Direct activity determination of 54Mn and 65Zn by a non-extrapolation liquid scintillation method.
The measurement of 54Mn and 65Zn by liquid scintillation coincidence counting results in low detection efficiencies. The activity obtained from the extrapolation of efficiency data can therefore become problematic if curvature is present. The simple decay scheme exhibited by these radionuclides, with the emission of an energetic gamma ray, allows the absolute activity to be determined from 4pie-gamma data by direct calculation without the need for efficiency extrapolation. The method, which relies on determining the probability of the gamma-ray interacting with the scintillator solution, is described and validated by measurements made on 60Co.


Expression and characterization of insulin growth factor-I-enhanced green fluorescent protein fused protein as a tracer for immunoassay.
The insulin-like growth factor-I (IGF-I) is an important polypeptide hormone under investigation for body metabolism study and for doping detection. Here, we describe for the first time the expression of a recombinant fusion protein of IGF-I and the enhanced green fluorescent protein (EGFP). The genetic fusion approach enables preparation of conjugates with 1:1 stoichiometry and homogeneous structure. The fused protein (EGFP-IGF-I) was expressed as a soluble protein in cytoplasm of Escherichia coli and its fluorescence and immunoreaction properties were thoroughly characterized. Finally, we demonstrated the utility of the EGFP-IGF-I fusion protein for the fluorescence immunoassay of IGF-1. The linear range of the assay is 1.6 x 10(-8) to 2.0 x 10(-6) M with a detection limit of 1.6 x 10(-8) M. To our knowledge, this is the first time that EGFP has been used as a quantitative label in a fusion protein to develop a quantitative assay for IGF-I. Furthermore, the use of genetically engineered fusion proteins, which combine peptide hormones with fluorescent protein, can lead to a new labeling approach to a number of bioanalytical applications.


Expression, purification, and crystallization of endopolygalacturonase from a pathogenic fungus, Stereum purpureum, in Escherichia coli.
Endopolygalacturonases (EC 184.108.40.206) catalyze random hydrolysis of the alpha-1,4 glycosidic linkages in polygalacturonic acid, a component of pectin. Previously, we reported crystal structures of endogenously produced Stereum purprureum endopolygalacturonase I (endoPG I), both in its native form and complexed with its product, galacturonate. However, the substrate-binding mechanism of endoPG I is still unclear, because crystals have not yet been obtained with a substrate analog, or with mutant enzymes that can bind substrates. We describe here an expression system using Escherichia coli and a purification method to prepare functionally active endoPG I for such mutation and crystallographic studies. Expression in E. coli strain Origami (DE3) provided a soluble and active enzyme with proper disulfide bond formation, whereas the enzyme expressed in BL21 (DE3) was localized in inclusion bodies. A sufficient amount of recombinant endoPG I produced by Origami (DE3) was purified by a single-step procedure using cation exchange chromatography. The specific activity of recombinant endoPG I was equivalent to that of the enzyme produced by S. purpureum. Recombinant endoPG I was crystallized under the same conditions as those used for the native enzyme produced by S. purpureum. The crystals diffracted beyond 1.0 A resolution with synchrotron radiation.


The Finnish Diabetes Risk Score (FINDRISC), incident diabetes and low-grade inflammation.
The FINDRISC was created to predict the development of type 2 diabetes mellitus (T2DM). Since T2DM associates with inflammation we evaluated if the FINDRISC could predict either current or incident T2DM, and elevated high sensitivity C-reactive protein (hs-CRP). 41,880 people (age 41.9 ± 9.7 years; 31% female) evaluated between 2008 and 2016 were included. First, the cross-sectional association between the FINDRISC with presence of either T2DM or hs-CRP ≥ 2.0 mg/L was tested. After a 5 ± 3 years follow-up we tested the score predictive value for incident T2DM and inflammation in respectively 10,559 individuals without diabetes and in a subset of 2,816 individuals having no elevated hs-CRP at baseline. In the cross sectional analysis the FINDRISC was associated with both T2DM (OR 1.24, 95% CI: 1.23-1.26, P < 0.001) and inflammation (OR 1.10, 95% CI: 1.09-1.11, P < 0.001) per FINDRISC unit, as well as in longitudinal analyses (OR 1.17, 95% CI: 1.14-1.20, P < 0.001; and OR 1.04, 95% CI: 1.02-1.07, P < 0.001; respectively, per FINDRISC unit). The C-statistic for incident T2DM and inflammation was 0.79 (95% CI 0.77-0.82) and 0.55 (95% CI 0.53-0.58), respectively. The FINDRISC shows good discrimination for incident T2DM but less for inflammation.


Antitrichomonal action of emodin in mice.
Emodin, an active component contained in the root and rhizome of Rheum palmatum L. (Polygonaceae), was found to have an inhibitory effect on the pathogenicity of Trichomonas vaginalis in mice. Emodin delayed the development of subcutaneous abscesses due to infection of this parasite. Also, it cures the intravaginal infection of trichomonads through oral administration. In cell cultures, it reduced the cytotoxic effect of this parasite towards mammalian cells. This inhibition was markedly reversed by the coexistence of free radical scavengers, indicating the possible mediation of free radicals.


PTEN regulates hematopoietic lineage plasticity via PU.1-dependent chromatin accessibility.
PTEN loss in fetal liver hematopoietic stem cells (HSCs) leads to alterations in myeloid, T-, and B-lineage potentials and T-lineage acute lymphoblastic leukemia (T-ALL) development. To explore the mechanism underlying PTEN-regulated hematopoietic lineage choices, we carry out integrated assay for transposase-accessible chromatin using sequencing (ATAC-seq), single-cell RNA-seq, and in vitro culture analyses using in vivo-isolated mouse pre-leukemic HSCs and progenitors. We find that PTEN loss alters chromatin accessibility of key lineage transcription factor (TF) binding sites at the prepro-B stage, corresponding to increased myeloid and T-lineage potentials and reduced B-lineage potential. Importantly, we find that PU.1 is an essential TF downstream of PTEN and that altering PU.1 levels can reprogram the chromatin accessibility landscape and myeloid, T-, and B-lineage potentials in Ptennull prepro-B cells. Our study discovers prepro-B as the key developmental stage underlying PTEN-regulated hematopoietic lineage choices and suggests a critical role of PU.1 in modulating the epigenetic state and lineage plasticity of prepro-B progenitors.


Patent foramen ovale percutaneous closure: the no-implant approach.
Currently available catheter techniques for closure of a patent foramen ovale (PFO) rely on the placement of an implantable closure device. Sievert et al. evaluated the safety and feasibility of transcatheter closure of PFO using radiofrequency energy without an implanted device in patients with cryptogenic stroke or transient ischemic attack. In total, 30 patients were enrolled (15 females; mean age 48 years). Technical success was achieved in 90% of the patients. All 30 patients did not present any serious procedure-related adverse events. No recurrent strokes, deaths or perforations occurred as a result of the procedure. The mean follow-up was 6 months, and 13 out of the 30 (43%) patients experienced PFO closure after the first procedure. Complete closure after a second procedure was achieved in 63% of the cases. The authors demonstrate that transcatheter closure of an intracardiac defect without a permanent implant is technically feasible. However, future improvements in the technique and materials are needed.


Predation in Gerris (Hemiptera): Reactive distances and locomotion rates.
Two of the parameters which determine the rate at which prey are encountered by a predator, i.e. the distance at which a predator responds to a prey and its rate of movement relative to the prey's, were determined for all the stages of five species of Gerris using gerrids and Drosophila as prey. These parameters allowed calculation of the swath, or "encounter path", a gerrid would cover as it moved across the water surface. Gerris species prefer to attack live prey in front of them, and tend to ignore prey if the attack requires a turn of more than 100°. Hunger was found to affect the responsive angle required to clicit an attack by G. remigis, and regardless of species, smaller gerrids required the prey to be closer before an attack was initiated. The rate of movement in Gerris was measured as a function of stride length and the number of strides made per unit time. Stride length varied according to the length of the mesothoracic leg, and the frequency of movement was observed to be species specific. G. remigis, a stream species, moved 4-6 times as often as the four other species studied, all of which are characteristically found on non-moving water surfaces. Within a species, gerrid size had no significant effect on the frequency of movement, although there was a tendency for smaller gerrids to move less.


COVID-19 in systemic lupus erythematosus: Data from a survey on 417 patients.
Systemic lupus erythematosus (SLE) is a chronic disease characterised by autoimmunity and increased susceptibility to infections. COVID-19 is a systemic viral disease currently spreading as a pandemic. Little is known about the impact of COVID-19 in patients with SLE. to acquire information on the impact of COVID-19 in SLE. A 26-item anonymous questionnaire investigating demographics, SLE clinical features, COVID-19 diagnoses and changes in treatments and daily habits was administered to patients with SLE from three referral centres through www.surveymonkey.com over 10 days. Data from the survey were compared to those from published estimates about the general population. Four-hundred-seventeen patients responded to the survey. More than 60% of subjects complained of symptoms that are also associated to COVID-19. Fourteen COVID-19 diagnoses (five confirmed by polymerase chain reaction) were reported, in contrast to a 0.73% prevalence of confirmed cases in Lombardy. One hospitalisation was reported. Fever, anosmia, dry cough, a self-reported history of neuropsychiatric SLE and a recent contact with confirmed COVID-19 cases were more strongly associated with COVID-19, as were symptoms and lower compliance to behavioural preventive measures in patients' contacts. No protective effect was seen in subjects on hydroxychloroquine. COVID-19 morbidity might only moderately be increased in most patients with SLE, although limited information can be inferred on more severe cases. Hydroxychloroquine apparently seems not to confer protection to infection per se, although other beneficial roles cannot be excluded. Containment policies and behavioural preventive measures could have a major role in limiting the impact of COVID-19 in patients with SLE.


Differences in haemagglutination activity and electrophoretic mobility of E protein between the parent SA14 and attenuated vaccine SA14-14-2 strains of Japanese encephalitis virus.
E protein characteristics of the attenuated Japanese encephalitis (JE) virus strain SA(A) derived from the live vaccine strain SA14-14-2 were compared with those of the virulent strain SA(V). SA(A) showed lower haemagglutination (HA) activity with broader optimum pH range of HA reaction than SA(V), and the E protein of SA(A) had slower electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) than that of SA(V). These properties of SA(A) E protein appear to be caused by eight amino acid changes found in the E protein coding region of the SA(A) virus genome.


Pharmacological evidence for the existence of multiple functional pools of brain serotonin: analysis of brain perfusate from conscious rats.
The serotonin reuptake inhibitor fluoxetine significantly reduced levels of endogenous 5-hydroxyindoleacetic acid (5-HIAA) in brain perfusate of rats implanted with push-pull cannulas. This occurred in conjunction with its suppressant effect upon fixed-ratio operant behavior. Behavior suppressed with the serotonin agonist lysergic acid diethylamide (LSD) occurred in conjunction with a reduction of 5-HIAA only after 5-HIAA was elevated, shortly before, by 5 mg/kg of the serotonin precursor 5-hydroxytryptophan. Our data demonstrate the likely existence of multiple functional pools of serotonin in brain and support the notion that LSD preferentially affects a newly synthesized pool of this transmitter.


Influence of protein deficiency on the inhibition of hepatic microsomal detoxication by methyl mercury in two rat strains.
N- and C-oxygenation of N,N-dimethylaniline was studied in liver microsomes from 2 rat strains (Wistar, Strain R and Sprague-Dawley) subjected to protein deprivation and methyl mercury pretreatment, separately and in combination. A striking interstrain difference was observed. Strain R microsomes from 2 rat strains (Wistar, Strain R and Sprague-Dawley) subjected to tion, but little effect after methyl mercury pretreatment. With Sprague-Dawley microsomes, C-oxygenation was slightly reduced after both treatments. N-oxygenation was little affected in either strain. Methyl mercury treatment of protein deprived rats strongly inhibited C-oxygenation in microsomes from both strains, with N-oxygenation being unaffected in strain R microsomes whereas markedly reduced in microsomes from Sprague-Dawley.


New bone formation and bone marrow differentiation induced in rats by extracellular bone matrix implantation: effect of local preirradiation on the process.
Subcutaneous implantation of demineralized diaphyseal rat bone matrix in ACI rats initiates a developmental cascade that results in the formation of new endochondral bone and an associated hematopoietic bone marrow differentiation. Irradiation (1500 rad, 60Co) of the implantation site 24 h prior to implantation suppresses the formation of endochondral bone and bone marrow. All phases of the developmental cascade, including chemotaxis, proliferation, and differentiation, are arrested by the irradiation. Simultaneous implantation with the extracellular matrix of bone marrow, bone, pieces of a four-day-old implant or of thoracic muscle--but not of brain, liver, or spleen tissue--results in the development of endochondral bone and bone marrow at the irradiated site. Concurrent implantation with the extracellular matrix of in vitro growing fibroblasts of marrow or ossicle origin does not restore the developmental cascade.


Long-term outcomes of vitrectomy for progressive X-linked retinoschisis.
To evaluate the long-term outcomes of vitrectomy for progressive X-linked retinoschisis. Prospective, nonrandomized, consecutive, interventional case series. Twenty-eight eyes of 22 patients who were diagnosed with progressive X-linked retinoschisis were divided into 2 groups: a nonsurgical group (n = 11) and a vitrectomy group (n = 17). The main outcome measures included best-corrected visual acuity, the area of the macular schisis cavity measured by optical coherence tomography, the retinal anatomic status, and complications. The mean follow-up period was 34.7 months (range, 10 to 68 months). The mean best-corrected visual acuity increased from 20/125 at baseline to 20/55 at the final follow-up in the vitrectomy group (P = .001), but decreased from 20/100 at baseline to 20/400 at the final follow-up in the nonsurgical group (P = .000). In the vitrectomy group, the macular schisis cavity resolved in all 17 eyes; the mean area of the macular schisis cavity decreased from 0.85 mm(2) at baseline to 0.23 mm(2) at the final follow-up (P = .000), and the retinas of 16 eyes (94%) were attached after surgery. In the nonsurgical group, retinal schisis progressively extended in 9 eyes (82%); the mean area of the macular schisis cavity increased from 0.82 mm(2) at baseline to 1.21 mm(2) at the final follow-up (P = .000); in 8 eyes (72%), retinal detachment developed, and 2 eyes (18%) experienced vitreous hemorrhage, which terminated the observations. Vitrectomy may be an effective and essential treatment for patients with progressive X-linked retinoschisis to prevent a deterioration of vision before severe complications developed in their eyes.


A comparison of dose calculations at points around an intracavitary cervix applicator.
An intercomparison was made between dose-rate calculations performed in 10 institute in The Netherlands for intracavitary applications with the Selectron-LDR remote afterloading machine. The results of 11 computer planning systems of five different manufacturers were compared with reference dose-rate calculations. The difference in clinically relevant dose-points like rectum and bladder, were less than 2% if the values of the coordinates of source and dose-points were given, except for one type of planning system, that showed differences up to 10%. The errors observed for the latter system were probably due to a coarse calculation grid, which becomes important in regions with a high dose gradient. If the reconstruction process of source and dose-point positions from radiographs was included as it usually is in practice, then the accuracy became worse and the planning system that showed large errors before, gave unacceptable errors of 30% to 40% in the rectal area. This is due to additional errors introduced in the reconstruction. The intercomparison showed that it is very important that computer treatment planning systems for brachytherapy calculations are tested before clinical use. The reconstruction technique for source and dose-point positions should be part of this test. Radiographs should be made of a phantom that simulates the cervix application, and the radiography technique should be similar to the one that is clinically employed.


Ultrasound backscatter microscopy images the internal structure of living tumour spheroids.
Ultrasound microscopes have the potential for imaging structure at depth in thick specimens, yet this is not possible in biological specimens using conventional ultrasound transmission or reflection methods. But, subsurfacing imaging is possible with ultrasound if a backscatter (pulse-echo) technique, similar to that used in medical imaging, is used. The central problem of extending backscatter imaging to ultrasound microscopy has been the development of high frequency (greater than 100 MHz) transducers with sufficient bandwidth and sensitivity to detect the low levels of backscatter from biological materials. We recently reported the development of such a transducer which we have now incorporated into a new ultrasound backscatter microscope capable of providing tomographic images at depths of up to 4 mm in biological specimens. Here we present the first ultrasound backscatter micrographs of living biological specimens. The benefits of this technique are demonstrated by its application to imaging the internal structures of living tumour spheroids showing striking contrast between the necrotic core and the viable rim of the spheroid.


Gender-specific association of alexithymia and norepinephrine/cortisol ratios. A preliminary report.
Alexithymia and posttraumatic stress disorder (PTSD) might share a neuroendocrine pattern characterized by increased urinary norepinephrine (N) and decreased cortisol (C) levels, resulting in a high N/C ratio, at least among male alcoholics. We aimed to explore if this association can also be found in other populations. Twenty-four-hour urine samples were obtained from 12 major depressive disorder (MDD) patients and 23 healthy controls (HC) and tested for N and free C. Participants completed the 20-item Toronto Alexithymia Scale (TAS) and the Symptom Check List (SCL). Controlling for depression, the neuroendocrine parameters did not differ between the MDD and HC participants nor between women and men. The TAS was not associated with N, C or the N/C ratio in the MDD and HC participants nor in females alone. However, in men, the N/C ratio correlated significantly with the TAS (r = .80). Our preliminary findings indicate that alexithymia is associated with an increased noradrenergic activity and a decreased basal activity of the hypothalamic-pituitary-adrenal (HPA) axis among men. This gender difference may reflect divergent underlying neurobiological processes of alexithymia in men and women.


How serious are common childhood fears? II. The parent's point of view.
In an earlier study [Muris, P., Merckelbach, H., Mayer, B., & Prins, E. (1999). How serious are common childhood fears? Behaviour Research and Therapy, in press.], the severity of common childhood fears was explored by means of a structured child interview measuring specific phobias as defined by the Diagnostic and Statistical Manual of Mental Disorders. It was found that in a substantial minority of the children, specific fears reflect clinically significant phobias. The present study examined further the connection between childhood fears and specific phobias by interviewing children's parents. The Diagnostic Interview Schedule for Children was administered to the parents of 160 children aged 4-12 years. In line with our previous study, results indicate that a sizable proportion of children (i.e. 17.6%) met the full criteria for specific phobia.


An investigation on catalytic performance and reaction mechanisms of Fe/OMS-2 for the oxidation of carbon monoxide, ethyl acetate, and toluene.
The octahedral molecular sieve (OMS-2)-supported Fe (xFe/OMS-2: x = 1, 3, 5, and 10) catalysts were prepared using the pre-incorporation method. Physicochemical properties of the as-synthesized materials were characterized by means of various techniques, and their catalytic activities for CO, ethyl acetate, and toluene oxidation were evaluated. Among all of the samples, performed the best, with the reaction temperature required to achieve 90% conversion (T90%) being 160°C for CO oxidation, 210°C for ethyl acetate oxidation, and 285°C for toluene oxidation. Such a good catalytic performance of 5Fe/OMS-2 was associated with its high (Mn3+ + Mn2+) content and adsorbed oxygen species concentration, and good low-temperature reducibility and lattice oxygen mobility as well as strong interaction between Fe and OMS-2. In addition, catalytic mechanisms of the oxidation of three pollutants over the 5Fe/OMS-2 catalyst were also studied. It was found that CO, ethyl acetate or toluene was first adsorbed, then the related intermediates were formed, and finally the formed intermediates were completely converted into CO2 and H2O.


Climate Change-Induced Stress Reduce Quantity and Alter Composition of Nectar and Pollen From a Bee-Pollinated Species (Borago officinalis, Boraginaceae).
In temperate ecosystems, elevated temperatures, and drought occur especially during spring and summer, which are crucial periods for flowering, pollination, and reproduction of a majority of temperate plants. While many mechanisms may underlie pollinator decline in the wake of climate change, the interactive effects of temperature and water stress on the quantity and quality of floral nectar and pollen resources remain poorly studied. We investigated the impact of temperature rise (+3 and +6°C) and water stress (soil humidity lower than 15%) on the floral resources produced by the bee-pollinated species Borago officinalis. Nectar volume decreased with both temperature rise and water stress (6.1 ± 0.5 μl per flower under control conditions, 0.8 ± 0.1 μl per flower under high temperature and water stress conditions), resulting in a 60% decrease in the total quantity of nectar sugars (mg) produced per flower. Temperature rise but not water stress also induced a 50% decrease in pollen weight per flower but a 65% increase in pollen polypeptide concentration. Both temperature rise and water stress increased the total amino acid concentration and the essential amino acid percentage in nectar but not in pollen. In both pollen and nectar, the relative percentage of the different amino acids were modified under stresses. We discuss these modifications in floral resources in regards to plant-pollinator interactions and consequences on plant pollination success and on insect nutritional needs.


Ellagic Acid Improves Antioxidant Capacity and Intestinal Barrier Function of Heat-Stressed Broilers via Regulating Gut Microbiota.
Heat stress (HS) has been revealed to damage the antioxidant system and intestinal barrier function, which greatly threatens poultry production. The present study investigated the effects of dietary ellagic acid (EA) on the antioxidant system, gut barrier function, and gut microbiota of heat-stressed broilers. Arbor Acres 14-day-old broilers numbering 360 were randomly divided into six groups, including one negative control group (NC) and five experimental groups. The broilers in the NC group were supplemented with a basal diet at a normal temperature (23 ± 2 °C). The broilers in the experimental groups were supplemented with basal diets containing EA at different doses (0, 75, 150, 300, and 600 mg/kg) at HS temperature (35 ± 2 °C). The experiment lasted for 4 weeks. Results showed that dietary EA reduced the corticosterone (CORT), LPS, and diamine oxidase (DAO) levels in the serum of heat-stressed broilers. Additionally, dietary EA improved the antioxidant enzyme activity and mRNA levels of Nrf2/HO-1 in the ileum of heat-stressed broilers. The relative abundances of Streptococcus, Ruminococcus_torques, Rothia, Neisseria, Actinomyces, and Lautropia in the cecum were significantly reduced by the EA supplementation in a dose-dependent manner. Notably, the LPS, DAO, and MDA in the serum were revealed to be positively correlated with the relative abundances of Rothia, Neisseria, Actinomyces, and Lautropia, while the GSH-px, SOD, and CAT levels in the serum were negatively correlated with the relative abundances of Ruminococcus_torques, Rothia, Neisseria, Actinomyces, Streptococcus, and Lautropia. Taken together, dietary EA improved the antioxidant capacity, intestinal barrier function, and alleviated heat-stressed injuries probably via regulating gut microbiota.


Functional hyperemia is reduced in skeletal muscle of aged rats.
To test the hypothesis that active hyperemia is reduced in skeletal muscle of old rats due to a decreased bioavailability of prostanoids, which in turn is due to increased oxidative stress. The microvasculature of the spinotrapezius muscle of 3-, 12-, and 24-month male Sprague-Dawley rats was examined using in vivo videomicroscopy. Arteriolar diameter and centerline red cell velocity were measured in resting and contracting muscle. The effect of prostanoids was examined using indomethacin (10 microM), and passive resting arteriolar diameters were determined using adenosine (100 microM). Lipid peroxidation was assessed ex vivo by measuring tissue levels of malondialdehyde. Arteriolar diameters and blood flow in resting muscle did not differ among the age groups, but increases in diameter and flow during muscle contraction in young rats were greater than in the two older age groups. Indomethacin did not affect resting arteriolar diameters and blood flow in 3- and 12-month rats, but significantly decreased both parameters in 24-month rats. Indomethacin had no effect on arteriolar diameter and blood flow responses during muscle contraction in any age group. Passive resting diameters of arterioles were significantly smaller in 12- and 24-month rats than in 3-month rats. Tissue levels of TBARS were not different among the three age groups. Arteriolar tone and blood flow in resting skeletal muscle of rats is not altered with age, whereas the increases in these variables that normally accompany muscle contraction are markedly impaired during aging. Neither cyclooxygenase metabolites nor lipid peroxidation appear to be involved in this impairment.


Can impaired diaphyseal fracture healing be predicted early?: A cohort study of biomarkers.
Currently, the clinico-radiological method was used to analyze the healing progression of fractures globally, but even they are also unable to presume the impaired healing early. Hence till date, no reliable methods are available to predict the impaired healing early, so that it could be interventionally managed as required within the time. In this prospective observational study, a total of 121 adults fractured patients and 108 healthy controls were analyzed. Peripheral blood samples were taken from controls (at once) and fractured cases (at different follow-ups) to quantify the Osteocalcin and Osteopontin mRNA and protein expression using qRT-PCR and western blotting assay respectively. In parallel to that the clinico-radiological follow-up examinations also done at various specific follow-up intervals up to 24th post-fracture weeks. As per the clinico-radiological status at the 24th week, fracture patients were divided into normal healing (n = 102) and impaired healing (n = 19) groups. Mean RUST score between normal healing and the impaired healing group showed a significant statistical difference at each follow-up. In both groups, expressions of Osteocalcin (mRNA & protein) were gradually up-regulated from the baseline to end of follow-ups, whereas Osteopontin mRNA as well as protein gradually up-regulated from the baseline to a peak value at 10th day, then declined. In general, the Osteocalcin and Osteopontin mean fold expressions were higher in normal healing as compared to the impaired healing groups.A significant correlation was found between the mRNA expressions of Osteocalcin and Osteopontin with the RUST score at most of the follow-ups. However, the protein expressions were not shown any significant correlation. The Osteocalcin and Osteopontin expression will provide an early prediction of the healing outcomes of tibial fractures. This may open a new horizon for innovations to deal with complications associated with impaired fracture healing, especially in tibial bone fractures.


Antiplasmodial and antioxidant isoquinoline alkaloids from Dehaasia longipedicellata.
The crude extract of the bark of Dehaasia longipedicellata exhibited antiplasmodial activity against the growth of Plasmodium falciparum K1 isolate (resistant strain). Phytochemical studies of the extract led to the isolation of six alkaloids: two morphinandienones, (+)-sebiferine (1) and (-)-milonine (2); two aporphines, (-)-boldine (3) and (-)-norboldine (4); one benzlyisoquinoline, (-)-reticuline (5); and one bisbenzylisoquinoline, (-)-O-O-dimethylgrisabine (6). Their structures were determined on the basis of 1D and 2D NMR, IR, UV, and LCMS spectroscopic techniques and upon comparison with literature values. Antiplasmodial activity was determined for all of the isolated compounds. They showed potent to moderate activity with IC50 values ranging from 0.031 to 30.40 µM. (-)-O-O-dimethylgrisabine (6) and (-)-milonine (2) were the two most potent compounds, with IC50 values of 0.031 and 0.097 µM, respectively, that were comparable to the standard, chloroquine (0.090 µM). The compounds were also assessed for their antioxidant activities with di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (IC50 = 18.40-107.31 µg/mL), reducing power (27.40-87.40 %), and metal chelating (IC50 = 64.30 to 257.22 µg/mL) having good to low activity. (-)-O-O-dimethylgrisabine (6) exhibited a potent antioxidant activity of 44.3 % reducing power, while di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium and metal chelating activities had IC50 values of 18.38 and 64.30 µg/mL, respectively. Thus it may be considered as a good reductant with the ability to chelate metal and prevent pro-oxidant activity. In addition to the antiplasmodial and antioxidant activities, the isolated compounds were also tested for their cytotoxicity against a few cancer and normal cell lines. (-)-Norboldine (4) exhibited potent cytotoxicity towards pancreatic cancer cell line BxPC-3 with an IC50 value of 27.060 ± 1.037 µM, and all alkaloids showed no toxicity towards the normal pancreatic cell line (hTERT-HPNE).


Stability Testing of Sirolimus in Medium-Chain Triglyceride Oil Using High-Performance Liquid Chromatography.
Recently, a premature neonate, born at 26.5 weeks, was treated with sirolimus for kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon at the University of New Mexico Children's Hospital. Because of the lipophilic properties of the drug and an inability to draw the correct dose needed for the neonate with the standard 1 mg/mL concentration, sirolimus was diluted to 0.01 mg/mL (10 mg/L) in medium-chain triglyceride (MCT) oil. The objective of this study was to evaluate the stability of sirolimus diluted in MCT oil. Commercially available sirolimus oral solution was diluted with MCT oil from 1 mg/mL to 10 mg/L. The diluted samples were prepared by measuring 0.1 mL of the commercial product in an oral syringe and mixing with 9.9 mL of MCT oil. The 3 diluted samples were placed in amber glass vials, stored at 10°C, and analyzed over 14 days. The initial concentration of the 3 samples ranged from 8.5 to 10.8 mg/L sirolimus, or 85% to 108% of the target value. No significant differences were seen between average concentrations on the days tested. However, the average drug concentration fell to approximately 90% of the theoretical 10 mg/L target concentration between days 7 and 10. This study shows that sirolimus oral solution diluted with MCT oil to a final concentration of 10 mg/L was stable for at least 7 days when stored at 10°C, suggesting that the beyond-use date should be 7 days.


Laser welding in urethral surgery: improved results with a protein solder.
Reconstruction of the rat urethra using the CO2 laser and a protein solder has dramatically decreased the postoperative fistula rate and decreased surgical time over conventional microsurgical reconstruction. Using the rat as a model, a partial transection of the ventral urethra was repaired in one of three ways in 39 animals: conventional microsuture repair, laser assisted microsuture repair and laser assisted microsuture repair with a protein solder. The success rate in each group was 50%, 58% and 90% respectively. Therefore, the laser repair is an efficacious as conventional microsuture repair. More importantly, laser with solder is significantly better than either the conventional method or laser alone.


1-[omega-(4-arylpiperazin-1-yl)alkyl]-3-diphenylmethylene-2,5- pyrrolidinediones as 5-HT1A receptor ligands: study of the steric requirements of the terminal amide fragment on 5-HT1A affinity/selectivity.
In the present paper, we report the synthesis and the binding profile on 5-HT1A, alpha 1 and D2 receptors of a new series of imide-arylpiperazines 3. The study of the length of the alkyl chain and the imide substructure allows us to suggest some important differences between the no-pharmacophoric sites of both 5-HT1A and alpha 1-adrenergic receptors, which could be of great importance in order to design new selective ligands.


Molecular mechanisms of cell adhesion in normal and transformed cells.
Alterations in the adhesive mechanisms of cancer cells are likely to play an important role in determining the invasive or metastatic potential of these cells. An understanding of these alterations at the molecular level is now within reach, due to recent progress in the identification and characterization of several cell adhesion molecules (CAMs). Two of these molecules, the neural cell adhesion molecule N-CAM and the liver cell adhesion molecule L-CAM, are expressed on a variety of cell types from early embryos and throughout adult life, and appear to play several important roles in early inductive events, formation of specific intercellular connections, and maintenance of adult tissues. Two other molecules, the neuron-glia adhesion molecule Ng-CAM and a molecule involved in the specific adhesion of lymphocytes, appear to be more restricted in their developmental expression and function. The molecular characterization of N-CAM made possible for the first time an examination of the effects of transformation on the expression of a defined cell adhesion molecule. In both established cell lines from rat cerebellum and embryonic chick neuroepithelial cells, transformation by Rous sarcoma virus caused a large reduction in expression of N-CAM. In both cases, the N-CAM-mediated adhesion was correspondingly reduced. The neuroepithelial cells also became more highly motile after transformation. The decrease in N-CAM coupled with this increase in cell motility may significantly enhance the invasiveness of these cells. Other surface antigens have also been identified that may be involved in essential steps of invasion and metastasis. Such studies represent the initial step toward a detailed understanding of the role of CAMs in the various steps of metastasis. The accessibility of CAMs on tumor cell surfaces, and the availability of specific antibodies to these components suggests that reagents may become available in the near future that will offer new opportunities for preventing the formation of metastases.


The pair of arginine codons AGA AGG close to the initiation codon of the lambda int gene inhibits cell growth and protein synthesis by accumulating peptidyl-tRNAArg4.
To analyse the mechanism by which rare codons near the initiation codon inhibit cell growth and protein synthesis, we used the bacteriophage lambda int gene or early codon substitution derivatives. The lambda int gene has a high frequency of rare ATA, AGA and AGG codons; two of them (AGA AGG) located at positions 3 and 4 of the int open reading frame (ORF). Escherichia coli pth (rap) cells, which are defective in peptidyl-tRNA hydrolase (Pth) activity, are more susceptible to the inhibitory effects of int expression as compared with wild-type cells. Cell growth and Int protein synthesis were enhanced by overexpression of Pth and tRNAArg4 cognate to AGG and AGA but not of tRNAIle2a specific for ATA. The increase of Int protein synthesis also takes place when the rare arginine codons AGA and AGG at positions 3 and 4 are changed to common arginine CGT or lysine AAA codons but not to rare isoleucine ATA codons. In addition, overexpression of int in Pth defective cells provokes accumulation of peptidyl-tRNAArg4 in the soluble fraction. Therefore, cell growth and Int synthesis inhibition may be due to ribosome stalling and premature release of peptidyl-tRNAArg4 from the ribosome at the rare arginine codons of the first tandem, which leads to cell starvation for the specific tRNA.


Development of an efficient two-element transposon tagging system in Arabidopsis thaliana.
Modified Ac and Ds elements, in combination with dominant markers (to facilitate monitoring of excision, reinsertion and segregation of the elements) were introduced into Arabidopsis thaliana ecotype Landsberg erecta. The frequencies of somatic and germinal transactivation of the Ds elements were monitored using a streptomycin resistance assay. Transactivation was significantly higher from a stable Ac (sAc) carrying a 537 bp deletion of the CpG-rich 5' untranslated leader of the transposase mRNA than from a wild-type sAc. However, substitution of the central 1.77 kb of the transposase open reading frame (ORF) with a hygromycin resistance marker did not alter the excision frequency of a Ds element. beta-Glucuronidase (GUS) or iaaH markers were linked to the transposase source to allow the identification of plants in which the transposase source had segregated away from the transposed Ds element, eliminating the possibility of somatic or germinal re-activation. Segregation of the excision marker, Ds and sAc was monitored in the progeny of plants showing germinal excision of Ds. 29% of the plants inheriting the excision marker carried a transposed Ds element.


Histological examination of tooth-derived biomaterials obtained from different devices.
The aim of the present study was to investigate the histological differences between samples processed by different devices and to confirm safe clinical application of different dentin matrix obtained from three devices: BonMaker, Tooth Transformer, and Smart Dentin Grinder in regeneration of maxillary defects. The study involved 39 patients with two-wall or three-wall defects who underwent bone augmentation procedures in the maxilla using dentin matrix grafts from the BonMaker, Tooth Transformer, and Smart Dentin Grinder devices. Histological examination was conducted on samples obtained from patients who received each device. In this article, histological samples have been selected and are presented. In all patients, bone defects were successfully augmented with ground dentin matrix. The histological examination revealed no inflammation and a good connection between the bone and dentin matrix and clinically all patients were qualified for implant placement. After comparing the BonMaker, Tooth Transformer, and Smart Dentin Grinder devices in our practice, we concluded that all these systems have the potential for obtaining regenerative material from the patient's teeth.


Circulating immune cells and immune complexes in peripheral blood of healthy and of bovine leukemia virus-infected cows and lymphosarcomatous calves.
The peripheral blood (lymphocytes and immune complexes (IC) from 20 healthy cows, 5 healthy calves, 10 bovine leukemia virus-infected cows and 4 lymphosarcomatous calves was investigated using 4 different immunological techniques. A highly significant increase in the percentage of surface immunoglobulin (SIg)-bearing peripheral blood lymphocytes of persistent lymphocytosis-cows could be demonstrated while the percentage was decreased in the lymphosarcomatous calves. Percentages of spontaneous sheep red blood cells(SRBC)-rosettes (E-rosettes) were not elevated. Antibodies to bovine leukemia virus-antigen were detected in the sera (immuno-diffusion test) of all the leukotic cows but not of the lymphosarcomatous calves. Although there seems to be an increased level of IC in the advanced stage, as compared to the beginning of the disease, there was no statistically significant difference in comparison with the control individuals. In the lymphosarcomatous calves as well as in the leukemic cows there was no statistical difference in the IC values between diseased animals and controls.


Appraising the Methodological Quality of Sports Injury Video Analysis Studies: The QA-SIVAS Scale.
Video analysis (VA) is commonly used in the assessment of sports injuries and has received considerable research interest. Until now, no tool has been available for the assessment of study quality. Therefore, the objective of this study was to develop and evaluate a valid instrument that reliably assesses the methodological quality of VA studies. The Quality Appraisal for Sports Injury Video Analysis Studies (QA-SIVAS) scale was developed using a modified Delphi approach including expert consensus and pilot testing. Reliability was examined through intraclass correlation coefficient (ICC3,1) and free-marginal kappa statistics by three independent raters. Construct validity was investigated by comparing QA-SIVAS with expert ratings by using Kendall's tau analysis. Rating time was studied by applying the scale to 21 studies and computing the mean time for rating per study article. The QA-SIVAS scale consists of an 18-item checklist addressing the study design, data source, conduct, report, and discussion of VA studies in sports injury research. Inter- and intra-rater reliability were excellent with ICCs > 0.97. Expert ratings revealed a high construct validity (0.71; p < 0.001). Mean rating time was 10 ± 2 min per article. QA-SIVAS is a reliable and valid instrument that can be easily applied to sports injury research. Future studies in the field of VA should adhere to standardized methodological criteria and strict quality guidelines.


The dialysis of Ochratoxin A (OTA).
Standard dialysis did not result in a decrease of the OTA level in the blood serum of patients regularly treated by dialysis. Therefore, we examined the effect of dialysis on both OTA bound to the blood plasma proteins and free OTA. We carried out an in vivo experiment to determine OTA levels in the serum of patients in the terminal stage of chronic renal insufficiency (CHRI) before and after dialysis and also in the dialysate in which we did not find OTA. OTA bound to blood plasma proteins did not penetrate the dialysis membrane. In contrast, free OTA during an in vitro experiment with the identical dialyzer (as during the in vivo experiment), easily penetrated the same dialysis membrane.


Shift of temporal responsivity curve of pattern reversal visually evoked potentials to lower frequencies in patients after recovery from optic neuritis.
To investigate the responsivity of the visual system to pattern reversal stimuli of different reversal rates in optic neuritis patients after a full recovery of visual acuity. Thirty eyes with optic neuritis and 30 eyes of age-matched normal controls were studied. Steady-state pattern reversal visually evoked potentials (P-VEPs) were recorded using reversal rates of 2, 10, 20 and 30 Hz. The relationship between the amplitudes of the P-VEPs and reversal rate was analysed. The temporal responsivity curves of the two groups were compared. The means ± standard deviations (SDs) of the P-VEP amplitudes in the normal controls were 7.08 ± 2.97, 8.60 ± 2.37, 4.69 ± 1.99 and 2.11 ± 1.24 μV at reversal rates of 2, 10, 20 and 30 Hz, respectively. The comparable amplitudes from the recovered optic neuritis patients were 8.01 ± 2.45, 6.57 ± 2.54, 2.73 ± 1.76 and 0.94 ± 1.27 μV. The mean amplitude of the P-VEPs elicited at a reversal rate of 2 Hz was not significantly different from that of normal controls. However, the amplitudes of the P-VEPs at reversal rates of 10, 20 and 30 Hz were significantly smaller in the recovered optic neuritis patients than in the controls. In addition, the average maximum amplitude of the P-VEPs was obtained at 10 Hz in normal subjects and at 2 Hz in the recovered optic neuritis patients. These results indicate that the peak of the temporal tuning curve of the P-VEP shifts to lower frequencies in recovered optic neuritis eyes, and that the reduced amplitudes at higher frequencies seem to be characteristic of the visual system of patients with recovered optic neuritis.


Cultural recycling of cortical maps.
Part of human cortex is specialized for cultural domains such as reading and arithmetic, whose invention is too recent to have influenced the evolution of our species. Representations of letter strings and of numbers occupy reproducible locations within large-scale macromaps, respectively in the left occipito-temporal and bilateral intraparietal cortex. Furthermore, recent fMRI studies reveal a systematic architecture within these areas. To explain this paradoxical cerebral invariance of cultural maps, we propose a neuronal recycling hypothesis, according to which cultural inventions invade evolutionarily older brain circuits and inherit many of their structural constraints.


[Role of licking and concomitant changes in the excitability of nerve centers in the elaboration of gustatory information in rats].
The mechanism of nervous control of licking was studied in the frame work of the electrophysiological analysis of conditioned taste aversion. The licking rhythm is so stable that the rats are unable to slow it down by 20 percent. If the solution which was previously used for establishing the conditioned taste aversion, appears in the drinking spout, the rat stops drinking after one or two licks. Analysis of temporal relationships between afferent and efferent impulse activity of licking shows that the comparison of gustatory signals with memory traces and the corresponding decision occurs within 80 to 120 ms after lick onset. Electrical stimulation of the hypothalamic centres through implanted electrodes has shown that the amplitude of evoked responses and the impairment of licking increases, in proportion to the delay between lick onset and stimulus application. Isolated discharges of epileptic foci in the frontal cortex and the hypothalamus cause an omission of one or several licks, without interfering with the activity of the licking generator.


The arterial anatomy of the human carpus. Part I: The extraosseous vascularity.
The vascular anatomy of the wrist was studied in 25 fresh cadaver limbs by injection and chemical debridement techniques. The extraosseous arterial pattern was formed by an anastomotic network of three dorsal and three palmar arches connected longitudinally at their medial and lateral borders by the ulnar and radial arteries. Additional longitudinal anastomoses were provided by the dorsal and palmar branches of the anterior interosseous artery. The most distal of the palmar arches was the deep palmar arch, formed by the anastomosis of the radial artery and the deep palmar branch of the ulnar artery. Two recurrent arteries, one radial and one ulnar, were consistently seen arising from the concavity of this arch, traversing proximally to frequently anastomose with the terminal branches of the anterior division of the anterior interosseous artery. This anastomosis provided the major collateral circulation about the wrist.


Qualitative investigation of factors contributing to effective nutrition education for Navajo families.
Obesity rates in American Indian and Alaskan Native children are a major health threat, yet effective ways to address this remain elusive. Building on an earlier dietary assessment of Navajo Head Start families which indicated a gap in parental nutrition awareness despite a strong program emphasis, the aim of this project was to identify culturally relevant nutrition education strategies for Navajo parents and educators of young children. Eight focus group interviews were conducted with 41 parents and early childhood education paraprofessionals to identify contributors to both healthful and unhealthy food ways of Navajo preschoolers. were presented in two community venues to verify the themes and discuss implications. Results Barriers to healthful eating included availability/cost, parenting/control, preferences/habits, time pressures, and knowledge/education. Enablers to healthful eating included the categories of schools/education, and support/modeling. Reactions to these findings during community forums suggested (1) the need for stronger parenting and parental control over the food environment; (2) community-level action to address these barriers; and (3) the need for knowledge and culturally relevant educational strategies for caregivers and children. Implications for interventions include building upon existing community resources to enhance culturally relevant and respectful parental, family, and community support for affordable and acceptable food experiences and choices for young children and their families.


Destruction of aflatoxins B1 and G 1 in bread making.
The effect of processing steps as well preservatives used in French bread making namely propionic acid and/or potassium sorbate (0.2%) on the destruction of aflatoxins B1 and G1 was studied.Mixing and baking processes showed marked destruction of aflatoxins B1 and G1; being 71.2% and 52.5% for aflatoxin B1 after mixing and baking steps, while reaching 73.9% and 54.5% for aflatoxin G1. Fermentation step caused additional 15.3% and 15.0% destruction of aflatoxins B1 and G1.On the other hand, aflatoxin B1 destruction was 79.2% and 50.7% when propionic acid was used and 75.3 and 56.7% in the presence of potassium sorbate and after mixing and baking steps respectively.Concerning aflatoxins G1 it was found that mixing and baking steps showed destruction of 81.9% and 53.4% in the presence of propionic acid and 75.1 and 49.4% in the presence of potassium sorbate in this respective order.Generally, it can be concluded that using propionic acid as preservative appeared to be more effective on the destruction of aflatoxins B1 and G1 than potassium sorbate in French bread making.


Are there differences in the characteristics of patients who respond to gemcitabine plus cisplatin chemotherapy and those who respond to pembrolizumab therapy for metastatic urothelial carcinoma? Multicenter retrospective study.
To evaluate factors to predict overall survival of metastatic urothelial carcinoma patients treated with gemcitabine plus cisplatin chemotherapy or pembrolizumab therapy. We retrospectively evaluated two metastatic urothelial carcinoma cohorts treated with (i) gemcitabine plus cisplatin or (ii) pembrolizumab. The gemcitabine plus cisplatin cohort was treated from December 2005 through December 2014 while the pembrolizumab cohort was treated from January 2018 through December 2020. Using multivariate analyses, we evaluated the risk factors for overall survival in each cohort and compared them. None of the gemcitabine plus cisplatin cohort patients were treated with pembrolizumab. All patients in the pembrolizumab cohort were treated with prior platinum-based chemotherapy. There were 184 patients in the gemcitabine plus cisplatin cohort and 91 in the pembrolizumab cohort. The mean follow-up periods were 714 and 284 days, respectively. In multivariate analysis, the risk factors for overall survival in the gemcitabine plus cisplatin cohort were liver metastasis, worse Eastern Cooperative Oncology Group performance status (1 or more), no primary site resection, and a high prognostic index (1 or more). In the pembrolizumab cohort, liver metastasis, bone metastasis, and worse Eastern Cooperative Oncology Group-performance status (1 or more), and high prognostic index (1 or more) were the risk factors for overall survival. In the pembrolizumab cohort, patients with a complete response or partial response during prior platinum-based chemotherapy had better overall survival with the following pembrolizumab treatment than those with stable or progressive disease (P = 0.004). Considering the similarity of these risk factors in two sequential treatments, it may be possible to predict the response to pembrolizumab according to the response to prior chemotherapy.


The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan.
The unique anatomical features of turtles have raised unanswered questions about the origin of their unique body plan. We generated and analyzed draft genomes of the soft-shell turtle (Pelodiscus sinensis) and the green sea turtle (Chelonia mydas); our results indicated the close relationship of the turtles to the bird-crocodilian lineage, from which they split ∼267.9-248.3 million years ago (Upper Permian to Triassic). We also found extensive expansion of olfactory receptor genes in these turtles. Embryonic gene expression analysis identified an hourglass-like divergence of turtle and chicken embryogenesis, with maximal conservation around the vertebrate phylotypic period, rather than at later stages that show the amniote-common pattern. Wnt5a expression was found in the growth zone of the dorsal shell, supporting the possible co-option of limb-associated Wnt signaling in the acquisition of this turtle-specific novelty. Our results suggest that turtle evolution was accompanied by an unexpectedly conservative vertebrate phylotypic period, followed by turtle-specific repatterning of development to yield the novel structure of the shell.


Apatinib potentiates irradiation effect via suppressing PI3K/AKT signaling pathway in hepatocellular carcinoma.
Limited effective intervention for advanced hepatocellular carcinoma (HCC) is available. This study aimed to investigate the potential clinical utility of apatinib, a highly selective inhibitor of the vascular endothelial growth factor receptor-2 (VEGFR2) tyrosine kinase, as a radiosensitizer in the treatment of HCC. Four human HCC cell lines SMMC-7721, MHCC-97H, HCCLM3 and Hep-3B were treated with apatinib, irradiation or combination treatment. Colony formation assay, flow cytometry and nuclear γ-H2AX foci immunofluorescence staining were performed to evaluate the efficacy of combination treatment. RNA sequencing was conducted to explore the potential mechanism. The impact of combination treatment on tumor growth was assessed by xenograft mice models. Colony formation assay revealed that apatinib enhanced the radiosensitivity of HCC cell lines. Apatinib suppressed repair of radiation-induced DNA double-strand breaks. Flow cytometry analysis showed that apatinib increased radiation-induced apoptosis. Apatinib radiosensitized HCC via suppression of radiation-induced PI3K/AKT pathway. Moreover, an in vivo study indicated apatinib combined with irradiation significantly decreased xenograft tumor growth. Our results indicate that apatinib has therapeutic potential as a radiosensitizer in HCC, and PI3K/AKT signaling pathway plays a critical role in mediating radiosensitization of apatinib.


Responsive microsecond-lifetime photoluminescent probes for analysis of protein kinases and their inhibitors.
Responsive ARC-Lum probes were used for measurement of the concentration of active protein kinases (PKs) and determination of affinity of inhibitors of PKs. ARC-Lum probes incorporate thiophene or a selenophene heterocycle and a fluorophore conjugated to the lysine residue in the peptide fragment. In the complex with a PK, ARC-Lum probes emit long-lifetime (microsecond-scale) luminescence at the emission wavelengths of the fluorescent label if the complex is illuminated at the excitation wavelength of the thiophene- or selenophene-containing phosphorescence donors. Bisubstrate ARC-Lum probes bind with sub-nanomolar affinity with several PKs of the AGC group. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).


Sucralfate versus cimetidine in duodenal ulcer--factors affecting healing and relapse.
An understanding of the factors affecting duodenal ulcer healing by different pharmacological agents should give some insight into the underlying pathophysiology of healing.


Cerebral glucose and energy metabolism, cerebral oxygen consumption, and blood flow in arterial hypoxaemia.
The influence of moderately reduced arterial oxygen tension (aPO2 of about 45 Torr) on the metabolism and the blood flow of the brain was tested in 20 anaesthetized, artificially ventilated normotensive, normocapnic beagle dogs. It is demonstrated that the decrease in systemic oxygen delivery to the brain is countered by an appropriate increase in flow (CBF being 60.3 ml/100 g min at normoxia and 84.5 mg/100 g min in hypoxaemia) which maintained the cerebral oxygen consumption unchanged (CMRO2 3.80 versus 3.32 ml/100 g min). The cortical tissue content of energy-rich phosphates such as ATP, ADP, AMP, and phosphocreatine was also found to be unaltered. Neuropathological examinations excluded any hypoxic cell damage. This reactive vasodilatory reaction of the cerebral vessels is apparently a sensitive regulatory process which protects the brain against marked oxygen lack. However, a normal carbohydrate metabolism is not restored by this cerebrovascular mechanism. For, significantly increased CMRlactate (0.32 versus 1.46 ml/100 g min) indicated raised cerebral glycolysis, and the tissue metabolites of glucose suggested an increased glycolytic flux in the brain. It is concluded that in moderate arterial hypoxaemia, which is not uncommon in clinical practice, cerebral blood flow plays an effective homeostatic role in preventing a disturbance of the energy metabolism of the brain.


Catalyst-Free Dynamic Networks for Recyclable, Self-Healing Solid Polymer Electrolytes.
Polymer networks with dynamic covalent cross-links act as solids but can flow at high temperatures. They have been widely explored as reprocessable and self-healing materials, but their use as solid electrolytes is limited. Here we report poly(ethylene oxide)-based networks with varying amounts of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) to understand the impact of a salt on the ion transport and network dynamics. We observed that the conductivity of our dynamic networks reached a maximum of 3.5 × 10-4 S/cm at an optimal LiTFSI concentration. Rheological measurements showed that the amount of LiTFSI significantly affects the mechanical properties, as the shear modulus varies between 1 and 10 MPa and the stress relaxation by 2 orders of magnitude. Additionally, we found that these networks can efficiently dissolve back to pure monomers and heal to recover their conductivity after damage, showing the potential of dynamic networks as sustainable solid electrolytes.


Plant mediated magnetic nano composite as promising scavenger's radionuclides for the efficient remediation in aqueous medium.
The present investigation demonstrates the environment friendly plant mediated green synthesis of magnetic bio composite nanoparticles by the chemical co-precipitation of magnetite phase from aqueous medium. Water contaminated with uranium is one of the most serious environmental issues. This study aims to overcome this issue by effectively adsorbing uranium from water at a pH range of 7. Several studies have recently been published throughout the world that demonstrates uranium adsorption from water, although they have all been conducted in acidic media with pH less than 6. This work addressed that issue, and maximal adsorption was achieved at pH 7 using a synthetic magnetic bio composites sorbent derived from tree bark (Amla). The magnetic bio composites were characterized by FTIR, XRD, FE-SEM, and EDX. The computations of the XRD data indicated that magnetic bio composites have nano composite with an average diameter of around 12.1 nm. This has an adsorption capacity of 121.95 mg g-1. The correlation regression (r2) coefficients obtained for the various isotherm models indicate that the sorption process conformed to the Langmuir and Temkin models. Thermodynamic studies revealed that the sorption process onto plant mediated magnetic bio material is endothermic and spontaneous, which is significant for reuse and recovery of adsorbed material. A desorption test was also performed to regenerate the material by removing the adsorbed uranium (VI) by HCL with an 84.3% success rate.


Cell death induced in lymphocytes expressing the elastin-laminin receptor by excess agonists: necrosis and apoptosis.
This manuscript summarizes our experiments carried out during the last years on the expression of the elastin-laminin receptor on human activated lymphocytes and cell death triggered by the activation of this receptor by its agonists, elastin peptides. We could distinguish two types of cell reactions, depending on the elastin peptide concentration added to the cell culture media of lymphocytes. At low concentrations (1-10 micrograms/mL, 1.3-13 x 10(-8) M) of kappa-elastin, there was a stimulation of cell proliferation, elastase biosynthesis and release. As the concentration of kappa-elastin was increased in the culture medium up to 100 micrograms/mL, lymphocyte proliferation and elastase production decreased and the proportion of dead cells increased. Cell death was shown to be due to both apoptotic and non-apoptotic mechanisms. Apoptotic cell death increased with agonist concentration and reached approximately 60% of the lymphocyte population at mg/mL elastin peptide concentrations. This observation was confirmed by the concomitant use of several different methodologies, such as flow cytometry and electron microscopy. The precise nature of the non-apoptotic cell death remains to be established.


Inhibition insights of hydrothermal liquid digestate in anaerobic digestion: Impact on organics conversion and inhibitor degradation.
Hydrothermal liquid digestate has been widely accepted as a substrate in anaerobic digestion (AD) for energy recovery. However, the potential negative impacts of hydrothermal liquid digestate on AD remain unclear. In this study, the organic biodegradability of hydrothermal liquid digestate produced from hydrothermal treatment (HTT) at different temperatures was analyzed, and the formation and degradation process of potential inhibitory substances were discussed. Results demonstrated that the AD lag phase of hydrothermal liquid digestate increased from 3 days at raw liquid digestate to 5-21 days. When the HTT temperature reached 220 °C, the methane yield decreased by 48%, and more than 71% of the organics in the hydrothermal liquid digestate were not utilized by AD. Biorefractory substances, such as fulvic and humic acids, accumulate in the hydrothermal liquid digestate. Potential inhibitory substances from Maillard reactions mainly affect the methanogenesis of AD. Most inhibitory substances were degraded within 7-22 days, with the degradation rate following the order of pyrroles > pyrazines > ketones > imidazoles > indoles. The AD community structure and methane conversion were partially re-established after most inhibitory substances were degraded. This study provides valuable information on eliminating the potential negative effects of hydrothermal liquid digestate on AD.


A large-deformation, finite-element study of chondrodiatasis in the canine distal femoral epiphyseal plate.
A large-deformation, finite-element analysis was conducted to model stress fields around the developing growth plate as a first approach to comprehend the clinical application of traction for limb lengthening procedures. The model chosen was a cross section through the distal femoral growth plate of a 14-week-old dog. The chosen section passed through two of the conformational bends (mammillary processes) formed by the natural convolutions of the physis. Three different loading conditions were applied to the distal femoral epiphyseal model. The model also examined the effects of different values of Young's modulus of the growth-plate cartilage. The cortical bone in all cases, experienced the highest stresses. In the growth plate, the highest principal stresses occurred where the physis intersects cortical bone. There were localized stresses that were higher than those that caused fracture in a rabbit model [Guse et al., J. Orthop. Res. 7, 667-673 (1989)]. Results also indicated the following: a small tilt of 0.1 degree in loading application increases the maximum principal stresses and the von Mises stresses in certain regions of the growth plate by about 8%; the shearing stresses in the growth plate are sensitive to Young's modulus of the growth plate; and traction pins that do not grip the cancellous bone in the epiphysis will increase the regions of high principal stress in the growth plate.


The Greatness of Glass: Importance of Blood Smear Evaluation.
An automated complete blood count (CBC), although quick and relatively effortless, is limited in its diagnostic usefulness because results can be affected by misclassification of cellular and noncellular components and abnormal cellular morphology. Microscopic evaluation of a blood smear allows for quality control of automated CBC results as well as identification of cellular morphology that cannot be detected by automated hematology analyzers, and its importance should not be overlooked, especially in clinically ill patients.


A Preoperative Assessment of Significant Coronary Stenosis Based on a Semiquantitative Analysis of Coronary Artery Calcification on Noncontrast Computed Tomography in Aortic Stenosis Patients Undergoing Aortic Valve Replacement.
Invasive coronary angiography (ICA) is the recommended assessment for coronary artery disease in patients undergoing elective aortic valve replacement (AVR). Noncontrast computed tomography (CT) is useful for evaluating lung lesions and calcifications at the cannulation site of the ascending aorta. The purpose of this study was to evaluate the role of noncontrast CT in the visual assessment of coronary artery calcification (CAC) in patients undergoing AVR. We retrospectively identified patients with significant aortic stenosis (AS) who were referred for AVR between January 2006 and December 2013. Among these, we included 386 patients (53.6% males, 69.2 ± 8.4 years) who underwent both noncontrast CT and ICA. Significant coronary artery stenosis (CAS) in the ICA was defined as luminal stenosis ≥70%. The 4 main coronary arteries were visually assessed on noncontrast CT and were scored based on the Weston score as follows: 0, no visually detected calcium; 1, a single high-density pixel detected; 3, calcium was dense enough to create a blooming artifact; and 2, calcium in between 1 and 3. Four groups were reclassified by the sum of the Weston scores from each vessel, as follows: noncalcification (0); mild calcification (1-4); moderate calcification (5-8); and severe calcification (9-12). Receiver-operating characteristic (ROC) analysis was generated to identify the cutoff Weston score values for predicting significant CAS. Diagnostic estimates were calculated based on these cutoffs. In the ICA analysis, 62 of the 386 patients (16.1%) had significant CAS. All patients were divided into 4 groups. The noncalcification group had 97 subjects (Weston score 0), the mild degree group had 100 (2.6 ± 1.0), the moderate calcification group had 114 (6.6 ± 1.1), and the severe calcification group had 75 (10.7 ± 1.1). The prevalence of significant CAS in the noncalcification, mild, moderate, and severe groups was 1% (1/97), 5% (5/100), 24% (27/114), and 39% (29/75), respectively. The group with CAS had significantly more CAC than the group without CAS (8.37 ± 2.93 vs 4.01 ± 3.75, P < 0.001). The cutoff value (by Weston score) for predicting significant CAS is ≥5 (sensitivity 90.3%, specificity 59.0%, positive predictive value 29.6%, and negative predictive value 97%). The degree of CAC detected on noncontrast CT can help to predict significant CAS in AS patients who are referred for AVR. For the clinicians, the visual assessment of CAC on noncontrast CT was easy and useful for estimating CAS. Therefore, ICA should be recommended to selective patients based on patients' CAC and Weston scores during the preoperative evaluation for elective AVR.


First 2-DE approach towards characterising the proteome and immunome of Besnoitia besnoiti in the tachyzoite stage.
Bovine besnoitiosis is caused by the cyst-forming apicomplexan parasite Besnoitia besnoiti. It is considered to be a re-emergent disease in Europe and is also present in Africa and Asia. Due to the chronic and debilitating course of the disease, bovine besnoitiosis is responsible for severe economic losses. However, many aspects of the disease and parasite biology remain unknown. Proteomics studies could help to investigate relevant biological processes as well as host immune response associated with parasite infection. Both the proteome and immunome of the tachyzoite stage of B. besnoiti of the Bb-Spain1 isolate are described herein for the first time. Tachyzoite protein extracts were first separated by 2-DE SDS-PAGE using pH 3-10 NL IPG strips for Coomassie Brilliant Blue-stained gels and immunoblots. Eighty-five out of 265 spots visualised on Coomassie-stained gels were immunogenic when pooled serum from naturally infected cattle was used, and the distribution of immunogenic spots correlated with the 1-DE IDA pattern. Because most spots were found in the acidic range of the pH gradient, pH 3-6 L IPG strips were used next, and 58 out of 123 visualised spots proved to be immunogenic. Twenty-seven spots were identified by MALDI TOF/TOF to be 20 different proteins due to the presence of protein species. All proteins identified corresponded to highly conserved proteins among eukaryotes. Six proteins identified are related to energy metabolism, 3 are heat shock proteins, 4 proteins are related to host cell invasion processes, and 2 proteins are involved in cell redox homeostasis. A tryptophanyl tRNA synthetase, a putative gbp1p, nucleoredoxin, a putative receptor for activated C kinase, and a nuclear movement domain-containing protein were also identified. Among these proteins, fructose-1,6-bisphosphate aldolase, lactate dehydrogenase, pyruvate kinase, enolase, HSP60, HSP70, HSP90, actin and profilin proved to be immunogenic, and 5 were cross-reactive antigens between B. besnoiti and N. caninum. This first proteomic approach carried out in B. besnoiti should be followed by other studies to identify more specific parasite proteins.


Breviscapine alleviates NASH by inhibiting TGF-β-activated kinase 1-dependent signaling.
NAFLD is a key component of metabolic syndrome, ranging from nonalcoholic fatty liver to NASH, and is now becoming the leading cause of cirrhosis and HCC worldwide. However, due to the complex and unclear pathophysiological mechanism, there are no specific approved agents for treating NASH. Breviscapine, a natural flavonoid prescription drug isolated from the traditional Chinese herb Erigeron breviscapus, exhibits a wide range of pharmacological properties, including effects on metabolism. However, the anti-NASH efficacy and mechanisms of breviscapine have not yet been characterized. We evaluated the effects of breviscapine on the development of hepatic steatosis, inflammation, and fibrosis in vivo and in vitro under metabolic stress. Breviscapine treatment significantly reduced lipid accumulation, inflammatory cell infiltration, liver injury, and fibrosis in mice fed a high-fat diet, a high-fat/high-cholesterol diet, or a methionine- and choline-deficient diet. In addition, breviscapine attenuated lipid accumulation, inflammation, and lipotoxicity in hepatocytes undergoing metabolic stress. RNA-sequencing and multiomics analyses further indicated that the key mechanism linking the anti-NASH effects of breviscapine was inhibition of TGF-β-activated kinase 1 (TAK1) phosphorylation and the subsequent mitogen-activated protein kinase signaling cascade. Treatment with the TAK1 inhibitor 5Z-7-oxozeaenol abrogated breviscapine-mediated hepatoprotection under metabolic stress. Molecular docking illustrated that breviscapine directly bound to TAK1. Breviscapine prevents metabolic stress-induced NASH progression through direct inhibition of TAK1 signaling. Breviscapine might be a therapeutic candidate for the treatment of NASH.


Peroxisome proliferator-activated receptor alpha agonists regulate cholesterol ester transfer protein.
Peroxisome proliferator-activated receptor alpha (PPARalpha) belongs to the nuclear receptor superfamily that regulates multiple target genes involved in lipid metabolism. Cholesterol ester transfer protein (CETP) is a secreted glycoprotein that modifies high-density lipoprotein (HDL) particles. In humans, plasma CETP activity is inversely correlated with HDL cholesterol levels. We report here that PPARalpha agonists increase CETP mRNA, protein and accordingly its activity. In a human CETP transgenic animal model harboring the natural flanking regions (Jiang et al. in J Clin Investigat 90:1290-1295, 1992), both fenofibrate and a specific synthetic PPARalpha agonist LY970 elevated human CETP mRNA in liver, serum protein and CETP activity. In hamsters, the endogenous liver CETP mRNA level and the serum CETP activity were dose-dependently upregulated by fenofibrate. In addition Wy14643, a PPARalpha agonist, also significantly elevated CETP mRNA and activity. In a carcinoma cell line of hepatic origin, HepG2 cells, overexpression of PPARalpha resulted in increased CETP mRNA and agonist treatment further elevated CETP mRNA levels. We conclude that PPARalpha agonists upregulate CETP expression and activity and may play an important role in PPARalpha (agonist mediated HDL cholesterol homeostasis in humans.


Parturient perineal distensibility tolerance assessed by EPI-NO: an observational study.
To determine how parturient women tolerate the use of a perineal distensibility assessment technique using the EPI-NO device. An observational study with a total of 227 full-term parturient women was performed. During the evaluation with EPI-NO, parturient patients were asked about their sensation of discomfort. The degree of discomfort was measured using the Visual Analogue Scale, with a score from zero to 10. The Mann-Whitney test was applied to assess perineal distensibility measured by EPI-NO and the degree of discomfort caused by the test according to parity. The relation between perineal distensibility and discomfort was analyzed by using the Spearman correlation test (r). The test with EPI-NO caused only slight discomfort (mean Visual Analogue Scale of 3.8), and primiparous women reported significantly greater discomfort (mean Visual Analogue Scale of 4.5) than did multiparous (mean Visual Analogue Scale=3.1), with p<0.001 women. A negative correlation was observed, in other words, the greater the perineal distensibility on the EPI-NO, the lower the pain reported by the patients (r=-0.424; p<0.001). The assessment of perineal distensibility with EPI-NO was well tolerated by the parturient women.


Gas-phase and particulate products from the atmospheric degradation of an isoxazole fungicide.
The isoxazole structure is present in several pesticides. However, there is a lack of information about its degradation products after the release to the atmosphere. The main atmospheric reactions of hymexazol (5-methylisoxazol-3-ol), selected as representative model, were investigated at a large outdoor simulation chamber. The predominant products of atmospheric degradations were gaseous nitrogen derivates (nitric acid, nitrogen dioxide, nitrogen oxide, nitrous acid, and peroxyacetylnitrate), ozone, and small oxygenated compounds (formic acid, formaldehyde, and methylglyoxal). The aerosol yields were lower than 5%, and an OH rate-dependence was observed in the nucleation, particle growth, and size distribution. Also, the chemical composition of minor multi-oxygenated products was studied for OH-photo-oxidations. More than 20 products were detected in the gas or particulate phase. The most abundant were heterocyclic cleavage products with C4-chain and oxygenated moieties at positions 1 and 3, such as 3,4-dioxobutanoic acid, 3-oxobutanoic acid, and 3-oxobutanal. The suggested reaction pathway is the opening of heterocycle ring by the cleavage of N-O bond and C-N bond, releasing nitrogen oxides.


Localization of mLin-7 at nectin-based cell-cell junctions.
In C. elegans, lin-7 as well as lin-2/lin-10 is involved in the proper localization of the LET-23 receptor tyrosine kinase that regulates vulval induction. The mammalian homologue, mLin-7, forms a ternary complex with the mammalian homologues of LIN-2 and LIN-10 and localizes at cell-cell junctions in epithelial cells, but the mechanism of this localization of mLin-7 is unknown. Nectin is an immunoglobulin-like cell-cell adhesion molecule that is involved in organization of adherens and tight junctions in epithelial cells. Nectin is indirectly associated with the cadherin-catenin system and the actin cytoskeleton through afadin, an actin filament-binding protein. We showed here that mLin-7 localized at the nectin-based cell-cell junctions. This localization of mLin-7 required the interaction of nectin with afadin, but not the cadherin-catenin system or the actin cytoskeleton. mLin-7 did not directly interact with nectin or afadin. The results indicate that mLin-7 localizes at cell-cell junctions through the nectin-afadin system.


Interferon alfa-2c in chronic myelogenous leukemia (CML): hematologic, cytogenetic and molecular-genetic response of patients with chronic phase CML previously resistant to therapy with interferon gamma.
Alpha- and gamma-interferons have been shown to actively suppress hematopoiesis in patients in the chronic phase of chronic myelogenous leukemia in vitro and in vivo. Since both interferons act through different receptors on their hematopoietic target cells, they are expected to be capable of independently inhibiting abnormal blood cell development in patients with chronic myelogenous leukemia. We have utilized recombinant human interferon alfa-2c to treat 11 patients with Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase, who were resistant to previous interferon gamma therapy. Ten of the patients were evaluable for hematologic, cytogenetic and molecular-genetic response following interferon alfa-2c therapy for 6 to 30 months. In 5 patients, IFN alfa-2c treatment failed due to lack of hematologic response. A complete hematologic or partial hematologic response was achieved in the remaining 5 patients. Three of these experienced cytogenetic improvement with reappearence of 100% diploid hematopoietic cells and disappearence of c-abl/bcr rearrangement in one patient. In two patients interferon alfa-2c did not prevent transformation of the disease into an accelerated state or blast crisis, respectively. We conclude that recombinant human interferon alfa-2c may also control hematopoiesis in interferon-gamma resistant chronic myelogenous leukemia patients, although the long-term response will need to be elucidated in further studies.


Omnipresent Maxwell's demons orchestrate information management in living cells.
The development of synthetic biology calls for accurate understanding of the critical functions that allow construction and operation of a living cell. Besides coding for ubiquitous structures, minimal genomes encode a wealth of functions that dissipate energy in an unanticipated way. Analysis of these functions shows that they are meant to manage information under conditions when discrimination of substrates in a noisy background is preferred over a simple recognition process. We show here that many of these functions, including transporters and the ribosome construction machinery, behave as would behave a material implementation of the information-managing agent theorized by Maxwell almost 150 years ago and commonly known as Maxwell's demon (MxD). A core gene set encoding these functions belongs to the minimal genome required to allow the construction of an autonomous cell. These MxDs allow the cell to perform computations in an energy-efficient way that is vastly better than our contemporary computers.


[Does the concept for the prevention of chronic ischemic heart disease correspond to current ideas on etiology and pathogenesis of arteriosclerosis?].
A summarizing description of the essential relations between the existence of risk factors and the course of the morphologic changes in the arteriosclerosis in the intima is given. In this process the low density lipoproteins play an important role which together with further etiologic factors contribute to an increased permeability of the endothelium and to the stimulation of the proliferation and modulation of the smooth muscle cells, which are of central importance in the vascular reaction. Certain effects on the progression of the arteriosclerosis as well as a regression of adequate morphologic changes are to be expected from an elimination of risk factors, provided the necessary measures begin in the early stages of the arteriosclerosis, i. e. in the preatheromatous stage.


Lipogenesis in human adipose tissue in vitro: effect of fat cell size on some enzymatic activities.
The incorporation of [1-C14] palmitate into palmitoyl CoA and triglycerides by homogenates of human adipose tissue have been studied. Adipose tissue samples were taken from three sites varying in adipocytes size (omentum, subcutaneous abdominal wall, buttock). The donors were normal weight women of constant weight. A significant positive correlation was found between initial velocity of palmitoyl CoA synthetase (EC 184.108.40.206) and total [1-C14] palmitate incorporation into triglycerides on one hand and adipocyte cell size on the other hand : these relations with cell size were apparent both within and between individuals. The mechanism of this "size effect" which is unrelated to the higher protein content of larger cells, is still unexplained. Lipogenesis, like most of the metabolic activities of adipose tissue increases with enlarging cell size. Acceleration of a lipogenesis-lipolysis cycle could constitute an energy wasting system able to limit the volume of the adipocytes.


The ureter as a landmark for robotic sacrocolpopexy.
The objective of this study was to report on the location of the ureters in relation to the sacral promontory at the level of the pelvic brim. Female patients undergoing indicated computed tomographic (CT) urograms were selected for this study. Charts and images from a defined 3-year study period were reviewed. The GE Centricity software was used to evaluate multiplanar CT views and measure the distance from the bilateral ureters to the midpoint of the distal sacral promontory for each subject. Sixty-three women underwent CT urography during the study period. Of these, 38 met the criteria for inclusion. Among these, the left ureter was 35.9 ± 4.9 mm lateral to the midsacral promontory. The right ureter was 29.7 ± 6.2 mm lateral to the sacral promontory. On average, the sacral promontory is located 29.7 mm medial to the right ureter at the level of the pelvic brim. This represents a landmark that may prove clinically useful, along with other visual cues, in choosing the proper location for careful dissection toward the anterior longitudinal ligament during robotic sacrocolpopexy.


An examination of Intolerance of Uncertainty and contingency instruction on multiple indices during threat acquisition and extinction training.
Individuals who score high in self-reported Intolerance of Uncertainty (IU) tend to find uncertainty aversive. Prior research has demonstrated that under uncertainty individuals with high IU display difficulties in updating learned threat associations to safety associations. Importantly, recent research has shown that providing contingency instructions about threat and safety contingencies (i.e. reducing uncertainty) to individuals with high IU promotes the updating of learned threat associations to safety associations. Here we aimed to conceptually replicate IU and contingency instruction-based effects by conducting a secondary analysis of self-reported IU, ratings, skin conductance, and functional magnetic resonance imaging (fMRI) data recorded during uninstructed/instructed blocks of threat acquisition and threat extinction training (n = 48). Generally, no significant associations were observed between self-reported IU and differential responding to learned threat and safety cues for any measure during uninstructed/instructed blocks of threat acquisition and threat extinction training. There was some tentative evidence that higher IU was associated with greater ratings of unpleasantness and arousal to the safety cue after the experiment and greater skin conductance response to the safety cue during extinction generally. Potential explanations for these null effects and directions for future research are discussed.


Unilateral uterine artery embolization and Bakri tamponade balloon insertion in the treatment of acute puerperal uterine inversion: a case report.
Acute puerperal uterine inversion is rare but may cause massive postpartum blood loss due to uterine atony. Therefore, these patients must be diagnosed, and uterine replacement must be performed as soon as possible. However, in some cases, active bleeding due to uterine atony becomes uncontrollable, even though the uterine inversion itself is treated. In these cases, additional treatments, including surgical procedures, are needed. A 41-year-old Japanese woman, gravida 1, para 0, was hospitalized for labor induction at 40 weeks and 3 days of gestational age. She had a vacuum-assisted delivery after 3 days of oxytocin administration, but acute uterine inversion occurred. Although replacement of the inverted uterus was successful by manual repositioning and Bakri balloon tamponade insertion, massive postpartum hemorrhage caused by uterine atony became uncontrollable. In this situation, since disseminated intravascular coagulation had developed, we used uterine artery embolization to stop the bleeding. After detecting the pseudo-aneurysmal sac and tortuous vessels of the right uterine artery, transcatheter right-sided uterine artery embolization was performed. Thirteen days after uterine artery embolization, she was discharged with no complications. In cases of disseminated intravascular coagulation caused by massive postpartum bleeding, uterine artery embolization may often be selected. In our case, since we performed angiography to detect the main bleeding site, the hemorrhage could be stopped with unilateral uterine artery embolization alone, without hysterectomy.


The influence of hands-on laser training on usage of the CO2 laser.
A questionnaire was distributed to all participants in the Rochester General Hospital CO2 laser training workshops for surgeons (1982 to January 1985). The results of this study indicate that, while laser training is necessary prior to being able to use the laser, only a small fraction of trainees actually use the laser in their clinical practice. Surgeons who are using the laser do so in a minority of their cases. New incentives for laser usage must be investigated.


Adjusting for outcome misclassification: the importance of accounting for case-control sampling and other forms of outcome-related selection.
Special care must be taken when adjusting for outcome misclassification in case-control data. Basic adjustment formulas using either sensitivity and specificity or predictive values (as with external validation data) do not account for the fact that controls are sampled from a much larger pool of potential controls. A parallel problem arises in surveys and cohort studies in which participation or loss is outcome related. We review this problem and provide simple methods to adjust for outcome misclassification in case-control studies, and illustrate the methods in a case-control birth certificate study of cleft lip/palate and maternal cigarette smoking during pregnancy. Adjustment formulas for outcome misclassification that ignore case-control sampling can yield severely biased results. In the data we examined, the magnitude of error caused by not accounting for sampling is small when population sensitivity and specificity are high, but increases as (1) population sensitivity decreases, (2) population specificity decreases, and (3) the magnitude of the differentiality increases. Failing to account for case-control sampling can result in an odds ratio adjusted for outcome misclassification that is either too high or too low. One needs to account for outcome-related selection (such as case-control sampling) when adjusting for outcome misclassification using external information.


Thyroid dysfunction following external irradiation to the neck for Hodgkin's disease in childhood.
Thyroid function was studied in 32 patients who had received neck irradiation during childhood for Hodgkin's disease. All except one patient received a dose of 2500-3000 rad over a period of 19-25 days. In 12 patients lymphangiography was performed. Clinically all patients were considered euthyroid. One had a thyroid swelling which was cystic in nature. Five (16%) patients were biochemically hypothyroid, 17 (53%) were euthyroid with an elevated basal serum TSH concentration and a further seven (22%) were euthyroid with a normal basal serum TSH level but an augmented thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH). Only three (9%) patients had completely normal thyroid function tests. The basal serum TSH concentration and the peak serum TSH response to TRH were significantly greater in the patients who received neck irradiation and lymphangiography than in those who received neck irradiation alone. In addition the free thyroxine index decreased significantly as the time interval between treatment and study increased in the lymphangiography group. These data demonstrate that the normal thyroid gland is vulnerable to the damaging effects of external irradiation, and that the combination of neck irradiation and lymphangiography is more likely to result in thyroid dysfunction than is neck irradiation alone. Furthermore, in view of the deterioration in thyroid function with time, periodic clinical and biochemical assessment of thyroid function is clearly indicated.


Age-based efficacy and safety of nivolumab for recurrent or metastatic head and neck squamous cell carcinoma: A multicenter retrospective study.
This study retrospectively investigated the efficacy and safety of nivolumab for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) classified using age <65 years as the cutoff. Overall, 88 patients with R/M HNSCC treated with nivolumab were classified into the young group (<65 years; n = 39) and elderly group (≥65 years; n = 49). Efficacy was evaluated using overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR). Safety was evaluated considering immune-related adverse events (irAEs). The median OS was 9.7 and 8.6 months in the young and elderly groups, respectively. The 1-year OS rate was 42.0% and 29.4% in the young and elderly groups, respectively. The median PFS was 3.0 and 4.2 months in the young and elderly groups, respectively. The 1-year PFS rate was 30.0% and 27.9% in the young and elderly groups, respectively. In the young group, the ORR was 10.3% and DCR was 33.3%. In the elderly group, the ORR was 18.4% and DCR was 53.1%. There were no significant differences in OS, PFS, ORR, and DCR (P = 0.36, 0.53, 0.29 and 0.06, respectively). Interstitial lung disease (ILD) as an irAE occurred in the young group at a significantly higher rate (20.5% vs 4.1%; P = 0.02). There were no significant differences in OS, PFS, ORR, and DCR between the young and elderly groups. DCR tended to be better in the elderly group (P = 0.06). ILD occurred at a significantly higher rate in the young group.


The subcortical generated somatosensory evoked potentials in non-cephalic, cephalic, and anterior neck referenced recordings in a patient with a cervico-medullary lesion: a clue to the identification of the P14/N14 and N13 generators.
Median nerve somatosensory evoked potentials (SEPs) were studied in a patient before and after the development of a cervico-medullary lesion. The first examination demonstrated normal subcortical generated potentials N13 and N14. The second examination, following a subarachnoid haemorrhage at the cervico-medullary junction, displayed a delayed and reduced amplitude P14/N14 peak on both sides. P14/N14 showed the same latency in all montages, using non-cephalic, cephalic and anterior neck references. The N13 component was not significantly changed in latency compared with the first examination. The latencies of the N13 peak were variable in the different montages. They increased from the lower (C7) to the upper (C2) neck, whereas the latency of the N13 onset was identical in all montages. This alteration might be caused by a delayed near-field activity at C2 overlapping the N13 component. These results fit the hypothesis of two major generators responsible for subcortical SEPs; a near-field N13 component at the level of the lower neck and a far-field P14 component arising from the level of the cervico-medullary junction. An additional minor near-field activity generated by the cuneate nucleus is suspected.


Mucosal pseudolipomatosis: an air pressure-related colonoscopy complication.
Mucosal pseudolipomatosis is a recently described colonoscopic finding, most likely caused by intramucosal air. We describe four asymptomatic patients with this lesion which completely resolved 3 weeks later on repeat colonoscopy. This is a benign, transient lesion with distinct endoscopic and histologic findings. The similarity between mucosal pseudolipomatosis and pneumatosis cystoides intestinalis is supportive of the mechanical theory for pneumatosis cystoides intestinalis.


Attunement and alignment of people with schizophrenia and their preferred alternative decision-makers: An exploratory pilot study comparing treatment and research decisions.
Schizophrenia is a serious mental disorder that may affect the decisional capacity, and as a consequence, preferred alternative decision-makers may be engaged to help with clinical care and research-related choices. Ideally, alternative decision-makers will seek to make decisions that fit with the views and preferences of the ill individual. Few data exist, however, comparing the views of alternative decision-makers to those of individuals with schizophrenia. We conducted a written survey with individuals with schizophrenia living in a community setting, and a parallel survey with the person whom the ill individual identified as being a preferred alternative decision-maker. Complete data were obtained on 20 pairs (n = 40, total). Domains queried included (a) burden, happiness, and safety of the ill individual and of his or her family in treatment and research decisions and (b) importance of ethical principles in every day life. Two-sided paired t-tests and graphical summaries were used to compare responses. Individuals with schizophrenia and their linked preferred alternative decision-makers were attuned on four of six aspects of treatment decision-making and on all six aspects of research decision-making that we queried. The preferred alternative decision-makers overall demonstrated attunement to the views of the ill individuals in this small study. Ill individuals and their preferred alternative decision-makers were aligned in their views of ethically-salient aspects of every day life. These novel findings suggest that alternative decision-makers identified by ill individuals may be able to guide choices based on an accurate understanding of the ill individuals' views and values.