STAT3-coordinated migration facilitates the dissemination of diffuse large B-cell lymphomas.
The motile characteristics and mechanisms that drive the dissemination of diffuse large B-cell lymphoma (DLBCL) are elusive. Here, we show that DLBCL initiates dissemination through activating STAT3-mediated amoeboid migration. Mechanistically, STAT3 activates RHOH transcription, which competes with the RhoGDP dissociation inhibitor RhoGDIγ to activate RhoA. In addition, activated STAT3 regulates microtubule dynamics and releases ARHGEF2 to activate RhoA. Both the JAK inhibitor ruxolitinib and the microtubule stabilizer Taxol suppress DLBCL cell dissemination in vivo. A clinical DLBCL sample analysis shows that STAT3-driven amoeboid movement is particularly important for the transition from stage I to stage II. This study elucidates the mechanism of DLBCL dissemination and progression and highlights the potential of combating advanced DLBCL with a JAK/STAT inhibitor or microtubule stabilizer to reduce DLBCL motility; these findings may have a great impact on the development of patient-tailored treatments for DLBCL.


Monovalent cation transport in myotonic dystrophy. Na-K pump ratio in erythrocytes.
Myotonic dystrophy is a dominantly-inherited disorder which affects skeletal muscle in combination with several other systems. Because of abnormalities in red blood cells, a universal membrane defect has been proposed as the primary disturbance. Erythrocyte cation pump ratios have also been reported to be abnormal. Hyperinsulinemia and glucose intolerance are present in a large number of patients. Since dramatic effects of insulin on membrane cation transport have been shown in several tissues, notably skeletal muscle, we wished first to confirm reports of altered pump ratio in these patients and then to evaluate the effects of insulin on cation fluxes. However, in our experiments myotonic dystrophy patients had normal pump ratios when compared with disease controls.


Measures of total stress-induced blood pressure responses are associated with vascular damage.
The role of cardiovascular reactivity to study hypertension, and the assessment methods, are still controversial. We aimed to verify the association of hypertension and vascular damage with several measures of cardiovascular response. We studied 40 patients with normal-high (132 +/- 1/87 +/- 1 mm Hg) blood pressure (Group 1) and 80 untreated hypertensive subjects. Postischemic forearm vascular resistance (mFVR) served to differentiate hypertensive subjects (142 +/- 2/92 +/- 1 mm Hg v 143 +/- 2/94 +/- 2 mm Hg, P = NS) with a lower (Group 2) and higher (Group 3) hemodynamic index of vascular damage (4.8 +/- .05 v 6.3 +/- .09, P < .001). Reactivity was induced by Stroop (5') and cold pressor (90") tests. We measured muscular contraction and skin conductance as indices of emotional arousal, blood pressure, heart rate, forearm blood flow, and vascular resistance. Reactivity measures included: a) change from baseline, b) residualized score, c) cumulative change from baseline and residualized score, and d) total reactivity as area-under-the-curve (AUC), including changes occurring during baseline and recovery phases. The AUC of systolic blood pressure, diastolic blood pressure, and mFVR progressively increased in the groups (P < .001). Corrections of anthropometric and metabolic confounders were introduced in the Pearson equation between mFVR and reactivity measures. The AUC of SBP, DBP, and forearm blood flow and resistance demonstrated the highest (P < .001) correlation. On multiple regression analysis, AUC of SBP (beta = 0.634) and forearm blood flow (beta = -0.337) were predictive (P < .001) of vascular damage. Total blood pressure stress response, as AUC, including baseline and recovery phases, was significantly better associated with hypertension and vascular damage than the other reactivity measures studied.


Substance P administration to neonatal rats increases adult sensitivity to substance P.
Substance P (SP) administered subcutaneously to neonatal rats on days 1-7 after birth produced long-term physiological changes. The changes included altered pain perception and increased sialogogic response to SP, although the hypotensive response to SP was unchanged. Early exposure to the peptide therefore influenced development, particularly with respect to two systems in which SP is physiologically active. Both changes may reflect an increased sensitivity of these systems to the effects of SP.


Spectral fingerprints of large-scale neuronal interactions.
Cognition results from interactions among functionally specialized but widely distributed brain regions; however, neuroscience has so far largely focused on characterizing the function of individual brain regions and neurons therein. Here we discuss recent studies that have instead investigated the interactions between brain regions during cognitive processes by assessing correlations between neuronal oscillations in different regions of the primate cerebral cortex. These studies have opened a new window onto the large-scale circuit mechanisms underlying sensorimotor decision-making and top-down attention. We propose that frequency-specific neuronal correlations in large-scale cortical networks may be 'fingerprints' of canonical neuronal computations underlying cognitive processes.


Selective blockade of dopamine-induced vasodilation by ergonovine maleate in the vasculatures of dogs and rabbits.
In urethane anesthetized rabbits, ergonovine maleate significantly attenuated dopamine-induced systemic hypotension. Initial pressor responses to dopamine were significantly prolonged and potentiated by ergonovine. Mesenteric vasodilation elicited by dopamine in dogs was competitively inhibited by ergonovine at doses of 0.09 and 0.18 mg/kg, i.a. Failure of ergonovine to inhibit vasodilatory responses to acetylcholine or isoproterenol suggested selective blockade. These results confirm existing evidence that ergonovine selectively antagonizes peripheral dopaminergic receptors subserving vasodilation.


Long-term morphologic and biochemical changes induced by O,O,S-trimethyl phosphorothioate in the rat lung.
The long-term pulmonary morphologic and biochemical changes induced by a single, sublethal dose of O,O,S-trimethyl phosphorothioate (OOS-TMP), an impurity present in organophosphorus insecticides, was examined in female WAG/Rij rats. Animals received either corn oil or a corn oil solution of OOS-TMP at a dose of 40 mg/kg body weight by gavage and were studied at the following time intervals after treatment: 10 days, 30 days, 90 days, 6 months, and 1 year. No control or OOS-TMP-treated animal died spontaneously. Significant increases in wet and dry lung weights occurred at all times examined in OOS-TMP-treated rats compared to those in age-matched controls. No difference was observed in percentage lung water content between treated and control rats. OOS-TMP treatment resulted in hypertrophy and hyperplasia of type II alveolar epithelial cells having morphologic alterations in the size and number of osmiophilic lamellar bodies. Interstitial changes were characterized as increased numbers of fibroblasts accompanied by increased amounts of collagen fibrils and basement membrane alterations. There was also a significant increase in pulmonary hydroxyproline content in OOS-TMP-treated animals compared to that in controls at all time periods. Collagen deposition was predominantly associated with the interalveolar septa rather than being oriented around airways. The results of this study indicate that a single, sublethal dose of OOS-TMP induces long-term structural and biochemical changes in the rat lung.


Unraveling the liquid gliding on vibrating solid liquid interfaces with dynamic nanoslip enactment.
Slip length describes the classical no-slip boundary condition violation of Newtonian fluid mechanics, where fluids glide on the solid surfaces. Here, we propose a new analytical model validated by experiments for characterization of the liquid slip using vibrating solid surfaces. Essentially, we use a microfluidic system integrated with quartz crystal microbalance (QCM) to investigate the relationship between the slip and the mechanical response of a vibrating solid for a moving fluid. We discover a liquid slip that emerges especially at high flow rates, which is independent of the surface wetting condition, having significant contributions to the changes in resonant frequency of the vibrating solid and energy dissipation on its surface. Overall, our work will lead to consideration of 'missing slip' in the vibrating solid-liquid systems such as the QCM-based biosensing where traditionally frequency changes are interpreted exclusively with mass change on the sensor surface, irrespective of the flow conditions.


Unveiling the structural transformation and activity origin of heteroatom-doped carbons for hydrogen evolution.
Heteroatom-doped carbon materials have been widely used in many electrocatalytic reduction reactions. Their structure-activity relationships are mainly explored based on the assumption that the doped carbon materials remain stable during electrocatalysis. However, the structural evolution of heteroatom-doped carbon materials is often ignored, and their active origins are still unclear. Herein, taking N-doped graphite flake (N-GP) as the research model, we present the hydrogenation of both N and C atoms and the consequent reconstruction of the carbon skeleton during the hydrogen evolution reaction (HER), accompanied by a remarkable promotion of the HER activity. The N dopants are gradually hydrogenated and almost completely dissolved in the form of ammonia. Theoretical simulations demonstrate that the hydrogenation of the N species leads to the reconstruction of the carbon skeleton from hexagonal to 5,7-topological rings (G5-7) with thermoneutral hydrogen adsorption and easy water dissociation. P-, S-, and Se-doped graphites also show similar removal of doped heteroatoms and the formation of G5-7 rings. Our work unveils the activity origin of heteroatom-doped carbon toward the HER and opens a door to rethinking the structure-performance relationships of carbon-based materials for other electrocatalytic reduction reactions.


Caspase lesions of PVN-projecting MnPO neurons block the sustained component of CIH-induced hypertension in adult male rats.
Obstructive sleep apnea is characterized by interrupted breathing that leads to cardiovascular sequelae including chronic hypertension that can persist into the waking hours. Chronic intermittent hypoxia (CIH), which models the hypoxemia associated with sleep apnea, is sufficient to cause a sustained increase in blood pressure that involves the central nervous system. The median preoptic nucleus (MnPO) is an integrative forebrain region that contributes to blood pressure regulation and neurogenic hypertension. The MnPO projects to the paraventricular nucleus (PVN), a preautonomic region. We hypothesized that pathway-specific lesions of the projection from the MnPO to the PVN would attenuate the sustained component of chronic intermittent hypoxia-induced hypertension. Adult male Sprague-Dawley rats (250-300 g) were anesthetized with isoflurane and stereotaxically injected bilaterally in the PVN with a retrograde Cre-containing adeno-associated virus (AAV; AAV9.CMV.HI.eGFP-Cre.WPRE.SV40) and injected in the MnPO with caspase-3 (AAV5-flex-taCasp3-TEVp) or control virus (AAV5-hSyn-DIO-mCherry). Three weeks after the injections the rats were exposed to a 7-day intermittent hypoxia protocol. During chronic intermittent hypoxia, controls developed a diurnal hypertension that was blunted in rats with caspase lesions. Brain tissue processed for FosB immunohistochemistry showed decreased staining with caspase-induced lesions of MnPO and downstream autonomic-regulating nuclei. Chronic intermittent hypoxia significantly increased plasma levels of advanced oxidative protein products in controls, but this increase was blocked in caspase-lesioned rats. The results indicate that PVN-projecting MnPO neurons play a significant role in blood pressure regulation in the development of persistent chronic intermittent hypoxia hypertension.NEW & NOTEWORTHY Chronic intermittent hypoxia associated with obstructive sleep apnea increases oxidative stress and leads to chronic hypertension. Sustained hypertension may be mediated by angiotensin II-induced neural plasticity of excitatory median preoptic neurons in the forebrain that project to the paraventricular nucleus of the hypothalamus. Selective caspase lesions of these neurons interrupt the drive for sustained hypertension and cause a reduction in circulating oxidative protein products. This indicates that a functional connection between the forebrain and hypothalamus is necessary to drive diurnal hypertension associated with intermittent hypoxia. These results provide new information about central mechanisms that may contribute to neurogenic hypertension.


Accelerating denitrification and mitigating nitrite accumulation by multiple electron transfer pathways between Shewanella oneidensis MR-1 and denitrifying microbial community.
The bio-denitrification was usually retarded by the unbalance of electron generation and consumption. In this study, mixing S. oneidensis MR-1 with denitrifying microbial community increased the nitrogen removal rate by 74.74 % via the interspecies electron transfer (IET), and reduced the accumulated nitrite from 9.90 ± 0.81 to 0.02 ± 0.03 mg/L. Enhanced denitrification still appeared but relatively decreased, when S. oneidensis MR-1 was separated by a dialysis bag (MW < 3000), indicating mediated interspecies electron transfer (MIET) counted in IET. The results of electron transfer activity and sludge conductivity suggested DIET and MIET jointly transfer electrons from MR-1 to electroactive denitrifying bacteria (EDB), improving denitrifying reductase activities. Electron distribution among denitrifying reductases was found to be associated with the IET rate. Microbial insights showed the total abundance of EDB was increased, and denitrifying genes were correspondingly enriched. Pseudomonas was found to cooperate with exoelectrogens in a complicated microbial community.


The morphology of Trianchoratus aecleithrium Price et Berry, 1966 (Dactylogyridae, Monogenea) from a new host Trichogaster trichopterus trichopterus (Pallas, 1777).
The monogenean parasite Trianchoratus aecleithrium Price et Berry, 1966 is comparatively described from the gills of Trichogaster trichopterus trichopterus from aquarium in Czechoslovakia. T. trichopterus trichopterus represents a new host record for this parasite.


Outcome and patterns of failure in testicular lymphoma: a multicenter Rare Cancer Network study.
To assess the outcome and patterns of failure in patients with testicular lymphoma treated by chemotherapy (CT) and/or radiation therapy (RT). Data from a series of 36 adult patients with Ann Arbor Stage I (n = 21), II (n = 9), III (n = 3), or IV (n = 3) primary testicular lymphoma, consecutively treated between 1980 and 1999, were collected in a retrospective multicenter study by the Rare Cancer Network. Median age was 64 years (range: 21-91 years). Full staging workup (chest X-ray, testicular ultrasound, abdominal ultrasound, and/or thoracoabdominal computer tomography, bone marrow assessment, full blood count, lactate dehydrogenase, and cerebrospinal fluid evaluation) was completed in 18 (50%) patients. All but one patient underwent orchidectomy, and spermatic cord infiltration was found in 9 patients. Most patients (n = 29) had CT, consisting in most cases of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with (n = 17) or without intrathecal CT. External RT was delivered to scrotum alone (n = 12) or testicular, iliac, and para-aortic regions (n = 8). The median RT dose was 31 Gy (range: 20-44 Gy) in a median of 17 fractions (10-24), using a median of 1.8 Gy (range: 1.5-2.5 Gy) per fraction. The median follow-up period was 42 months (range: 6-138 months). After a median period of 11 months (range: 1-76 months), 14 patients presented lymphoma progression, mostly in the central nervous system (CNS) (n = 8). Among the 17 patients who received intrathecal CT, 4 had a CNS relapse (p = NS). No testicular, iliac, or para-aortic relapse was observed in patients receiving RT to these regions. The 5-year overall, lymphoma-specific, and disease-free survival was 47%, 66%, and 43%, respectively. In univariate analyses, statistically significant factors favorably influencing the outcome were early-stage and combined modality treatment. Neither RT technique nor total dose influenced the outcome. Multivariate analysis revealed that the most favorable independent factors predicting the outcome were younger age, early-stage disease, and combined modality treatment. In this multicenter retrospective study, CNS was found to be the principal site of relapse, and no extra-CNS lymphoma progression was observed in the irradiated volumes. More effective CNS prophylaxis, including combined modalities, should be prospectively explored in this uncommon site of extranodal lymphoma.


Ingested nano- and microsized polystyrene particles surpass the intestinal barrier and accumulate in the body.
Plastic pollution is a major global challenge of our times, baring a potential threat for the environment and the human health. The increasing abundance of nanoplastic (NP) and microplastic (MP) particles in the human diet might negatively affect human health since they - particularly in patients suffering from inflammatory bowel disease (IBD) - might surpass the intestinal barrier. To investigate whether ingested plastic particles cross the intestinal epithelium and promote bowel inflammation, mice were supplemented with NP or MP polystyrene (PS) particles for 24 or 12 weeks before inducing acute or chronic dextran sodium sulfate (DSS) colitis with continuous plastic administration. Although ingested PS particles accumulated in the small intestine and organs distant from the gastrointestinal tract, PS ingestion did not affect intestinal health nor did it promote colitis severity. Although the lack of colitis-promoting effects of small PS particles might be a relief for IBD patients, potential accumulative effects of ingested plastic particles on the gastrointestinal health cannot be excluded.


Stereospecific abstraction of epsilon-pro-R-hydrogen of L-lysine by L-lysine epsilon-dehydrogenase from Agrobacterium tumefaciens.
The stereochemical aspects of the L-lysine epsilon-dehydrogenase reaction were examined with (6R)-L-[6-3H]lysine and (6S)-DL-[6-3H]lysine. When (6S)-DL-[6-3H]lysine was used as a substrate, the tritium was found in the product, delta 1-piperideine-6-carboxylate. In contrast, the radioactivity from (6R)-L-[6-3H]lysine was not retained in the product. Thus, the pro-R hydrogen at the prochiral C-6 carbon of L-lysine is specifically abstracted by the enzyme: the enzyme behaves stereochemically as an amino acid D-dehydrogenase.


Treatment of achalasia by the endoscopic-pneumatic dilatation method.
There is no definite cure for the loss of oesophageal peristalsis and incomplete relaxation of the lower oesophageal sphincter associated with achalasia. Pneumatic dilatation is a simple and safe method of achieving symptomatic improvement of the oesophageal passage. By this means five young patients became free of complaints within an average observation period of 6 3/4 years.


Increases in protein intake, protein distribution score, and micronutrient intakes in older adults in response to a whole food-based dietary intervention.
Changes in nutrient intakes and protein distribution were analyzed in response to a whole food-based dietary intervention targeting high-protein meals in older adults. Community-dwelling older adults (n = 56; M/F, 28/28; age, 69.3 ± 4.0 years) completed a 12-week intervention after randomization to exercise only (EX, n = 19), nutrition only (NUTR, n = 16), or nutrition plus exercise (NUTR + EX, n = 21). NUTR and NUTR + EX followed a dietary intervention targeting ~ 0.4 g/kg of protein at each of breakfast, lunch and dinner. Relative protein intake increased in NUTR (0.99 ± 0.34 to 1.43 ± 0.39 g/kg, P < 0.001) and NUTR + EX (0.90 ± 0.20 to 1.57 ± 0.49 g/kg, P < 0.001). Intakes of cholesterol, B vitamins, selenium and iodine were increased in both NUTR and NUTR + EX (P < 0.05 for all). This dietary intervention was effective at increasing daily protein intake and achieving an even distribution pattern. Changes in micronutrient intake were marked, and reflect the increase in consumption of animal-derived protein-rich food sources.


The outbreaks and prevalence of antimicrobial resistant Salmonella in poultry in the United States: An overview.
Salmonella is a Gram-negative, rod-shaped, facultative anaerobic, and non-spore-forming bacterium that belongs to the family of Enterobacteriaceae and is the causative agent for typhoid/paratyphoid fever and salmonellosis. Salmonella causes the highest amount of foodborne illness among bacteria at 15.5 cases per 100,000 and causes an estimated 410,000 antibiotic-resistant infections each year in the U.S. The use of antibiotics has been a staple in poultry production for the prevention of diseases and growth promotion for the last 70 years. Due to the over-and misusage of antibiotics, there has been an emerging public health crisis. Salmonella is developing resistance and may render antibiotics inoperative in a foodborne outbreak. Poultry, when not handled properly, is a major carrier and transmitter of Salmonella, causing human illness and fatality. This review summarizes the major Salmonella outbreaks over the past three decades, the prevalence of Antimicrobial Resistant (AMR) Salmonella related to poultry, and the control measures being implemented to reduce and prevent AMR Salmonella in poultry.


Predictors of Alcohol Use after Bariatric Surgery.
Patients undergoing bariatric surgery are at risk for devloping an alcohol use disorder (AUD). The purpose of this study was to investigate pre-surgical psychosocial risk factors for post-surgical alcohol consumption and hazardous drinking. Participants (N = 567) who underwent bariatric surgery between 2014 and 2017 reported their post-surgical alcohol use. Information was collected from the pre-surgical evaluation including history of alcohol use, psychiatric symptoms, and maladaptive eating behaviors (i.e., binge eating, purging, and emotional eating). Younger age and pre-surgical alcohol use predicted post-surgical alcohol use and hazardous drinking. In addition, higher levels of depressive symptoms and maladaptive eating patterns predicted post-surgical binge drinking. Clinicians conducting pre-surgical psychosocial evaluations should be aware of the multiple risk factors related to post-surgical problematic alcohol use. Future research should evaluate whether preventive interventions for high-risk patients decrease risk for post-surgical alcohol misuse.


NMR spectrometry. A new method for total stool fat quantification in chronic pancreatitis.
In the present investigation, suitability of nuclear magnetic resonance (NMR) spectrometry for total stool fat quantification in patients with normal or impaired exocrine pancreatic function (chronic pancreatitis) has been analyzed in comparison with a conventional chloroform-methanol extraction technique. Basic temperature-dependence studies of NMR spectrometry (90 degrees/180 degrees radiofrequency pulse sequence) on 21 chloroform-methanol extracted pure total stool lipid standards (weight range: 0.05-1.6 g) revealed significantly (P less than 0.05) improving correlations between NMR signal amplitudes and corresponding weights at increasing temperatures (r = 0.952/40 degrees C, r = 0.965/60 degrees C, r = 0.988/80 degrees C), thus indicating 80 degrees C as optimal temperature for NMR spectrometric total stool fat quantification. In subsequent comparative measurements of lyophilized stool samples, NMR spectrometry (at 80 degrees C) and conventional chloroform-methanol extraction provided significantly (P less than 0.001) correlated results with respect to total fecal fat contents/day of quantitatively collected and homogenized stools in 93 patients with known exocrine pancreatic function (secretin-pancreozymin test), irrespective of whether correlations were determined for all 93 patients (r = 0.983) or separately for patients with normal (N = 45; r = 0.867), moderately reduced (N = 31; r = 0.946), or highly reduced (N = 17; r = 0.992) exocrine pancreatic function and correspondingly increased total fecal fat excretions.


Relative effects of VEGF-A and VEGF-C on endothelial cell proliferation, migration and PAF synthesis: Role of neuropilin-1.
Vascular endothelial growth factor (VEGF-A) is an inducer of endothelial cell (EC) proliferation, migration, and synthesis of inflammatory agents such as platelet-activating factor (PAF). Recently, neuropilin-1 (NRP-1) has been described as a coreceptor of KDR which potentiates VEGF-A activity. However, the role of NRP-1 in numerous VEGF-A activities remains unclear. To assess the contribution of NRP-1 to VEGF-A mediated EC proliferation, migration, and PAF synthesis, we used porcine aortic EC (PAEC) recombinantly expressing Flt-1, NRP-1, KDR or KDR and NRP-1. Cells were stimulated with VEGF-A, which binds to Flt-1, KDR and NRP-1, and VEGF-C, which binds to KDR only. VEGF-A was 12.4-fold more potent than VEGF-C in inducing KDR phosphorylation in PAEC-KDR. VEGF-A and VEGF-C showed similar potency to mediate PAEC-KDR proliferation, migration, and PAF synthesis. On PAEC-KDR/NRP-1, VEGF-A was 28.6-fold more potent than VEGF-C in inducing KDR phosphorylation and PAEC-KDR/NRP-1 proliferation (1.3-fold), migration (1.7-fold), and PAF synthesis (4.6-fold). These results suggest that cooperative binding of VEGF-A to KDR and NRP-1 enhances KDR phosphorylation and its biological activities. Similar results were obtained with bovine aortic EC that endogenously express both KDR and NRP-1 receptors. In contrast, stimulation of PAEC-Flt-1 and PAEC-NRP-1 with VEGF-A or VEGF-C did not induce proliferation, migration, or PAF synthesis. In conclusion, the presence of NRP-1 on EC preferentially increases KDR activation by VEGF-A as well as KDR-mediated biological activities, and may elicit novel intracellular events. On the other hand, VEGF-A and VEGF-C have equipotent biological activities on EC in absence of NRP-1.


Molecular structures of 2-arylaminomethyl-1H-benzimidazole: spectral, electrochemical, DFT and biological studies.
In the present work, structural studies on (1H-benzimidazol-2-ylmethyl)-N-(4-chloro-phenyl)-amine (L(1)) and (1H-benzimidazol-2-ylmethyl)-N-(4-iodo-phenyl)-amine (L(2)) have been done extensively by a variety of physico-chemical techniques. Optimized geometrical structures, harmonic vibrational frequencies, natural bonding orbital (NBO) analysis, and Frontier molecular orbitals (FMO) were obtained by DFT/B3LYP method. TD-DFT calculations help to assign the electronic transitions. The polarizable continuum model (PCM) fails to describe the experimental chemical shift associated with the NH protons as calculated by applying Gauge-invariant atomic orbital (GIAO) method, but a very good correlation between the theoretical and experimental values was achieved by taking into account the specific solute-solvent interactions. DFT calculations showed a good agreement between the theoretical and observed results. These compounds exhibited a high biological activity through the inhibition of the metabolic growth of the investigated bacteria.


Metabolism of Cytokinins by Tissue Culture Lines of Oil Palm (Elaeis guineensis Jacq.) Producing Normal and Abnormal Flowering Palms.
The metabolism of cytokinins in tissue cultures of two oil palm clones previously known to regenerate palms ultimately manifesting normal and abnormal flowering was studied using radiolabeled benzyladenine and isopentenyladenosine, with particular regard to the kinetics of formation of the cytokinin 9-glucoside. Labeled products were separated by high performance liquid chromatography and identified by comparison of retention times with authentic cytokinin standards run immediately before or after the experimental sample. Using benzyladenine, which is insensitive to cytokinin oxidase, ribotide appeared rapidly and then declined. 6-Benzylaminopurine (BA) 9-glucoside quickly became the major soluble product with some formation of riboside. No other ethanol-soluble products were found. Over an incubation period of 24 h up to 30% of label appeared in the ethanol-insoluble fraction. The uptake of label was consistently faster in the normal than the abnormal clone. Dose-rate and time course experiments produced an in vivo asymptotic dose-response curve for the accumulation of BA 9-glucoside analogous to a Michaelis-Menten first-order reaction with a ~~"Vmax" of 3.5 nmol.g-1.h-1 (on a fresh weight basis) and a "Km" of 0.12 mm. There were no differences between clones in the rate of synthesis. Using isopentenyladenosine, which is susceptible to cytokinin oxidase and cannot be glucosylated without prior deribosylation, a complex pattern of metabolism was seen, with much slower production of 9-glucoside. A number of transient unidentified compounds were seen, together with adenosine and adenine. Comparison of normal and abnormal flowering clones showed striking differences in the kinetics of production of a compound thought to be [9R]Z and in a transient compound eluting at 22 min which accounted for 42% of the radioactivity after a 7-h incubation in the abnormal line. By 17 h there was no difference between normal and abnormal lines in the radioactivity in this compound. Cytokinin uptake was slower in the abnormal than in the normal flowering clone. Key Words. Cytokinin-Oil palm-Tissue culture-Abnormal flowering


From laparoscopic to open Kasai portoenterostomy: the outcome after reintroduction of open Kasai portoenterostomy in infant with biliary atresia.
Apparently superior result was observed after open Kasai portoenterostomy in infant with biliary atresia. Our institute stopped performing laparoscopic portoenterostomy since 2007. We aimed to investigate the outcome after reintroduction of open portoenterostomy. 27 non-syndromic infants underwent open Kasai portoenterostomy from 2007 to 2012. The age and the sex of the patient, the bilirubin level before the operation, the early clearance of jaundice (total bilirubin <20 μmol/L within 6 month of portoenterostomy), the native liver survival at 2 years after the operation were reviewed. The results were retrospectively compared with all 16 infants who underwent laparoscopic Kasai portoenterostomy before 2007. All infants had type III biliary atresia. No statistical difference was observed regarding the age at operation and the pre-operative bilirubin level. The early clearance of jaundice rate was 81% (22/27) after open operation and was 50% (8/16) after laparoscopic operation (p = 0.03). At 2 years after the operation, the native liver survival was 81% (22/27) after open operation and was 50% (8/16) after laparoscopic operation (p = 0.03). Reintroduction of open Kasai portoenterostomy was associated with superior early clearance of jaundice rate and 2-year native liver survival rate.


Optic radiation atrophy in Lewy body disease with visual hallucination on phase difference enhanced magnetic resonance images.
Visual hallucinations (VH) occur commonly in Lewy body disease (LBD), including Parkinson's disease (PD), PD with dementia, and dementia with Lewy bodies. We aimed to use phase difference enhanced imaging (PADRE) to assess structural abnormalities of optic radiation (OR) in patients with Lewy body disease (LBD) concomitant with VH. Firstly, two radiologists reviewed the OR appearances in healthy subjects (HS) on PADRE. Next, based on the OR abnormalities, two reviewers assessed the PADRE images from 18 HS and 38 and 110 patients with LBD, with and without VH, respectively, in a blinded manner. Finally, all patients with LBD without VH were eventually followed up for at least 5 years after magnetic resonance imaging to determine the appearance of VH. The radiologists identified three layers, namely external sagittal stratum, internal sagittal stratum, and tapetum, in OR on the PADRE in HS. Moreover, they were able to consensually define the OR as abnormal when the layers were obscured and the disappearance of the cranial side. The sensitivity/specificity of abnormal OR for each case was 68%/81% (LBD with VH vs. LBD without VH). Furthermore, VH appeared in 12 of the 21 (57%) patients with LBD and abnormal OR during the follow-up period. However, no patients without abnormal OR reported VH. Patients with LBD and VH demonstrated the abnormal OR. This, in turn, might be a useful marker to distinguish the patients with VH from those without VH and HS. Moreover, abnormal OR on PADRE may precede the appearance of VH in LBD.


An MRI-based scoring system for pretreatment risk stratification in locally advanced rectal cancer.
Accurately assessing the risk of recurrence in patients with locally advanced rectal cancer (LARC) before treatment is important for the development of treatment strategies. The purpose of this study is to develop an MRI-based scoring system to predict the risk of recurrence in patients with LARC. This was a multicenter observational study that enrolled participants who underwent neoadjuvant chemoradiotherapy. To evaluate the risk of recurrence in these patients, we developed the mrDEC scoring system and assessed inter-reader agreement. Additionally, we plotted Kaplan-Meier curves to compare the 3-year disease-free survival (DFS) and 5-year overall survival (OS) rates among patients with different mrDEC scores. A total of 1287 patients with LARC were included in this study. We observed substantial inter-reader agreement for mrDEC. Based on the mrDEC scores ranging from 0 to 3, the patients were categorized into four groups. The 3-year DFS rates for the groups were 91.0%, 79.5%, 65.5%, and 44.0% (P < 0.0001), respectively, and the 5-year OS rates were 92.9%, 87.1%, 74.8%, and 44.5%, respectively (P < 0.0001). The mrDEC scoring system proved to be an effective tool for predicting the prognosis of patients with LARC and can assist clinicians in clinical decision-making.


Simultaneous breakdown of multiple antibiotic resistance mechanisms in S. aureus.
In previous studies, the oligo-acyl-lysyl (OAK) C12(ω7)K-β12 added to cultures of gram-positive bacteria exerted a bacteriostatic activity that was associated with membrane depolarization, even at high concentrations. Here, we report that multidrug-resistant Staphylococcus aureus strains, unlike other gram-positive species, have reverted to the sensitive phenotype when exposed to subminimal inhibitory concentrations (sub-MICs) of the OAK, thereby increasing antibiotics potency by up to 3 orders of magnitude. Such chemosensitization was achieved using either cytoplasm or cell-wall targeting antibiotics. Moreover, eventual emergence of resistance to antibiotics was significantly delayed. Using the mouse peritonitis-sepsis model, we show that on single-dose administration of oxacillin and OAK combinations, death induced by a lethal staphylococcal infection was prevented in a synergistic manner, thereby supporting the likelihood for synergism to persist under in vivo conditions. Toward illuminating the molecular basis for these observations, we present data arguing that sub-MIC OAK interactions with the plasma membrane can inhibit proton-dependent signal transduction responsible for expression and export of resistance factors, as demonstrated for β-lactamase and PBP2a. Collectively, the data reveal a potentially useful approach for overcoming antibiotic resistance and for preventing resistance from emerging as readily as when bacteria are exposed to an antibiotic alone.


Identification and Quantification of β-Sitosterol β-d-Glucoside of an Ethanolic Extract Obtained by Microwave-Assisted Extraction from Agave angustifolia Haw.
β-sitosterol β-d-glucoside (BSSG) was extracted from "piña" of the Agave angustifolia Haw plant by microwave-assisted extraction (MAE) with a KOH solution such as a catalyst and a conventional maceration method to determine the best technique in terms of yield, extraction time, and recovery. The quantification and characterization of BSSG were done by high-performance thin layer chromatography (HPTLC), Fourier-transform infrared spectroscopy (FT-IR), and high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS). With an extraction time of 5 s by MAE, a higher amount of BSSG (124.76 mg of β-sitosterol β-d-glucoside/g dry weight of the extract) than those for MAE extraction times of 10 and 15 s (106.19 and 103.97 mg/g dry weight respectively) was shown. The quantification of BSSG in the extract obtained by 48 h of conventional maceration was about 4-5 times less (26.67 mg/g dry weight of the extract) than the yields reached by the MAE treatments. MAE achieved the highest amount of BSSG, in the shortest extraction time while preserving the integrity of the compound's structure.


Effect of experimental mouthrinses containing the combination of NaF and TiF4 on enamel erosive wear in vitro.
This study analysed the anti-erosive effect of experimental solutions containing TiF4 and NaF. Bovine enamel samples (n=15) were treated with: (1) commercial solution with SnCl2/NaF (Erosion Protection(®)); (2) experimental solution with 0.0815% TiF4; (3) 0.105% NaF; (4) 0.042% NaF + 0.049% TiF4; (5) 0.063% NaF + 0.036% TiF4 or (6) control. The samples were submitted to pH cycles and daily fluoride applications for seven days. The enamel wear was measured using a contact profilometer and analysed by ANOVA (p < 0.05). The best anti-erosive effect was found for experimental solution with 0.0815% TiF4 (99% reduction in enamel wear), followed by SnCl2/NaF (78%) and 0.049% TiF4 + 0.042% NaF solution (41%). The experimental solution containing a specific combination of TiF4 + NaF has the ability to partially reduce enamel erosion.


Some aspects of the behavior of the hypothalamus-pituitary-adrenal axis in patients with uncomplicated Plasmodium falciparum malaria: Cortisol and dehydroepiandrosterone levels.
We studied the behavior of cortisol and dehydroepiandrosterone (DHEA) in 24 patients with uncomplicated Plasmodium falciparum malaria of the Evandro Chagas Institute, Belém, Pará, Brazil. The patients were evaluated before treatment (Day 0), 24h after the beginning of medication (Day 1) and on Day 8 of follow-up (Day 7). Steroid levels were correlated with parasitemia, temperature and time of the disease. The levels of these hormones were found to be significantly higher on Day 0 than on Day 7, showing no correlation with parasitemia or temperature, but temperature had a positive effect on the correlation between cortisol and dehydroepiandrosterone. Cortisol was not correlated with the time of disease, but a significant negative correlation was observed between DHEA and time of disease on Day 7, suggesting a decline in the adrenal reserve of this steroid. In conclusion, an increase in cortisol and dehydroepiandrosterone is observed in patients with falciparum malaria, with these levels declining with decreasing parasitemia. The finding that temperature interfered with the correlation between cortisol and dehydroepiandrosterone suggests a common mechanism for the activation of these hormones in malaria.


Food Insecurity Increases the Odds of Obesity Among Young Hispanic Children.
Obesity is a growing public health concern and is more prevalent among low-income and minority populations. Food insecurity may increase the odds of obesity in children. We investigated the association between food insecurity and obesity among low-income, Hispanic, mother-child dyads (n = 74). The United States Department of Agriculture 18-item Household Food Security Survey was used to determine food security status. The majority of households were food insecure (74 %) and one-third (30 %) of children were obese. Food insecurity increased the odds of childhood obesity (OR 10.2; 95 % CI 1.2, 85.5) with stronger associations found within households where mothers were also overweight/obese compared to normal weight (p-for interaction < 0.05). Rates of household food insecurity and childhood obesity were high among this low-income Hispanic sample. Future studies should elucidate the mechanisms through which food insecurity impacts childhood obesity.


Insulin receptor and insulin sensitivity in a chicken hepatoma cell line.
Insulin receptors have been characterized in a cell line recently isolated from a chicken hepatoma (LMH). The binding of 125I-insulin to LMH cells or membranes displayed the expected criteria for insulin receptors: affinity, temperature dependency, curvilinearity of Scatchard plot, rank order of potency for insulin analogs and insulin induced down-regulation. The alpha-subunit of LMH cell insulin receptors exhibited a normal size of 135 kDa. Following autophosphorylation, LMH WGA-purified receptors revealed a 95 kDa beta-subunit and a 72 kDa protein (pp72). Both proteins were phosphorylated in a time-, insulin- (and insulin-like growth factor 1; IGF-1) and manganese-dependent manner, and were precipitated by antiphosphotyrosine and two anti-insulin receptor antibodies. The 72 kDa protein was not present under non-reducing condition PAGE or in normal chicken liver. These results strongly suggest that pp72 is either a truncated form of the insulin receptor beta-subunit specific to LMH cells or a degradation product. Lectin-purified insulin receptors from LMH cells or chicken liver membranes exhibited similar tyrosine kinase activity, using artificial substrate poly(Glu-Tyr) 4:1. Finally, amino acid uptake by LMH cells was insulin stimulatable.


Modulation of acute inflammation by targeting glycosaminoglycan-cytokine interactions.
Glycosaminoglycans (GAGs) located on cellular membranes and the extracellular matrix (ECM) are able to interact with chemokines and pro-inflammatory cytokines, leading to local cytokine/chemokine accumulation. The tissue-bound cytokines/chemokines function in promoting leukocyte migration and activation, contributing to local inflammation. Hence, targeting of GAG-cytokine interactions may provide an avenue for the attenuation of inflammatory responses. A cationic peptide (MC2) derived from the heparin-binding sequence of mouse IFN-gamma was previously shown by our laboratory to delay allograft rejection in an animal model. In order to further investigate potential anti-inflammatory properties of the MC2 peptide, we have studied its activity in an acute peritoneal inflammation model. Groups of C57Bl/6 mice were injected intraperitoneally with either ConA or thioglycollate and treated with saline (control), the MC2 peptide or two control cationic peptides, poly-l-lysine (PLL) and poly-l-arginine (PLA). Treatment with the MC2 peptide, but not PLA or PLL, resulted in statistically significant reductions in total cell numbers, concentration of total proteins and concentrations of pro-inflammatory cytokines (TNFalpha, IL-6 or IL-1 beta) in peritoneal lavage fluids, without alterations to the qualitative cellular composition of the exudate. These results suggest that targeting GAG-cytokine interaction is a viable approach to reduce inflammation.


Staff and Veteran Perspectives on Residential Treatment Programs' Responses to COVID-19: A Qualitative Study Guided by the WHO's After Action Review Framework.
Healthcare must rapidly and systematically learn from earlier COVID-19 responses to prepare for future crises. This is critical for VA's Mental Health Residential Rehabilitation and Treatment Programs (RRTPs), offering 24/7 care to Veterans for behavioral health and/or homelessness. We adapted the World Health Organization's After Action Review (AAR) to conduct semi-structured small-group discussions with staff from two RRTPs and Veterans who received RRTP care during COVID-19, to examine COVID-19's impact on these programs. Six thematic categories emerged through qualitative analysis (participant-checked and contextualized with additional input from program leadership), representing participants' recommendations including: Keep RRTPs open (especially when alternative programs are inaccessible), convey reasons for COVID-19 precautions and programming changes to Veterans, separate recovery-oriented programming from COVID-19-related information-sharing, ensure Wi-Fi availability for telehealth and communication, provide technology training during orientation, and establish safe procedures for off-site appointments. AAR is easily applicable for organizations to debrief and learn from past experiences.


Analysis of the effects of pulsatile capillary blood flow and volume on gas exchange.
Blood flow into the pulmonary capillaries and the volume of blood within the capillary bed are both pulsatile with the cardiac cycle. We have developed a quantitative model of diffusional gas exchange in the lung to investigate the effects of coupling between these two time-varying parameters on lung O2 and CO2 exchange. For normal man breathing room air at rest, the computed results agree well with previous predictions for the constant flow and volume case, and for the case of pulsatile flow alone. When coupled time-varying pulmonary capillary blood flow and volume are included, using the best data available in the literature to define these parameters, diffusional O2 exchange is improved over the cases of pulsatile flow or volume alone, and closely approximates that obtained for the hypothetical constant flow and volume case. CO2 exchanges, and O2 exchange during hypoxia, are not affected by pulsatile flow and/or volume. These results suggest that O2 exchange is efficient in the presence of coupled blood flow and blood volume pulsations as they exist in the lung capillaries, and that these conditions may be optimal for gas exchange under certain physiological (or pathological) conditions.


Diagnosis of isolated small bowel injury following blunt abdominal trauma.
A review of the case histories of 29 patients with isolated rupture of the small bowel was undertaken to determine which diagnostic tests were most sensitive in the early diagnosis of this notoriously occult injury. Results indicate that peritoneal lavage was the most useful test for this purpose, clearly more sensitive than standard clinical or radiographic signs. All patients in this series had indications for peritoneal lavage, and 85% of the patients who underwent peritoneal lavage in the emergency department had positive results and prompt operation. Reliance on the development of clinical peritonitis or the detection of pneumoperitoneum leads to long delays before operation.


Gut microbiota, malnutrition, and immunity: COVID-19's confounding triad.
The coronavirus disease has swept the world, bringing scientists from multiple disciplines together to work on a focused cause. In this forum, we discuss different roles that microbiota, malnutrition, and immunity have on severity of coronavirus disease and the importance of studying them from a gut-systemic perspective using multi-omics approaches.


Long-term alterations in opiate antinociception resulting from infant fentanyl tolerance and dependence.
Postnatal day-14 (P14) infant rats remained naive or were implanted with osmotic minipumps infusing saline or fentanyl (50 microg kg(-1) h(-1)). Fentanyl was administered 72 h later for measurement of antinociception in the tail-flick test. The potency of fentanyl was 3.0-fold lower in fentanyl-infused compared to saline-infused P17 rats. Fentanyl-infused P17 rats injected with naloxone underwent withdrawal characterized by increases in spontaneous activity, wall climbing, diarrhea, abdominal stretching, forepaw treading/tremors, wet-dog shakes, jumping, ptosis, rhinorrhea and hypothermia. Other naive, saline-infused and fentanyl-infused P17 rats not challenged with fentanyl or naloxone were housed until maturing into P42 juveniles. Fentanyl's potency was equal among each treatment group. However, morphine's potency was reduced in juveniles tolerant to fentanyl as infants. Morphine was also less potent in P90 adults tolerant to fentanyl as infants. Thus, chronic opiate exposure during infancy may affect the developing central nervous system, and desensitize animals and humans to opiate analgesia throughout life.


Biologic markers in breast carcinoma. IV. Serum fucose-protein ratio. Comparisons with carcinoembryonic antigen and human chorionic gonadotrophin.
Serum fucose-protein ratio was evaluated as a potential biologic marker for patients with metastatic breast cancer. By analysis of the same blood samples, comparisons were made with carcinoembryonic antigen (CEA) and human chorionic gonadotrophin (hCG). For 150 patients with metastatic breast cancer, 85% had a value for serum-fucose protein ratio above the normal range in comparison to 75% for CEA and 40% for hCG. Serum fucose-protein ratio was exclusively increased in 12% of the patients, CEA in 4% and hCG in 2%. Both serum-fucose protein ratio and CEA were elevated in 39% of the patients, and together, either in combination of alone, were increased in 93% of the patients. Raised values for serum fucose-protein ratio as well as for CEA decreased with change in disease status from pretreatment to response for patients with measurable disease parameters and increased correspondingly with overt disease progression. Preliminary data indicate both serum fuxose-protein ratio and CEA frequently become elevated when patients progress from a disease free interval after surgery to recurrence.


[Efficacy of newly developed kombucha-based specialized food product for treatment of constipation-predominant irritable bowel syndrome].
According to studies, the prevalence of constipation in the population can reach 27% due to the low intake of dietary fiber. Increasing dietary fiber intake can improve bowel movements. The aim of the study was to assess the efficacy of a non-alcoholic fermented pasteurized kombucha drink enriched with inulin and vitamins in patients with constipation-predominant irritable bowel syndrome (IBS). Material and methods. The study (NCT05164861) was approved by Local Ethics Committee and enrolled subjects with IBS (according to ROME IV). The subjects were randomized to receive either 220 ml of a non-alcoholic drink, based on pasteurized kombucha (KG), enriched with inulin (1.15 g/100 ml) or 220 ml water (control group, CG), for 10 days. Standard examination included evaluation of stool frequency (bowel movements per day), stool form (with the Bristol stool scale) and evaluation of concomitant symptoms (abdominal pain/discomfort, abdominal fullness, bloating, and feeling of incomplete bowel emptying) with the use of 5-point Likert scale before (BL) and 10 days after the start of intervention (EOT). Using visual analog scales (VAS), the palatability of the studied food was assessed at the beginning and end of the observation period. Results. Significant increase of stool frequency was found at the EOT compared to BL in KG (n=20), Mean±SD: 0.60±0.31 to 0.85±0.19 times/day; p=0.004, while there was no change in CG (n=20): 0.63±0.33 vs 0.72±0.28, p=0.6. Mean values of stool scale form increased in KG (3.0±1.2 to 4.4±1.0, p=0.001), while remained unchanged in CG (2.9±1.2 vs 3.4±1.2, p=0.6). Mean values of the Bristol stool scale in KG and CG differed significantly at EOT (p=0.018). Significant decrease in mean values of incomplete bowel emptying feeling was found in KG (1.88±0.78 at BL vs 1.41±0.56 points at EOT, p=0.015), but not in the control group. There were no statistically significant differences between patient's reports of the studied groups for other symptoms (bitterness and dryness in the mouth, heartburn, nausea, abdominal pain and heaviness in the stomach after eating). Conclusion. The effectiveness of a pasteurized fermented non-alcoholic drink based on kombucha enriched with inulin has been proven by reducing the intensity of complaints significant for constipation, normalizing the frequency and consistency of stools.


Pathogen inactivation of whole blood and red cell components: an overview of concept, design, developments, criteria of acceptability and storage lesion.
Multilayer preventative strategies have been instituted to enhance transfusion safety for patients in need of critical blood components. Presently blood safety is at its highest levels, with the implementation of precautionary/preventative measures against vCJD, bacterial and viral contamination of the blood supply. The implementation of these strategies together with advances in automation and computerization led to significant improvements in standardisation for transfusion practices. These include validation, verification, adherence to GLP and GMP and other regulatory requirements. In most European countries, universal prestorage leukodepletion is routine practice. In France proactive pathogen inactivation treatments [PITs] have been implemented emphasizing patient safety. This at least conceptually reduces the risk of transfusing viable WBCs, emerging bacteria and viruses, all with potential transfusion complications. In the UK, prion removal filters for red cell products are used selectively for special groups of patients. Some research establishments are exploring the potential impact of pathogen inactivation of whole blood or red cell components, using the new generation of S-303 PIT and the prion removal filters in combination. It needs to be determined whether such a combined strategy, applied synergistically, enhances red cell transfusion safety without compromising the overall criteria of acceptability. It is necessary to critically examine the impact of a new generation of PIT technologies, which may exacerbate the red cell storage lesion and cause the development of undesirable antibodies in the recipient. The development of innovative laboratory tools is vital to study impacts of these measures on the quality of stored blood and their clinical outcome. The ultimate aim of red cell transfusion is to provide oxygen enriched red blood cells to the microcirculations and tissues. Definitive studies are needed to establish the potential unforeseen negative long term toxicity, overall efficacy/quality and the clinical outcome of treated stored blood.


Bone cysts after osteochondral allograft repair of cartilage defects in goats suggest abnormal interaction between subchondral bone and overlying synovial joint tissues.
The efficacy of osteochondral allografts (OCAs) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12months in vivo. The objectives of this study were to further analyze OCAs and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral bone (ScB) and trabecular bone (TB) structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCAs was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCAs was lower than Non-Op and other OCAs. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCAs did not vary compared to Non-Op, but BS/TV was lower. (2) OCAs contained "basal" cysts, localized to deeper regions, some "subchondral" cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These findings suggest that cysts occurring after OCAs may result from aberrant mechanobiology due to (1) altered compartmentalization that normally separates overlying cartilage and subchondral bone, either from distinct ScB channels or more general ScB plate deterioration, and (2) bone resorption at the basal graft-host interface.


Biochemical nature and cellular distribution of the paired immunoglobulin-like receptors, PIR-A and PIR-B.
PIR-A and PIR-B, paired immunoglobulin-like receptors encoded, respectively, by multiple Pira genes and a single Pirb gene in mice, are relatives of the human natural killer (NK) and Fc receptors. Monoclonal and polyclonal antibodies produced against a recombinant PIR protein identified cell surface glycoproteins of approximately 85 and approximately 120 kD on B cells, granulocytes, and macrophages. A disulfide-linked homodimer associated with the cell surface PIR molecules was identified as the Fc receptor common gamma (FcRgammac) chain. Whereas PIR-B fibroblast transfectants expressed cell surface molecules of approximately 120 kD, PIR-A transfectants expressed the approximately 85-kD molecules exclusively intracellularly; PIR-A and FcRgammac cotransfectants expressed the PIR-A/ FcRgammac complex on their cell surface. Correspondingly, PIR-B was normally expressed on the cell surface of splenocytes from FcRgammac-/- mice whereas PIR-A was not. Cell surface levels of PIR molecules on myeloid and B lineage cells increased with cellular differentiation and activation. Dendritic cells, monocytes/macrophages, and mast cells expressed the PIR molecules in varying levels, but T cells and NK cells did not. These experiments define the coordinate cellular expression of PIR-B, an inhibitory receptor, and PIR-A, an activating receptor; demonstrate the requirement of FcRgammac chain association for cell surface PIR-A expression; and suggest that the level of FcRgammac chain expression could differentially affect the PIR-A/PIR-B equilibrium in different cell lineages.


The salivary effector protein Sg2204 in the greenbug Schizaphis graminum suppresses wheat defence and is essential for enabling aphid feeding on host plants.
Aphids secrete diverse repertoires of salivary effectors into host plant cells to promote infestation by modulating plant defence. The greenbug Schizaphis graminum is an important cereal aphid worldwide. However, the secreted effectors of S. graminum are still uncharacterized. Here, 76 salivary proteins were identified from the watery saliva of S. graminum using transcriptome and proteome analyses. Among them, a putative salivary effector Sg2204 was significantly up-regulated during aphid feeding stages, and transient overexpression of Sg2204 in Nicotiana benthamiana inhibited cell death induced by BAX or INF1. Delivering Sg2204 into wheat via the type III secretion system of Pseudomonas fluorescens EtAnH suppressed pattern-triggered immunity (PTI)-associated callose deposition. The transcript levels of jasmonic acid (JA)- and salicylic acid (SA)-associated defence genes of wheat were significantly down-regulated, and the contents of both JA and SA were also significantly decreased after delivery of Sg2204 into wheat leaves. Additionally, feeding on wheat expressing Sg2204 significantly increased the weight and fecundity of S. graminum and promoted aphid phloem feeding. Sg2204 was efficiently silenced via spray-based application of the nanocarrier-mediated transdermal dsRNA delivery system. Moreover, Sg2204-silenced aphids induced a stronger wheat defence response and resulted in negative impacts on aphid feeding behaviour, survival and fecundity. Silencing of Sg2204 homologues from four aphid species using nanocarrier-delivered dsRNA also significantly reduced aphid performance on host plants. Thus, our study characterized the salivary effector Sg2204 of S. graminum involved in promoting host susceptibility by suppressing wheat defence, which can also be regarded as a promising RNAi target for aphid control.


Circannual variation in the fatty acid composition of high-density lipoprotein phospholipids during acclimatization in trout.
A circannual variation in the fatty acid composition of plasma and high-density lipoprotein (HDL) phospholipids occurs in rainbow trout (Oncorhynchus mykiss) in response to seasonal alterations in environmental water temperature. The compensatory mechanisms employed in cold adaptation include a decrease in the level of saturated fatty acids and of monoenes of the oleic acid (n-9) family and an increase in the level of unsaturated fatty acids of the linolenic acid (n-3) family, especially in docosahexaenoic acid (22:6(n-3)). The present study demonstrates that in trout, a poikilothermic vertebrate, the weight percentage of 22:6(n-3) in HDL phospholipids is inversely correlated (r = -0.88, P < 0.0001) with water temperature.


Different characteristics of circular staplers make the difference in anastomotic tensile strength.
Anastomotic leak after gastrointestinal surgery is a severe complication associated with relevant short and long-term sequelae. Most of the anastomoses are currently performed with a surgical stapler that is required to have appropriate characteristics in order to guarantee good performances. The aim of our study was to evaluate, ex vivo, pressure resistance and tensile strength of anastomosis performed with different circular staplers available in the market. We studied 7 circular staplers of 3 different companies, 3 of them used for gastrointestinal anastomosis and 4 staplers for hemorrhoidal prolapse excision. A total of 350 anastomoses, 50 for each of the 7 staplers, were performed using healthy pig fresh intestine, then injected saline solution and recorded the leaking pressure. There were no statistically significant differences between the mean pressure necessary to induce an anastomotic leak in the various instruments (p>0.05). For studying tensile strength, we performed a total of 350 anastomoses with 7 different circular staplers on a special strong paper (Tyvek), and then recorded the maximal tensile force that could open the anastomosis. There were statistically significant differences between one brand stapler vs other 2 companies staplers about the strength necessary to open the staple line (p<0.05). In conclusion, we demonstrated that different circular staplers of three companies available in the market give comparable anastomotic pressure resistance but different tensile strengths. This is probably due to different technical characteristics.


Uptake of triglyceride fatty acids in adipose tissue in vivo in man.
Currently available information on adipose tissue metabolism in man is mainly based on studies in vitro. In the present work adipose tissue lipid uptake was studied in vivo in man. 100 g glucose and 120 g milk fat with 10 microCi U-14C oleic acid were given in the overnight fasting state to eight women and 2 h after a carbohydrate-rich meal to eight women. After 4 h, 1-day, 1 week and 1 month radioactivity levels were determined in the lipids of adipose tissue in the femoral and abdominal regions and in plasma. At 4 h 30 and 20% of the oleic acid was estimated to remain in the extracellular space in the fasted and fed groups respectively, measured in plasma. Contents of oleic acid radioactivity was higher in the abdominal than femoral region. An estimated 27 and 46 g of fat was taken up in adipose tissue of the fasted and fed groups, constituting 1/3 and 1/2 of total tissue uptake respectively. After 1 day these figures were 43 and 60 g respectively. At 1 week and 1 month adipose tissue radioactivity was increasing slowly. Lipoprotein lipase (LPL) activity in adipose tissue at 4 h was higher in the femoral than abdominal adipose tissue and higher in the fed than fasted state in the abdominal region. A significant correlation was found between uptake and LPL in abdominal adipose tissue only. These results show that uptake of fat measured in vivo is probably not necessarily reflected by LPL measurements only, suggesting other regulatory factors.(ABSTRACT TRUNCATED AT 250 WORDS)


Mediastinal lymph node necrosis: a newly recognized complication of mediastinoscopy.
Eight cases of partial mediastinal lymph node necrosis identified at thoracotomy two to 17 days after cervical mediastinoscopy are described. In 6 cases, the involved nodes were grossly abnormal at operation, requiring frozen section interpretation. In the first 2 patients, the areas of nodal infarction were misinterpreted as necrotic tumor. Permanent sections from all 8 patients showed no evidence of tumor in the infarcted nodes. Factors predisposing to nodal infarction included right-sided tumor, central tumor, and large mediastinoscopic biopsy specimens. In all instances, the infarcted nodes were subcarinal and/or main bronchial. In 2 patients, left recurrent laryngeal nerve palsy occurred after mediastinoscopy. Necrosis in distal nodal areas should be recognized as a complication of thorough mediastinoscopic sampling, presumably due to interruption of arteries supplying these nodes. Awareness of this phenomenon by surgeons and pathologists may avert falsely positive gross or microscopic diagnoses of metastatic malignancy at thoracotomy.


Bone and cartilage turnover markers, bone mineral density, and radiographic damage in men with ankylosing spondylitis.
To determine the levels of bone and cartilage turnover markers in men with ankylosing spondylitis (AS) and to investigate their associations with disease activity, bone mineral density, and radiographic damage of the spine. This cross-sectional study enrolled 35 men with newly diagnosed AS. The bone mineral densities (BMD) of their lumbar spines and proximal femurs, Bath AS Disease Activity Index (BASDAI), and Bath AS Radiographic Index (BASRI) were evaluated. Urinary C-terminal telopeptide fragments of type I collagen (CTX-I) and type II collagen (CTX-II) levels were determined by enzyme-linked immunosorbent assay, and serum levels of bone-specific alkaline phosphatase (BALP) and osteocalcin were determined by an enzyme immunoassay. Levels of biochemical markers were compared with those of 70 age-matched healthy men. Patients with AS had significantly higher mean urinary CTX-I and CTX-II levels than control subjects (p<0.05). Elevated urinary CTX-I levels correlated well with BASDAI, femoral BMD, and femoral T score (p<0.05), and elevated urinary CTX-II levels correlated well with spinal BASRI (p<0.05) in patients with AS. Mean serum BALP and osteocalcin levels did not differ between patients and controls and did not show any significant correlations with BMD, BASDAI, or BASRI in men with AS. Elevated CTX-I reflects disease activity and loss of femoral BMD while elevated CTX-II levels correlate well with radiographic damage of the spine, suggesting the usefulness of these markers for monitoring disease activity, loss of BMD, and radiographic damage in men with AS.


Considerations for realistic atmospheric environments: An application to corrosion testing.
Measured salt compositions in dust collected over roughly the last decade from surfaces of in-service stainless-steel alloys at four locations around the United States are presented, along with the predicted brine compositions that would result from deliquescence of these salts. The salt compositions vary greatly from ASTM seawater and from laboratory salts (i.e., NaCl or MgCl2) commonly used on corrosion testing. The salts contained relatively high amounts of sulfates and nitrates, evolved to basic pH values, and exhibited deliquescence relative humidity values (RH) higher than seawater. Additionally, inert dust in components were quantified and considerations for laboratory testing are presented. The observed dust compositions are discussed in terms of the potential corrosion behavior and are compared to commonly used accelerated testing protocols. Finally, ambient weather conditions and their influence on diurnal fluctuations in temperature (T) and RH on heated metal surfaces are evaluated and a relevant diurnal cycle for laboratory testing a heated surface has been developed. Suggestions for future accelerated tests are proposed that include exploration of the effects of inert dust particles on atmospheric corrosion, chemistry considerations, and realistic diurnal fluctuations in T and RH. Understanding mechanisms in both realistic and accelerated environments will allow development of a corrosion factor (i.e., scaling factor) for the extrapolation of laboratory-scale test results to real world applications.


Angiotensin IV protects against angiotensin II-induced cardiac injury via AT4 receptor.
Angiotensin II (Ang II) is an important regulator of cardiac function and injury in hypertension. The novel Ang IV peptide/AT4 receptor system has been implicated in several physiological functions and has some effects opposite to those of Ang II. However, little is known about the role of this system in Ang II-induced cardiac injury. Here we studied the effect of Ang IV on Ang II-induced cardiac dysfunction and injury using isolated rat hearts, neonatal cardiomyocytes and cardiac fibroblasts. We found that Ang IV significantly improved Ang II-induced cardiac dysfunction and injury in the isolated heart in response to ischemia/reperfusion (I/R). Moreover, Ang IV inhibited Ang II-induced cardiac cell apoptosis, cardiomyocyte hypertrophy, and proliferation and collagen synthesis of cardiac fibroblasts; these effects were mediated through the AT4 receptor as confirmed by siRNA knockdown. These findings suggest that Ang IV may have a protective effect on Ang II-induced cardiac injury and dysfunction and may be a novel therapeutic target for hypertensive heart disease.


Occult multifocal papillary thyroid microcarcinoma presenting as a supraclavicular mass containing anaplastic thyroid carcinoma.
There are reports in the literature of anaplastic thyroid carcinoma in cervical lymph nodes with evidence of only papillary carcinoma in the thyroid gland. There have been no cases of this clinical scenario with only papillary microcarcinoma in the thyroid gland. We describe the case of a 60-year-old man who initially presented with an enlarged right, level 5, supraclavicular lymph node. Initial fine-needle aspiration demonstrated evidence of papillary thyroid carcinoma. The final pathologic finding in the thyroid gland showed only multiple foci of papillary thyroid microcarcinoma. The index neck mass showed evidence of anaplastic thyroid carcinoma. This is the first instance in the literature in which anaplastic thyroid carcinoma has appeared in metastatic cervical lymph nodes with only a focus of papillary microcarcinoma in the thyroid gland. With this case, we hope to build awareness of this rare finding.


Interactive effects of microplastics and benzo[a]pyrene on two species of marine invertebrates.
This study aimed to evaluate B[a]P and low-density polyethylene microplastics (MPs) toxicty, alone and in mixture (0.03 to 30 μg L-1 of B[a]P; and 5, 50 and 500 mg L-1 for MPs). Five mg L-1 of MPs is considerably higher than commonly reported environmental concentrations, although it has been reported for marine environments. Individual (sea urchin embryo-larval development and mortality of mysids) and sub-individual responses (LPO and DNA damage in mysids) were assessed. The toxicity increased as the B[a]P concentration increased, and microplastics alone did not cause toxicity. B[a]P toxicity was not modified by the lowest concentration of MPs (5 mg L-1), but at higher MPs concentrations (50 and 500 mg L-1), the effects of B[a]P on sea urchin development and in biomarkers in mysids were diminished. Microplastics interacted with B[a]P in seawater, reducing its toxicity, probably due to adsorption of B[a]P to the surface of microplastics.


Ascorbate concentration in human cerebrospinal fluid (CSF) and serum. Intrathecal accumulation and CSF flow rate.
Concentrations of ascorbate (vitamin C) in cerebrospinal fluid (CSF) from human controls (median 163 mumol/l, n = 63) were found to be in the same range as CSF samples from patients (n = 56) with various neurological diseases, but excluding those with blood-CSF barrier dysfunction. The CSF/serum concentration ratio in the former group is non-linear, decreasing with increasing serum concentration. Surprisingly, ascorbate concentration in blood (median 41 mumol/l, n = 119) was decreased significantly in cases of neurological diseases with a blood-CSF barrier dysfunction (median 26 mumol/l, n = 30). In this latter group a linear CSF to serum ratio with a mean of 5.7:1 (with CSF/serum albumin quotients QAlb = 7.8-70.8 x 10(-3), median 10.0 x 10(-3)) was observed, approaching a value > 12.5:1 in the case of complete stop of CSF flow. Serum ascorbate concentrations decreased with decreasing CSF flow rate (1 square root of QAlb), indicating a CSF flow-dependent constant contribution from high intrathecal ascorbate concentration to the varying diet-dependent concentrations in blood. In the control group the biological coefficient of variation for CSF ascorbate concentrations (C.V. = 21.1%) was smaller than for serum concentrations (C.V. = 42.6%), confirming an efficient ascorbate homeostasis in human brain. This was different from uric acid which was used as a reference molecule with an inversed gradient in the same group of control patients. Similar variations in CSF(y) and serum(x) for urate concentrations are observed due to the strong correlation y = 0.1x +/- 10 mumol/l, including 99% of the cases with an urate serum concentration range from 80 mumol/l to 460 mumol/l.


Drosophila Met and Gce are partially redundant in transducing juvenile hormone action.
The Drosophila Methoprene-tolerant (Met) and Germ cell-expressed (Gce) bHLH-PAS transcription factors are products of two paralogous genes. Both proteins potentially mediate the effect of juvenile hormone (JH) as candidate JH receptors. Here we report that Met and Gce are partially redundant in transducing JH action. Both Met and gce null single mutants are fully viable, but the Met gce double mutant, Met(27) gce(2.5k), dies during the larval-pupal transition. Precocious and enhanced caspase-dependent programmed cell death (PCD) appears in fat body cells of Met(27) gce(2.5k) during the early larval stages. Expression of Kr-h1, a JH response gene that inhibits 20-hydroxyecdysone (20E)-induced broad (br) expression, is abolished in Met(27) gce(2.5k) during larval molts. Consequently, expression of br occurs precociously in Met(27) gce(2.5k), which may cause precocious caspase-dependent PCD during the early larval stages. Defective phenotypes and gene expression changes in Met(27) gce(2.5k) double mutants are similar to those found in JH-deficient animals. Importantly, exogenous application of JH agonists rescued the JH-deficient animals but not the Met(27) gce(2.5k) mutants. Our data suggest a model in which Drosophila Met and Gce redundantly transduce JH action to prevent 20E-induced caspase-dependent PCD during larval molts by induction of Kr-h1 expression and inhibition of br expression.


The steady state activity of succinate dehydrogenase in the presence of opposing effectors.II. Reductive activation of succinate dehydrogenase in presence of oxaloacetate.
The extent of the deactivation of the mitochondrial succinate dehydrogenase by oxaloacetate is a function of the redox state of the enzyme. Oxidized enzyme is deactivated by much lower concentrations of oxaloacetate than those needed to deactivate reduced enzyme. An accurate method for measuring this relationship is the redox titration of the enzymic activity of succinate dehydrogenase, carried out in the presence of oxaloacetate. For each concentration of oxaloacetate a different redox titration curve was reported with the apparent mid-potential decreasing with increasing oxaloacetate. These results are compatible with a model which proposes that both oxidized and reduced enzymes can form the catalytically non-active complex with oxaloacetate, but that the complex formed the the oxidized enzyme is more stable than that formed by the reduced enzyme. When the oxaloacetate concentration is low, reduction of the enzyme will lower the fraction of the succinate dehydrogenase-oxaloacetate complex, a reaction which we observe as reductive activation of the enzyme. If this experiment is repeated in the presence of high concentration of oxaloacetate, no activation of the enzyme takes place, but the low stability of the reduced enzyme oxaloacetate complex is revealed by the rapid exchange of the enzyme-bound oxaloacetate with the free ligand. The rate of this exchange is extremely slow at high positive potential and becomes faster upon lowering of the poise potential. The reductive activation of the succinate dehydrogenase is regarded as a two step reaction. In the first step the reduced non-active complex releases the oxaloacetate and in the second step the active form of the enzyme is evolved. These two steps can be observed experimentally; Reductive activation at a redox potential higher than the mid-potential of the oxaloacetate-malate couple (minus 166 mV) is characterized by Ea = 18 Kca/mole, the final equilibrium level of activation decreases upon lowering of the temperature. Reduction activation of the enzyme at minus 240 mV is a very rapid reaction which goes to completion at all temperatures tested and has an activation energy of 12.5 Kcal/mole. The mechanism of the reductive activation and its possible role in the regulation of succinate dehydrogenase in the mitochondria is discussed.


A critical comparison of commonly used procedures for the assay of terminal deoxynucleotidyl transferase in crude tissue extracts.
Terminal deoxynucleotidyl transferase (TdT) is a non-template directed DNA polymerase normally found in vertebrate thymus and bone marrow. Quantitative assay of TdT activity is being widely used as a tool in the differential diagnosis of acute leukemias in man. Clinical specimens of blood and bone marrow often contain 10(7) or fewer cells and require a specific and rapid assay for transferase which can be carried out in crude cell extracts. Commonly used assay methods do not meet these requirements, but can be easily modified to do so.


Emission and distribution of PCDD/Fs and CBzs from two co-processing RDF cement plants in China.
An analysis of the emission and distribution characteristics of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and chlorobenzenes (CBzs) from two cement kilns (CK1 and CK2) is done. Six measurements in CK1 showed an increase of PCDD/F emission from 76 to 97 pg I-TEQ/Nm(3) after feeding 10 ton/h RDF (refuse derived fuel). For CK2, the effect of increasing the RDF substitution rates from 0 to 21 t/h on the emission of PCDD/Fs was investigated. The correlation analysis indicated that replacing parts of the conventional fuel with RDF could not increase the emission of PCDD/Fs. Furthermore, the gas/particle partitions of PCDD/Fs and CBzs in stack gas were investigated, indicating that PCDD/Fs and CBzs were more associated in gas phase, especially for the lower chlorinated ones. Moreover, the bag filter fly ash was characterized by its particle distribution, XRD- and EDS-analysis. Additionally, the level of PCDD/Fs in outflowing fly ash escalates for smaller particle size. In order to evaluate the environmental effect on inhabitants, the levels of PCDD/Fs were also determined in samples of ambient air collected in the vicinity of CK2 (~200 m).


Use of a balloon and N-butyl-2-cyanoacrylate for treatment of arteriovenous fistula.
We report a patient who developed a large arteriovenous fistula in right lower extremity after gunshot injury. Because other endovascular methods failed, the patient was successfully treated with concomitant use of detachable latex balloon and N-butyl-2-cyanoacrylate (NBCA). The combination of detachable balloon and NBCA can be effectively used for endovascular treatment of peripheral arteriovenous fistulas in selected cases when effective embolization could not be achieved with other embolizing agents or their various combinations.


Fat loading experiments with the vitamins A and E suggest that in postprandial lipemia transfer/diffusion of chylomicron lipids to VLDL contributes to beta-VLDL formation.
Vitamins A and E differ in hydrophobicity. When added to a fat load more or less specific labeling of chylomicrons and their remnants can be expected and this allows to approach the mechanism of postprandial lipemia from a new sight of view. Applied in a study in which 20 patients participated (eight patients with familial dysbetalipoproteinemia (FD), six patients with familial combined hyperlipidemia (FCH) and six controls) we found that vitamin A, no longer paralleled the apo B-48 concentrations from 9 h after a fat load, especially in the remnant fraction with Sf 15-100. Qualitatively, the distribution of vitamin A to the more dense fractions mirrored that of vitamin E, but the latter was more rapid. Both vitamins at the maximum of remnant-accumulation, at 14 h after the fat load, correlated with the cholesterol content of the remnant fraction. For vitamin E there was a similar concentration dependent distribution to all other lipoprotein fractions. The results confirm our view that the lipoprotein mechanism can be regarded as a dynamic system. During regular episodes following the meals, exogenous fat is, like the vitamins, distributed over all endogenously formed lipoproteins. This transfer process results in the formation of beta-VLDL and contributes to the pathogenesis of FCH and FD.


Successful ageing for psychiatrists.
This paper aims to explore the concept and determinants of successful ageing as they apply to psychiatrists as a group, and as they can be applied specifically to individuals. Successful ageing is a heterogeneous, inclusive concept that is subjectively defined. No longer constrained by the notion of "super-ageing", successful ageing can still be achieved in the face of physical and/or mental illness. Accordingly, it remains within the reach of most of us. It can, and should be, person-specific and individually defined, specific to one's bio-psycho-social and occupational circumstances, and importantly, reserves. Successful professional ageing is predicated upon insight into signature strengths, with selection of realistic goal setting and substitution of new goals, given the dynamic nature of these constructs as we age. Other essential elements are generativity and self-care. Given that insight is key, taking a regular stock or inventory of our reserves across bio-psycho-social domains might be helpful. Importantly, for successful ageing, this needs to be suitably matched to the professional task and load. This lends itself to a renewable personal ageing plan, which should be systemically adopted with routine expectations of self-care and professional responsibility.


Inflammatory status of transmigrating primary rat monocytes in a novel perfusion model simulating blood flow.
It remains unclear whether monocyte infiltration plays a protective or detrimental role in neurodegenerative disease. The present study characterizes the inflammatory status of primary monocytes in a novel in vitro perfusion model. Monocytes under perfusion do not undergo elevated cell death. However, perfusion does lead to altered morphology, which can be counteracted by anti-inflammatory drugs. Functional studies indicate that cytokine levels are significantly reduced in perfusion compared to stationary conditions and enhanced with brain slices or capillary endothelial cells. Understanding monocyte properties could lead to refined treatment and new ways to interfere with inflammation in diseased brains.


Allotype specific interactions of drugs and HLA molecules in hypersensitivity reactions.
It is hypothesised that associations between adverse drug reactions and specific alleles of the human leukocyte antigens arise due to specific interactions between the human leukocyte antigen molecules and the causative drug that stimulate immune responses targeting drug exposed tissues. To date this has only been definitively demonstrated for abacavir, an antiretroviral that causes a systemic adverse drug reaction, abacavir hypersensitivity syndrome, solely in HLA-B*57:01+ individuals. Whilst this has informed the modification of abacavir to remove immunogenicity, there remains an imperative to define other interactions between drugs and specific HLA in order to understand the scope of interactions that can drive T cell mediated drug hypersensitivity. Here we review the current state of understanding of these interactions.


Converging or Crossing Curves: Untie the Gordian Knot or Cut it? Appropriate Statistics for Non-Proportional Hazards in Decitabine DACO-016 Study (AML).
Among patients with acute myeloid leukemia (AML), the DACO-016 randomized study showed reduction in mortality for decitabine [Dacogen(®) (DAC), Eisai Inc., Woodcliff Lake, NJ, USA] compared with treatment choice (TC): at primary analysis the hazard ratio (HR) was 0.85 (95% confidence interval 0.69-1.04; stratified log-rank P = 0.108). With two interim analyses, two-sided alpha was adjusted to 0.0462. With 1-year additional follow-up the HR reached 0.82 (nominal P = 0.0373). These data resulted in approval of DAC in the European Union, though not in the United States. Though pre-specified, the log-rank test could be considered not optimal to assess the observed survival difference because of the non-proportional hazard nature of the survival curves. We applied the Wilcoxon test as a sensitivity analysis. Patients were randomized to DAC (N = 242) or TC (N = 243). One-hundred and eight (44.4%) patients in the TC arm and 91 (37.6%) patients in the DAC arm selectively crossed over to subsequent disease modifying therapies at progression, which might impact the survival beyond the median with resultant converging curves (and disproportional hazards). The stratified Wilcoxon test showed a significant improvement in median (CI 95%) overall survival with DAC [7.7 (6.2; 9.2) months] versus TC [5.0 (4.3; 6.3) months; P = 0.0458]. Wilcoxon test indicated significant increase in survival for DAC versus TC compared to log-rank test. Janssen-Cilag GmbH.


Gerbode defect: A comprehensive review of its history, anatomy, embryology, pathophysiology, diagnosis, and treatment.
The purpose of this paper is to survey the literature on Gerbode defect and provide an overview of its history, anatomy, development, pathophysiology, diagnosis, and treatment options. The available literature on this topic, including case reports, was thoroughly reviewed. Gerbode defect is defined as abnormal shunting between the left ventricle and right atrium resulting from either a congenital defect or prior cardiac insults. The pathophysiology underlying the development of Gerbode defect is a disease process that injures the atrioventricular septum and leads to the abnormal shunting of blood. Although the most prevalent cause of Gerbode defect has historically been congenital, an increasing trend towards acquired cases has recently been reported owing to improved diagnostic capabilities and a greater number of invasive cardiac procedures. In conclusion, Gerbode defect is an increasingly recognized condition that warrants further study.


Patient preparation for cardiac fluorine-18 fluorodeoxyglucose positron emission tomography imaging of inflammation.
Although the number of clinical applications for fluorine-18 fluorodeoxyglucose (18F-FDG) cardiac positron emission tomography (PET) has continued to grow, there remains a lack of consensus regarding the ideal method of suppressing normal myocardial glucose utilization for image optimization. This review describes various patient preparation protocols that have been used as well as the success rates achieved in different studies. Collectively, the available literature supports using a high-fat, no-carbohydrate diet for at least two meals with a fast of 4-12 hours prior to 18F-FDG PET imaging and suggests that isolated fasting for less than 12 hours and supplementation with food or drink just prior to imaging should be avoided. Each institution should adopt a protocol and continuously monitor its effectiveness with a goal to achieve adequate myocardial suppression in greater than 80% of patients.


Bar-code/eMAR combo reduces errors.
Study covers usage of system in multiple hospital units. Make sure your system meets the specific needs of your facility. Compliance should be viewed as a journey, not an isolated event.


Femoral nailing with transverse locking screws through the femoral neck.
We treated 55 patients with subtrochanteric or comminuted femoral fractures with a transverse locking femoral nail (Alta, Howmedica). This nail was positioned more cephalad than usual so that at least one fixation screw was located in the femoral neck or head. Forty-seven fractures (20 subtrochanteric and 27 diaphyseal) were available for follow-up averaging 12 months (3-35). The time to radiographic healing averaged 7 months (3-21). There was one delayed union, one non-union, two superficial infections, one broken proximal screw, one compartment syndrome of the thigh, and one peroneal nerve palsy. There were no femoral neck fractures, avascular changes of the femoral head, or gluteal irritation at the most recent follow up. The described technique appears safe and effective, is technically easy, and avoids intra-articular screws.


The application of Fourier-transform Raman spectroscopy to the analysis of pharmaceuticals and biomaterials.
Near infrared Fourier-transform (FT) Raman spectroscopy is shown to be a useful spectroscopic tool for the molecular structural analysis of drugs and biomedical polymers. The technique has been applied to the non-invasive investigation of the hydrolytic degradation of a biodegradable polymer in water over a period of 15 days and to the analysis of a drug within a polymer vehicle over a wide drug concentration range. This work demonstrates the potential value of FT Raman spectroscopy in the field of pharmaceutical science.


Rheumatoid arthritis and work: The impact of rheumatoid arthritis on absenteeism and presenteeism.
For patients with rheumatoid arthritis (RA), being in paid work is very important, and it increases self-esteem and financial independence. Although the management of RA has changed in the last 15 years to early aggressive treatment and the introduction of biologic treatments, many patients still have to take sick leave or even stop working because of their RA (i.e., absenteeism). For those remaining in paid work, patients may experience problems due to RA resulting in productivity loss while at work (i.e., presenteeism). The costs attributed to absenteeism and presenteeism (i.e., indirect costs) have been estimated to be very high, and they even exceed direct costs. However, there is no consensus on how to calculate these costs. This manuscript examines the relationship between the use of biologic therapy and absenteeism, with a focus on sick leave, and on presenteeism, and it provides an overview of indirect costs of absenteeism and presenteeism in those treated with biologic therapies.


Characterization of antibiotic resistance genes in the species of the rumen microbiota.
Infections caused by multidrug resistant bacteria represent a therapeutic challenge both in clinical settings and in livestock production, but the prevalence of antibiotic resistance genes among the species of bacteria that colonize the gastrointestinal tract of ruminants is not well characterized. Here, we investigate the resistome of 435 ruminal microbial genomes in silico and confirm representative phenotypes in vitro. We find a high abundance of genes encoding tetracycline resistance and evidence that the tet(W) gene is under positive selective pressure. Our findings reveal that tet(W) is located in a novel integrative and conjugative element in several ruminal bacterial genomes. Analyses of rumen microbial metatranscriptomes confirm the expression of the most abundant antibiotic resistance genes. Our data provide insight into antibiotic resistange gene profiles of the main species of ruminal bacteria and reveal the potential role of mobile genetic elements in shaping the resistome of the rumen microbiome, with implications for human and animal health.


Transjugular Intrahepatic Portosystemic Shunt is effective to treat portal hypertension due to sinusoidal obstructive syndrome.
Transjugular Intrahepatic Portosystemic Shunt (TIPS) is an established procedure for the complications of portal hypertension, such as variceal bleeding, refractory ascites and hepatic hydrothorax. We report an original case of a renal transplant patient successfully treated with TIPS for portal hypertension due to sinusoidal obstructive syndrome (SOS) induced by azathioprine (AZA). By reporting this case, we wish to draw the attention of healthcare professionals managing organ transplant patients, especially nephrologists, to the possible occurrence of liver toxicity due to AZA, and to emphasize the role of TIPS as an effective therapeutic option for portal hypertension-related complications.


The RNA polymerase "switch region" is a target for inhibitors.
The alpha-pyrone antibiotic myxopyronin (Myx) inhibits bacterial RNA polymerase (RNAP). Here, through a combination of genetic, biochemical, and structural approaches, we show that Myx interacts with the RNAP "switch region"--the hinge that mediates opening and closing of the RNAP active center cleft--to prevent interaction of RNAP with promoter DNA. We define the contacts between Myx and RNAP and the effects of Myx on RNAP conformation and propose that Myx functions by interfering with opening of the RNAP active-center cleft during transcription initiation. We further show that the structurally related alpha-pyrone antibiotic corallopyronin (Cor) and the structurally unrelated macrocyclic-lactone antibiotic ripostatin (Rip) function analogously to Myx. The RNAP switch region is distant from targets of previously characterized RNAP inhibitors, and, correspondingly, Myx, Cor, and Rip do not exhibit crossresistance with previously characterized RNAP inhibitors. The RNAP switch region is an attractive target for identification of new broad-spectrum antibacterial therapeutic agents.


Labor induction in China: a nationwide survey.
Overmedicalization in labor management and delivery, including labor induction, is an increasing global concern. But detailed epidemiological data on labor induction in China remains unclear. This was a cross-sectional study of data (2015-2016) from 96 hospitals in 24 (of 34) Chinese administrative divisions. Multivariable logistic regression analysis was used to assess the association between medical conditions and cesarean delivery among women undergoing induction. Linear regression analysis was performed to assess the association between the prelabor cesarean delivery and labor-induction rates in each hospital. The impacts of labor induction and prelabor cesarean delivery on maternal and neonatal outcomes were compared in low-risk women. Among 73 901 eligible participants, 48.1% were nulliparous. The overall weighted rate of labor induction in China was 14.2% (95% CI, 11.1-17.2%), with 18.4% (95% CI, 14.5-22.3%) in nulliparas and 10.2% (95% CI, 7.7-12.8%) in multiparas. Regardless of the induction method, the overall vaginal delivery rate was 72.9% (95% CI, 68.6-77.3%) in nulliparas and 86.6% (95% CI, 79.7-93.5%) in multiparas. Hospitals with a higher rate of nonmedically indicated cesarean delivery had a lower labor-induction rate in nulliparas (β = - 0.57%; 95% CI, - 0.92 to - 0.22%; P = 0.002). Compared with prelabor cesarean delivery, labor induction in low-risk women was not associated with adverse maternal and neonatal outcomes. The 2015-2016 labor-induction rate in China was 18.4% in nulliparas and 10.2% in multiparas. The proportion of prelabor cesarean delivery may contribute to regional differences in the labor-induction rate. Compared with prelabor cesarean delivery, labor induction in low-risk women may not increase severe maternal and neonatal morbidity.


Characteristics of heart, arteries, and veins in low and high cardiac output preeclampsia.
To assess the feasibility of non-invasive measurements of maternal cardiac output in relation to birth weight percentile and cardiovascular physiology in preeclampsia. In a cohort of 62 women with preeclampsia, impedance cardiography was used to measure cardiac output and to evaluate heart and arteries. Venous characteristics were assessed by combined electrocardiogram-Doppler ultrasonography. Statistical differences were evaluated by Mann-Whitney U-tests. Cardiac output correlated with birth weight percentile (P=.002), with more small for gestational age newborns in low cardiac output preeclampsia (<7.5L/min) than in high cardiac output preeclampsia (≥8.9L/min) (12/29 vs. 2/16, P=.044). This was associated with lower aortic flow indices and shorter venous pulse transit times in low than in high cardiac output preeclampsia. Non-invasive impedance cardiography measurements of maternal cardiac output correlate with birth weight percentile and are associated with different functionality of heart, arteries, and veins in low and high cardiac output preeclampsia.