Balloon-occluded retrograde transvenous obliteration for gastric varices improves hepatic functional reserve in long-term follow-up.
Balloon-occluded retrograde transvenous obliteration (BRTO) has been widely adopted for the management of gastric fundal varices (GVs). There are a few reports that BRTO leads to the improvement of mid-term and long-term hepatic functional reserve (HFR). We retrospectively investigated the long-term effect on HFR and prognosis among patients who had undergone BRTO for GVs. This single-center, retrospective study included 57successful patients out of 60 patients who underwent BRTO for GVs from December 2005 to September 2018. We examined the indicators of HFR (e.g., encephalopathy and ascites statuses, serum total bilirubin and albumin levels, % prothrombin time, and Child-Pugh and albumin-bilirubin [ALBI] scores) during 3 years of follow-up after BRTO. We analyzed survival using the Kaplan-Meier method and identified the independent prognostic factors via multivariate analyses. GVs disappeared in all patients who were successfully treated by BRTO. At 3 years after BRTO, serum albumin levels were significantly elevated (from 3.3 to 4.0 g/dL, P = 0.008), while Child-Pugh and ALBI scores were significantly decreased (from 7.0 to 5.7, P = 0.043, and from -1.94 to -2.60, P = 0.006, respectively). The median survival time among all patients was 2207 days; the survival rates after BRTO were 87.0% at 1 year, 81.8% at 3 years, 67.3% at 5 years, and 44.1% at 10 years. Multivariate analyses revealed that ascites, hepatic encephalopathy, and malignant neoplasms were independently associated with poor prognosis. BRTO for GVs has a favorable effect on long-term HFR.


Theoretical study on the origin of the dual phosphorescence emission from organic aggregates at room temperature.
Purely organic materials with dual room temperature phosphorescence (RTP) phenomenon were reported recently, but the underlying mechanism was still ambiguous. Herein, we revealed the source of dual RTP emission, taking CzDPS crystal as prototype, by using hybrid quantum mechanics and molecular mechanics (QM/MM) coupled with the thermal vibration correlation function rate theory. Theoretical calculations verified that the emission lifetimes are prolonged from 70 ms in the higher triplet state T2 to 216 ms in the lowest triplet state T1, which is well consistent with the increase of RTP lifetimes from 74 ms for the peak at 465 nm to 627 ms for the band at 565 nm. This is because the radiative and nonradiative decay rates are larger for T2 → S0 than that of T1 → S0, which was mainly contributed by the synergistic effect of the increase of spin-orbit coupling and excitation energy, as well as the decrease of reorganization energy. Moreover, the simulated RTP spectra agree well with the experimental ones, including the emission position and profiles. Therefore, the upper-lying triplet excited states are responsible for the dual RTP in CzDPS crystal. This work could contribute to further understanding on the multiple luminescence of organic aggregates.


Fetal response to maternal exercise in pregnancies with uteroplacental insufficiency.
The purpose of this study was to determine the fetal response to submaximal maternal exercise at 22 to 26 weeks in pregnancies with abnormal uterine artery Doppler. This was a prospective comparison of singleton pregnancies with uteroplacental vascular insufficiency (UPVI) (mean uterine pulsatility index [PI] values >1.45 [n = 12]) and those with normal uterine artery Doppler (n = 23). Maternal and fetal cardiovascular responses to 5 minutes of steady state cycling at 10% and at 15% of predicted work rate maximum were studied. Umbilical artery Doppler deteriorated after exercise in patients with UPVI (pre PI 1.4 [0.35-2.14], post PI 1.64 [0.45-2.18]). Three (25%) had transient absent-end diastolic flow (AEDF) in umbilical artery, 2 of which developed early-onset intrauterine growth restriction (IUGR) with AEDF. Fetal cardiac output studies remained stable during the examinations. Submaximal steady state exercise had a transient deleterious effect in a subset of women with uteroplacental vascular insufficiency destined to develop early-onset IUGR.


Tbx18 is essential for normal development of vasculature network and glomerular mesangium in the mammalian kidney.
Tbx18 has been shown to be essential for ureteral development. However, it remains unclear whether it plays a direct role in kidney development. Here we addressed this by focusing on examining the pattern and contribution of Tbx18+ cells in the kidney and its role in kidney vascular development. Expression studies and genetic lineage tracing revealed that Tbx18 is expressed in renal capsule, vascular smooth muscle cells and pericytes and glomerular mesangial cells in the kidney and that Tbx18-expressing progenitors contribute to these cell types. Examination of Tbx18(-/-) kidneys revealed large reduction in vasculature density and dilation of glomerular capillary loops. While SMA+ cells were reduced in the mutant, PDGFRβ+ cells were seen in early capillary loop renal corpuscles in the mutant, but fewer than in the controls, and further development of the mesangium failed. Analysis of kidney explants cultured from E12.5 excluded the possibility that the defects observed in the mutant were caused by ureter obstruction. Reduced proliferation in glomerular tuft and increased apoptosis in perivascular mesenchyme were observed in Tbx18(-/-) kidneys. Thus, our analyses have identified a novel role of Tbx18 in kidney vasculature development.


The effect of zinc status on the immune function of diabetic rats.
To evaluate the role of zinc status in immune system dysfunction in diabetic animals, the interleukin-2 production and the lymphocyte mitogenic response to phytohaemagglutinin, concanavalin A and lipopolysaccharide were measured in streptozotocin-induced diabetic rats, diabetic rats treated with insulin and their non-diabetic controls maintained on low zinc, normal zinc and high zinc diets for 3 weeks. Unstimulated lymphocyte proliferation was significantly lower in diabetic rats compared to nondiabetic control rats maintained on normal zinc diet (1505 +/- 318 vs 3447 +/- 497 cpm) (p less than 0.005) or low zinc diet (546 +/- 191 vs 4011 +/- 628 cpm) (p less than 0.005). High zinc diet attenuated the difference between the diabetic rats (2404 +/- 833 cpm) and control rats (3929 +/- 713 cpm). Insulinised diabetic rats were similar to control rats. Phytohaemagglutinin-stimulated lymphocyte proliferation was not significantly altered with dietary zinc changes, but diabetic rats on low zinc diet had significantly lower (p less than 0.025) values compared to control rats on the same diet (41470 +/- 7874 vs 72308 +/- 8895 cpm). Insulinisation did not normalise phytohemaegglutinin-stimulated lymphocyte proliferation (40711 +/- 3666 cpm). Similarly, cells from diabetic rats on low zinc diet, unlike their controls, failed to respond to concanavalin A stimulation. Compared to control rats the diabetic rats on either low or normal zinc diets had lower lipopolysaccharide-stimulated lymphocyte proliferation. High zinc diet or insulinisation normalised mitogenic response of lymphocytes to lipopolysaccharide. Unlike the diabetic rats alterations in dietary zinc intake did not significantly affect the lymphocyte proliferation in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Angiographically occult cerebral vascular malformations with abnormal computed tomography.
Two cases of histologically proven cerebrovascular malformation were detected by computed tomography (CT) scanning but not by cerebral angiography. One of the patients had a cavernous angioma and the other an arteriovenous malformation. Caution is advised in assuming that angiographically avascular lesions demonstrable by CT scanning are not vascular malformations.


A mechanical evaluation of an elastic femoral prosthetic stem.
Studies are being conducted in our laboratory to test the concept of introducing an elastomer to attenuate and damp forces applied to the bone interface in a major weightbearing joint replacement prosthesis. An analogue of a fully constrained intramedullary stem type prosthesis has been developed in a segmental femoral replacement prosthesis of the dog. The layer of silastic was introduced to damp forces at the bone-prosthesis interface. This paper describes the response of this elastomer prosthesis to torsional and bending loads, and defines the upper limits of elastomer strain. The low modulus silastic displayed surprisingly low strain for applied loads, particularly in bending tests, in this prosthetic configuration. The results of these mechanical studies serve as a bench mark for the eventual design and material selection of an elastomer for human prosthetic use.


Effect of the melanocortin receptor stimulation or inhibition on ethanol intake in alcohol-preferring rats.
It has been recently reported that acute intracerebroventricular injection of 1 nmol/rat of the non-selective melanocortin 3 and 4 receptor (MC3/4) agonist MTII reduces ethanol intake in female AA alcohol-preferring rats and alters opioid peptide levels in the ventral tegmental area of rats. To better understand the role of the MC system in the control of ethanol intake, we tested the acute and chronic effects of lateral ventricular (LV) injections of 0.01-1 nmol MTII, of 0.1-1 nmol of the MC3/4R receptor antagonist agouti related peptide (AgRP), and 0.1-0.5 nmol of the MC3/4R receptor antagonist SHU9119 on food, water, and 10% ethanol intake in Marchigian-Sardinian alcohol-preferring (msP) rats, which spontaneously ingest pharmacologically relevant quantities of ethanol both under short and long term access conditions. The data showed that with 2h/day ethanol access, LV MTII injections reduced intake of food and ethanol intakes. When food, water, and ethanol were available ad libitum and 0.01 nmol MTII was given by daily LV injection, however, ethanol intake was reduced for only the first 2 days, whereas food intake was reduced for all 5 days of treatment. Finally, acute LV injection of neither AgRP nor SHU9119 affected ethanol intake under ad libitum conditions, although both antagonists significantly increased food and water intake. In conclusion, these data fail to support a role for endogenous MC3/4R in the control of spontaneous ethanol intake in the msP rat. MC3/4R agonism, however, reduced ethanol intake in association with reduced food intake, suggesting that MTII might reduce nutrient-related controls of ethanol intake rather than, or in addition to, reward-related controls of ethanol intake.


Direct Oral Anticoagulant (DOAC) Dosing in Patients with Non-valvular Atrial Fibrillation (NVAF) in the United Kingdom: A Retrospective Cohort Study Using CPRD Gold Database.
Per-label dosing of direct oral anticoagulants (DOACs) is important for the prevention of stroke and systemic embolism among patients with non-valvular atrial fibrillation (NVAF), especially those with poor renal function, advanced age, low body weight or concomitant P-glycoprotein inhibitors. The study described DOAC use and dosing patterns in patients with NVAF in the UK. Using Clinical Practice Research Datalink (CPRD Gold), patients' profiles were described at DOAC initiation (1 January 2016-31 March 2021) and followed for a mean [standard deviation (SD)] 2 (1) years. Patients were categorised as under-dosing: received a lower dose with no indication for a reduced dose; over-dosing: received a standard dose with an indication for a reduced dose; per-label dosing, according to Summary Product Characteristics (SmPC). Forty thousand seven hundred forty-four adult patients with NVAF were identified (mean age: 75.3 (11.2) years; males: 55.4%); 22,827 (56.0%) initiated treatment with apixaban, 930 (2.3%) dabigatran, 5633 (13.8%) edoxaban and 11,354 (27.9%) rivaroxaban. Baseline Charlson comorbidity index ≥ 4 was 65.1%; CHA2DS2-VASc score ≥ 4 was 22.5%; HAS-BLED score ≥ 3 was 18.3%; ~ 2% had prior major bleed and 4.4% a stroke ≤ 2 years before DOAC initiation. Overall, 18.0% of patients received incorrect dosing (~ one in five). Under-dosing was highest for dabigatran (156, 16.8%) and over-dosing was highest for rivaroxaban (1084, 9.6%). Per-label dosing was highest for edoxaban (4773, 84.7%), followed by apixaban (18,756, 82.2%), rivaroxaban (9161, 80.7%) and dabigatran (732, 78.7%). Treatment persistence (no switching or discontinuation) was 79% among edoxaban users, followed by 75% for apixaban, 69% for rivaroxaban and 62% for dabigatran. About 15% of dabigatran users, 10% of rivaroxaban users, 5% of apixaban users and 4% of edoxaban users switched treatment to another DOAC during follow-up. Although most patients received per-label dosing, ~ one in five patients was incorrectly dosed with DOAC, which may lead to serious clinical consequences and increased healthcare burden.


Ambroxol inhibits platelet-derived growth factor production in human monocytic cells.
Several growth factors, including platelet-derived growth factor (PDGF), have been implicated in the mechanism of lung and airway remodeling. We investigated the effect of ambroxol, trans-4-[(2-amino-3,5-dibromobenzyl) amino] cyclohexanol hydrochloride, on the lipopolysaccharide-induced PDGF production in human monocytic cells, THP-1. Ambroxol inhibited the lipopolysaccharide-induced PDGF-AB production via PDGF-A mRNA expression. Lipopolysaccharide activated p44/42 extracellular signal-regulated kinase (ERK), and ambroxol attenuated the lipopolysaccharide-induced p44/42 ERK activation. Furthermore, mitogen-activated protein kinase kinase (MEK)-1-specific inhibitor, 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD 98059), blocked the lipopolysaccharide-induced p44/42 ERK activation and PDGF production. These findings indicate that ambroxol inhibits the lipopolysaccharide-induced PDGF production due to the suppression of p44/42 ERK activity.


Barium meal appearance simulating superficial ulceration.
Five cases of diffuse gastric spiculation seen on single contrast barium meal examination are reported. This appearance may spuriously suggest superficial mucosal ulceration in cases in which no evidence of this is found endoscopically or histologically. This radiological appearance may be due to filling of the grooves between the areae gastricae and may thus represent a normal anatomical variant.


Factor VIII-related antigen and factor VIII coagulant activity in normal and pre-eclamptic pregnancy.
The changes in the ratio between factor VIII-related antigen and factor VIII activity were compared in ten patients with normal pregnancies and in ten patients with severe pre-eclampsia. In the patients with pre-eclampsia, a highly significant increase in the ratio was observed during the third trimester. No difference in the ratio between the two groups was found on day 7 of the puerperium. In the pre-eclamptic patients, the highest ratios for factor VIII-related antigen to factor VIII activity were associated with either a perinatal death or with the delivery of a severely growth retarded infant. These findings are in keeping with an increased rate of thrombin production in women with pre-eclampsia, and suggest that the ratio of factor VIII-related antigen to factor VIII activity may reflect the severity of the effect of the disease process on the fetus.


Electrophysiology and immunohistochemistry in the hippocampal ca1 and the dentate gyrus of rats chronically exposed to 1-bromopropane, a substitute for specific chlorofluorocarbons.
1-Bromopropane is a newly introduced substitute for specific chlorofluorocarbons whose production was prohibited because of depletion of ozone layers. In this study, we analyzed disinhibitory effects induced by repetitive inhalation of 1-bromopropane for 12 weeks in the hippocampal CA1 and the dentate gyrus. In addition, reversal of the disinhibitory effects was examined 4 weeks after 1-bromopropane inhalation ceased. Exposure rats were placed in a stainless steel inhalation chamber at a concentration of 700 ppm, while the control group was provided only room air in the same type of chamber. Paired-pulse inhibition of population spike was considerably decreased (P<0.05) at 5 ms interpulse intervals in the CA1, and at 10 and 20 ms (P<0.05) interpulse intervals in the dentate gyrus in slices obtained from exposed rats following 4-, 8- and 12-week inhalation periods. The paired-pulse inhibition was decreased at 5 ms interpulse intervals in the dentate gyrus after 12 weeks of inhalation. These changes were not associated with the paired-pulse ratio of field excitatory postsynaptic potentials, suggesting a reduction of recurrent inhibition. The disinhibition was counteracted with the N-methyl-d-aspartate receptor antagonist dl-2-amino-5-phosphonopentameric acid in the dentate gyrus, whereas it was unchanged in the CA1. Tiagabine, a selective inhibitor of GABA transporter GAT1, increased the paired-pulse inhibition in the dentate gyrus, and the increase was less in the exposed rats compared with control rats (P<0.0003). The changes in both areas recovered to control levels 4 weeks after cessation of inhalation. Our electrophysiological studies suggest differential and reversible disinhibitory effects in the dentate gyrus and the CA1. 1-Bromopropane-induced disinhibition was further analyzed by immunohistochemical methods. There were no apparent morphological defects in either excitatory or inhibitory neuronal components, supporting the reversibility of physiological changes. In conclusion, chronic inhalation of 1-bromopropane induces a disinhibition in the CA1 and dentate gyrus that is reversible following cessation of exposure.


Synergistic effects of antibodies against high-mobility group box 1 and tumor necrosis factor-α antibodies on D-(+)-galactosamine hydrochloride/lipopolysaccharide-induced acute liver failure.
High-mobility group box 1 (HMGB1) protein is released into the serum after tissue damage, and serves as a warning signal to enhance the inflammatory response. Acute liver injury is one of the diseases that starts with tissue damage and ends with systemic inflammation. We used D-(+)-galactosamine hydrochloride (D-GalN)/lipopolysaccharide (LPS)-treated mice as an acute liver injury model to explore the functions of HMGB1 in more detail. HMGB1 is released into the serum at a very early stage of D-GalN/LPS-induced acute liver injury. It upregulates the expression of tumor necrosis factor-α (TNF-α), interleukin-6, inducible nitric oxide synthase, and tissue factor. TNF-α and HMGB1 form a positive feedback loop to amplify the downstream signals. mAbs against HMGB1 and TNF-α have synergistic effects in protecting mice from D-GalN/LPS-induced acute liver failure. The results suggest that HMGB1 is a key mediator in D-GalN/LPS-induced acute liver injury. Tissue damage and cell necrosis shortly after administration of D-GalN and LPS lead to early HMGB1 release, and HMGB1 acts synergistically with TNF-α to promote pathological processes in acute liver failure.


Repeater F waves: a comparison of sensitivity with sensory antidromic wrist-to-palm latency and distal motor latency in the diagnosis of carpal tunnel syndrome.
Thirty-five thousand six hundred supramaximal shocks were applied to 209 healthy and 147 entrapped median nerves (carpal tunnel syndrome--CTS) to characterize the backfiring behavior of the alpha motor neuron pool of abductor pollicis brevis in health and the modifying effect of a compressive neuropathy. A contraction of the normal subpopulation of active F-wave generators was found in CTS, while active neurons backfired at higher than normal frequencies (p less than 0.001). These modifications in spinal behavior are reflected in the % Repeater F-wave value, whose sensitivity in the detection of CTS approaches that of sensory wrist-to-palm latency estimation. This technique offers an alternative to latency measurement in the diagnosis of CTS. An economical strategy for the electrodiagnosis of CTS is proposed.


Localization of radioactivity in rat organs after oral administration of tritiated 8-methoxypsoralen in therapeutic doses.
Tritiated 8-methoxypsoralen was given perorally to rats in amounts corresponding to therapeutic human doses. The rats were exposed to UVA light or kept in darkness. None of the fractions (apart from 3H2O from the lens) examined changed their level of radioactivity under the influence of UVA light. Time-radioactivity curves were recorded for the skin, lens, residual eye, and the liver. Four fractions were measured: 3H2O, soluble pool, DNA-RNA, and protein. Tritiated water appeared already 1 h after ingestion, and attained maximum value 9-24 h after ingestion, indicating the efficiency with which the liver degrades 8-MOP. 3H-8-MOP and metabolites could be detected in the soluble pool in maximum amounts 2-3 h after the administration. Pretreatment with trypsin increased the concentration of 3H-8-MOP and metabolites; the origin of this extra radioactivity was the protein fraction. The 3H-8-MOP binding to DNA or RNA was studied by pretreatments of the homogenates with DNase or RNase followed by measurement of radioactivity in the TCA extracts. This indicated that no measurable amount of 3H-8-MOP had been bound to DNA or RNA. We conclude that 8-MOP administered to rats in amounts corresponding to human therapeutic doses does not bind to DNA or RNA in measurable amounts either after UV-light or in darkness. The experiments have shown proteins to be the main binding site in rat organs.


Elastosis in benign sclerosing ductal proliferation of the female breast.
Elastosis, an abundance of elastic tissue, is commonly present in breast carcinoma. However, its diagnostic significance remaines an unsettled issue. This study documents 17 cases of elastosis occurring in a distinctive benign sclerosing ductal lesion of the female breast (Fenoglio and Lattes: Cancer 33: 691-700, 1974). Elastosis was characterized by staining reactions and, in several instances, by elastase digestion and electron microscopy. Yellow streaks and flecks may be apparent grossly and probably reflect the increased elastic tissue. Histologically, the lesion is generally stellate with central sclerosis and marked peripheral intraductal and ductular hyperplasia which is often papillary. Elastosis, which may be marked, is a constant finding and is predominantly periductal in location. It is emphasized that the gross and histologic features of the lesion may mimic carcinoma and that elastosis may be found in benign ductal lesions of the breast.


Comparison of effects of pentagastrin and gastrin on rat colon mucosa.
The trophic effect of chronic endogenous hypergastrinemia is compared with that of short term injected pentagastrin on colon mucosa of rats. Hypergastrinemia was achieved by antral exclusion. Pentagastrin (2 mg/kg) was administered to a group of sham operated rats every 12 hr for 48 hr prior to sacrifice. Normogastrinemic antrectomized and sham operated animals were studied as controls. Tissue content and synthesis of DNA, RNA, and protein were all markedly increased by both endogenous gastrin and exogenous pentagastrin. The stimulation by gastrin was significantly stronger than that of pentagastrin at the chosen schedule of administration.


Generation of induced pluripotent stem cell GZLSL-i001-A derived from urine-derived cells of Hemophilia A patient with Inv22 mutation.
Hemophilia A (HA), is a X-linked recessive congenital bleeding disorder, caused by deficiency of the coagulation factorVIII (FVIII) which is encoded by coagulation factor 8 (F8). HA affects 1 of every 5,000 males worldwide. The intron 22 inversion (Inv22) mutation of F8 causes about 45% of severeHA cases.Here, we generated induced pluripotent stem cells (iPSCs) from a HA patient with Inv22 mutation by electroporation of urine-derived cells (UCs) with episomal plasmids under feeder-free, virus-free, serum-free condition and without oncogene c-MYC. This iPSCs line could facilitate future applications of human iPSCs by provide a valuable cell model.


Honeybees use their wings for water surface locomotion.
Honeybees display a unique biolocomotion strategy at the air-water interface. When water's adhesive force traps them on the surface, their wetted wings lose ability to generate aerodynamic thrust. However, they adequately locomote, reaching a speed up to 3 body lengths·s-1 Honeybees use their wetted wings as hydrofoils for their water surface propulsion. Their locomotion imparts hydrodynamic momentum to the surrounding water in the form of asymmetric waves and a deeper water jet stream, generating ∼20-μN average thrust. The wing kinematics show that the wing's stroke plane is skewed, and the wing supinates and pronates during its power and recovery strokes, respectively. The flow under a mechanical model wing mimicking the motion of a bee's wing further shows that nonzero net horizontal momentum is imparted to the water, demonstrating net thrust. Moreover, a periodic acceleration and deceleration of water are observed, which provides additional forward movement by "recoil locomotion." Their water surface locomotion by hydrofoiling is kinematically and dynamically distinct from surface skimming [J. H. Marden, M. G. Kramer, Science 266, 427-430 (1994)], water walking [J. W. M. Bush, D. L. Hu, Annu. Rev. Fluid Mech. 38, 339-369 (2006)], and drag-based propulsion [J. Voise, J. Casas, J. R. Soc. Interface 7, 343-352 (2010)]. It is postulated that the ability to self-propel on a water surface may increase the water-foraging honeybee's survival chances when they fall on the water.


Electroanatomical mapping of the stomach with simultaneous biomagnetic measurements.
Gastric motility is coordinated by bioelectric slow waves (SWs) and dysrhythmic SW activity has been linked with motility disorders. Magnetogastrography (MGG) is the non-invasive measurement of the biomagnetic fields generated by SWs. Dysrhythmia identification using MGG is currently challenging because source models are not well developed and the impact of anatomical variation is not well understood. A novel method for the quantitative spatial co-registration of serosal SW potentials, MGG, and geometric models of anatomical structures was developed and performed on two anesthetized pigs to verify feasibility. Electrode arrays were localized using electromagnetic transmitting coils. Coil localization error for the volume where the stomach is normally located under the sensor array was assessed in a benchtop experiment, and mean error was 4.2±2.3mm and 3.6±3.3° for a coil orientation parallel to the sensor array and 6.2±5.7mm and 4.5±7.0° for a perpendicular coil orientation. Stomach geometries were reconstructed by fitting a generic stomach to up to 19 localization coils, and SW activation maps were mapped onto the reconstructed geometries using the registered positions of 128 electrodes. Normal proximal-to-distal and ectopic SW propagation patterns were recorded from the serosa and compared against the simultaneous MGG measurements. Correlations between the center-of-gravity of normalized MGG and the mean position of SW activity on the serosa were 0.36 and 0.85 for the ectopic and normal propagation patterns along the proximal-distal stomach axis, respectively. This study presents the first feasible method for the spatial co-registration of MGG, serosal SW measurements, and subject-specific anatomy. This is a significant advancement because these data enable the development and validation of novel non-invasive gastric source characterization methods.


BODIPY based red emitters: Synthesis, computational and biological studies.
Donor-Acceptor type BODIPYs with strong absorption and fluorescence in the red region (550-800 nm) are reported. The aromatic groups like N-butylcarbazole/ N-butylphenothiazine/ benzothiadiazole were attached to the C-8 position of the BODIPY core with furan or thiophene spacers. TD-DFT studies indicated significant charge distribution between C-8 aromatic heterocycles and BODIPY core in all the molecules. The in-vitro studies of the N-butylcarbazole substituted BODIPYs indicated significant localization in the endoplasmic reticulum and lysosomes of the cancer cells. The BODIPYs showed decent cytotoxicity after 48 h incubation period (14.9 to 31.8 μM) in HeLa and A549 cancer cells, indicating their potential application as theranostic agents.


[Current evaluation of efficacy of radon baths of various concentrations during rehabilitation of patients with seronegative spondylarthritis].
141 patients with seronegative spondylarthritis including ankylosing spondylarthritis (n = 90), reactive arthritis and Reiter's disease (n = 51) took water radon baths (concentration 1.5, 3.0 and 4.5 kB/l). The baths proved similarly effective in patients with seronegative spondylarthritis. They produced analgetic, anti-inflammatory actions, raised quality of life for such patients.


The effect of tray selection, viscosity of impression material, and sequence of pour on the accuracy of dies made from dual-arch impressions.
Dual-arch trays are often used to generate impressions of prepared teeth and of the opposing arch simultaneously. There is concern that accuracy of the casts generated with this technique can be affected by the type of tray, viscosity of the impression material, and sequence of pouring the cast. This study compared the accuracy of working dies made from impressions with metal and plastic dual-arch trays, for 2 different viscosities of impression tray material and by altering which side of the impression was poured first. Impressions were made of a typodont mandibular arch containing a circular stainless steel crown preparation (standard). There were 3 variables: type of dual-arch tray, impression material viscosity, and order of pour of the impressioned arches. A balanced design with independent samples was used (n=10). Two types of dual-arch trays, plastic (Triple Tray) and metal (COE Impression Tray), and 2 viscosities of addition silicone for the tray were used (Aquasil Rigid and Aquasil Monophase). Type IV gypsum (Fuji-Rock) with a ratio of 20 mL of distilled water to 100 g of powder was hand-mixed for 10 seconds then mixed under vacuum for 40 seconds and poured into the trays while being vibrated. One side of the dual-arch impression was poured with 35 g of stone and allowed to set for 1 hour before the other side was poured with 35 g of stone. The order of pour was randomized, and all casts were allowed to set for 24 hours at room temperature before removal. The dies were measured in 3 dimensions (buccolingual, mesiodistal, and occlusogingival) with a measuring microscope. The gypsum working dies were placed into a custom jig fabricated to permit measurement at a fixed, reproducible position under the microscope. Each dimension of the working dies was measured 3 times, and the mean was used for the sample value. The same 3 aspects of the stainless steel standard were measured multiple times, before and then at the conclusion of measuring all working dies, to arrive at the 3 standard values to which all working die means were compared. The means for the standard used in the statistical analysis were those taken at the conclusion of the study. The intraexaminer variation for measuring the standard was 0.001 mm. A 3-factor analysis of variance was used for the statistical analysis with hypothesis testing at alpha=.05. Statistically significant differences were found with viscosity selection for the buccolingual and occlusogingival dimensions of the working die. The rigid material produced working dies slightly taller (1 microm) than the standard, and those from the monophase material were 4 microm shorter. Regarding tray selection, metal trays were slightly more accurate in the mesiodistal dimension, and when monophase was used in a plastic tray, gypsum dies were nearly 30 microm smaller in the mesiodistal dimension (P<.05). Differences were not detected for sequence of pouring impressions. Within the limitations of this study, the monophase material, when compared with the rigid impression material, was most accurate for the occlusogingival and mesiodistal dimensions, although not as accurate in the buccolingual. This buccolingual difference (0.002 mm-0.006 mm) would be clinically inconsequential with the application of die spacer. The rigid impression material was also unaffected by tray selection for the mesiodistal, whereas monophase was affected. When a monophase impression material was used, plastic dual-arch trays yielded gypsum dies which were significantly smaller (0.029 mm) than the ones generated from the metal trays (0.006 mm). Thus rigid impression materials can be recommended for use in dual-arch trays; however, the magnitude of the differences would generally not be clinically significant because they could be compensated for with several coats of die spacer.


Speech function following maxillectomy reconstructed by rectus abdominis myocutaneous flap.
Post-surgical maxillary defects have recently been reconstructed by microvascularized free flaps. However, few reports have evaluated the resulting speech function. This study compared the speech intelligibility of four maxillectomy patients who underwent reconstruction by rectus abdominis myocutaneous flaps (RAMCF) with that of four non-reconstructed patients who were treated with split-skin grafts and prostheses, to explore ways of achieving better speech function. Speech function was assessed by a Japanese language speech intelligibility test. Intelligibility scores ranged from 57.3% to 75.8% (mean, 70.4%) in the non-reconstructed group and from 66.2% to 77.2% (mean, 71.0%) in the reconstructed group. An analysis of articulatory manners and sites revealed that speech disorders resulted mainly from poor oronasal separation in the non-reconstructed group and from incorrect linguopalatal contact in the reconstructed group, especially for linguodentoalveolar and linguovelar sounds. Therefore, for higher speech function in the reconstructed group, dentoalveolar and palatal contours of the maxilla must be restored as closely as possible. This must also be done in patients whose maxillae are reconstructed by other types of microvascularized myocutaneous or cutaneous flaps that have similar postoperative palatal contours.


The impact of episodic screening interruption: COVID-19 and population-based cancer screening in Canada.
Population-based cancer screening can reduce cancer burden but was interrupted temporarily due to the COVID-19 pandemic. We estimated the long-term clinical impact of breast and colorectal cancer screening interruptions in Canada using a validated mathematical model. We used the OncoSim breast and colorectal cancers microsimulation models to explore scenarios of primary screening stops for 3, 6, and 12 months followed by 6-24-month transition periods of reduced screening volumes. For breast cancer, we estimated changes in cancer incidence over time, additional advanced-stage cases diagnosed, and excess cancer deaths in 2020-2029. For colorectal cancer, we estimated changes in cancer incidence over time, undiagnosed advanced adenomas and colorectal cancers in 2020, and lifetime excess cancer incidence and deaths. Our simulations projected a surge of cancer cases when screening resumes. For breast cancer screening, a three-month interruption could increase cases diagnosed at advanced stages (310 more) and cancer deaths (110 more) in 2020-2029. A six-month interruption could lead to 670 extra advanced cancers and 250 additional cancer deaths. For colorectal cancers, a six-month suspension of primary screening could increase cancer incidence by 2200 cases with 960 more cancer deaths over the lifetime. Longer interruptions, and reduced volumes when screening resumes, would further increase excess cancer deaths. Interruptions in cancer screening will lead to additional cancer deaths, additional advanced cancers diagnosed, and a surge in demand for downstream resources when screening resumes. An effective strategy is needed to minimize potential harm to people who missed their screening.


Intensive topical steroid regimen for enhanced very early recovery after small incision lenticule extraction.
This study aims to investigate the topical steroid regimen after small incision lenticule extraction (SMILE) for its effect on very early restoration of visual quality. A total of 180 patients (360 eyes) who underwent SMILE were enrolled. These patients were randomly assigned to three groups, with 60 patients in each group. The only difference among these three groups was the administration of 0.1% fluorometholone (FML) eye drops within two hours after SMILE: no FML in group A, 0.1% FML once every hour in group B and 0.1% FML once every half hour in group C. The corrected distance visual acuity (CDVA), objective scattering index (OSI), modulation transfer function (MTF) cut-off, Strehl ratio (SR) and incidence of subjective symptoms were evaluated preoperatively, at 2, 4 and 24 h and one week after SMILE. The CDVA, MTF cut-off and SR values were significantly higher in group C, when compared to the other two groups, at 2 and 4 h after SMILE (p < 0.05). Furthermore, the OSI and incidence of subjective symptoms were significantly lower in group C, when compared to the other two groups, at 2 and 4 h after SMILE (p < 0.05). However, no significant differences in CDVA, MTF cut-off, SR, OSI and the incidence of subjective symptoms were detected among the three groups at 24 h and one week after SMILE (p > 0.05). The administration of 0.1% FML eye drops every half hour within two hours after SMILE accelerates the restoration of visual and optical quality, and reduces the incidence of subjective symptoms during the very early phase after surgery.


Hydrophobic oligopeptide-based star-block copolymers as unimolecular nanocarriers for poorly water-soluble drugs.
Hydrophobic oligopeptide (HOP)-based star-block copolymers of the form PEI-g-(HOP-b-PEG) were synthesized, characterized and evaluated as nanocarriers for poorly water-soluble drugs. The designed PEI-g-(HOP-b-PEG) polymers were composed of a hyperbranched polyethylenimine (PEI) core, a HOP [i.e., oligo(l-tryptophan), oligo(l-phenylalanine), oligo(l-leucine), oligo(γ-benzyl-l-glutamate) and oligo(ɛ-benzyloxycarbonyl-l-lysine)] inner shell and a hydrophilic poly(ethylene glycol) (PEG) outer shell. The synthesized polymers were characterized using (1)H NMR, gel permeation chromatography (GPC) and transmission electron microscopy (TEM). Their micellization behavior was investigated by the dynamic light scattering (DLS) and fluorescence spectroscopy using pyrene as a probe; the results demonstrated that these star-block copolymers predominantly resembled unimolecular micelles, particularly when shorter HOP blocks and/or elongated PEG chains were incorporated. The encapsulation properties of these unimolecular micelles were evaluated using pyrene, oil-red O (OR) and doxorubicin (DOX) as guest hydrophobic compounds, which revealed that poorly water-soluble guests can be efficiently solubilized in PEI-g-(HOP-b-PEG) with a loading capacity of up to 10%. The encapsulated DOX demonstrated sustained release from PEI-g-(HOP-b-PEG). The synthesized star-block copolymers, given their structural versatility, water solubility and biodegradability, could potentially be used as unimolecular nanocarriers for the delivery of poorly water-soluble drugs.


Quality of life survey of urinary diversion patients: comparison of ileal conduits versus continent Kock ileal reservoirs.
There has been a recent marked increase in interest in continent urinary diversions. While considerable time has been spent on the technical aspects of these diversions the psychological impact has not yet been fully explored. We describe an extensive survey that was conducted among 100 consecutive adults (87 respondents) who had undergone urinary diversion via an ileal conduit and 100 consecutive adults (85 respondents) in whom a continent Kock ileal reservoir was created during the last 3 to 5 years at our university by the same surgeons. The Kock pouch patients were stratified further into 63 with primary diversion and 22 who underwent conversion from previous conduit diversions. The survey consisted of a questionnaire that included a social and sexual survey, the Beck Depressive Inventory, the Profile of Mood States and a physical impact study. The results revealed that all patients surveyed generally were satisfied with the diversions and they had adapted reasonably socially, physically and psychologically. The key to adaptation seemed to be a detailed, realistic preoperative education about the type of diversion used. Patients with ileal conduit diversions had the lowest expectations of the form of diversion as defined by the preoperative awareness of the need to wear an external ostomy appliance with its associated inconveniences and change in the external body image. Postoperatively, ileal conduit patients also had the poorest self images as defined by a decrease in sexual desire and in all forms of physical contact (sexual and nonsexual). The subset of patients who underwent conversion from conduit diversions to Kock pouches, however, were statistically the most satisfied, and they were the most physically and sexually active. We conclude that the Kock continent urostomy offers an important alternative to noncontinent forms of diversion.


Synthesis and preliminary pharmacological evaluation of N-2-(4-(4-(2-substitutedthiazol-4-yl) piperazin-1-yl)-2-oxoethyl)acetamides as novel atypical antipsychotic agents.
A series of N-2-(4-(4-(2-substitutedthiazol-4-yl) piperazin-1-yl)-2-oxoethyl)acetamides were synthesized in an effort to prepare novel atypical antipsychotic agents. The compounds were synthesized by either microwave irradiation technique or by conventional synthesis and were characterized by spectral data (IR, (1)H NMR, and MS) and the purity was ascertained by microanalysis. All the synthesized compounds were screened for their in vivo pharmacological activity in Swiss albino mice. D(2) antagonism studies were performed using climbing mouse assay model and 5-HT(2A) antagonism studies were performed using quipazine induced head twitches in mice. It was observed that none of the new chemical entities exhibited catalepsy. AG 3 was found to be the most active compound.


Do factors that influence pregnancy planning differ by maternal age? A population-based survey.
The objectives of this analysis were to describe factors that influenced the decision to conceive among first-time mothers in two Canadian urban centres and to determine if these differed according to the age at which a woman became a mother. Women who had given birth to their first live born infant between July 2002 and September 2003 in Calgary and Edmonton were randomly selected from regional notice of birth databases. Women were contacted by telephone, and those who agreed to participate completed a 20-minute survey over the telephone. This analysis was conducted using data from participants with a planned pregnancy. The top three factors that influenced childbearing among women planning a pregnancy were similar regardless of age. They were being in a secure relationship (97%), feeling in control of one's life (82%), and feeling prepared to parent (77%). Less than 30% of women reported career goals as being "very important" in their decision. Women under 25 years of age were less likely than women 25 years or older to indicate the following as being "very important" in the timing of starting a family: being in a stable job (32%), owning a home (36%), financial security (42%), educational training (36%), and career goals (9%) (all P < 0.001). This information provides a basis for developing strategies to support couples in their efforts to balance the age-related biomedical risks of delaying childbearing with a desire for relationship security and other factors that strongly influence childbearing decisions.


T-helper type 2 polarization among asthmatics during and following pregnancy.
Asthma is the most common medical condition during pregnancy. While increased production of T helper cytokines has been reported to occur in both asthma and pregnancy, the effect of T-helper type 2 (Th2) polarization on asthma symptoms during pregnancy has not been well-characterized. We hypothesized that systemic Th2 cytokine and chemokine polarization occurs among asthmatics to a greater extent during their pregnancy, and is associated with more severe asthma and increased Th2 polarization in the newborn. Fifty-six pregnant asthmatics were recruited from prenatal clinics affiliated with New York Presbyterian Hospital. Systemic production of interleukin-4, interferon-gamma, eotaxin and IP10 were measured by intracytoplasmic staining or ELISA at recruitment, peripartum and post-partum, and in the cord blood. The frequency of asthma symptoms was measured by questionnaires and compared with Th biomarkers. The chemokine ratio (IP10/eotaxin) declined over the course of pregnancy (from 3.3 +/- 1.3 to 1.4 +/- 0.2, P = 0.016), but IP10 and eotaxin increased post-partum. The decrease in the chemokine ratio was associated with more frequent asthma symptoms. A non-significant trend towards decreased interferon-gamma and increased interleukin-4 production was detected. Cord blood eotaxin levels correlated with maternal levels (r = 0.35, P = 0.03). Other peripartum biomarkers were not associated with Th2 polarization nor with subsequent respiratory symptoms in the newborn. IP10/eotaxin declined over the course of pregnancy and was associated with worse asthma symptoms. Alterations of Th1/Th2 chemokine balance during pregnancy may identify women prone to more severe asthma during pregnancy.


"Semi-open" muscle biopsy technique. A simple outpatient procedure.
An easy and safe method for muscle biopsy is described. The biopsy instrument is an alligator forceps (Weil-Bladesley's conchotome). With this method an adequate amount of muscle tissue can be obtained for both chemical and morphological studies. The method combines the advantage of the "open-surgical" method - sufficient quantity of material - with the advantages of the needle methods - easy to perform, not incapacitating and only slightly uncomfortable for the patient. Out of 959 consecutive biopsies with this method only 19 were impossible to evaluate because of too much artefact or too little tissue.


Characterization of the alnumycin gene cluster reveals unusual gene products for pyran ring formation and dioxan biosynthesis.
Alnumycin is closely related to the benzoisochromanequinone (BIQ) polyketides such as actinorhodin. Exceptional structural features include differences in aglycone tailoring that result in the unique alnumycin chromophore and the existence of an unusual 4-hydroxymethyl-5-hydroxy-1,3-dioxan moiety. Cloning and sequencing of the alnumycin gene cluster from Streptomyces sp. CM020 revealed expected biosynthesis genes for polyketide assembly, but several genes encoding subsequent tailoring enzymes were highly atypical. Heterologous expression studies confirmed that all of the genes required for alnumycin biosynthesis resided within the sequenced clone. Inactivation of genes aln4 and aln5 showed that the mechanism of pyran ring formation differs from actinorhodin and granaticin pathways. Further inactivation studies identified two genes, alnA and alnB, involved in the synthesis and attachment of the dioxan moiety, and resulted in the production of the polyketide prealnumycin.


Exposure of lentiviral vectors to subneutral pH shifts the tropism from Purkinje cell to Bergmann glia.
Cerebellar Purkinje cells play an important role in cerebellar function; lesions of Purkinje cells result in the disruption of motor coordination and motor learning. Although selective gene delivery to Purkinje cells would be a powerful technique for the study of pathophysiology in the cerebellum, a method for such a delivery has not yet been established. Here we employed human immunodeficiency virus-derived lentiviral vectors pseudotyped with vesicular stomatitis virus glycoprotein to transduce Purkinje cells and examined factors that critically affect the viral tropism for Purkinje cells. Viral vectors encoding GFP were generated using different protocols, and were then injected into the mouse cerebellum. At 7 days and 2 months post-transduction, the relative proportions of transduced Purkinje cells were determined. Lentiviral vectors harvested from a medium of pH 7.2 preferentially transduced Purkinje cells (about half of the transduced cells). In contrast, when the viral vector was harvested from medium of <or= pH 7.0, only 12-26% of transduced cells were identified as Purkinje cells and 68-77% as Bergmann glia. A similar decrease in the efficiency of transduction for Purkinje cells, depending on the pH of the medium at the viral harvest, was observed in dissociated cell cultures. These results indicate that lentivector tropism for Purkinje cells is extremely sensitive to pH: a subtle decrease in the pH of the medium at the harvest shifts viral tropism strikingly towards Bergmann glia.


Differential expression of cyclin D1 in mantle cell lymphoma and other non-Hodgkin's lymphomas.
Mantle-cell lymphomas are associated with a characteristic chromosomal translocation, t(11;14)(q13;q32). This translocation involves rearrangement of the bcl-1 proto-oncogene from chromosome 11 to the immunoglobulin heavy chain gene on chromosome 14, resulting in an overexpression of cyclin D1 mRNA (also known as bcl-1 and PRAD1). In the current study performed on paraffin-embedded tissue, cyclin D1 mRNA could be detected in 23 of 24 mantle-cell lymphomas by reverse transcription polymerase chain reaction (RT-PCR) whereas only 9 of 24 demonstrated a t(11;14) by PCR. However, we also found that cyclin D1 mRNA could be detected in the majority (11 of 17, 65%) of non-mantle-cell lymphomas and in a minority of atypical lymphoid hyperplasias (3 of 7, 43%). Cyclin D1 mRNA expression was not observed in floridly reactive lymph nodes (0 of 9) or in unstimulated lymph nodes (0 of 20), suggesting that it is a sensitive adjunct marker for malignant lymphoproliferative processes, but not specific for mantle-cell lymphoma. A semiquantitative RT-PCR assay was developed that compared the ratio of cyclin D1 to the constitutively expressed gene beta2-microglobulin. Using this assay on a limited number of our specimens, cyclin D1 overexpression in mantle-cell lymphoma could be reliably distinguished from its expression in other non-Hodgkin's lymphomas. This assay for cyclin D1 expression, designed for formalin-fixed, paraffin-embedded tissue, was a very sensitive and specific marker for mantle-cell lymphoma.


Resetting of parathyroid hormone secretion after vitamin D3 treatment in hypoparathyroidism and after parathyroid adenectomy in primary hyperparathyroidism.
The relationship between parathyroid hormone (PTH) secretion and extracellular calcium (Ca) level is reciprocal causality. The equilibrium operating point determines basal PTH secretion rate and basal extracellular Ca level. We studied how this equilibrium was achieved in the subjects with decreased PTH secretion or decreased parathyroid glands number. Basal/maximum ratio of serum PTH, which reflects the basal secretory state of parathyroid glands, was increased in 9 hypoparathyroid patients treated with vitamin D3 (VD3) [7 patients with idiopathic hypoparathyroidism] and in seven of nine parathyroid adenectomized patients. There was a negative correlation between the ratio and basal serum Ca level in the patients with IHP after VD3 treatment (r = 0.7167, P < 0.05) and in the patients after parathyroid adenectomy (r = 0.7760, P < 0.05). The regression curves in these two groups coincided regardless of the difference in maximum PTH secretion rate, which suggested that the basal secretory state of parathyroid glands was determined by extracellular Ca level in a similar manner in these subjects. There was a sigmoidal relationship between basal/maximum ratio of serum PTH and basal serum Ca level, when the data were collected from 15 hypoparathyroid patients before or after VD3 treatment, 9 parathyroid adenectomized patients, and 10 normal subjects (r = 0.9057, P < 0.001). This sigmoidal curve is thought to represent the fundamental relationship between the basal secretory state of parathyroid glands and extracellular Ca level.


SwissPKcdw - A clinical data warehouse for the optimization of pediatric dosing regimens.
Clinical trials have been performed mainly in adults and accordingly the necessary information is lacking for pediatric patients, especially regarding dosage recommendation for approved drugs. This gap in information could be filled with results from pharmacokinetic (PK) modeling, based on data collected in daily clinical routine. In order to make this data accessible and usable for research, the Swiss Pharmacokinetics Clinical Data Warehouse (SwissPKcdw ) project has been set up, including a clinical data warehouse (CDW) and the regulatory framework for data transfer and use within. Embedded into the secure BioMedIT network, the CDW can connect to various data providers and researchers in order to collaborate on the data securely. Due to its modularity, partially containerized deployment and open-source software, each of the components can be extended, modified, and re-used for similar projects that require integrated data management, data analysis, and web tools in a secure scientific data and information technology (IT) environment. Here, we describe a collaborative and interprofessional effort to implement the aforementioned infrastructure between several partners from medical health care and academia. Furthermore, we describe a real-world use case where blood samples from pediatric patients were analyzed for the presence of genetic polymorphisms and the results were aggregated and further analyzed together with the health-related patient data in the SwissPKcdw .


Sequence recognition and self-sorting of a dipeptide by cucurbit[6]uril and cucurbit[7]uril.
Cucurbit[7]uril forms very strong complex with zwitterionic dipeptide Phe-Gly with affinity exceeding 10(7) M(-1) and effectively recognizes peptide sequence of Phe-Gly over Gly-Phe as well as Tyr-Gly over Gly-Tyr and Trp-Gly over Gly-Trp with relative affinities of 23 000, 18 000 and 2000, respectively.


Frequency Offset Corrected Inversion Pulse for B0 and B1 Insensitive Fat Suppression at 3T: Application to MR Neurography of Brachial Plexus.
The 3D short tau inversion recovery (STIR) sequence is routinely used in clinical MRI to achieve robust fat suppression. However, the performance of the commonly used adiabatic inversion pulse, hyperbolic secant (HS), is compromised in challenging areas with increased B0 and B1 inhomogeneities, such as brachial plexus at 3T. To demonstrate the frequency offset corrected inversion (FOCI) pulse as an efficient fat suppression STIR pulse with increased robustness to B0 and B1 inhomogeneities at 3T, compared to the HS pulse. Prospective. Initial evaluation was performed in phantoms and one healthy volunteer by varying the B1 field, while subsequent comparison was performed in three healthy volunteers and five patients without varying the B1 . 3T; 3D TSE-STIR with HS and FOCI pulses. Brachial plexus images were qualitatively evaluated by two musculoskeletal radiologists independently using a four-point grading scale for fat suppression, shading artifacts, and nerve visualization. The Wilcoxon signed-rank test with P < 0.05 was considered statistically significant. Simulations and phantom experiments demonstrated broader bandwidth (2.5 kHz vs. 0.83 kHz, increased B0 robustness) at the same adiabatic threshold and lower adiabatic threshold (5 μT vs. 7 μT at 3.5 ppm, increased B1 robustness) at the same bandwidth with the FOCI pulse compared to the HS pulse With increased bandwidth, the FOCI pulse achieved robust fat suppression even at 50% of maximum B1 strength, while the HS pulse required >75% of maximum B1 strength. Compared to the standard 3D TSE-STIR with HS pulse, the FOCI pulse achieved uniform fat suppression (P < 0.05), better nerve visualization (P < 0.05), and minimal shading artifacts (P < 0.01) in brachial plexus at 3T. The FOCI pulse has increased robustness to B0 and B1 inhomogeneities, compared to the HS pulse, and enables uniform fat suppression in brachial plexus at 3T. 1 Techinical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;48:1104-1111.


[Prosthetic rehabilitation of a young patient after surgical-radiation treatment].
The surgery and radiumtherapy injuries able to reduce neoplastic lesions can determine very dreadful deformities on the younger patient's face. The peculiar treatment aim at achieve a real and sure abridgement of the aforesaid chronic lesions. To hit this target is necessary a therapeutic plain carry out, in fallow periods, by no a single but a whole of specialized doctors. The Authors report a very interesting observation concerning a very younger boy that, following a personal method, had reached a very well adaptations of the present injuries.


Determination of hydroxycinnamic acids present in Rhododendron species.
Hydroxycinnamates including free hydroxycinnamic acids and their chlorogenic acid derivatives and glycosides have been profiled in leaf extracts of 98 Rhododendron species using LC-MS techniques. In total, 69 hydroxycinnamic acid derivatives were identified in the leaves of 98 Rhododendron species. Some derivatives serve as unique phytochemical marker for a single species, whereas other compounds are limited to certain subgenera. The distribution of compounds among six different subgenera of Rhododendron was studied using PCA and PLS-DA. This contribution presents data that provide unique metabolomic insight in the distribution of a class of secondary metabolites within a large selection of species from the botanically diverse plant genus Rhododendron.


Adjudicated morbidity and mortality outcomes by age among individuals with HIV infection on suppressive antiretroviral therapy.
Non-AIDS conditions such as cardiovascular disease and non-AIDS defining cancers dominate causes of morbidity and mortality among persons with HIV on suppressive combination antiretroviral therapy. Accurate estimates of disease incidence and of risk factors for these conditions are important in planning preventative efforts. With use of medical records, serious non-AIDS events, AIDS events, and causes of death were adjudicated using pre-specified criteria by an Endpoint Review Committee in two large international trials. Rates of serious non-AIDS which include cardiovascular disease, end-stage renal disease, decompensated liver disease, and non-AIDS cancer, and other serious (grade 4) adverse events were determined, overall and by age, over a median follow-up of 4.3 years for 3,570 participants with CD4+ cell count ≥300 cells/mm³ who were taking antiretroviral therapy and had an HIV RNA level ≤500 copies/mL. Cox models were used to examine the effect of age and other baseline factors on risk of a composite outcome of all-cause mortality, AIDS, or serious non-AIDS. Five-year Kaplan-Meier estimates of the composite outcome, overall and by age were 8.3% (overall), 3.6% (<40), 8.7% (40-49) and 16.1% (≥50), respectively (p<0.001). In addition to age, smoking and higher levels of interleukin-6 and D-dimer were significant predictors of the composite outcome. The composite outcome was dominated by serious non-AIDS events (overall 65% of 277 participants with a composite event). Most serious non-AIDS events were due to cardiovascular disease and non-AIDS cancers. To date, few large studies have carefully collected data on serious non-AIDS outcomes. Thus, reliable estimates of event rates are scarce. Data cited here, from a geographically diverse cohort, will be useful for planning studies of interventions aimed at reducing rates of serious non-AIDS events among people with HIV.


Generation and selection of monoclonal antibodies identifying surface molecules discriminating between fetal and adult fibroblasts.
The present report describes the reactivity of two murine monoclonal antibodies, i.e., CB11 and CB43, the first obtained by using embryonic material as immunizer and the second elicited against a human cell line. These reagents recognize two distinct molecules marking a peculiar differentiation stage on fetal/embryonic fibroblasts. The first structure is a single chain of 14.5 kd, the second one a heterodimer of 40-80 kd. Even if these reagents are not strictly fibroblast restricted, translineage expression does not diminish the medical relevance of the reagents; in fact, they may have application in prenatal diagnostics and amniocentesis testing, in which it is necessary to discriminate between fetal and maternal cells.


The effect of supine cycling and progressive lower body negative pressure on cerebral blood velocity responses.
Moderate-intensity aerobic exercise increases cerebral blood velocity (CBv) primarily due to hyperpnea-induced vasodilation; however, the integrative control of cerebral blood flow (CBF) allows other factors to contribute to the vasodilation. Although lower body negative pressure (LBNP) can reduce CBv, the exact LBNP intensity required to blunt the aforementioned exercise-induced CBv response is unknown. This could hold utility for concussion recovery, allowing individuals to exercise at higher intensities without symptom exacerbation. Thirty-two healthy adults (age: 20-33 yr; 19 females/13 males) completed a stepwise maximal exercise test during a first visit to determine each participant's wattage associated with their exercise-induced maximal CBv increase. During the second visit, following supine rest, participants completed moderate-intensity exercise at their determined threshold, while progressive LBNP was applied at 0, -20, -40, -60, -70, -80, and ∼88 Torr. Bilateral middle cerebral artery blood velocities (MCAvs), mean arterial pressure (MAP), heart rate, respiratory rate, and end-tidal carbon dioxide levels were measured continuously. Two-way analysis of variance with effect sizes compared between sexes and stages. Compared with resting supine baseline, averaged MCAv was elevated during 0 and -20 Torr LBNP (q value > 7.73; P < 0.001); however, no differences were noted between baseline and -40 to -70 Torr (q value < |4.24|; P > 0.262). Differences were present between females and males for absolute MCAv measures (q value > 11.2; P < 0.001), but not when normalized to baseline (q value < 0.03; P > 0.951). Supine cycling-elicited increases in MCAv are able to be blunted during the application of LBNP ranging from -40 to -70 Torr. The blunted CBv response demonstrates the potential benefit of allowing individuals to aerobically train (moderate-intensity supine cycling with LBNP) without exacerbating symptoms during the concussion recovery phase.NEW & NOTEWORTHY The current investigation demonstrated that moderate-intensity supine cycling-induced increases in cerebral blood velocities were balanced by the lower body negative pressure-induced decreases in cerebral blood velocity. Although performed in a healthy population, the results may lend themselves to a potential treatment option for individuals recovering from concussion or experience persistent concussion symptoms.


History of thoracic outlet syndrome.
Thoracic outlet syndrome (TOS), a condition in which neurovascular structures in the thoracic outlet region are compressed, can be caused by anatomical abnormalities or acquired changes in the soft tissues and bony structures in the region. The brachial plexus is the most frequently affected structure. TOS is one of the most difficult neurovascular compressions in the upper extremity to manage because of the variability of complaints and the high risk associated with surgical treatment.


Needle myringotomy: a useful technique with the increased prevalence of the human immunodeficiency virus.
Myringotomy is one of the most common procedures performed by ENT surgeons. Use of the tip of a hypodermic needle not only provides a neat and precise incision into the tympanic membrane, but is also a cheap and disposable means of doing so. Sterility is virtually guaranteed avoiding any possibility of cross contamination between consecutive patients.


Risk of adverse gastrointestinal events from inhaled corticosteroids.
To determine whether patients prescribed inhaled corticosteroids are at risk for adverse gastrointestinal effects. Retrospective cohort study. Urban health center with an academic affiliation. A total of 19,443 adults (mean age 31.8 yrs) with airways disease, defined as a diagnosis of asthma or chronic obstructive pulmonary disease, and who were prescribed both an inhaled corticosteroid and albuterol (7156 patients) or inhaled albuterol alone (12,287 patients) between November 1977 and February 2002. The frequency of adverse gastrointestinal events in the patients who used inhaled corticosteroids and albuterol was compared with that in the patients who used albuterol alone. Adverse gastrointestinal outcomes included events such as gastritis, ulcers, and bleeding. Cox proportional hazards models were used to determine the risk of adverse events, controlling for possible confounders such as alcohol use or nonsteroidal antiinflammatory drug use. Adverse gastrointestinal events were observed in 461 (6.4%) patients using inhaled corticosteroids and albuterol and in 302 (2.5%) patients using only albuterol. After controlling for potential confounders, patients who used inhaled corticosteroids and albuterol had an increased risk for adverse gastrointestinal events compared with patients who used only inhaled albuterol (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.02-1.56). A prescription for a spacer device reduced this risk among patients using an inhaled corticosteroid (HR 0.26, 95% CI 0.20-0.34). Patients using inhaled corticosteroids appear to have a slight risk for adverse gastrointestinal events that is mitigated in patients who used a spacer device.


Tarsonemid mites (Acari: Tarsonemidae) on myrtaceous plants of the Atlantic Forest, Brazil, with description of a new species of Tarsonemus Canestrini amp; Fanzago.
A survey of tarsonemid mites associated with plants of the family Myrtaceae was conducted in seven areas of the Atlantic Forest biome. Fourteen known species were registered; other 21 morphospecies was identified up to genus level. Additionally, a new species, Tarsonemus conduru Lofego Cavalcante sp. nov. is described based on specimens collected in the Atlantic Forest of Bahia state.


Combined surgery and cidofovir is an effective treatment for genital warts in HIV-infected patients.
To evaluate the efficacy of surgical-cidofovir (SCT), surgical (ST) and cidofovir (CT) treatment of genital warts in HIV-infected patients. Open randomized prospective pilot study. Outpatients attending the sexually transmitted disease service of the II Dept of Infectious Diseases, L Sacco Hospital, Milan-Italy. Consenting HIV-positive patients with anal-genital warts recruited from January 2000 to March 2001. Three treatment arms: surgical excision by electrocautery, topical 1% cidofovir-gel (5 days per week, maximum 6 weeks) and electrocautery-cidofovir treatment with 1% cidofovir-gel applied within 1 month of surgical treatment (5 days per week for 2 weeks). Rate of wart clearance and time and rate of relapses within a 6-month follow-up period. Complete response was achieved in 93.1% of 29 patients treated by ST, 76.2% of 26 treated by CT and in 100% of 19 patients treated by SCT (P = 0.0033). The relapse rate in 49 patients followed-up was 73.68% in ST, 35.29% in CT and 27.27% in SCT patients (P = 0.018). Median time to relapses in ST patients was 66 days (Kaplan-Meyer, P = 0.0012). Human papillomavirus DNA was cleared in 52.63% of 19 patients evaluated. The rate of clearance of high risk and low risk genotypes was 0% and 57.14% 25% and 50% 100% and 71.42% in ST, CT and SCT patients, respectively. A combination of surgical and medical treatment was most effective in clearing lesions completely and in reducing the relapse rate. Human papillomavirus DNA clearance can be attributed to the antiviral effect of cidofovir and could explain the low relapse rate observed. Larger studies are required to determine the most appropriate medical treatment for viral eradication after surgery.


Targeting High-Risk Neuroblastoma Patient-Derived Xenografts with Oncolytic Virotherapy.
Cancer is the leading cause of death by disease in children, and over 15% of pediatric cancer-related mortalities are due to neuroblastoma. Current treatment options for neuroblastoma remain suboptimal as they often have significant toxicities, are associated with long-term side effects, and result in disease relapse in over half of children with high-risk disease. There is a dire need for new therapies, and oncolytic viruses may represent an effective solution. Oncolytic viruses attack tumor cells in two ways: direct infection of tumor cells leading to cytolysis, and production of a debris field that stimulates an anti-tumor immune response. Our group has previously shown that M002, an oncolytic herpes simplex virus (oHSV), genetically engineered to express murine interleukin-12 (mIL-12), was effective at targeting and killing long term passage tumor cell lines. In the current study, we investigated M002 in three neuroblastoma patient-derived xenografts (PDXs). PDXs better recapitulate the human condition, and these studies were designed to gather robust data for translation to a clinical trial. We found that all three PDXs expressed viral entry receptors, and that the virus actively replicated in the cells. M002 caused significant tumor cell death in 2D culture and 3D bioprinted tumor models. Finally, the PDXs displayed variable susceptibility to M002, with a more profound effect on high-risk neuroblastoma PDXs compared to low-risk PDX. These findings validate the importance of incorporating PDXs for preclinical testing of oncolytic viral therapeutics and showcase a novel technique, 3D bioprinting, to test therapies in PDXs. Collectively, our data indicate that oHSVs effectively target high-risk neuroblastoma, and support the advancement of this therapy to the clinical setting.


Characteristics of colorectal cancers among Alaska Native people before and after implementing programs to promote screening.
Alaska Native (AN) people have the highest rates of colorectal cancer (CRC) globally. Increasing CRC screening has been effective in reducing CRC-related morbidity and mortality in other populations. To examine recent descriptive epidemiology and longer-term CRC trends among AN people. To determine any changes in the descriptive epidemiology of CRC among AN people concurrent with increases in screening prevalence. We estimated age-specific CRC incidence and mortality rates 2000-2017. To examine longer-term trends in incidence and mortality 1990-2017, we conducted Joinpoint regression analyses of three-year rolling average incidence and mortality rates. We calculated descriptive statistics for two time-periods: 2000-2008, and 2009-2017. Finally, we examined five-year survival probability. CRC incidence increased over time (1990-2017) among AN people aged less than 50 years, while there were modest declines in AN people older than 50 years old since 2000. Overall, AN CRC mortality rates declined between 1990 and 2004, but have been increasing steadily since that time. Comparing 2000-2008 with 2009-2017 we observed no difference in CRC incidence and mortality, age at diagnosis, tumor size, tumor location, or stage distribution. Survival analyses indicated no change in hazard of death between 2004-2008 and 2009-2017 (HR 1.02, 95 % CI: 0.74, 1.38, P = 0.93). Colorectal cancer prevention and control efforts across the Alaska Tribal Health System have not yet resulted in reduced mortality rates, or induced earlier stage migration. Intensified efforts will be necessary to reduce the burden of CRC among this high-risk population. Continued and increased focus on primary and secondary prevention efforts is warranted.


Friendship or Competition? Symmetry in Social Play within the Two Packs of German Shepherd Puppies.
The symmetry of social play in Canids has been previously studied, especially in wolves, free-ranging dogs, and within mixed-aged groups, however our study focused on symmetry and asymmetry within play interactions in two litters (14 puppies) of German Shepherd dogs (GSDs). At the age of 7 weeks, we evaluated 1287 dyadic interactions (litter 1: n = 339 interactions, litter 2: n = 948 interactions), and at the age of 9 weeks we evaluated 1255 dyadic interactions (litter 1: n = 433 interactions, litter 2: n = 822 interactions). Dyadic interactions were observed and the winning indexes were calculated for 43 pairs (dyads). The groups of puppies studied were all the same age, therefore we focused on the aspects of sex and body size as primary variables. The weight and chest circumference of all puppies were measured. The distribution of interactions showed a slight inclination to mixed-sex dyads, but we did not obtain any statistically significant results concerning the impact of body size on play interactions. Symmetry in play was observed within litter 1 at the age of 7 weeks and at the age of 9 weeks, and within litter 2 at the age of 7 weeks. Since the number of puppies in this study was too small, these results should be interpreted regarding this limitation, and cannot be generalized to a larger population of domestic dogs nor the GSD breed. In further studies, it would be interesting to compare larger samples of different breeds, under different breeding conditions, and the effect of the environment on the style of social play.


The endocannabinoid anandamide is an airway relaxant in health and disease.
Chronic obstructive airway diseases are a global medical burden that is expected to increase in the near future. However, the underlying mechanistic processes are poorly understood so far. Herein, we show that the endocannabinoid anandamide (AEA) induces prominent airway relaxation in vitro and in vivo. In contrast to 2-arachidonlyglycerol-induced airway relaxation, this is mediated by fatty acid amide hydrolase (FAAH)-dependent metabolites. In particular, we identify mouse and also human epithelial and airway smooth muscle cells as source of AEA-induced prostaglandin E2 production and cAMP as direct mediator of AEA-dependent airway relaxation. Mass spectrometry experiments demonstrate reduced levels of endocannabinoid-like compounds in lungs of ovalbumin-sensitized mice indicating a pathophysiological relevance of endocannabinoid signalling in obstructive airway disease. Importantly, AEA inhalation protects against airway hyper-reactivity after ovalbumin sensitization. Thus, this work highlights the AEA/FAAH axis as a critical regulator of airway tone that could provide therapeutic targets for airway relaxation.


Curcumin nanocrystals self-stabilized Pickering emulsion freeze-dried powder: Development, characterization, and suppression of airway inflammation.
Curcumin, a diketone compound extracted from turmeric's rhizome, is an effective anti-inflammatory drug with multiple pharmacological activities. However, its low oral bioavailability due to its low water solubility and permeability severely limits its clinical applications. Therefore, to enhance the oral bioavailability of curcumin, further enhance its anti-inflammatory effects, and improve its potential in the treatment of airway inflammation, a curcumin nanocrystalline self-stabilizing Pickering emulsion (Cur-NSSPE) was prepared through high-pressure homogenization. Next, Cur-NSSPE was dried using a freeze-drying method to produce Cur-NSSPE-FDP. The prepared Cur-NSSPE and Cur-NSSPE-FDP were physically characterized. The release behavior and transmembrane transport capability of Cur-NSSPE-FDP in vitro were evaluated. Pharmacokinetic study was performed to evaluate its oral bioavailability. The anti-inflammatory effects of Cur-NSSPE-FDP in vivo and in vitro were investigated using RAW 264.7 macrophage inflammation model induced by LPS and IFN-γ and asthma model in BALB/c mice induced by OVA. The average particle size of Cur-NSSPE was (163.66 ± 6.78) nm, and the average drug content was (2.78 ± 0.01) mg/mL. The transmission electron microscopy results showed that the droplets were spherical in shape with a relatively uniform size, and the curcumin nanocrystals formed a spherical core-shell structure wrapped at the interface of the droplets. The scanning electron microscopy showed that Cur-NSSPE-FDP was a neatly arranged, having loose and porous network structure. Furthermore, it can significantly improve the cumulative release of curcumin in vitro and improve oral bioavailability in rats, increase the uptake of RAW264.7 and Caco-2 cells, promote the transport of curcumin across Caco-2 cells, significantly inhibit the expression of inflammatory factors NO, IL-6, TNF-a, MDA, IgE and ICAM-1, and improve the expression of IL-10 and SOD. These results indicated that the curcumin nanocrystalline self-stabilizing Pickering emulsion-freeze dried powder improved the oral bioavailability of curcumin and enhanced its therapeutic effect in airway inflammation.


Glaucoma drainage implants in pediatric patients.
Approximately, one fifth of primary congenital glaucoma patients fail primary surgery. Also, some pediatric glaucomas respond poorly to goniotomy or trabeculectomy. In these situations, clinicians often choose trabeculectomy with mitomycin-C or a drainage implant as a surgical treatment. Glaucoma drainage device implantation is a useful option in refractory patients. When other surgical treatments have a poor prognosis for success, prior conventional surgery fails, or significant conjunctival scarring precludes filtration surgery, glaucoma drainage implant may effectively control intraocular pressure. Patients often require adjunctive glaucoma medications after surgery and may develop complications. Most of these complications, however, are reversible or resolve spontaneously, and most are not associated with vision loss.


Cytoplasmic expression of DCLK1-S, a novel DCLK1 isoform, is associated with tumor aggressiveness and worse disease-specific survival in colorectal cancer.
Isoform-specific function of doublecortin-like kinase 1 (DCLK1) has highlighted the key role of the DCLK1-S (short isoform) in the maintenance, progression, and invasion of the tumor. This study was designed to produce an anti-DCLK1-S polyclonal antibody to evaluate DCLK1-S in human colorectal cancer (CRC) specifically. The expression pattern and clinical significance of DCLK1-S were assessed in a well-defined tissue microarray (TMA) series of 348 CRC and 51 adjacent normal tissues during a follow-up period of 108 months. Expression of DCLK1-S was significantly higher in CRC samples compared to adjacent normal samples (P< 0.001). Cytoplasmic expression of DCLK1-S was significantly higher in the tumors at the advanced stage of cancer and with poorer differentiation (P< 0.001, P= 0.02). The patients with CRC whose tumors showed higher cytoplasmic expression of DCLK1-S had worse disease-specific survival (DSS) (log-rank test, P= 0.03) and 5-year DSS rates (P= 0.01). Additionally, an improved prognostic value was observed in the patients with CRC with high DCLK1-S expression vs. its moderate expression (HR: 2.70, 95% CI: 0.98-7.38; p= 0.04) by multivariate analysis. Our findings strongly supported that high cytoplasmic expression of DCLK1-S compared to its moderate expression could be considered an independent prognostic factor influencing DSS.


Late results of mitral valve repair for mitral regurgitation.
This study was undertaken to evaluate the long-term results of mitral valve repair for mitral regurgitation. Between 1991 and 2000, 301 patients with mitral regurgitation underwent mitral valve repair. There were 167 men and 134 women whose mean age was 56 +/- 14 years. The patients were comprised of 7 patients in Carpentier's type I, 277 patients in type II, and 17 patients in type III. Chordal replacement with expanded polytetrafluoroethylene sutures had been prospectively applied to repair the anterior mitral leaflet prolapse. Ring annuloplasty was performed in 230 patients (76%). The follow-up was complete and mean follow-up was 67 +/- 33 months, for a cumulative follow-up of 1,624 patient-years. There were 5 hospital deaths and 11 late deaths (2 cardiac and 9 noncardiac). All survivors except those with stroke were in the New York Heart Association (NYHA) functional class I or II. At 10 years, the actuarial survival was 90 +/- 3%, the freedom from embolism was 86 +/- 4%, the freedom from reoperation was 96 +/- 2%, and the freedom from valve-related events was 77 +/- 4%. At 10 years, the freedom from reoperation in the patients with anterior leaflet prolapse was 90 +/- 5%. Mitral valve repair is feasible in most patients with mitral regurgitation and is associated with low mortality and low rates of valve related events. Chordal replacement with expanded polytetrafluoroethylene sutures is effective, safe, and durable at long-term follow-up for patients with anterior leaflet prolapse.


Evaluative Conditioning: The "How" Question.
Evaluative conditioning (EC) refers to attitude formation or change toward an object due to that object's mere co-occurrence with another valenced object or objects. This chapter focuses on the "how" question, that is, the question of what cognitive processes intervene between mere co-occurrence and attitude formation or change. Though EC has typically been thought of as occurring through a single, albeit contentious, mechanism, we begin by pointing out that both the heterogeneity of EC methodologies and the abundance of inconsistent results suggest that multiple processes with different characteristics can produce EC. We describe how the earliest posited process of EC, Pavlovian conditioning or signal learning, is a valid mechanism of EC that appears to have operated in some experiments but is unlikely to have operated in others and also cannot account for various EC findings. We describe other mechanisms of EC, when they can be expected to occur, and what characteristics they have. We particularly focus our attention on a process model of EC we have recently introduced, the implicit misattribution model. Finally, we describe the implications of a multi-process view of EC, which we argue can help resolve theoretical controversies and further the application of EC as a practical intervention for influencing attitudes in various domains.


The assessment of the readiness of five countries to implement child maltreatment prevention programs on a large scale.
This study aimed to systematically assess the readiness of five countries - Brazil, the Former Yugoslav Republic of Macedonia, Malaysia, Saudi Arabia, and South Africa - to implement evidence-based child maltreatment prevention programs on a large scale. To this end, it applied a recently developed method called Readiness Assessment for the Prevention of Child Maltreatment based on two parallel 100-item instruments. The first measures the knowledge, attitudes, and beliefs concerning child maltreatment prevention of key informants; the second, completed by child maltreatment prevention experts using all available data in the country, produces a more objective assessment readiness. The instruments cover all of the main aspects of readiness including, for instance, availability of scientific data on the problem, legislation and policies, will to address the problem, and material resources. Key informant scores ranged from 31.2 (Brazil) to 45.8/100 (the Former Yugoslav Republic of Macedonia) and expert scores, from 35.2 (Brazil) to 56/100 (Malaysia). Major gaps identified in almost all countries included a lack of professionals with the skills, knowledge, and expertise to implement evidence-based child maltreatment programs and of institutions to train them; inadequate funding, infrastructure, and equipment; extreme rarity of outcome evaluations of prevention programs; and lack of national prevalence surveys of child maltreatment. In sum, the five countries are in a low to moderate state of readiness to implement evidence-based child maltreatment prevention programs on a large scale. Such an assessment of readiness - the first of its kind - allows gaps to be identified and then addressed to increase the likelihood of program success.


Characterization of a novel endo-β-1,4-glucanase from Armillaria gemina and its application in biomass hydrolysis.
A novel endo-β-1,4-glucanase (EG)-producing strain was isolated and identified as Armillaria gemina KJS114 based on its morphology and internal transcribed spacer rDNA gene sequence. A. gemina EG (AgEG) was purified using a single-step purification by gel filtration. The relative molecular mass of AgEG by sodium dodecyl sulfate polyacrylamide gel electrophoresis was 65 kDa and by size exclusion chromatography was 66 kDa, indicating that the enzyme is a monomer in solution. The pH and temperature optima for hydrolysis were 5.0 and 60 °C, respectively. Purified AgEG had the highest catalytic efficiency with carboxymethylcellulose (k(cat)/K(m) = 3,590 mg mL⁻¹ s⁻¹) unlike that reported for any fungal EG, highlighting the significance of the current study. The amino acid sequence of AgEG showed homology with hydrolases from the glycoside hydrolase family 61. The addition of AgEG to a Populus nigra hydrolysate reaction containing a commercial cellulase mixture (Celluclast 1.5L and Novozyme 188) showed a stimulatory effect on reducing sugar production. AgEG is a good candidate for applications that convert lignocellulosic biomass to biofuels and chemicals.


Hypertension in elderly patients. A comparative study between indapamide and hydrochlorothiazide.
Diuretic therapy is still regarded as the first-step approach in elderly patients with benign or moderate arterial hypertension. Traditional preparations such as thiazides, or potassium-sparing agents, are not devoid of significant side effects, however. Indapamide, a nonthiazide diuretic, has been shown to reduce blood pressure at low doses, in several clinical reports. In the present study, the effect of indapamide (2.5 mg per day) was compared with that of hydrochlorothiazide (50 mg per day) on blood pressure and serum chemistry of 47 elderly hypertensive patients (ages 65 to 91). After a six-week placebo-treatment period, patients were randomly assigned to receive either indapamide or hydrochlorothiazide. At that moment, blood pressure of patients in the supine position averaged 185 +/- 2/107 +/- 2, and 181 +/- 3/102 +/- 2 mm Hg, in the indapamide and hydrochlorothiazide groups, respectively. After 48 weeks of therapy, blood pressure was 162 +/- 3/89 +/- 2 and 170 +/- 2/94 +/- 2 mm Hg in the same groups, respectively. Serum sodium levels remained unchanged in indapamide-treated patients, but decreased progressively from 141 +/- 1 to 134 +/- 1 meq/liter in hydrochlorothiazide-treated patients. Serum potassium levels decreased from 4.50 +/- 0.12 to 4.04 +/- 0.10 meq/liter in indapamide-treated patients, whereas in the patients receiving hydrochlorothiazide, kalemia decreased from 4.23 +/- 0.09 to 3.33 +/- 0.01 meq/liter. Finally, serum uric acid levels did not increase significantly in patients receiving indapamide, whereas it rose from 6.5 +/- 0.4 to 8.7 +/- 0.3 mg/dl in patients treated with hydrochlorothiazide. In conclusion, indapamide resulted in a better control of systolic and diastolic blood pressure in this group of elderly hypertensive patients. In addition, the effect of each drug on blood chemistry differed markedly: indapamide failed to alter significantly the serum ionic composition, whereas hydrochlorothiazide was associated with both hyponatremia and hypokalemia.


Colchicine-light effects on growth and mitotic behaviour in germinating lettuce achenes.
Root and shoot growth were severely suppressed in colchicine-pretreated lettuce achenes germinated in the dark and under illumination of 150 lux. Abnormal nuclear morphology rather than normal-appearing restitution nuclei was evident in these drug-pretreated achenes, there being no evidence of normal mitotic behaviour or cytokinetic activity in the root and shoot tissues examined. Root extension and lateral root meristem differentiation were evident in colchicine-pretreated achenes germinated under an illumination of 3000 lux, normal-appearing anaphase figures and cytokinetic activity being evident in both the primary root apices and lateral root meristems. Thus, the growth and mitotic behaviour of germinating colchicine-pretreated lettuce achenes were observed to be influenced significantly by the environmental light intensity in which germination occurred.


Messenger ribonucleic acid levels of interleukin-1 beta, interleukin-6 and interleukin-8 in the lower uterine segment increased significantly at final cervical dilatation during term parturition, while those of tumor necrosis factor alpha remained unchanged.
To investigate the content of tumor necrosis factor alpha, interleukin-1 beta, interleukin-6 and interleukin-8 messenger ribonucleic acid (mRNA) in the lower uterine segment during term parturition. mRNA extracts from the lower uterine segment obtained from 53 women undergoing non-elective caesarean section at term were analyzed by semi-quantitative reverse transcriptase polymerase chain reaction. The patients were grouped according to cervical dilatation (less than 2 cm, n=18; 2 to less than 4 cm, n=13; 4-6 cm, n=7; more than 6 cm, n=15) at the time of caesarean section. Interleukin-1 beta and interleukin-8 mRNA-contents at more than 6 cm cervical dilation were significantly higher than at less than 2 cm. The levels of interleukin-6 were already significantly increased in the 4-6 cm group, while the tumor necrosis factor alpha ribonucleic acid content did not change during parturition. The process of cervical dilatation during parturition at term is associated with an increased expression of interleukin-1 beta, interleukin-6 and interleukin-8 mRNA in the lower uterine segment. These findings support the theory that the activation of the inflammatory network plays an important role in the progress of cervical dilatation.


Construction of improved plasmid vectors for promoter characterization in Pseudomonas aeruginosa and other gram-negative bacteria.
We report the construction of two broad host range promoter-probe plasmid vectors for rapid analysis of promoters in Gram-negative bacteria. The new vectors, pME4507 and pME4510, carry carbenicillin and gentamycin resistance genes, respectively, and are small sized (4 kb) with a flexible multiple cloning site to facilitate directional cloning of putative promoter elements. The vectors allow rapid plate-based screening for promoter activities, using beta-galactosidase as the reporter enzyme. In the absence of an inserted promoter fragment, they display very low background activity, making them a useful tool for analysis of low expression level promoters.


Diet quality of Japanese adults with respect to age, sex, and income level in the National Health and Nutrition Survey, Japan.
Although several studies in Western countries show that higher socioeconomic status is associated with higher diet quality, no study has observed this association in Japan. In the current study, we examined the association between diet quality and the combinations of age, sex, and household income, and also compared the dietary intake between diet quality levels according to household income. Cross-sectional study. National Health and Nutrition Survey, Japan in 2014. 2785 men and 3215 women. Higher Japanese Food Guide Spinning Top scores (better diet quality) were observed in older women, especially those with higher household income, whereas lower scores were observed in younger men with lower household income. Those having low quality diet, especially in low income households, had higher odds of not meeting the recommended amounts of the Japanese dietary guidelines, than those having high quality diet. Diet quality in Japanese adults differed by age and sex as well as by household income level. A different approach to diet quality improvement is needed according to population characteristics including not only age and sex but also social economic status.


Kinetic stability modelling of keratinolytic protease P45: influence of temperature and metal ions.
The activity and kinetic stability of a keratinolytic subtilisin-like protease from Bacillus sp. P45 was investigated in 100 mM Tris-HCl buffer (pH 8.0; control) and in buffer with addition of Ca(2+) or Mg(2+) (1-10 mM), at different temperatures. Addition of 3 mM Ca(2+) or 4 mM Mg(2+) resulted in a 26% increment on enzyme activity towards azocasein when compared to the control (100%; without added Ca(2+) or Mg(2+)) at 55 °C. Optimal temperature for activity in the control (55 °C) was similar with Mg(2+); however, temperature optimum was increased to 60 °C with 3 mM Ca(2+), displaying an enhancement of 42% in comparison to the control at 55 °C. Stability of protease P45 in control buffer and with Mg(2+) addition was assayed at 40-50 °C, and at 55-62 °C with Ca(2+) addition. Data were fitted to six kinetic inactivation models, and a first-order equation was accepted as the best model to describe the inactivation of protease P45 with and without metal ions. The kinetic and thermodynamic parameters obtained showed the crucial role of calcium ions for enzyme stability. As biocatalyst stability is fundamental for commercial/industrial purposes, the stabilising effect of calcium could be exploited aiming the application of protease P45 in protein hydrolysis.


MRI-defined sarcopenia predicts mortality in patients with chronic liver disease.
To explore whether sarcopenia, diagnosed by an abbreviated magnetic resonance imaging (MRI) protocol is a risk factor for hepatic decompensation and mortality in patients with chronic liver disease (CLD). In this retrospective single-centre study we included 265 patients (164 men, mean age 54 ± 16 years) with CLD who had undergone MRI of the liver between 2010 and 2015. Transverse psoas muscle thickness (TPMT) was measured on unenhanced and contrast-enhanced T1-weighted and T2-weighted axial images. Sarcopenia was defined by height-adjusted and gender-specific cut-offs in women as TPMT < 8 mm/m and in men as TPMT < 12 mm/m respectively. Patients were further stratified into three prognostic stages according to the absence of advanced fibrosis (FIB-4 < 1.45, non-advanced CLD), compensated-advanced CLD (cACLD) and decompensated-advanced CLD (dACLD). The inter-observer agreement for the TPMT measurements (κ = 0.98; 95% confidence interval [95% CI]:0.96-0.98), as well as the intra-observer agreement between the three image sequences (κ = 0.99; 95% CI: 0.99-1.00) were excellent. Sarcopenia was not predictive of first or further hepatic decompensation. In patients with cACLD and dACLD, sarcopenia was a risk factor for mortality (cACLD: hazard ratio (HR):3.13, 95% CI: 1.33-7.41, P = .009; dACLD:HR:2.45, 95% CI: 1.32-4.57, P = .005) on univariate analysis. After adjusting for the model of end-stage liver disease (MELD) score, albumin and evidence of clinical significant portal hypertension, sarcopenia (adjusted HR: 2.76, 95% CI: 1.02-7.42, P = .045) remained an independent risk factor for mortality in patients with cACLD. Sarcopenia can be easily evaluated by a short MRI exam without the need for contrast injection. Sarcopenia is a risk factor for mortality, especially in patients with cACLD.


Ionic strength-dependent interaction of rat liver casein kinase I with plasma membrane.
Casein kinase I binding to rat liver plasma membrane was rapidly released from membrane by increasing the ionic strength above physiological level. The released activities at 250-300 mM NaCl were 3-4-fold higher than those obtained under lower ionic strength below 100 mM NaCl. This reaction occurred nonenzymatically and was reversible. By lowering the ionic strength from 250 mM to 50 mM NaCl by dilution at least 50% of the released enzyme was rebound to plasma membrane. By gel filtration analysis, most of the released enzyme activity under higher NaCl concentration was recovered around the molecular mass of 35,000 which corresponded to that of casein kinase I. This enzyme showed the tendency to aggregate under lower ionic strength (50 mM NaCl), but existed as monomer under higher ionic strength (250 mM NaCl). These results suggest that the release of casein kinase I from plasma membrane and the rebinding to membrane induced by the alteration of ionic strength seem to be an important regulatory mechanism in determining the subcellular distribution of this enzyme.


Bilateral testicular dislocation with unilateral rupture.
A case of bilateral luxation of the testes associated with testicular rupture is presented. Bilateral traumatic dislocation of the testes is uncommon and its association with testicular rupture has not been reported previously. The etiology, classification and treatment of testicular luxation are reviewed briefly. Reports in the literature have indicated initial non-operative management but our case demonstrates the need for early surgical exploration.


Relation of Gamma-Glutamyl Transferase to Cardiovascular Events in Patients With Acute Coronary Syndromes.
The prognostic value of gamma-glutamyl transferase (GGT) in patients with acute coronary syndromes (ACS) has been incompletely investigated. We investigated this clinically relevant question in 2,534 consecutive patients with ACS who underwent percutaneous coronary intervention (PCI). GGT activity was measured before PCI procedure in all patients. Statin therapy at hospital discharge was prescribed in 94% of the patients. The primary outcome was 3-year mortality. Patients were divided into 3 groups: the group with GGT in the first tertile (GGT <28 U/L; n = 848 patients), the group with GGT in the second tertile (GGT 28 to <50 U/L; n = 843 patients), and the group with GGT in the third tertile (GGT ≥50 U/L; n = 843 patients). The primary outcome (all-cause deaths) occurred in 250 patients: 70 deaths (9.7%) among patients of the first, 69 deaths (9.0%) among patients of the second, and 111 deaths (14.8%) among patients of the third GGT tertile (adjusted hazard ratio [HR] 1.24, 95% CI 1.08 to 1.42, p = 0.002) and cardiac and noncardiac deaths occurred in 157 (63%) and 93 patients (37%), respectively. GGT was associated with the increased risk of noncardiac mortality (adjusted HR 1.35 [1.09 to 1.66], p = 0.005) but not cardiac mortality (adjusted HR 1.16 [0.97 to 1.38], p = 0.098; all 3 risk estimates were calculated per SD increase in the logarithmic scale of GGT activity). In conclusion, in contemporary patients with ACS treated with PCI and on statin therapy, elevated GGT activity was associated with the increased risk of all-cause and noncardiac mortality but not with the risk of cardiac mortality.