventions that eliminated bed bugs. The microbial communities of bed bug-infested homes were radically different from those of uninfested homes, and the bed bug endosymbiont Wolbachia was the major driver of this difference. After bed bugs were eliminated, the microbial community gradually shifted toward the community composition of uninfested homes, strongly implicating bed bugs in shaping the dust-associated environmental microbiome. Further studies are needed to understand the viability of these microbial communities and the potential risks that bed bug-associated microbes and their metabolites pose to human health.


Updates on preimplantation embryo research.
Preimplantation development is the only stage of human development that can be studied outside the body in real time, as human embryos can be produced by in vitro fertilization and cultured in the laboratory as self-contained structures until the blastocyst stage. Here, we focus some of the key cellular and morphogenetic processes by which the 1-cell embryo is transformed gradually into a blastocyst ready for implantation. Although most of our knowledge about the dynamic series of events patterning preimplantation human development derives from work in mouse embryos, we discuss key differences that could exist with humans. Furthermore, we highlight how new approaches may enable to reveal many of the unknown processes driving human preimplantation development, particularly using noninvasive imaging and genetic technologies.


Cell Population Data-Driven Acute Promyelocytic Leukemia Flagging Through Artificial Neural Network Predictive Modeling.
A targeted and timely offered treatment can be a benefitting tool for patients with acute promyelocytic leukemia (APML). Current round of study made use of potential morphological and immature fraction-related parameters (cell population data) generated during complete blood cell count (CBC), through artificial neural network (ANN) predictive modeling for early flagging of APML cases. We collected classical CBC items along with cell population data (CPD) from hematology analyzer at diagnosis of 1067 study subjects with hematological neoplasms. For morphological assessment, peripheral blood films were examined. Statistical and machine learning tools including principal component analysis (PCA) helped in the evaluation of predictive capacity of routine and CPD items. Then selected CBC item-driven ANN predictive modeling was developed to smartly use the hidden trend by increasing the auguring accuracy of these parameters in differentiation of APML cases. We found a characteristic triad based on lower (53.73) platelet count (PLT) with decreased/normal (4.72) immature fraction of platelet (IPF) with addition of significantly higher value (65.5) of DNA/RNA content-related neutrophil (NE-SFL) parameter in patients with APML against other hematological neoplasm's groups. On PCA, APML showed exceptionally significant variance for PLT, IPF, and NE-SFL. Through training of ANN predictive modeling, our selected CBC items successfully classify the APML group from non-APML groups at highly significant (0.894) AUC value with lower (2.3 percent) false prediction rate. Practical results of using our ANN model were found acceptable with value of 95.7% and 97.7% for training and testing data sets, respectively. We proposed that PLT, IPF, and NE-SFL could potentially be used for early flagging of APML cases in the hematology-oncology unit. CBC item-driven ANN modeling is a novel approach that substantially strengthen the predictive potential of CBC items, allowing the clinicians to be confident by the typical trend raised by these studied parameters.


Changes in motoneuron excitability of masseter muscle following exteroceptive stimuli in Parkinson's disease.
Changes in motoneuron activity of masseter muscle to exteroceptive stimuli were evaluated in parkinsonian patients. Two different electrophysiological procedures were applied, consisting of exteroceptive suppression of the masseter or excitability curves of the masseteric reflex obtained by using exteroceptive conditioning stimuli. Seven patients not yet treated with dopaminergic or anticholinergic drugs were compared with 10 age-matched normal volunteers. Only the second phase of exteroceptive suppression was examined because correct measurement of the first phase was impossible due to the stimulus artefact. No significant differences were observed in exteroceptive suppression between parkinsonian patients and normals. Early and late inhibitory phases of the excitability curve of the masseteric reflex were obtained in both normals and patients. However, parkinsonians showed less inhibitory change than normals in both early and late phase of the curve. This study confirms that reduced inhibition of the masseteric reflex to exteroceptive stimuli is present in Parkinson's disease. The excitability curve of the masseteric reflex represents a more reliable method than exteroceptive suppression in detecting these abnormalities.


Production of human chorionic gonadotrophin by a hepatoblastoma resulting in precocious puberty.
A two year old boy presented with precocious puberty associated with hepatoblastoma. Serum concentrations of beta human chorionic gonadotrophin and alpha-fetoprotein were raised. An aggressive chemotherapeutic regimen resulted in useful palliation and interesting changes in the beta human chorionic gonadotrophin and alpha-fetoprotein concentrations. In contrast to a previous report, the ultrastructure of the tumour showed frequent Golgi apparatus but no other electron dense membrane bound vesicles.


Combining canopy reflectance spectrometry and genome-wide prediction to increase response to selection for powdery mildew resistance in cultivated strawberry.
High-throughput phenotyping is an emerging approach in plant science, but thus far only a few applications have been made in horticultural crop breeding. Remote sensing of leaf or canopy spectral reflectance can help breeders rapidly measure traits, increase selection accuracy, and thereby improve response to selection. In the present study, we evaluated the integration of spectral analysis of canopy reflectance and genomic information for the prediction of strawberry (Fragaria × ananassa) powdery mildew disease. Two multi-parental breeding populations of strawberry comprising a total of 340 and 464 pedigree-connected seedlings were evaluated in two separate seasons. A single-trait Bayesian prediction method using 1001 spectral wavebands in the ultraviolet-visible-near infrared region (350-1350 nm wavelength) combined with 8552 single nucleotide polymorphism markers showed up to 2-fold increase in predictive ability over models using markers alone. The integration of high-throughput phenotyping was further validated independently across years/trials with improved response to selection of up to 90%. We also conducted Bayesian multi-trait analysis using the estimated vegetative indices as secondary traits. Three vegetative indices (Datt3, REP_Li, and Vogelmann2) had high genetic correlations (rA) with powdery mildew visual ratings with average rA values of 0.76, 0.71, and 0.71, respectively. Increasing training population sizes by incorporating individuals with only vegetative index information yielded substantial increases in predictive ability. These results strongly indicate the use of vegetative indices as secondary traits for indirect selection. Overall, combining spectrometry and genome-wide prediction improved selection accuracy and response to selection for powdery mildew resistance, demonstrating the power of an integrated phenomics-genomics approach in strawberry breeding.


[Detection of HIV-1 antigen--determination using 3 different test systems].
51 human sera containing antibodies to human immunodeficiency virus 1 (= HIV-1) were examined for HIV-1-antigen by three different enzyme immunoassay procedures (= EIA) of Abbott, Organon and Dupont. Sensibilities, handling as well as the correlation with the clinical stages of HIV-infection were compared. The EIA's diagnosed in accordance 6 sera which contained HIV-1-antigen and 42 sera to be HIV-1-antigen negative. 3 sera showed differences: according to the EIA of Organon none of these sera contained HIV-1-antigen, the EIA of Abbott (but not of Dupont) analysed HIV-1-antigen in one of these sera, in the other two sera only the EIA of Dupont showed HIV-1-Antigen. It is concluded that the differences in these 3 serum samples may originate not only in the different types of EIA used (indirect/direct procedure) but also in the different capture antibodies provided (antibodies against p-24 antigen or polyvalent antibodies).


Epidural and Non-epidural Analgesia in Patients Undergoing Open Pancreatectomy: a Retrospective Cohort Study.
The use of epidural analgesia (EA) in pancreatic surgery remains under debate. This study compares patients treated with EA versus non-EA after open pancreatectomy in a tertiary referral center. All patients undergoing open pancreatectomy from 2013 to 2017 were retrospectively reviewed. (Non-)EA was terminated on postoperative day (POD) 3 or earlier if required. In total, 190 (72.5%) patients received EA and 72 (27.5%) patients received non-EA (mostly intravenous morphine). EA was terminated prematurely in 32.6% of patients and non-EA in 10.5% of patients. Compared with non-EA patients, EA patients had significantly lower pain scores on POD 0 (1.10 (0-3.00) versus 3.00 (1.67-5.00), P < 0.001) and POD 1 (2.00 (0.50-3.41) versus 3.00 (2.00-3.80), P = 0.001), though significantly higher pain scores on POD 3 (3.00 (2.00-4.00) versus 2.33 (1.50-4.00), P < 0.001) and POD 4 (2.50 (1.50-3.67) versus 2.00 (0.50-3.00), P = 0.007). EA patients required more vasoactive medication perioperatively and had higher cumulative fluid balances on POD 1-3. Postoperative complications were similar between groups. In our cohort, patients with EA experienced significantly lower pain scores in the first PODs compared with non-EA, yet higher pain scores after EA had been terminated. Although EA patients required more vasoactive medication and fluid therapy, the complication rate was similar.


Batch interaction of emerging tetracycline contaminant with novel phosphoric acid activated corn straw porous carbon: Adsorption rate and nature of mechanism.
In this work, corn straw (CS) based porous carbon was prepared by one-step phosphoric acid (H3PO4) low temperature activation. The impregnation ratios (H3PO4/CS, g/g) played an important role in the pore development. ACS300-1 engineered at 300 °C and the impregnation ratio of 1.0 showed the maximal specific surface area of 463.89 m2/g with total pore volume of 0.387 cm3/g, attaining a high tetracycline (TC) uptake of 227.3 mg/g. The adsorption of TC onto ACS300-1 was found tolerant with wide pH (2.0-10.0) and high ionic strength (0 - 0.5 M). The adsorption data can be fitted well by the pseudo-second order kinetic model and Langmuir isotherm model. The endothermic and spontaneous properties of the adsorption system was implied by Thermodynamic study. The findings of the current work conclude that one-step H3PO4 activation is a green and promising method for corn straw based porous carbon that may be found with great potentials in antibiotic containing wastewater treatment.


Discrimination Between Glioblastoma and Solitary Brain Metastasis Using Conventional MRI and Diffusion-Weighted Imaging Based on a Deep Learning Algorithm.
This study aims to develop and validate a deep learning (DL) model to differentiate glioblastoma from single brain metastasis (BM) using conventional MRI combined with diffusion-weighted imaging (DWI). Preoperative conventional MRI and DWI of 202 patients with solitary brain tumor (104 glioblastoma and 98 BM) were retrospectively obtained between February 2016 and September 2022. The data were divided into training and validation sets in a 7:3 ratio. An additional 32 patients (19 glioblastoma and 13 BM) from a different hospital were considered testing set. Single-MRI-sequence DL models were developed using the 3D residual network-18 architecture in tumoral (T model) and tumoral + peritumoral regions (T&P model). Furthermore, the combination model based on conventional MRI and DWI was developed. The area under the receiver operating characteristic curve (AUC) was used to assess the classification performance. The attention area of the model was visualized as a heatmap by gradient-weighted class activation mapping technique. For the single-MRI-sequence DL model, the T2WI sequence achieved the highest AUC in the validation set with either T models (0.889) or T&P models (0.934). In the combination models of the T&P model, the model of DWI combined with T2WI and contrast-enhanced T1WI showed increased AUC of 0.949 and 0.930 compared with that of single-MRI sequences in the validation set, respectively. And the highest AUC (0.956) was achieved by combined contrast-enhanced T1WI, T2WI, and DWI. In the heatmap, the central region of the tumoral was hotter and received more attention than other areas and was more important for differentiating glioblastoma from BM. A conventional MRI-based DL model could differentiate glioblastoma from solitary BM, and the combination models improved classification performance.


Proteolytic cleavages in alpha 1-antitrypsin and microheterogeneity.
Antitrypsin was resolved into two pools by ion-exchange chromatography. Pool 2 contained three anodal isoinhibitors and an N-terminal sequence identical with the one found by others. Pool 1 contained, in addition to the anodal ones two cathodal isoinhibitors as well. The sequencing data of Pool 1 indicate that the cathodal proteins are formed from the anodals by a cleavage of the Gly5-Asp6 bond in the molecule.


Four day inhibition of prolyl oligopeptidase causes significant changes in the peptidome of rat brain, liver and kidney.
Prolyl oligopeptidase (PREP) cleaves short peptides at the C-side of proline. Although several proline containing neuropeptides have been shown to be efficiently cleaved by PREP in vitro, the actual physiological substrates of this peptidase are still a matter of controversy. The aim of this study was to evaluate the changes in the peptidome of rat tissues caused by a repeated 4-day administration of the potent and specific PREP inhibitor KYP-2047, using our recently developed iTRAQ-based technique. We found tissue-dependent changes in the levels of specific subsets of peptides mainly derived from cytosolic proteins. Particularly in the kidney, where the levels of cytochrome c oxidase were found decreased, many of the altered peptides originated from mitochondrial proteins being involved in energy metabolism. However, in the hypothalamus, we found significant changes in peptides derived from hormone precursors. We could not confirm a role of PREP as the metabolising enzyme for β-endorphin, galanin, octadecaneuropeptide, neuropeptide-glutamic acid-isoleucine, substance P, somatostatin, enkephalin and neuropeptide Y. Furthermore, changes in the degradation patterns of some of these neuropeptides, and also most of those derived from other larger proteins, did not follow specificity to proline. After a 4-day treatment, we found a significant amount of peptides, all derived from secreted pro-proteins, being cleaved with pair of basic residue specificity. In vitro experiments indicated that PREP modifies the endogenous dibasic residue specific proteolysis, in a KYP-2047 sensitive way. These findings suggest that PREP may act indirectly within the routes leading to the specific peptide changes that we observed. The data reported here suggest a wider tissue specific physiological role of PREP rather than the mere metabolism of proline containing active peptides and hormones.


Deletion of scavenger receptor A protects mice from progressive nephropathy independent of lipid control during diet-induced hyperlipidemia.
Scavenger receptor A (SR-A) is a key transmembrane receptor in the endocytosis of lipids and contributes to the pathogenesis of atherosclerosis. To assess its role in hyperlipidemic chronic kidney disease, wild-type and SR-A-deficient (knockout) mice underwent uninephrectomy followed by either normal or high-fat diet. After 16 weeks of diet intervention, hyperlipidemic wild-type mice presented characteristic features of progressive nephropathy: albuminuria, renal fibrosis, and overexpression of transforming growth factor (TGF)-β1/Smad. These changes were markedly diminished in hyperlipidemic knockout mice and attributed to reduced renal lipid retention, oxidative stress, and CD11c(+) cell infiltration. In vitro, overexpression of SR-A augmented monocyte chemoattractant protein-1 release and TGF-β1/Smad activation in HK-2 cells exposed to oxidized low-density lipoprotein. SR-A knockdown prevented lipid-induced cell injury. Moreover, wild-type to knockout bone marrow transplantation resulted in renal fibrosis in uninephrectomized mice following 16 weeks of the high-fat diet. In contrast, knockout to wild-type bone marrow transplantation led to markedly reduced albuminuria, CD11c(+) cell infiltration, and renal fibrosis compared to wild-type to SR-A knockout or wild-type to wild-type bone marrow transplanted mice, without difference in plasma lipid levels. Thus, SR-A on circulating leukocytes rather than resident renal cells predominantly mediates lipid-induced kidney injury.


Safety and efficacy of lorlatinib against ALK-driven refractory or relapsed neuroblastoma.
We spotlight the promising preliminary findings reported by Goldsmith et al. of a phase 1 first-in-child study showcasing the safety and efficacy of lorlatinib against treatment-refractory or relapsed ALK-driven neuroblastoma.1.


Predictive factors in chronic allograft nephropathy.
Chronic allograft nephropathy (CAN) is characterized by progressive renal dysfunction leading in many cases to graft loss. The pathogenesis of CAN involves both immune and nonimmune factors. Concerning immune factors, one of the most remarkable predictors of CAN is acute rejection, which is associated with a worse prognosis if there are multiple episodes or when late onset occurs. Delayed graft function is also a major risk factor for CAN because of a correlation between late restoration of renal function after transplantation and long-term decreased graft survival. High creatinine levels at 6 months and 1 year after transplantation, proteinuria, viral infections, and cardiovascular risk factors are additional significant parameters for the development of CAN. Recent findings suggest that a high renal segmental arterial resistance index measured by Doppler ultrasonography in intrarenal vessels is associated with poor allograft function. Moreover, the study of patient genetic profile represents a new approach to identify predictive factors for CAN.


[The locked pin: a simple method to avoid migration in slight osteosynthesis].
The authors propose to broaden the principle of the pin lock in slight osteosyntheses. The purpose of the inserted tip device is to prevent the forward migration of the pin, the skin perforation by retrograde and to ease its removal after bone union.


Constrictive pericarditis heart failure in a patient with atrial fibrillation: A diagnostic challenge.
Constrictive pericarditis is an infrequent cause of heart failure. Diagnosis is challenging and requires a high level of suspicion. Subtle echocardiographic findings, as the pericardial bounce, could be the clue to diagnosis.


Trans-unsaturated lipid dynamics: modulation of dielaidoylphosphatidylcholine acyl chain motion by ethanol.
Acyl chain dynamics of the trans-unsaturated lipid, dielaidoylphosphatidylcholine (DEPC), were studied by conventional and saturation transfer electron paramagnetic resonance spectroscopy of aqueous dispersions of DEPC spin labeled with lecithins having doxyl groups at positions 5, 10, and 14 on the sn-2 chain. The gel to liquid crystalline transition is concerted with simultaneous increases in rotational motion about the long axis of the acyl chain (libration) and in gauche-trans conformational interconversions (wobble). Relative to saturated lecithins at similar reduced temperatures the double bond (a) slowed libration by an order of magnitude in both phases, while wobble motions were several times slower, and (b)-produced a pronounced stiffness of the acyl chain near the double bond. Ethanol (0-1.6 M), in addition to its well-known colligative effect on the phase transition, was found to decrease the bilayer order in a concentration-dependent manner. This effect was smaller in the gel than in the liquid crystalline phase, most pronounced next to the double bond, and weakest deep in the bilayer. Ethanol affected slow motions little in the gel phase but wobble and libration correlation times were markedly decreased in the liquid crystalline phase.


'Role reversal' for the receptor PAR1 in sepsis-induced vascular damage.
Sepsis is a deadly disease characterized by considerable derangement of the proinflammatory, anti-inflammatory and coagulation responses. Protease-activated receptor 1 (PAR1), an important regulator of endothelial barrier function and blood coagulation, has been proposed to be involved in the lethal sequelae of sepsis, but it is unknown whether activation of PAR1 is beneficial or harmful. Using a cell-penetrating peptide (pepducin) approach, we provide evidence that PAR1 switched from being a vascular-disruptive receptor to a vascular-protective receptor during the progression of sepsis in mice. Unexpectedly, we found that the protective effects of PAR1 required transactivation of PAR2 signaling pathways. Our results suggest therapeutics that selectively activate PAR1-PAR2 complexes may be beneficial in the treatment of sepsis.


Temporal references in dreams and autobiographical memory.
In an attempt to determine whether temporal references identified in dreams follow the same temporal distributions as those documented for autobiographical memories, 28 younger women (18-35 years of age) and 30 older women (60-77 years of age) kept a home dream diary for 1 week and then slept 1 night in the laboratory for rapid eye movement sleep dream collection. The following morning, they identified temporal references in their dreams and produced a sample of autobiographical memories using the semantic cuing method. For both groups, there was a linear decrease in temporal references identified in dreams and autobiographical memories with increased remoteness for the last 30 years. As predicted, for the older group, there were similar cubic trends reflecting a disproportionately higher number of both temporal references identified in dreams and autobiographical memories from adolescence/early adulthood compared with adulthood and childhood. The results support the notion of continuity between waking and dreaming memory processes.


Profilin1 Promotes Renal Tubular Epithelial Cell Apoptosis in Diabetic Nephropathy Through the Hedgehog Signaling Pathway.
Profilin-1 (PFN1) regulates the dynamic balance of actin and plays an important role in cell functions as a hub protein in signaling molecule interaction networks. Dysregulation of PFN1 is related to pathologic kidney diseases. Diabetic nephropathy (DN) was recently reported as an inflammatory disorder, however, the molecular mechanisms of PFN1 in DN remain unclear. Therefore, the present study was conducted to explore the molecular and bioinformatic characteristics of PFN1 in DN. Bioinformatics analyses were performed on the chip of database in DN kidney tissues. A cellular model of DN was established in human renal tubular epithelial cells (HK-2) induced by high glucose. The PFN1 gene was overexpressed or knocked-down to investigate its function in DN. Flow cytometry was used to detect cell proliferation and apoptosis. PFN1 and proteins in the related signaling pathways were evaluated by Western blotting. The expression of PFN1 was significantly increased in DN kidney tissues (P < 0.001) and was correlated with a high apoptosis-associated score (Pearson's correlation = 0.664) and cellular senescence-associated score (Pearson's correlation = 0.703). PFN1 protein was mainly located in cytoplasm. Overexpression of PFN1 promoted apoptosis and blocked the proliferation of HK-2 cells treated with high levels of glucose. Knockdown of PFN1 led to the opposite effects. Additionally, we found that PFN1 was correlated with the inactivation of the Hedgehog signaling pathway in HK-2 cells treated with high levels of glucose. PFN1 might play an integral role in the regulation of cell proliferation and apoptosis during DN development by activating the Hedgehog signaling pathway. This study provided molecular and bioinformatic characterizations of PFN1, and contributed to the understanding of the molecular mechanisms leading to DN.


The influence of passive-dynamic ankle-foot orthosis bending axis location on gait performance in individuals with lower-limb impairments.
Passive-dynamic ankle-foot orthoses are commonly prescribed to augment impaired ankle muscle function, however their design and prescription are largely qualitative. One design includes a footplate and cuff, and flexible strut connecting the two. During gait, deflection occurs along the strut, with the greatest deflection at a central bending axis. The vertical location of the axis can affect lower extremity biomechanics. The goal of this study was to investigate the influence of bending axis location on gait performance. For thirteen participants with unilateral ankle muscle weakness, an additive manufacturing framework was used to fabricate passive-dynamic ankle-foot orthosis struts with central and off-center bending axes. Participants walked overground while electromyographic, kinetic and kinematic data were collected for three different bending axes: proximal (high), central (middle) and distal (low), and the participants indicated their order of bending axis preference after testing. Gait measures and preference effect sizes were examined during six regions of the gait cycle. A few differences between bending axes were observed: in the first double-leg support peak plantarflexion angle, peak dorsiflexion moment and positive hip work, in the early single-leg support peak knee extension moment and positive ankle and knee work, and in the late single-leg support gastrocnemius activity and vertical ground reaction force impulse. In addition, preference was strongly related to various gait measures. Despite the observed statistical differences, altering bending axis location did not produce large and consistent changes in gait performance. Thus, individual preference and comfort may be more important factors guiding prescription.


Laryngeal tetany: an unusual presentation of chronic renal failure.
The presenting features and subsequent management of two adult patients with chronic renal failure complicated by laryngospasm are described. Possible mechanisms to explain this uncommon phenomenon are discussed but its rarity remains unexplained.


A simplified technique for quantifying 24-h whole body retention of 99mTc-labeled methylene diphosphonate (MDP).
A simple technique for measuring 24-h whole-body retention (24-h WBR) of 99mTc-labeled methylene diphosphonate (MDP) is described. We chose a standard thyroid probe-scaler system (Picker-Magna Scanner) as our counting instrument and characterized it relative to: photon saturability; optimum counting time post administration; patient positioning; and results with prostate cancer patients with positive/negative scintigram diagnoses for bone metastases. Whole body retention values of 99mTc at 24 h were easily measured with our instrumentation. Initially whole body count rates were determined at 5-min post injection and, again at 24 h. Data accumulated prior to the 5-min time period were inaccurate due to a higher sensitivity for the activity in the early circulation. Also, initial count rates obtained from patients injected with (740 MBq) (20 mCi) 99mTc-MDP usually required a correction due to detector saturation. The data observed at 24 h, representing skeletal tracer uptake, required no such correction. Patient positioning was rigorously controlled for the two time intervals to insure constant geometry. The 24 h-WBR values measured for prostate cancer patients with positive bone scintigrams was significantly different from those patients with negative scintigrams (58.8 +/- 8.7% and 29.2 +/- 9.6% respectively). Measurement of the 24 h-WBR has great potential for following various pathologies in the clinical setting.


Injuries due to deliberate violence in areas of Denmark. I. The extent of violence.
As part of a transcultural investigation of violent behavior in Denmark and South America an analysis was made during a one year period of the incidents involving deliberate violence as registered at 3 Danish emergency wards, and at the Institute of Forensic Medicine in Copenhagen. In the three emergency wards a total of 1316 victims of deliberate violence were observed corresponding to a rate of about 3.3/1000 per year in a provincial/rural district, the catchment region of Holbaek County Hospital, 5.5/1000 per year in a mainly middle income area of the metropolis Copenhagen, the catchment region of Frederiksberg Hospital, and 7.6/1000 per year in a mainly low income area of Copenhagen, the catchment region of the Rigshospital. The highest risk, 28/1000 per year, was found for young men between 15 and 19 years of age living in the low income area of Copenhagen. The risk was low for people greater than or equal to 60 years of age in all three areas investigated, ranging from 0 (men) to 1.3/1000 per year (women). Skilled and unskilled workers were greatly over represented as victims of violence, considering their share of the background population. Seventy percent of the victims were men. At least 44% of the men and 32% of the women were alcohol intoxicated when arriving in the emergency ward. The incidents took place in restaurants or in the vicinity of restaurants for 30% of the male and 11% of female victims respectively, while 45% of the women had been subject to deliberate violence at home. The rate of fatal cases of deliberate violence in the Eastern part of Denmark, the catchment area for the Institute of Forensic Medicine in Copenhagen, was found to be 0.02/1000 per year. The risk of becoming a victim of deliberate violence has not increased during the last 4 years comparing with similar investigations from other parts of Denmark. However, the rate of homicide seems to have increased, and so has the severity of the injuries caused by deliberate violence. The pattern of deliberate violence appears to be associated with socio-economic and cultural factors, and to be closely linked with alcohol intoxication.


A longitudinal study on hand and wrist skeletal maturation in chimpanzees ( Pan troglodytes), with emphasis on growth in linear dimensions.
Skeletal maturation in the chimpanzee hand and wrist (the RUS system; radius, ulna, and short bones) was studied both longitudinally and cross-sectionally. Maturity states were evaluated in each of the 13 bones of the RUS system based on the TW2 method (Tanner and Whitehouse method), and the RUS score was calculated by the summation of scores for these bones. Individual variation was examined by means of residual curves and pseudo-velocity curves of RUS score and anterior trunk length (ATL). Norms of the age change pattern in RUS skeletal maturation and the growth of ATL were determined for each sex, and the relationships among ATL growth and skeletal and reproductive maturation were examined. We found a fairly good relationship between ATL growth and RUS skeletal maturation. Comparison of growth and development between humans and chimpanzees showed that growth characteristics are coupled with each other at puberty in male chimpanzees and in both sexes of humans. Although nutritional condition influenced ATL growth in infancy, it had no effect on the RUS maturational process. Social relationships appeared to influence both ATL growth and RUS maturation. Analyses on relationships between RUS skeletal maturation, ATL growth, and reproductive maturation, showed that RUS skeletal maturation is a good indicator of "physiological age".


Aortic regurgitation in the heterotopic rat heart transplant: effect on ventricular remodeling and diastolic function.
Use of the heterotopic rat cardiac isograft model is limited by ventricular atrophy attributable to the left ventricle's non-working state. Previous studies indicate that increased left ventricular pressure-volume work minimizes atrophy. We used a simpler approach to increase ventricular work, imposing aortic regurgitation on the transplant. We hypothesized that this would prevent atrophy and preserve left ventricular compliance. We analyzed heterotopic transplants with aortic valvotomy and without aortic valvotomy (controls). Recipient native hearts served as separate controls. After 15 to 25 days, we measured cardiac wet weight, dry weight, and water content of all groups and measured echocardiographic left ventricular wall thickness and end-diastolic and end-systolic diameters in both transplant groups. Left ventricular volume infusions yielded pressure-volume data that we analyzed using regression methods. Aortic regurgitant transplants weighed more than control transplants (dry weight, 0.109 +/- 0.013 g vs 0.097 +/- 0.016 g; p = 0.020, 2-way analysis of variance), but all transplants weighed less than native hearts weighed (p = 0.001). Control transplants were less compliant than regurgitant transplants (p = 0.002), but the latter were similar to their own native hearts (p = 0.34). Wall thickness decreased in regurgitant vs control transplants (p = 0.020, Student's t-test), but end-diastolic and end-systolic diameters increased (p < or = 0.001). Aortic regurgitation in heterotopic transplants improves left ventricular compliance through chamber dilatation without preventing atrophy. Moderate acute aortic regurgitation affects ventricular remodeling more than it stimulates myocardial hypertrophy. Smaller end-diastolic diameter, greater wall thickness, and myocardial edema may explain decreased compliance in non-working transplants.


Wegener's granulomatosis: observations on treatment with antimicrobial agents.
Twelve patients with Wegener's granulomatosis were treated with antimicrobial agents, chiefly trimethoprim-sulfamethoxazole. The clinical course improved in 11 of the 12 patients who received this treatment. The success of antimicrobial treatment suggests the possibility of a microbial infection as the inciting cause of Wegener's granulomatosis in some patients. Alternatively, these agents--in particular, trimethoprim-sulfamethoxazole--may possess immunosuppressant activity.


Cannulation strategies for percutaneous extracorporeal membrane oxygenation in adults.
Extracorporeal membrane oxygenation (ECMO) has revolutionized treatment of severe isolated or combined failure of lung and heart. Due to remarkable technical development the frequency of use is growing fast, with increasing adoption by interventional cardiologists independent of cardiac surgery. Nevertheless, ECMO support harbors substantial risk such as bleeding, thromboembolic events and infection. Percutaneous ECMO circuits usually comprise cannulation of two large vessels ('dual' cannulation), either veno-venous for respiratory and veno-arterial for circulatory support. Recently experienced centers apply more advanced strategies by cannulation of three large vessels ('triple' cannulation), resulting in veno-veno-arterial or veno-arterio-venous cannulation. While the former intends to improve drainage and unloading, the latter represents a very potent method to provide circulatory and respiratory support at the same time. As such triple cannulation expands the field of application at the expense of increased complexity of ECMO systems. Here, we review percutaneous dual and triple cannulation strategies for different clinical scenarios of the critically ill. As there is no unifying terminology to date, we propose a nomenclature which uses "A" and all following letters for supplying cannulas and all letters before "A" for draining cannulas. This general and unequivocal code covers both dual and triple ECMO cannulation strategies (VV, VA, VVA, VAV). Notwithstanding the technical evolution, current knowledge of ECMO support is mainly based on observational experience and mostly retrospective studies. Prospective controlled trials are urgently needed to generate evidence on safety and efficacy of ECMO support in different clinical settings.


Verrucous carcinoma of the scalp associated with human papillomavirus type 33.
Verrucous carcinoma (VC) is a low-grade, well-differentiated squamous cell carcinoma of the skin or mucosae, and human papillomavirus (HPV) infection has been considered to be one of the causative factors of VC at three main sites, including the oral cavity, the genitoanal region, and the foot. However, the relationship between cutaneous VC at other sites and HPV infection remains obscure. We describe a rare case of cutaneous VC originating in a burn scar on the scalp and our attempt to find HPV infection in the lesion. We investigated the presence of HPV by polymerase chain reaction-restriction fragment length polymorphisms and immunohistochemical analysis. HPV type 33 was detected in the lesion, and positive stains for HPV were observed in several cell nuclei at the upper stratum malpighi. Since HPV type 33, as well as HPV types 16 and 18, is regarded as a high-risk, mucosal type, HPV type 33 infection likely contributed to the development of the lesion. We suggest that HPV infection should be relevant to a subset of cutaneous VC.


Stopped-flow front-face fluorometer: a prototype design to measure hemoglobin R----T transition kinetics.
Stopped-flow techniques are successfully used to study the kinetics of the R----T transition of hemoglobin (Hb). We have previously used front-face fluorometry to demonstrate that (i) the intrinsic fluorescence of Hb primarily originates from beta 37 Trp; (ii) the intrinsic fluorescence is sensitive to the R----T transition; and (iii) the emission of the fluorescent probes bound to specific sites on the Hb molecule (beta 93 Cys) is sensitive to the R----T transition. These findings suggested that a stopped-flow front-face fluorometer could probe R----T transitions at specific sites, such as the aromatic amino acids and sites selectively binding extrinsic fluorophores. We have developed a prototype instrument using as the core a Gibson-Durrum stopped-flow apparatus on line with a digital data analysis system using a modified Marquardt algorithm. Excitation (470 nm) and emission light (520 nm) were selected by narrow band pass filters. To study the R----T transition, a solution of purified oxy Hb A covalently bound to the fluorescent probe 5-iodoacetamidofluorescein (Hb A-AF) (1.0 g%) was mixed rapidly with deoxygenated buffer (pH 7.35, 0.05 M potassium phosphate) containing 2 mg/ml of sodium dithionite. The hemoglobin, at a final concentration of 0.5 g% after mixing, is essentially completely tetrameric. A first-order reaction was observed with a rate constant near 8 s-1, similar to the oxygen dissociation rate reported for oxy Hb A.(ABSTRACT TRUNCATED AT 250 WORDS)


A charged and contoured surface on the nucleosome regulates chromatin compaction.
Local nucleosome-nucleosome interactions in cis drive chromatin folding, whereas interactions in trans lead to fiber-fiber oligomerization. Here we show that peptides derived from the histone H4 tail and Kaposi's sarcoma herpesvirus LANA protein can replace the endogenous H4 tail, resulting in array folding and oligomerization. Neutralization of a LANA binding site on the histone surface enhanced rather than abolished nucleosome-nucleosome interactions. We maintain that the contoured nucleosome surface is centrally involved in regulating chromatin condensation.


Localization of neurons expressing choline acetyltransferase, serotonin and/or FMRFamide in the central nervous system of the decapod shore crab Hemigrapsus sanguineus.
Although it is now established that neurons in crustacea contain multiple transmitter substances, little is know about patterns of expression and co-expression or about the functional effects of such co-transmission. The present study was designed to characterize the distributions and potential colocalization of choline acetyltransferase (ChAT), serotonin (5-HT) and neuropeptide H-Phe-Met-Arg-Phe-NH2 (FMRFamide) in the central nervous system (CNS) of the Asian shore crab, Hemigrapsus sanguineus using immunohistochemical analyses in combination with laser scanning confocal microscopy. ChAT was found to be expressed by small, medium-sized, and large neurons in all regions of the brain and ventral nerve cord (VNC). For the most part, ChAT, FMRFamide, and 5-HT are expressed in different neurons, although some colocalization of ChAT- with FMRFamide- or 5-HT-LIR is observed in small and medium-sized cells, mostly neurons that immunostain only weakly. In the brain, such double immunolabeling is observed primarily in neurons of the protocerebrum and, to a particularly great extent, in local olfactory interneurons of the deutocerebrum. The clusters of neurons in the VNC that stain most intensely for ChAT, FMRFamide, and 5-HT, with colocalization in some cases, are located in the subesophageal ganglia. This colocalization appears to be related to function, since it is present in regions of the CNS characterized by multiple afferent projections and outputs to a variety of functionally related centers involved in various physiological and behavioral processes. Further elucidation of the functional significance of these neurons and of the widespread process of co-transmission in the crustaceans should provide fascinating new insights.


Ligand-binding radioassay for the antifolate compounds: application in patients receiving methotrexate.
The general principles of ligand-binding radioassays are reviewed and a specific noncompetitive system is described for the measurement of methotrexate (MTX) using dihydrofolate reductase as the binding determinant. This type of radioassay can also be exploited to measure any antifolate compound which binds to this enzyme even if [3H]MTX is used as the tracer. The radioassay has now been used to measure MTX in all types of body fluids, tissue extracts, and rbc lysates from patients receiving this drug.


Complications associated with symptomatic diagnosis in infants with cystic fibrosis.
To determine the complication and hospitalization rates in children with cystic fibrosis (CF) by mode of diagnosis. Newly diagnosed cases of CF were identified from the Cystic Fibrosis Foundation National Patient Registry for 2000 through 2002. Cases were categorized as symptomatic diagnosis (SYMP; n = 1760), prenatal diagnosis (PRE; n = 66), diagnosis by means of newborn screening (NBS; n = 256), or presentation with meconium ileus (MI; n = 484). Complications were defined for the calendar year of diagnosis as stunting (length <3rd percentile), wasting (weight <3rd percentile), positive Pseudomonas aeruginosa culture results, and hypoelectrolytemia or edema and hypoproteinemia. For infants (age <12 months), 70% of patients with SYMP had at least 1 complication or hospitalization, compared with 29% for patients with NBS diagnosis (P < .0001). Cross-sectional data for 2002 showed that patients with SYMP had significantly more complications compared with patients with NBS diagnosis as old as 20 years. When compared with patients with NBS diagnosis, patients with SYMP had increased mucoid P aeruginosa (P < .05) and decreased pulmonary function as assessed by means of forced expiratory volume in 1 second (P < .01). SYMP of CF is associated with increased complication rates throughout infancy, childhood, and adolescence when compared with NBS diagnosis.


Fetal control of calcium transport across the rat placenta.
Control of maternofetal calcium transfer across the in situ perfused rat placenta at day 21 of gestation (term 23 d) was investigated in both intact fetuses and those parathyroidectomized by decapitation on day 19. Decapitation resulted in significant fetal hypocalcemia. Injection of fetuses subcutaneously through the uterine wall with 0.43 micrograms bovine (b) PTH(1-84), 20 ng 1,25(OH)2D3 or 10 microL of the appropriate diluent resulted 2 h later in a raised fetal blood ionized Ca concentration only with bPTH(1-84) in both normal and decapitated fetuses. Fetal decapitation caused a significant (p less than 0.001) fall in the clearance of 45Ca across the placenta (Kmf45Ca), which was significantly (p less than 0.05) reversed after fetal bPTH(1-84) and 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) injection, but not back to normal levels. There was no effect of either hormone on Kmf45Ca in placentas from intact fetuses, or on Kmf51Cr-EDTA (used as an extracellular marker) in either group. When 4 ng/mL r[Nle8,21, Tyr34] PTH(1-34), 50 pg/mL 1,25(OH)2D3 or the appropriate diluent was perfused through placentas the only response observed was a significant (p less than 0.05) increase in Kmf45Ca with 1,25(OH)2D3 perfusion in placentas from decapitated fetuses, Kmf51Cr-EDTA being unchanged. Finally, perfusion with 10(-5) M forskolin (an activator of adenylate cyclase) stimulated Kmf45Ca in placentas from both normal and decapitated fetuses. Although there was also some effect on Kmf51Cr-EDTA in the latter, there was none in the placentas from normal fetuses, and here the effect on Kmf45Ca was dose dependent with an initial response at 10(-6) M.(ABSTRACT TRUNCATED AT 250 WORDS)


Neurenteric cyst of the craniovertebral junction treated to reduce recurrence using different strategies: Two case reports and a literature review.
Neurenteric cysts are rare benign lesions that are usually located in the lower cervical and upper thoracic spine and extremely rare in the craniovertebral junction. It is generally challenging to completely remove the neurenteric cysts of the craniovertebral junction. We report the cases of 2 patients with neurenteric cyst in the ventral craniovertebral junction managed using different treatment strategies. The first patient was a 64-year-old man. He man was admitted with headache, posterior neck pain, and a tingling sensation in both the forearms. The second patient was a 53-year-old woman. She was admitted with tingling sensations and numbness in both the hands and feet. Cervical spine magnetic resonance imaging showed 2 intradural extramedullary cystic lesions in case 1 and a C2 to C3 intradural extramedullary cystic mass in case 2. The patient of the case 1 underwent a left C1 to C2 hemi-laminectomy and the cysts were completely removed. Eleven years after the surgery, there was no recurrence. In case 2, we performed a left C2 to C3 hemi-laminectomy and removed only a part of the outer membrane to enable sufficient communication with the surrounding normal subarachnoid space. After removing the cyst wall, the patient underwent C1 to 2 trans articular screw fixation to prevent cervical instability. Ten years after surgery, there was no recurrence of the cyst or new lesions. Clinicians should consider neurenteric cyst in the differential diagnosis of arachnoid cyst or epidermoid cyst. If performing a complete surgical removal is difficult, partial surgical removal, using a cysto-subarachnoid shunt and stabilization, such as screw fixation, could be an alternative treatment option to reduce the risk of mortality and morbidity.


The association of influenza infection and vaccine with myocardial infarction: systematic review and meta-analysis of self-controlled case series.
Introduction: Influenza vaccination may be beneficial in coronary disease patients; however the infection and vaccination are associated with acute inflammation, a trigger of cardiovascular events. We aimed to review the risk of myocardial infarction (MI) associated with Influenza infection and the safety of vaccination in self-controlled case series (SCCS).Methods: We performed a systematic review with meta-analysis of SCCS studies to evaluate the risk of MI associated with Influenza infection/vaccination. Database search was performed in August/2018. The data were reported using the incident rate ratio (IRR) and 95% confidence interval (95%CI).Results: three studies for Influenza infection and two studies for Influenza vaccination were eligible. The risk of MI following an Influenza infection was significantly increased in the first 3 days (IRR 5.79; 95%CI: 3.59-9.38) and between 4-7 days (IRR 4.52; 95%CI: 2.80-7.32). In the first 4 weeks following the Influenza vaccination, there was a significant decrease of MI risk (IRR 0.84, 95%CI: 0.78-0.91).Conclusions: Short-term MI risk in Influenza infection is significantly increased, with a low-to-moderate confidence in the pooled evidence. The Influenza vaccine was safe regarding the short-term risk for MI, and the risk reduction is possibly related to a healthy period bias.


Intrinsic Brain Abnormalities in Patients with Hepatitis C Virus Infection with Cognitive Impairment: A Preliminary Resting-State fMRI Study.
Patients with a hepatitis C virus (HCV) infection frequently exhibit various neuropsychiatric complications such as cognitive decline. This study is aimed at investigating alterations in regional and network-level neural function in patients with HCV infection and examining the association between these alterations and patients' cognition dysfunction. The study included 17 patients with HCV infection and 17 healthy controls. These individuals had undergone resting-state functional magnetic resonance imaging as well as cognitive assessment using a battery of tests that were collectively called the "psychometric hepatic encephalopathy score (PHES)" examination. Analyses of amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were conducted to assess, respectively, regional neural function and functional integration. HCV-infected patients performed significantly worse in cognitive tests. In the HCV group, ALFF decreased in Region 1 (left medial frontal gyrus and bilateral anterior cingulate gyrus) and Region 2 (right middle and superior frontal gyrus). The HCV group showed lower FC between Region 1 and right middle frontal gyrus, whereas they presented an increase in FC between Region 2 and the left supramarginal gyrus/superior temporal gyrus and right supramarginal gyrus. No significant correlation was observed between ALFF/FC measurements and PHES result. This preliminary study presents additional evidence that HCV infection affects brain function, including local intrinsic neural activity and global functional integration.


Clinical Value of a One-Stop-Shop Low-Dose Lung Screening Combined with (18)F-FDG PET/CT for the Detection of Metastatic Lung Nodules from Colorectal Cancer.
The aim of this study was to evaluate the clinical usefulness of additional low-dose high-resolution lung computed tomography (LD-HRCT) combined with (18)F-fluoro-2-deoxyglucose positron emission tomography with CT ((18)F-FDG PET/CT) compared with conventional lung setting image of (18)F-FDG PET/CT for the detection of metastatic lung nodules from colorectal cancer. From January 2011 to September 2011, 649 patients with colorectal cancer underwent additional LD-HRCT at maximum inspiration combined with (18)F-FDG PET/CT. Forty-five patients were finally diagnosed to have lung metastasis based on histopathologic study or clinical follow-up. Twenty-five of the 45 patients had ≤5 metastatic lung nodules and the other 20 patients had >5 metastatic nodules. One hundred and twenty nodules in the 25 patients with ≤5 nodules were evaluated by conventional lung setting image of (18)F-FDG PET/CT and by additional LD-HRCT respectively. Sensitivities, specificities, diagnostic accuracies, positive predictive values (PPVs), and negative predictive values (NPVs) of conventional lung setting image of (18)F-FDG PET/CT and additional LD-HRCT were calculated using standard formulae. The McNemar test and receiver-operating characteristic (ROC) analysis were performed. Of the 120 nodules in the 25 patients with ≤5 metastatic lung nodules, 66 nodules were diagnosed as metastatic. Eleven of the 66 nodules were confirmed histopathologically and the others were diagnosed by clinical follow-up. Conventional lung setting image of (18)F-FDG PET/CT detected 40 of the 66 nodules and additional LD-HRCT detected 55 nodules. All 15 nodules missed by conventional lung setting imaging but detected by additional LD-HRCT were <1 cm in size. The sensitivity, specificity, and diagnostic accuracy of the modalities were 60.6 %, 85.2 %, and 71.1 % for conventional lung setting image and 83.3 %, 88.9 %, and 85.8 % for additional LD-HRCT. By ROC analysis, the area under the ROC curve (AUC) of conventional lung setting image and additional LD-HRCT were 0.712 and 0.827 respectively. Additional LD-HRCT with maximum inspiration was superior to conventional lung setting image of (18)F-FDG PET/CT for the detection of metastatic lung nodules from colorectal cancer (P < 0.05).


Searching for genes in diabetes and the metabolic syndrome.
Evidence for a genetic basis for type 2 diabetes and the metabolic syndrome has been derived from studies of families, twins and populations with genetic admixture. Identification of genes associated with disease pathogenesis is now underway using techniques such as genome scanning by positional cloning and the candidate gene approach. Genome scanning in several different ethnic groups has identified chromosome regions harbouring type 2 diabetes susceptibility genes such as the novel gene, calpain 10 (CAPN10). The hepatic nuclear factor 4alpha (HNF4alpha) gene partly explains the linkage peak on chromosome 20, while the upstream transcription factor (USF1) is associated with familial combined hyperlipidaemia (FCHL) and maps close to the type 2 diabetes associated 1q peak. Peroxisome proliferator-activated receptor gamma (PPARgamma) was identified as a candidate gene based on its biology. A Pro12Ala variant of this gene has been associated with an increased risk of type 2 diabetes. Many genes accounting for monogenic forms of diabetes have been identified--such as maturity onset diabetes of the young (MODY); glucokinase (GCK) and HNF1alpha mutations being the most common causes of MODY. GCK variants result in 'mild' diabetes or impaired glucose tolerance (IGT) and relatively few cardiovascular complications, while HNF1alpha-associated MODY is more typical of type 2 diabetes, frequently being treated with sulphonylureas or insulin and resulting in microvascular complications. Testing for single gene disorders associated with type 2 diabetes and obesity may determine cause, prognosis and appropriate treatment; however, for the more common polygenic diseases this is not the case. In type 2 diabetes, molecular genetics has the potential to enhance understanding of disease pathogenesis, and help formulate preventative and treatment strategies.


Comparison of old cherry cultivars grown in Czech Republic by chemical composition and bioactive compounds.
Sweet cherry fruits are readily consumed by humans, and they contain significant quantities of bioactive compounds. Fifteen sweet cherry (Prunus avium L.) old cultivars grown in the Czech Republic were examined. In fresh fruits the contents of sugars, organic acids, and phenolic compounds, and antioxidant capacity were determined. The analyses showed that the fruits of sweet cherry are characterized by high contents of bioactive compounds. Four organic acids - malic, quinic, shikimic, and fumaric acid - were determined in examined fruits. The cultivar 'Lyonská Raná' was characterized by the highest total polyphenol content (202.28mg GAE/100g FW) and high antioxidant activity (ABTS - 2765.3µmol TE/100g FW, FRAP - 1663.67µmol TE/100g FW), with the lowest content of organic acids. The 'Šakvická' cultivar was characterized by the highest content sum of sugars (16.36g/100g FW) and sweetness (19.08g/100g FW), with low contents of polyphenols and antioxidant activity.


Use of Adair four-step kinetics in mathematical simulation of oxygen transport in the microcirculation.
The Adair four-step kinetic model for the reactions of haemoglobin and oxygen recognizes five haemoglobin species, corresponding to deoxyhaemoglobin and one species for each level of oxygenation of the four haem groups. Thus, an oxygen transport problem involves a system of five simultaneous non-linear partial differential equations for diffusion with chemical reaction. This mathematical complexity has impeded application of the Adair model despite its theoretical advantages over the one-step model often used in practice. The Adair kinetic model has been incorporated into a simulation of microcirculatory oxygen transport. The results show that the usual one-step kinetic model is inaccurate in comparison with the Adair model. However, an empirical modification can be made to the one-step model to ensure compatibility with the equilibrium curve. This modified one-step kinetic model (the VRC model) is much more tractable mathematically than the Adair model. In the physiological range of fluxes, the VRC kinetic model appears to be of sufficient accuracy for most purposes, and the mathematical complexity of the Adair model is not required.


Advances in 3D bioprinting technology for cardiac tissue engineering and regeneration.
Cardiovascular disease is still one of the leading causes of death in the world, and heart transplantation is the current major treatment for end-stage cardiovascular diseases. However, because of the shortage of heart donors, new sources of cardiac regenerative medicine are greatly needed. The prominent development of tissue engineering using bioactive materials has creatively laid a direct promising foundation. Whereas, how to precisely pattern a cardiac structure with complete biological function still requires technological breakthroughs. Recently, the emerging three-dimensional (3D) bioprinting technology for tissue engineering has shown great advantages in generating micro-scale cardiac tissues, which has established its impressive potential as a novel foundation for cardiovascular regeneration. Whether 3D bioprinted hearts can replace traditional heart transplantation as a novel strategy for treating cardiovascular diseases in the future is a frontier issue. In this review article, we emphasize the current knowledge and future perspectives regarding available bioinks, bioprinting strategies and the latest outcome progress in cardiac 3D bioprinting to move this promising medical approach towards potential clinical implementation.


Enzymatic extraction of cobalamin from monoclonal antibody captured haptocorrin and transcobalamin.
Current extraction methods for cobalamins from serum influence the molecular characteristics of the vitamin. Therefore, an extraction procedure that leaves the cobalamins unchanged is needed. Monoclonal antibodies towards transcobalamin (TC) and haptocorrin (HC) (in house) linked to magnetic microspheres were used for precipitation of the proteins. The cobalamins were subsequently released by degradation of TC or HC with subtilisin Carlsberg (EC.220.127.116.11). Recovery for the extraction of (57)Co-cyanocobalamin ((57)Co-hydroxycobalamin) was higher than 99 (93)% and 92 (93)% from TC and HC respectively (n=10 (3)). No change in retention time and recovery was observed for (57)Co-hydroxycobalamin analyzed with HPLC before and after extraction with subtilisin Carlsberg. Endogenous cobalamin in serum was extracted from TC and HC and measured with routine methods. Enzymatic extracted cobalamin constituted 118-187% of that measured in serum with routine methods (n=16). We present a method that allows extraction of cobalamins from their binding proteins without modifying the vitamin. The procedure may be useful especially for extractions aiming at characterizing the cobalamins bound to individual cobalamin binding proteins.


2D Autocorrelation, CoMFA, and CoMSIA modeling of protein tyrosine kinases' inhibition by substituted pyrido[2,3-d]pyrimidine derivatives.
2D Autocorrelation, comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA) were undertaken for a series of substituted pyrido[2,3-d]pyrimidine derivatives to correlate platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), and c-Src tyrosine kinases' inhibition with 2D and 3D structural properties of 22 known compounds. QSAR models with considerable internal as well as external predictive ability were obtained. The relevant 2D autocorrelation descriptors for modeling each protein tyrosine kinase (PTK) inhibitory activity were selected by genetic algorithm (GA) and multiple linear regression (MLR) approach. The 2D autocorrelation space brings different descriptors for each PTK inhibition and suggests the atomic properties relevant for the inhibitors to interact with each PTK active site. CoMFA and CoMSIA were developed with a focus on interpretative ability using coefficient contour maps. CoMSIA produced significantly better results for all correlations. The results indicate a strong correlation between the inhibitory activity of the modeled compounds and the hydrophobic and H-bond donor fields around them.


Combinatorial approach of statistical optimization and mutagenesis for improved production of acidic phytase by Aspergillus niger NCIM 563 under submerged fermentation condition.
Combination of statistical optimization and mutagenesis to isolate hypersecretory strains is studied to maximize phytase production from Aspergillus niger NCIM 563 under submerged fermentation. The overall results obtained show a remarkable 5.98-fold improvement in phytase production rates when compared to that using basal medium. Optimization of culture conditions from parent strain is studied first by the Plackett-Burman technique to evaluate the effects of 11 variables for phytase production. The results showed that glucose, MgSO(4), KCl, incubation period, and MnSO(4) are the most significant variables affecting enzyme production. Further optimization in these variables, using a central composite design technique, resulted in 3.74-fold increase in the yield of phytase production to 254,500 U/l when compared with the activity observed with basal media (68,000 U/l) in shake flask. Our experiments show that the phytase from A. niger NCIM 563 exhibits desirable activity in simulated gastric fluid conditions with low pH and also improved thermostability when compared to commercial phytase. The improved yield demonstrates the potential applicability of phytase enzyme as a source of phytase supplement for phosphorus nutrition and environmental protection in animal feed industry. Physical and chemical mutagenesis experiments were carried out in parallel to isolate hypersecretory mutants that could possibly further enhance the enzyme production. Using optimized media conditions of the parent strain, our results show that mutant strain A. niger NCIM 1359 increased the phytase activity by another 1.6-fold to 407,200 U/l.


Vitamin A status and body pool size of infants before and after consuming fortified home-based complementary foods.
Home fortification using sachets of micronutrient powder (e.g. "Sprinkles") is a food-based approach offering an alternative to high dose vitamin A (VA) supplements for infants. The primary objective was to investigate the impact of VA-home fortification on infant VA pool size. The secondary objective was to compare VA status of infants assessed by the modified relative dose response (MRDR) test before and the (13)C-retinol isotope dilution ((13)C-RID) test in the same infants after vitamin A supplementation. A randomized-controlled trial was conducted in 7-9 month old infants in Ghana. Eligible children were randomly allocated to receive a daily sachet of "Sprinkles" with or without VA for 5 months added to complementary foods. The MRDR test indirectly determined VA liver reserves at baseline and the (13)C-RID determined VA body pool at follow-up in the same cohort of children. At baseline, the MRDR values (95 % CI) for infants were comparable in the intervention and control groups: normal at 0·032 (SD 0·018) (0·025-0·038) and 0·031 (SD 0·018) (0·024-0·038), respectively. After intervention, total body stores (TBS) and liver retinol concentrations did not differ between intervention and control groups; TBS were 436 (SD 303) and 434 (SD 186) μmol, respectively, and estimated liver concentrations were 0·82 (SD 0·53) and 0·79 (SD 0·36) μmol/g liver, indicating adequate reserves in all children. Both the MRDR and (3)C-RID tests confirmed that the infants had adequate VA status before and after home fortification of their complementary foods. These tests offered more information than serum retinol concentrations alone, which predicted VA deficiency using current suggested cutoffs not corrected for inflammation status.


Identifying and understanding determinants of high healthcare costs for breast cancer: a quantile regression machine learning approach.
To identify and rank the importance of key determinants of high medical expenses among breast cancer patients and to understand the underlying effects of these determinants. The Oncology Care Model (OCM) developed by the Center for Medicare & Medicaid Innovation were used. The OCM data provided to Mount Sinai on 2938 breast-cancer episodes included both baseline periods and three performance periods between Jan 1, 2012 and Jan 1, 2018. We included 11 variables representing information on treatment, demography and socio-economics status, in addition to episode expenditures. OCM data were collected from participating practices and payers. We applied a principled variable selection algorithm using a flexible tree-based machine learning technique, Quantile Regression Forests. We found that the use of chemotherapy drugs (versus hormonal therapy) and interval of days without chemotherapy predominantly affected medical expenses among high-cost breast cancer patients. The second-tier major determinants were comorbidities and age. Receipt of surgery or radiation, geographically adjusted relative cost and insurance type were also identified as important high-cost drivers. These factors had disproportionally larger effects upon the high-cost patients. Data-driven machine learning methods provide insights into the underlying web of factors driving up the costs for breast cancer care management. Results from our study may help inform population health management initiatives and allow policymakers to develop tailored interventions to meet the needs of those high-cost patients and to avoid waste of scarce resource.