Glucose metabolism, H+ production and Na+/H+-exchanger mRNA levels in ischemic hearts from diabetic rats.
Glycolysis uncoupled from glucose oxidation is a major reason for the intracellular acidosis that occurs during severe myocardial ischemia. The imbalance between glycolysis and glucose oxidation, and the resultant H+ produced from glycolytically derived ATP hydrolysis in the diabetic rat heart is the focus of this study. Isolated working hearts from 6 week streptozotocin diabetic rat hearts were perfused with 11 mM glucose and 1.2 mM palmitate and subjected to a 25 min period of global ischemia. A second series of experiments were also performed in which hearts from control, diabetic, and islet-transplanted diabetic rats were subjected to a 30 min aerobic perfusion, followed by a 60 min period of low-flow ischemia (coronary flow = 0.5 ml/min) and 30 min of aerobic reperfusion. H+ production from glucose metabolism was measured throughout the two protocols by simultaneous measurement of glycolysis and glucose oxidation using perfusate labelled with [5-3H/U-14C]-glucose. Rates of H+ production were calculated by measuring the difference between glycolysis and glucose oxidation. The H+ production throughout the perfusion was generally lower in diabetic rat hearts compared to control hearts, while islet-transplantation of diabetic rats increased H+ production to rates similar to those seen in control hearts. This occurred primarily due to a dramatic increase in the rates of glycolysis. Despite the difference in H+ production between control, diabetic and islet-transplanted diabetic rat hearts, no difference in mRNA levels of the cardiac Na+/H+-exchanger (NHE-1) was seen. This suggests that alterations in the source of protons (i.e. glucose metabolism) are as important as alterations in the fate of protons, when considering diabetes-induced changes in cellular pH. Furthermore, our data suggests that alterations in Na+/H+-exchange activity in the diabetic rat heart occur at a post-translational level, possibly due to direct alterations in the sarcolemmal membranes.


Modulation of morphological differentiation of human endothelial cells in culture by the synthetic peptide YIGSR and cytochalasin B.
Matrigel is a solubilized tissue basement membrane gel extracted from the mouse Engelbreth-Holm-Swarm sarcoma. Cultures of human endothelial cells could be induced to undergo extremely rapid morphological differentiation into capillary-like structures by Matrigel. The present study demonstrates the following: (a) Matrigel-induced tube formation by endothelial cells is laminin-dependent and, particularly, the YIGSR peptide site in the B1 chain of laminin may be necessary for endothelial cell differentiation resulting in capillary formation; (b) endothelial cells may be preprogrammed for rapid differentiation into blood vessels and do not require DNA, RNA or protein synthesis in order to undergo tube formation on Matrigel; and (c) microfilament assembly and function is important for Matrigel-induced tube formation.


Edrophonium for the antagonism of neuromuscular blockade in dogs.
Neuromuscular, electrocardiographic and autonomic nervous changes were studied when edrophonium and four combinations of edrophonium and atropine were used to antagonise vecuronium-induced neuromuscular blockade in 87 dogs anaesthetised with halothane. Edrophonium (500 micrograms/kg body-weight) was given alone, or with atropine (40 micrograms/kg) or one minute after a dose of 600 micrograms of atropine, and a lower dose of edrophonium (250 micrograms/kg) was used with high (40 micrograms/kg) and low (20 micrograms/kg) doses of atropine. The neuromuscular blockade was antagonised when some recovery was present. The reversal was rapid and complete in 75 cases, but the remaining 12 dogs which received the low dose of edrophonium required a second injection. Trials with the high dose of edrophonium alone were discontinued because cardiac arrest occurred in one dog and bronchosecretion with profuse salivation in another. The heart rate increased with the low dose of edrophonium and the high dose of atropine, and increased and then decreased when edrophonium was followed by 600 micrograms of atropine. The heart rate was stable when the high and low doses of atropine and edrophonium were matched. All the treatments caused atrioventricular blockade. Non-cardiac autonomic changes (salivation and bronchosecretion) occurred in only two of the 87 dogs.


Efficacy of bupropion and the selective serotonin reuptake inhibitors in the treatment of major depressive disorder with high levels of anxiety (anxious depression): a pooled analysis of 10 studies.
The goal of this work was to compare the efficacy of the norepinephrine and dopamine reuptake inhibitor bupropion with the selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder with high levels of anxiety (anxious depression). Ten double-blind, randomized studies from 1991 through 2006 were combined (N = 2122). Anxious depression was defined as a 17-item Hamilton Rating Scale for Depression (HAM-D-17) anxiety-somatization factor score >or= 7. Among patients with anxious depression (N = 1275), response rates were greater following SSRI than bupropion treatment according to the HAM-D-17 (65.4% vs. 59.4%, p = .03) and the Hamilton Rating Scale for Anxiety (61.5% vs. 54.5%, p = .03). There was also a greater reduction in HAM-D-17 mean +/- SD scores (-14.1 +/- 7.6 vs. -13.2 +/- 7.9, p = .03) and a trend toward statistical significance for a greater reduction in HAM-A mean +/- SD scores (-10.5 +/- 7.4 vs. -9.6 +/- 7.6, p = .05) in favor of SSRI treatment among patients with anxious depression. There was no statistically significant difference in efficacy between bupropion and the SSRIs among patients with moderate/low levels of anxiety. There appears to be a modest advantage for the SSRIs compared to bupropion in the treatment of anxious depression (6% difference in response rates). Using the number-needed-to-treat (NNT) statistic as 1 indicator of clinical significance, nearly 17 patients would need to be treated with an SSRI than with bupropion in order to obtain 1 additional responder. This difference falls well above the limit of NNT = 10, which was suggested by the United Kingdom's National Institute of Clinical Excellence. Nevertheless, the present work is of theoretical interest because it provides preliminary evidence suggesting a central role for serotonin in the regulation of symptoms of negative affect such as anxiety.


Effect of dietary sucrose on synthesis and degradation of intestinal sucrase.
Rates of synthesis and degradation of sucrase-isomaltase were measured along the crypt-villus unit of intestinal mucosa of rats fed either a high-sucrose or a carbohydrate-free diet. The objective of the study was to investigate i) the biochemical basis for the accumulation of sucrase during migration and differentiation of the enterocyte, leading to changes in distribution of activity of sucrase along the villus, and ii) the mechanism for the adaptation of sucrase activity to the amount of dietary carbohydrate. The results indicate that synthesis of sucrase is more rapid than degradation at the crypt-villus junction and in the lower part of the villus, producing a progressive accumulation of enzyme. The decreased activity at the tip of the villus is the consequence of a decided diminution of synthesis while the rate of degradation remains elevated. In rats fed a diet high in sucrose, the increased activity (3.25 times) is associated with much more rapid synthesis (2.6 times), while degradation is only slightly slower (0.8 times) than in those animals deprived of carbohydrate.


Effect of thermal processing on T cell reactivity of shellfish allergens - Discordance with IgE reactivity.
Crustacean allergy is a major cause of food-induced anaphylaxis. We showed previously that heating increases IgE reactivity of crustacean allergens. Here we investigate the effects of thermal processing of crustacean extracts on cellular immune reactivity. Raw and cooked black tiger prawn, banana prawn, mud crab and blue swimmer crab extracts were prepared and IgE reactivity assessed by ELISA. Mass spectrometry revealed a mix of several allergens in the raw mud crab extract but predominant heat-stable tropomyosin in the cooked extract. PBMC from crustacean-allergic and non-atopic control subjects were cultured with the crab and prawn extracts and proliferation of lymphocyte subsets was analysed by CFSE labelling and flow cytometry. Effector responses were assessed by intracellular IL-4 and IFN-γ, and regulatory T (CD4+CD25+CD127loFoxp3+) cell proportions in cultures were also compared by flow cytometry. For each crustacean species, the cooked extract had greater IgE reactivity than the raw (mud crab p<0.05, other species p<0.01). In contrast, there was a trend for lower PBMC proliferative responses to cooked compared with raw extracts. In crustacean-stimulated PBMC cultures, dividing CD4+ and CD56+ lymphocytes showed higher IL-4+/IFN-γ+ ratios for crustacean-allergic subjects than for non-atopics (p<0.01), but there was no significant difference between raw and cooked extracts. The percentage IL-4+ of dividing CD4+ cells correlated with total and allergen-specific IgE levels (prawns p<0.01, crabs p<0.05). Regulatory T cell proportions were lower in cultures stimulated with cooked compared with raw extracts (mud crab p<0.001, banana prawn p<0.05). In conclusion, cooking did not substantially alter overall T cell proliferative or cytokine reactivity of crustacean extracts, but decreased induction of Tregs. In contrast, IgE reactivity of cooked extracts was increased markedly. These novel findings have important implications for improved diagnostics, managing crustacean allergy and development of future therapeutics. Assessment of individual allergen T cell reactivity is required.


Visits to the college health service for alcohol-related injuries.
A study of alcohol-related injuries presenting to the local emergency room and the campus health service indicated an annualized rate of 25.16 injuries per thousand students. Twenty-four percent of injuries presenting to the emergency room were assessed as alcohol-related; another 6% were listed as being "suspected." Less than 4% of the injuries presenting to the campus health service were assessed as alcohol-related, and a similar number were listed as "suspected." Males had a significantly higher rate of alcohol-related injuries than females, and undergraduates had a higher rate than graduate students. Differences among the undergraduate classes were not significant. An investigation of the time of presentation indicated that most alcohol-related injuries occurred after hours and on weekends.


Sensory Neuron-Specific Deletion of TRPA1 Results in Mechanical Cutaneous Sensory Deficits.
The nonselective cation channel transient receptor potential ankyrin 1 (TRPA1) is known to be a key contributor to both somatosensation and pain. Recent studies have implicated TRPA1 in additional physiologic functions and have also suggested that TRPA1 is expressed in nonneuronal tissues. Thus, it has become necessary to resolve the importance of TRPA1 expressed in primary sensory neurons, particularly since previous research has largely used global knock-out animals and chemical TRPA1 antagonists. We therefore sought to isolate the physiological relevance of TRPA1 specifically within sensory neurons. To accomplish this, we used Advillin-Cre mice, in which the promoter for Advillin is used to drive expression of Cre recombinase specifically within sensory neurons. These Advillin-Cre mice were crossed with Trpa1fl/fl mice to generate sensory neuron-specific Trpa1 knock-out mice. Here, we show that tissue-specific deletion of TRPA1 from sensory neurons produced strong deficits in behavioral sensitivity to mechanical stimulation, while sensitivity to cold and heat stimuli remained intact. The mechanical sensory deficit was incomplete compared to the mechanosensory impairment of TRPA1 global knock-out mice, in line with the incomplete (∼80%) elimination of TRPA1 from sensory neurons in the tissue-specific Advillin-Cre knock-out mice. Equivalent findings were observed in tissue-specific knock-out animals originating from two independently-generated Advillin-Cre lines. As such, our results show that sensory neuron TRPA1 is required for mechanical, but not cold, responsiveness in noninjured skin.


Profiles and spatial distributions of heavy metals, microbial communities, and metal resistance genes in sediments from an urban river.
The occurrence and propagation of resistance genes due to exposure to heavy metals (HMs) in rivers is an emerging environmental issue. Little is known about resistance genes in microbial communities in river sediments with low HM concentrations. The profiles and spatial distributions of HMs, the microbial community, and metal resistance genes (MRGs) were analyzed in sediment samples from the Zhilong River basin in Yangjiang city, near the Pearl River Delta. Concentrations of copper (Cu), cadmium (Cd), lead (Pb), chromium (Cr), and nickel (Ni) were relatively low compared with those in other urban river sediments in China. HM chemical composition and fractions and the structure of the microbial community varied along the main channel, but the composition and abundance of MRGs were relatively homogeneous. Variations in HMs and microbial communities in mid- to upstream areas were related to the presence of tributaries, whose inputs were one of the major factors affecting HM chemical fractions and genera structure in mainstream sediments. There were no significant correlations (p < 0.05) between HM concentrations, bacterial communities, and the MRG profiles; thus, HM concentrations were not the main factor affecting MRGs in sediments. These results contribute to understanding the propagation of MRGs in urban rivers in developing cities.


Study on Dynamic Monitoring of Wire Rope Tension Based on the Particle Damping Sensor.
Real-time monitoring of wire rope tension is of great significance to the safe operation of mine hoist. Due to the longitudinal and lateral coupling vibration of wire ropes during the operation of hoist, there are high frequency components in measured tension signals of wire ropes, which cannot effectively characterize the actual lifting load. To overcome this problem, a particle damping sensor with a vibration dissipation function is designed in this paper. Multilayered steel balls are placed into the cylindrical cavity of the sensor. Damping vibration and energy dissipation will occur when the sensor is subjected to external excitation. Then, to obtain the optimal sensor characteristics, relevant parameters of the particles and the spoke structure are simulated. Finally, the sensor based on the optimized parameters is manufactured and tested in a coal mine. Compared with the general pressure sensor, the particle damping sensor can effectively eliminate the influence of wire ropes vibration on tension measurement and achieve accurate measurement results.


Electrochemical Cloth-Based DNA Sensors (ECDSs): A New Class of Electrochemical Gene Sensors.
Electrochemical (EC) sensors have been widely developed for DNA detection, but they are seldom used in a simple, economic, and efficient manner. In this work, for the first time, EC cloth-based DNA sensors (ECDSs) are developed as a new class of EC DNA sensors, without the need for cumbersome chip fabrication and high-cost peripheral facilities. Carbon ink- and solid wax-based screen printing were used to produce ultracheap sensing devices (the cost of one sensor is estimated to be $0.045). Also, a CdTe QDs/MWCNTs nanocomposite (CdTe-MWCNTs) was applied to modify the sensing interface to obtain a stronger EC signal. Specifically, the newly developed double linear hybridization chain reaction (DL-HCR) greatly amplified the EC signal, relative to the conventional linear HCR. Under optimized conditions, target DNA (TD) samples (75-bp DNA fragments prepared via PCR amplification) were determined in a range from 20 fM to 5 nM, with a detection limit of 8.74 fM and relative standard deviations of 2.04% and 4.75% for intra- and inter-assays at 50 pM TD, respectively. Additionally, the ECDSs had an acceptable storage stability and high selectivity. Importantly, the ECDSs, coupled with simple enzyme digestion, could detect genomic DNA from Listeria monocytogenes (L. monocytogenes), and a detection limit of 0.039 ng/μL was obtained. When coupled with enzyme digestion and PCR amplification, the ECDSs could determine L. monocytogenes in milk samples, with detection limits of approximately 1.64 × 104 and 11 CFU/mL. These results demonstrate that the method offers a broad prospect for cost-effective, reliable, and highly sensitive gene-sensing applications.


Primary Clear Cell Renal Cell Carcinoma with Marked Intraluminal Mucin Secretion.
Clear cell renal cell carcinoma with mucin secretion is an unexpected situation. Primary renal adenocarcinoma and various metastatic carcinomas should be considered in the differential diagnosis. Prognostic significance is not yet fully known due to the limited number of reported cases, and these lesions have been grouped under unclassified renal cell carcinoma. In our study, clear cell renal cell carcinoma with significant luminal mucin secretion is discussed with its histological, histochemical and immunohistochemical features.


Cytotoxicity of NF-kappaB inhibitors Bay 11-7085 and caffeic acid phenethyl ester to Ramos and other human B-lymphoma cell lines.
The viability of normal and malignant B-cells was shown to depend on the constitutive activation of the nuclear factor (NF)- kappaB pathway. Thus, attempts to find efficient inhibitors of NF-kappaB play a central role in the search for novel anti-B lymphoma therapies. We studied the effects of two NF-kappaB inhibitors, Bay 11-7085 (BAY) and caffeic acid phenethyl ester (CAPE), on the viability of B-lymphoma cell lines. We investigated the mechanism(s) of the cytotoxic effect of the NF-kappaB inhibitors, BAY, and CAPE on human-lymphoma and nonhematological cell lines. BAY and CAPE were shown to kill Ramos-Burkitt's lymphoma cells with IC(50) values of 0.7 microM and 4 microM, respectively. The rapid killing by BAY (h) vs the slower killing by CAPE (1-3 days), and their differential effects on the stages of the cell cycle, indicated that these drugs induce killing by different mechanisms. BAY and CAPE induced a loss of the cytoplasmic compartment and generated pyknotic nuclei, which lacked nuclear or nucleosomal fragmentation, features characteristic of necrosis rather than apoptosis. BAY also induced a rapid loss of the mitochondrial potential and rapid inhibition of p65 NF-kappaB binding to its kappaB motif without reducing the level of nuclear p65. Our results indicate that BAY causes a necrotic rather than apoptotic cell death, either through its effect on the NF-kappaB pathway and/or by affecting additional molecular targets. The high sensitivity of B-lymphoma cell lines to the cytotoxicity of BAY, justify further research to explore its potential therapeutic effect on human B lymphomas.


Mead Johnson Critical Care Symposium for the Practising Surgeon. 3. Monitoring and investigation of intra-abdominal sepsis.
Diagnosis and management of intra-abdominal sepsis continue to be major problems in critically ill patients. Multiple system organ failure secondary to intra-abdominal sepsis continues to cause serious morbidity and death. The first step in management is to recognize the infection, while providing careful supportive therapy. A number of radiologic investigations, including ultrasonography and computed tomography, will help to diagnose a potential source of infection, which can be positively identified by fine-needle aspiration and culture. The septic focus must be drained either percutaneously or, if this fails, surgically. Use of specific antibiotics is imperative. Delay in diagnosis and surgery increases the death rate, so all available diagnostic modalities should be utilized, but these should not replace careful ongoing clinical assessment.


[Relation between extra- and intracardiac anti-strophanthin properties of anti-arrhythmic agents].
Animal experiments have shown that beta-adrenoblockers have the most marked antistrophanthin properties while antiarrhythmic agents with locally anesthetic attributes are less active. All the substances studied have proved to be ineffective on the cellular model of strophanthin arrhythmia. The data obtained suggest that the antiarrhythmic effect of the substances under study including beta-adrenoblockers is exercised on the level of the receptor apparatus of the postsynaptic membrane. The membrane stabilizing properties do not play the decisive role in ensuring the antiarrhythmic effect in strophanthin arrhythmia.


Syllabic discrimination in premature human infants prior to complete formation of cortical layers.
The ontogeny of linguistic functions in the human brain remains elusive. Although some auditory capacities are described before term, whether and how such immature cortical circuits might process speech are unknown. Here we used functional optical imaging to evaluate the cerebral responses to syllables at the earliest age at which cortical responses to external stimuli can be recorded in humans (28- to 32-wk gestational age). At this age, the cortical organization in layers is not completed. Many neurons are still located in the subplate and in the process of migrating to their final location. Nevertheless, we observed several points of similarity with the adult linguistic network. First, whereas syllables elicited larger right than left responses, the posterior temporal region escaped this general pattern, showing faster and more sustained responses over the left than over the right hemisphere. Second, discrimination responses to a change of phoneme (ba vs. ga) and a change of human voice (male vs. female) were already present and involved inferior frontal areas, even in the youngest infants (29-wk gestational age). Third, whereas both types of changes elicited responses in the right frontal region, the left frontal region only reacted to a change of phoneme. These results demonstrate a sophisticated organization of perisylvian areas at the very onset of cortical circuitry, 3 mo before term. They emphasize the influence of innate factors on regions involved in linguistic processing and social communication in humans.


Enantioseparation of benzoxazolinone aminoalcohols and their aminoketone precursors, potential adrenergic ligands, by analytical and preparative liquid chromatography on amylose chiral stationary phases and characterization of the enantiomers.
To obtain milligram amounts of the enantiomers of benzoxazolinone derivatives to be tested for binding to adrenergic sites, analytical HPLC methods using derivatized amylose chiral stationary phases were developed for the direct enantioseparation of benzoxazolinone aminoalcohols and their aminoketone precursors, derivatives with one or two chirals centers. The separations were made using normal phase methodology with a mobile phase of n-hexane-alcohol (ethanol, 1-propanol, or 2-propanol) in various proportions, and silica-based amylose (tris-3, 5-dimethylphenylcarbamate) Chiralpak AD and (tris-(S)-1-phenylethylcarbamate) Chiralpak AS columns. The effects of concentration of various aliphatic alcohols in the mobile phase were studied. The best separation was achieved on Chiralpak AS, so preparative HPLC was set up with this chiral stationary phase using a mobile phase consisting of n-hexane-alcohol using isocratic conditions and multiple repetitive injections. Physicochemicals properties of enantiomers were reported The effect of structural features of the solutes on discrimination between the enantiomers was examined. Limit of detection (LD) and limit of quantification (LQ) were determined using both ultra-violet (UV) and evaporative light-scattering detection (ELSD).


Spatial and temporal variations in salt marsh microorganisms of the Wadden Sea.
Salt marshes exist at the interface of the marine and the terrestrial system. Shore height differences and associated variations in inundation frequency result in altered abiotic conditions, plant communities, and resource input into the belowground system. These factors result in three unique zones, the upper salt marsh (USM), the lower salt marsh (LSM), and the pioneer zone (PZ). Marine detritus, such as micro- and macroalgae, is typically flushed into the PZ daily, with storm surges moving both salt marsh detritus and marine detritus into higher salt marsh zones. Microbial assemblages are essential for the decomposition of organic matter and have been shown to sensitively respond to changes in abiotic conditions such as oxygen supply and salinity. However, temporal and spatial dynamics of microbial communities of Wadden Sea salt marshes received little attention. We investigated the dynamics of soil microbial communities across horizontal (USM, LSM, and PZ), vertical (0-5 and 5-10-cm sediment depth), and temporal (spring, summer, and autumn) scales in the Wadden Sea salt marsh of the European North Atlantic coast using phospholipid fatty acid (PLFA) analysis. Our results show strong spatial dynamics both among salt marsh zones and between sediment depths, but temporal dynamics to be only minor. Despite varying in space and time, PLFA markers indicated that bacteria generally were the dominant microbial group across salt marsh zones and seasons, however, their dominance was most pronounced in the USM, whereas fungal biomass peaked in the LSM and algal biomass in the PZ. Only algal markers and the stress marker monounsaturated to saturated fatty acid ratio responded to seasonality. Overall, therefore, the results indicate remarkable temporal stability of salt marsh microbial communities despite strong variability in abiotic factors.


Sol-gel transition temperature of PLGA-g-PEG aqueous solutions.
Aqueous solutions of poly(DL-lactic acid-co-glycolic acid)-g-poly(ethylene glycol) copolymers exhibited sol-to-gel transition with increasing temperature. Further increase in temperature makes the system flow and form a sol phase again. Subcutaneous injection of a copolymer aqueous solution (0.5 mL) resulted in a formation of a hydrogel depot by temperature-sensitive sol-to-gel transition in a rat model. The reliable determination and control of sol-to-gel transition temperatures are the most important issues for this kind of sol-gel reversible hydrogel. The sol-to-gel transition temperature determined by the test tube inverting method, falling ball method, and dynamic mechanical analysis coincided within 1-2 degrees C. Fine tuning of the sol-to-gel transition temperature was achieved by varying the ionic strength of the polymer solutions and by mixing two polymer aqueous solutions with different sol-to-gel transition temperatures. The sol-to-gel transition temperature of polymer mixture aqueous solutions was well described by an empirical equation of miscible blends, indicating miscibility of the two polymer systems in water on the molecular level.


Molecular basis of X-linked non-specific mental retardation.
Mental retardation (MR) is a common disorder, affecting 1-3% of the total population. This condition results from failure to develop cognitive abilities and intelligence level appropriate for the age group. Mental retardation is basically a clinically as well as etiologically heterogeneous type of condition and both genetic and non-genetic factors have been found to be involved. There are more than 1000 entries in Online Mendelian Inheritance in Man (OMIM) database under the name of mental retardation. In recent years 15 genes for X linked non-specific mental retardation have been identified which provide important clues regarding molecular and cellular processes involved in signal transduction cascade in central nervous system. Recent advancements in identification and characterization of X-linked non-specific mental retardation genes have been discussed in this review. Understanding of the molecular pathways of disease causing genes would be helpful in developing effective therapeutic approaches for mental retardation.


Integrating medical and psychological health care for children with atopic dermatitis.
To present descriptive data from a hospital-based interdisciplinary program that provides integrated medical and psychological health-care for children with atopic dermatitis (AD). Clinical records were reviewed for 69 children seen in our program to examine parent-reported AD-related presenting concerns, as well as common problems and interventions addressed during family visits with the program psychologist. The most common presenting concerns included child itching and scratching and associated sleep problems. Parent initial request for a meeting with the program psychologist was not related to child disease severity, but was associated with child sleep problems and parent emotional and practical challenges in managing the child's condition. Results support the need for, acceptance of, and feasibility of providing integrated care for children with AD and their families. Changes to our clinical model based on study findings are discussed.


[Long-term functional and aesthetic sequelae after complex facial trauma associated with a mild brain injury].
Most victims of complex facial trauma will have permanent sequelae. The goal of our work was to evaluate, by means of a retrospective study, the long-term sequelae in these patients. 102 victims of complex facial trauma were treated in our department between 1995 and 2000. Twenty-four could be re-examined in 2006 in order to evaluate their long-term sequelae. All the patients suffered a mild brain injury. The overall satisfaction rate was good (19/24), but all patients presented either functional or aesthetic sequelae. The major functional sequelae were dental lost (17/24), sensory impairment of the trigeminal nerve (15/24), partial or complete loss of vision (10/24), pain (10/24), hypo- or anosmia (9/24), stenosis of the lacrimal ducts (8/24) and symptomatic deviation of the nasal septum (7/24). The main esthetic sequelae were facial scarring (23/24), facial asymmetry (13/24), dystopia of the eyeball (11/24) and modification of the aspect of the nose (10/24). The prognosis of severe facial trauma is highly dependent on the quality of the initial pluridisciplinary care. Secondary revision procedures are technically more difficult and only enable partial resolution of persisting sequelae. Thus, primary single-course surgical procedures should be a priority, recognizing that complete recovery is almost always illusory.


The Prognostic and Clinicopathological Roles of Sirtuin-3 in Various Cancers.
Sirtuin-3 (SIRT3) is a major mitochondrial NAD(+)-dependent deacetylase and plays a key role in the progression and development of human cancers. Although the prognostic and clinicopathological features of SIRT3 expression in various cancers have been investigated by different research groups, however, inconsistent and opposing results can be observed. In this study, we therefore performed a meta-analysis to evaluate the significance of SIRT3 expression in various cancers. Systematic literature searching was performed in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang Data up to November 2015. Total effect analyses and subgroup analyses were performed to evaluate the relationship between SIRT3 expression and overall survival, cancer/non-cancer tissues, lymph node metastasis, pathological differentiation, tumor node metastasis (TNM) stage, tumor size, and gender, in various cancer patients. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to clarify the risk or hazard association. A total of 14 studies comprising 2165 cancer patients were included to assess the association between SIRT3 immunohistochemical expression and overall survival or clinicopathological characteristics. SIRT3 expression was significantly associated with overall survival in gastric cancer (HR = 0.62, 95% CI = 0.43-0.89, P = 0.009) and hepatocellular carcinoma patients (HR = 0.56, 95% CI = 0.42-0.74, P<0.0001), cancer/non-cancer tissues in hepatocellular carcinoma patients (OR = 0.04, 95% CI = 0.01-0.16, P<0.0001), lymph node metastasis in breast cancer patients (OR = 2.20, 95% CI = 1.49-3.26, P<0.0001), and also pathological differentiation in hepatocellular carcinoma patients (OR = 0.69, 95% CI = 0.48-0.98, P = 0.04) and gastric cancer patients (OR = 0.33, 95% CI = 0.21-0.50, P<0.00001), by subgroup analyses. Furthermore, SIRT3 expression was significantly associated with pathological differentiation in total effect analysis (OR = 0.46, 95% CI = 0.29-0.74, P = 0.001). No detectable relation between SIRT3 expression and other clinicopathological parameters were found. This meta-analysis indicates that SIRT3 expression level is associated with prognostic and clinical features in specific cancers.


Preliminary results of pre-radiation neck dissection in head and neck cancer patients undergoing organ preservation treatment.
Pre-RT ND in patients with HNSCC undergoing organ preservation treatment is safe, advantageous, poses no additional morbidity owing to the elective neck dissection, and may possibly improve survival outcomes. Establish the role of pre-radiation neck dissection (pre-RT ND) in patients with head & neck squamous cell carcinoma (HNSCC) undergoing organ preservation treatment. Fourteen patients with histologically confirmed HNSCC in stages III approximately IV with proven regional metastasis were enrolled in the organ preservation approach incorporating pre-RT ND at a tertiary referral center between May 1998 and August 2004. Site matched patients treated with organ preservation intent in the conventional fashion were used as controls. Data were collected for their diagnosis, management, treatment outcome, and follow up. Disease free survival was significantly better for the pre-RT ND group. There was no significant difference in overall survival, pattern of recurrence, and primary organ preservation rate between the two groups. No significant morbidity owing to neck dissection was noted in patients who underwent neck dissection. Although the delivery of radiation to the primary site was delayed for patients in the pre-RT ND group, it did not influence the major outcomes.


Frequency and Manifestations of Autoimmunity Among Children Registered in the Kuwait National Primary Immunodeficiency Registry.
Objectives: To present a prospective report on the characteristics of autoimmune manifestations in patients with primary immunodeficient children registered in the Kuwait National PIDs Registry (KNPIDR). Methods: The data were obtained from the Kuwait National Primary Immunodeficiency Disorders Registry during the period of January 2004 to December 2019. Results: A total of 286 PID children were registered in KNPIDR during the study period with a predominance of immunodeficiencies affecting cellular and humoral immunity followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. Fifty-seven (19.9%) patients presented with a total of 107 autoimmune manifestations. There was no significant statistical association between autoimmune manifestations and gender. Patients with autoimmune manifestations were older at onset of PID symptoms compared to those with no such manifestations, but this did not reach level of significance. The diagnosis delay was longer in patients with autoimmune manifestations compared to those with no such manifestations (p = 0.038). Forty-seven percent of these manifestations were among the presenting symptoms while 53% were documented later during the course of the disease. Fifty-seven percent of the patients developed 1 autoimmune manifestation, 30% developed 2 such manifestations, and 16% had ≥3 autoimmune manifestations. The most common autoimmune manifestation was cytopenia, followed by gastrointestinal manifestations and manifestations of the skin, hair, and nails. Autoimmune cytopenia were more common in patients with immune dysregulation syndromes, while gastrointestinal and skin manifestations predominate in patients with immunodeficiencies affecting cellular and humoral immunity and endocrine manifestations were more common in immune dysregulation syndromes. There were significant statistical associations between developing autoimmune manifestations and death as well as PID categories, being more common in patients with immune dysregulation. The frequency of autoimmunity was high among patients with RAG, WAS, STAT5b, NF-κB2, Fas, FasL, LRBA, APECED, IL-10, and C4 deficiencies. Conclusions: Autoimmunity is frequent in patients with PIDs in Kuwait. This should prompt the suspicion of a PID in patients who present initially with autoimmunity, especially autoimmune cytopenia. Such patients should be managed with extra care since they are at a higher risk of death.


Functional bladder neck obstruction in females--a revisit.
Functional bladder neck obstruction is supposed to be nonexistent or a very rare clinical disorder. In the past two and a half years, detailed synchronous, video pressure flow EMG studies were done in all the female patients who had evidence of obstructed voiding, poor flow and acute or chronic retention. The subjects of this study are nine females who had high sustained detrusor pressure, high opening pressure, low uroflow and silent sphincter during pressure-flow EMG study. A simultaneous urovideo recording showed either a closed bladder neck, inadequate funneling, intermittent or improper opening during voiding (when Pdet was high and sustained). These patients did not have any anatomical urethral obstruction, neurogenic disorder or systemic disease (like diabetes) affecting voiding. This stringent criteria of functional bladder neck obstruction was observed in nine patients. Five patients had acute or chronic retention and three patients had varying degree of renal failure. Initially all patients were managed by clean intermittent self catheterisation (CIC). Alpha blockers were empirically tried in six patients and had shown variable results. Bladder neck incision (BNI) was performed in two patients with rewarding success.


Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment.
This review focuses on advances and updates in the epidemiology, pathogenesis, diagnosis, and treatment of food allergy over the past 3 years since our last comprehensive review. On the basis of numerous studies, food allergy likely affects nearly 5% of adults and 8% of children, with growing evidence of an increase in prevalence. Potentially rectifiable risk factors include vitamin D insufficiency, unhealthful dietary fat, obesity, increased hygiene, and the timing of exposure to foods, but genetics and other lifestyle issues play a role as well. Interesting clinical insights into pathogenesis include discoveries regarding gene-environment interactions and an increasing understanding of the role of nonoral sensitizing exposures causing food allergy, such as delayed allergic reactions to carbohydrate moieties in mammalian meats caused by sensitization from homologous substances transferred during tick bites. Component-resolved diagnosis is being rapidly incorporated into clinical use, and sophisticated diagnostic tests that indicate severity and prognosis are on the horizon. Current management relies heavily on avoidance and emergency preparedness, and recent studies, guidelines, and resources provide insight into improving the safety and well-being of patients and their families. Incorporation of extensively heated (heat-denatured) forms of milk and egg into the diets of children who tolerate these foods, rather than strict avoidance, represents a significant shift in clinical approach. Recommendations about the prevention of food allergy and atopic disease through diet have changed radically, with rescinding of many recommendations about extensive and prolonged allergen avoidance. Numerous therapies have reached clinical trials, with some showing promise to dramatically alter treatment. Ongoing studies will elucidate improved prevention, diagnosis, and treatment.


[Listeria-induced host cellular actin cytoskeleton rearrangement and phospholipase D].
Either phagocytosis of macrophage to pathogen or pathogen-induced invasion into non-professional phagocytes, such as epithelial cells, require actin cytoskeletal rearrangements and remodeling of the plasma membrane, which are regulated precisely by monogeric GTPase and the correlated proteins. As a key signaling molecule in the cell, phosphotidicphospholipase D (PLD) regulates or interacts directly with cellular actin cytoskeleton rearrangement. Phospholipase D plays an important role in FcgammaRI and C-reactive protein-mediated phagocytosis and phosphorylated cofilin, a ADF (actin depolymerizing factor) is able to bind to phospholipase D and stimulate it; meanwhile, the Listeria-induced actin cytoskeleton rearrangement during the infection is controlled by the phosphorylation of cofilin. Thus, it made challenge to disclose the function of PLD on the regulation of Listeria-induced actin cytoskeleton rearrangement during infection, furthermore, it may provide us more understanding on the role of PLD in the infection and inflammation, which is essential to dissect the molecular mechanism of bacterial-host interaction more thoroughly.


Biofilm formation and antimicrobial resistance in methicillin-resistant Staphylococcus aureus isolated from burn patients, Iran.
Burns are the most serious forms of trauma and a major cause of mortality worldwide. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common pathogens of burn wound infections; treatment has faced serious problems due to antibiotic resistance in these strains. Biofilm formation, which increases antibiotic resistance capabilities and is considered to be a virulence factor, also causes treatment failure and recurrent staphylococcal infections in burn patients. A total of 135 pus/wound swabs were collected; S. aureus was identified by confirmatory tests. The icaA/D and mecA genes were detected in DNA extracts by polymerase chain reaction assay separately. To determine the prevalence of biofilm formation, a modified Congo red agar and the microtiter plate method were used. Investigation of antibiotic resistance was performed using the disk diffusion method. S. aureus (48.87%) was identified in 65 (48.87%) samples, of which 40 (61.53%) were confirmed to be MRSA. Among MRSA and methicillin-sensitive S. aureus (MSSA) isolates, 97.5% and 60% produced biofilm, respectively. Resistance of MRSA isolates to amikacin, ceftriaxone, ciprofloxacin, erythromycin, gentamicin, mupirocin, rifampin, tetracycline, and tobramycin was 64.1%, 76.92%, 51.28%, 87.18%, 71.8%, 10.26%, 5.13%, 89.74%, and 61.54%, respectively. All MRSA and MSSA isolates were susceptible to fusidic acid, linezolid, teicoplanin, tigecycline, and vancomycin. The high prevalence of biofilm-producing, drug-resistant S. aureus isolates in our study suggests that epidemiological studies on the characteristics of common strains found in burn centers and a definition of their antibiotic resistance pattern would be helpful for therapeutic decisions.


What kind of evidence does qualitative research offer cardiovascular nurses?
In this article I have tried to present a brief overview of qualitative research and to suggest some of the ways in which it may be of use to practitioners. Traditionally, we have not included qualitative studies in our discussion of research utilization. I think this is an unfortunate omission. Qualitative studies have a great deal to offer the practitioner and there are ways in which she or he can make use of them without doing so prematurely and without bringing harm to the client or patient. The required ingredients are twofold. First, from the research side we need scientifically sound studies. Second, from the practice side we need curious and informed consumers-consumers who are willing to take new information into their practice repertoires and let it inform those repertoires. Simple ingredients ... hard to get the cake to rise sometimes, though.


Lymphocytic angiitis following streptokinase therapy.
A palpable, purpuric, nonpruritic eruption occurred in a 64-year-old man nine days after he received intravenous streptokinase therapy, which was successful in treating acute myocardial infarction. Perivascular mononuclear and eosinophilic infiltration was noted on routine staining of skin biopsy specimens: immune complexes, fibrin, and complement deposition in the skin microvasculature were demonstrated on immunofluorescent studies. These findings confirm the diagnosis of lymphocytic angiitis induced by streptokinase. Intermediate-type hypersensitivity reactions to streptokinase apparently have variable levels of severity. Clinicians who use streptokinase as a therapeutic agent should be aware of this potentially serious complication.


The impact of part-time post-registration degrees on practice.
This study aimed to identify how graduates from part-time, post-registration degree courses in nursing and midwifery perceived that their practice had changed as a result of the knowledge and skills acquired on their courses. Despite increasing investment in continuing professional education and expansion of nursing roles, little work has been undertaken to assess the impact of graduates' skills on nursing care and clinical outcomes. Postal questionnaires were used to survey all graduates of post-registration Bachelor's and Master's courses in nursing and midwifery from one institution in the United Kingdom (UK) (n=60). Respondents were asked to describe how they felt their graduate skills were used in practice and if this was influenced by any factors in the workplace. Data were analysed descriptively, and by content analysis. Forty-three of 58 graduates contacted responded (74%). The majority (33/43, 77%) of respondents felt that their graduate skills were used in practice. Although most felt that their clinical practice had changed as a result of their degree studies, no practical examples of this were given, despite specific questioning. Many examples of academic and research skills acquired on the course were cited, which raises the question of whether the degree courses provided graduates with academic rather than clinical knowledge. There was ambivalence as to their perceptions of barriers in the workplace, which may have impeded the application of knowledge acquired on the courses. The clinical effectiveness of education initiatives depends on the learners, the course and the workplace. To maximize the benefits accruing to patients from continuing professional education and role expansion, further exploration of the contribution of higher education programmes to clinical practice is required.


Food Insecurity and Dental Caries in Rural Mexican Populations.
Food insecurity (FI) is a priority for government and health organizations. Over 95% of the world's population has a carious lesion or will develop one before death. This study evaluated the association between FI and oral health in two rural communities in Chiapas, Mexico. The study was conducted with patients attending an oral health campaign for dental checkups. Data were collected between April and August 2017 using the Latin-American and Caribbean Scale of Food Security (ELCSA) and the International Caries Detection and Assessment System (ICDAS). We included 209 participants from Siltepec and Huehuetan, Mexico; 67% were women. The results of the ELCSA were mild FI in 43% (n = 91), moderate FI in 22% (n = 45), and severe FI (n = 6) in 3%; 32% had food security. The ICDAS results were initial decay with a mean of 6.22, moderate decay with a mean of 1.81, and extensive decay with a mean of 1.77. FI is associated with dental caries, and food-insecure individuals have a higher probability of severe dental caries. In this study, the FI level was lower than in other rural populations in Mexico. Identifying these individuals and addressing the factors related to FI can be useful in the rural communities.


The Balance between Recombination Enzymes and Accessory Replicative Helicases in Facilitating Genome Duplication.
Accessory replicative helicases aid the primary replicative helicase in duplicating protein-bound DNA, especially transcribed DNA. Recombination enzymes also aid genome duplication by facilitating the repair of DNA lesions via strand exchange and also processing of blocked fork DNA to generate structures onto which the replisome can be reloaded. There is significant interplay between accessory helicases and recombination enzymes in both bacteria and lower eukaryotes but how these replication repair systems interact to ensure efficient genome duplication remains unclear. Here, we demonstrate that the DNA content defects of Escherichia coli cells lacking the strand exchange protein RecA are driven primarily by conflicts between replication and transcription, as is the case in cells lacking the accessory helicase Rep. However, in contrast to Rep, neither RecA nor RecBCD, the helicase/exonuclease that loads RecA onto dsDNA ends, is important for maintaining rapid chromosome duplication. Furthermore, RecA and RecBCD together can sustain viability in the absence of accessory replicative helicases but only when transcriptional barriers to replication are suppressed by an RNA polymerase mutation. Our data indicate that the minimisation of replisome pausing by accessory helicases has a more significant impact on successful completion of chromosome duplication than recombination-directed fork repair.


Current knowledge on psoriasis and autoimmune diseases.
Psoriasis is a prevalent, chronic inflammatory disease of the skin, mediated by crosstalk between epidermal keratinocytes, dermal vascular cells, and immunocytes such as antigen presenting cells (APCs) and T cells. Exclusive cellular "responsibility" for the induction and maintenance of psoriatic plaques has not been clearly defined. Increased proliferation of keratinocytes and endothelial cells in conjunction with APC/T cell/monocyte/macrophage inflammation leads to the distinct epidermal and vascular hyperplasia that is characteristic of lesional psoriatic skin. Despite the identification of numerous susceptibility loci, no single genetic determinant has been identified as responsible for the induction of psoriasis. Thus, numerous other triggers of disease, such as environmental, microbial and complex cellular interactions must also be considered as participants in the development of this multifactorial disease. Recent advances in therapeutics, especially systemic so-called "biologics" have provided new hope for identifying the critical cellular targets that drive psoriasis pathogenesis. Recent recognition of the numerous co-morbidities and other autoimmune disorders associated with psoriasis, including inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus suggest common signaling elements and cellular mediators may direct disease pathogenesis. In this review, we discuss common cellular pathways and participants that mediate psoriasis and other autoimmune disorders that share these cellular signaling pathways.


Hyperthyroidism and pulmonary hypertension.
In recent years, many authors have described several cases revealing an association between hyperthyroidism and pulmonary hypertension (PH). This observational study was designed to evaluate the incidence of PH in hyperthyroidism and was set in a department of internal medicine and pulmonary diseases with an out-patients department of endocrinology. Thirty-four patients, 25 women and nine men, with a mean age of 38 +/- 15 SD years participated. Twenty had Graves' disease and 14 had a nodular goitre. The patients were divided into two equally matched groups: those with a recently diagnosed hyperthyroidism, taking no drugs (group 1; n = 17) and those in a euthyroid state taking methimazole (group 2; n= 17). Transthoracic Doppler echocardiography was performed and systolic pulmonary artery pressurements of (PAPs) was determined by the tricuspid regurgitation method using the Bernoulli equation. Measurements of triiodothyronine, tetraiodothyronine, free thyroxine (Ft4), thyroid-stimulating hormone (TSH) and antithyroglobulin and antimicrosomal antibodies were also taken. We found a mild PH in seven patients of group 1 and in none of group 2. The mean +/- SD systolic pulmonaryartery pressurewas 28.88 +/- 6.41 in group 1 and 22.53 +/- 1.84 ingroup 2 (P<0.0001). A correlation was found between the TSH value and PAPs (r = -082;P < 0.001) and Ft4 and PAPs (r = 0 85; P < 0.001) in group 1. These findings indicate the presence of a frequent association between PH and hyperthyroidism. We suggest that hyperthyroidism be included in the differential diagnosis of PH.


Label-free photoacoustic imaging of the cardio-cerebrovascular development in the embryonic zebrafish.
Zebrafish play an important role in biology, pharmacology, toxicology, and medicine. The cardio-cerebrovascular development of zebrafish is particularly critical to understand both brain disorders and cardiovascular diseases in human. In this paper, we applied optical resolution photoacoustic microscopy (ORPAM) to image the whole-body vasculature of the embryonic zebrafish with a special focus on the development of the cardio-cerebrovascular system. Using the intrinsic optical absorption contrast of the embryo, we successfully visualized the formation of the cardio-cerebrovascular network in high-resolution using a 10 × objective, and monitored the whole-body vascular development using a 4 × objective. In addition, we evaluated the impact of the eggshell and pigment inhibitor on the image quality. Our results suggest that ORPAM is capable of studying the cardio-cerebrovascular development of zebrafish in the embryonic stage, and thus has the potential to investigate the cardiovascular and cerebrovascular diseases of human in the future.


Drimanes and other terpenoids from the fern Thelypteris hispidula (Decne.) Reed.
The drimane-type sesquiterpenoids (-)-polygodial (1), (-)-isopolygodial (4), drimenin (5), and isodrimenin (6) were isolated from a pungent Argentine collection of the fern Thelypteris hispidula, along with other terpenoids. As the mentioned drimanes have been previously found in liverworts, the present results strongly support the theory that Pteridophytes and Bryophytes share the same line of evolution. Our present investigations indicate that two chemotypes of T. hispidula are widespread in the northwest of Argentina. Plants belonging to the pungent chemotype contain drimanes, while nonpungent plants lack drimanes.


Good behavior game - study protocol for a randomized controlled trial of a preventive behavior management program in a Swedish school context.
Early conduct problems and school failure are prominent risk factors for several adverse outcomes in later life. With the potential of reaching many children at early stages of their life, school-based interventions constitute a valuable approach to universal prevention. Good behavior game (GBG) is a promising school-based behavior management program, having shown immediate reductions in conduct problems along with several long-term positive effects. Adapting interventions to new contexts may however affect their effectiveness. The current study aims to evaluate the effectiveness of a Swedish adaption of GBG under pragmatic conditions. The intervention is hypothesized to reduce conduct problems in the classroom (primary outcome). Secondary analyses will investigate changes in conduct problems in common school areas, classroom climate, teacher collective efficacy, on-task behavior, as well as investigating behavioral management practices, implementation, and barriers to implementation. This is a cluster-randomized trial with two parallel groups. Schools will be randomized (1,1, stratified by their areas sociodemographic index score) to be provided training in GBG or perform business-as-usual. The intervention and data collection lasts for a school year. Data will be collected at three time points: at baseline in the beginning of the school year (prior to training in GBG), after three months, and after nine months (at the end of the school year; primary endpoint). Data consists of teacher-rated measures of conduct problems, classroom climate, teacher collective efficacy, behavior management practices, and implementation factors, along with demographic factors. In addition, data will be collected by independent and blinded observers using corresponding measures in a subset of randomly chosen classrooms. Procedural fidelity will be rated and collected by GBG-trainers during nine observations throughout the school year. Statistical analysis will include frequentist intention-to-treat analysis, and comparisons of estimates with a corresponding Bayesian model using weakly informative priors. The study has currently completed data collection. This study will provide knowledge in universal prevention and school-based interventions with high reach, as well as specific knowledge concerning the effectiveness of an adapted version of GBG under real-world conditions, along with factors affecting its implementation and effects. ClinicalTrials.gov, identifier NCT05794893.


[Familial diffuse interstitial fibrosis of prolonged onset worsening during pregnancy].
Familial idiopathic interstitial pulmonary fibrosis is rare. In this case report the diagnosis was confirmed histologically in four members of the same family. A woman whose father and two paternal uncles had developed pulmonary fibrosis was hospitalised from birth on account of delayed growth and dyspnoea. At the age of one year an increase in dyspnoea and the development of hypoxaemia and diffuse interstitial shadowing led to a surgical lung biopsy. The histological diagnosis was idiopathic interstitial fibrosis. Immunosuppressive treatment for one year led to clinical improvement with relief of the hypoxaemia but persistence of the interstitial shadowing. A pneumothorax at the age of 15 required pleurectomy. The clinical state remained stable with a restrictive ventilatory defect up to the age of 26 when respiratory insufficiency developed in the course of pregnancy. The outcome following delivery was severe respiratory failure complicated by pulmonary arterial hypertension leading to death the following year. This case is distinguished by a histological diagnosis in four members of a family of whom one was an infant, the prolonged stabilisation after immunosuppressive therapy and the possible role of pregnancy in the progression.


Adenosquamous carcinoma of the liver arising in biliary cystadenocarcinoma: clinical, radiologic, and pathologic features with review of the literature.
Primary biliary cystadenoma, cystadenocarcinoma, squamous carcinoma, and adenosquamous carcinoma of the liver are rare tumors. We describe a middle-aged woman with recurrent fever and a clinical diagnosis of hepatic abscess who proved at laparotomy to have adenosquamous carcinoma of the liver arising in a biliary cystadenocarcinoma. The pathologic features of the tumor and findings on ultrasonography, angiography, and computed tomography are described in detail. The pathogenetic relationships of this unusual tumor to chronic biliary inflammation, biliary cystadenoma, and cystadenocarcinoma and to bile duct malformations (von Meyenburg complexes) are considered.


Capacitive coupling synchronizes autonomous microfluidic oscillators.
Even identically designed autonomous microfluidic oscillators have device-to-device oscillation variability that arises due to inconsistencies in fabrication, materials, and operation conditions. This work demonstrates, experimentally and theoretically, that with appropriate capacitive coupling these microfluidic oscillators can be synchronized. The size and characteristics of the capacitive coupling needed and the range of input flow rate differences that can be synchronized are also characterized. In addition to device-to-device variability, there is also within-device oscillation noise that arises. An additional advantage of coupling multiple fluidic oscillators together is that the oscillation noise decreases. The ability to synchronize multiple autonomous oscillators is also a first step towards enhancing their usefulness as tools for biochemical research applications where multiplicate experiments with identical temporal-stimulation conditions are required.


A real-time impedance-based screening assay for drug-induced vascular leakage.
Vascular leakage is a serious side effect of therapies based on monoclonal antibodies or cytokines which may lead to life-threatening situations. With the steady increase of new drug development programs for large molecules, there is an urgent need for reliable tools to assess this potential liability of new medicines in a rapid and cost-effective manner. Using human umbilical vein endothelial cells (HUVECs) as a model for endothelium, we established an impedance-based assay measuring the integrity of the endothelial cell monolayer in real time. We could demonstrate that the HUVEC monolayer in our system was a relevant model as cells expressed major junctional proteins known to be responsible for maintaining tightness as well as receptors targeted by molecules known to induce vascular leakage in vivo. We assessed the time-dependent loss of barrier function using impedance and confirmed that signals obtained corresponded well to those from standard transwell assays. We assayed a series of reference molecules which led to the expected change of barrier integrity. A nonspecific cytotoxic effect could be excluded by using human fibroblasts as a nonresponder cell line. Finally, we could show reversibility of vascular permeability induced by histamine, IL-1β, or TNF-α by coincubation with established antagonists, further demonstrating relevance of this new model. Taken together, our results suggest that impedance in combination with HUVECs as a specific model can be applied to assess clinically relevant vascular leakage on an in vitro level.


Expression of human FUS protein in Drosophila leads to progressive neurodegeneration.
Mutations in the Fused in sarcoma/Translated in liposarcoma gene (FUS/TLS, FUS) have been identified among patients with amyotrophic lateral sclerosis (ALS). FUS protein aggregation is a major pathological hallmark of FUS proteinopathy, a group of neurodegenerative diseases characterized by FUS-immunoreactive inclusion bodies. We prepared transgenic Drosophila expressing either the wild type (Wt) or ALS-mutant human FUS protein (hFUS) using the UAS-Gal4 system. When expressing Wt, R524S or P525L mutant FUS in photoreceptors, mushroom bodies (MBs) or motor neurons (MNs), transgenic flies show age-dependent progressive neural damages, including axonal loss in MB neurons, morphological changes and functional impairment in MNs. The transgenic flies expressing the hFUS gene recapitulate key features of FUS proteinopathy, representing the first stable animal model for this group of devastating diseases.


MDSCs and T cells in solid tumors and non-Hodgkin lymphomas: an immunosuppressive speech.
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous subset of cells expanded during multiple pathological settings, including cancers. In tumors, MDSCs are dominant drivers of T-cell immunosuppression. To accomplish their job, they exploit multiple mechanisms ultimately leading to the paralysis of anti-tumor immunity. Among the variety of MDSC-ways of working within the tumor microenvironment, the generation of reactive species and the metabolic reprogramming have emerged as pivotal determinants of their immunosuppressive power. In this review we will overview integral mechanisms of MDSC-mediated immunosuppression in solid tumors, with a particular focus on Non-Hodgkin lymphoma.


Sludge management in anaerobic swine lagoons: A review.
Sludge is nutrient and mineral rich residue of anaerobic treatment that is often utilized as a fertilizer. Sludge management is crucial to maintain the function of anaerobic treatment lagoons and ensure efficient nutrient utilization. Intensive livestock production has resulted in accumulation of sludge residue in regions where nutrients are in surplus. This situation adversely impacts the sustainability of livestock production. Alternative uses of sludge needs to be developed and adopted to reduce the negative impacts associated with the nutrients accumulation on farms and nearby crop fields. A thorough understanding of sludge composition is necessary to identify appropriate end use. This review explores swine lagoon sludge (SLS) in relation to its composition, sampling techniques, management approaches, fertilizer value, challenges and opportunities for further development.


Kawasaki disease presenting with hepatitis and prolonged fever: report of one case.
Kawasaki disease predominantly affects children younger than 5 years. Coronary artery aneurysms were found in around 20% of untreated patients. We report on a case of a 10-year-old boy who had atypical presentation of Kawasaki disease with significant hepatobiliary dysfunction, including hepatomegaly and jaundice, and persistent fever. He did not have conjunctivitis until the 8th day of fever, and periungual desquamation and strawberry tongue until the 13th day of fever when Kawasaki disease was diagnosed. Echocardiography revealed multiple coronary artery aneurysms. Such atypical clinical pictures of Kawasaki disease may cause delay in the treatment, and the fatality rate can be increased. So, a persistent fever with jaundice should evoke the differential diagnosis of Kawasaki disease.


Three-dimensional models of the oligomeric human asialoglycoprotein receptor (ASGP-R).
The work presented here is aimed at suggesting plausible hypotheses for functional oligomeric forms of the human asialoglycoprotein receptor (ASGP-R), by applying a combination of different computational techniques. The functional ASGP-R is a hetero-oligomer, that comprises of several subunits of two different kinds (H1 and H2), which are highly homologous. Its stoichiometry is still unknown. An articulated step-wise modeling protocol was used in order to build the receptor model in a minimal oligomeric form, necessary for it to bind multi-antennary carbohydrate ligands. The ultimate target of the study is to contribute to increasing the knowledge of interactions between the human ASGP-R and carbohydrate ligands, at the molecular level, pertinent to applications in the field of hepatic tissue engineering.


Activity of ceftolozane-tazobactam and comparators when tested against bacterial surveillance isolates collected from patients at risk of infections caused by resistant gram-negative pathogens.
Ceftolozane-tazobactam is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. Ceftolozane-tazobactam has been approved for treatment of complicated urinary tract infections and acute pyelonephritis, for complicated intra-abdominal infections (with metronidazole) in adults, and for hospital-acquired bacterial pneumonia including ventilator-associated bacterial pneumonia. This study analyzed gram-negative pathogen susceptibility in US and European patients who are considered at risk for infections caused by pathogens resistant to commonly used antimicrobials: patients in the intensive care unit (ICU), patients on the hematology/oncology or transplant service who may be immunocompromised, and patients >65 years old (yo). ICU patients had the lowest susceptibility for Enterobacterales and PSA. The susceptibility for isolates from the immunocompromised and >65 yo groups was similar. Ceftolozane-tazobactam was the most active agent against PSA, with ≥90%S for >65 yo and immunocompromised, and >80%S for ICU. Meropenem and ceftolozane-tazobactam were the most active agents against Enterobacterales.


Homeopathic drug therapy. Homeopathy in Chikungunya Fever and Post-Chikungunya Chronic Arthritis: an observational study.
To observe the effect of homeopathic therapy in Chikungunya Fever (CF) and in Post-Chikungunya Chronic Arthritis (PCCA) in a primary health care setting. A prospective observational study was conducted at Delhi Government Homeopathic Dispensary, Aali Village, New Delhi, India, for a period of 6 months, from 1st October 2010 to 31st March 2011. 126 patients (75 CF, 51 PCCA) were enrolled based on predefined inclusion criteria. A single homeopathic medicine was prescribed for each patient after case taking with the help of Materia Medica and/or Repertory. Results were evaluated on the basis of visual analogue scale and symptom scores. Complete recovery was seen in 84.5% CF cases in a mean time of 6.8 days. 90% cases of PCCA recovered completely in a mean time of 32.5 days. Homeopathic therapy may be effective in CF and PCCA. A randomized controlled trial should be considered.


Air ambulance tasking: mechanism of injury, telephone interrogation or ambulance crew assessment?
The identification of serious injury is critical to the tasking of air ambulances. London's Air Ambulance (LAA) is dispatched by a flight paramedic based on mechanism of injury (MOI), paramedical interrogation of caller (INT) or land ambulance crew request (REQ).This study aimed to demonstrate which of the dispatch methods was most effective (in accuracy and time) in identifying patients with serious injury. A retrospective review of 3 years of data (to December 2010) was undertaken. Appropriate dispatch was defined as the requirement for LAA to escort the patient to hospital or for resuscitation on-scene. Inaccurate dispatch was where LAA was cancelled or left the patient in the care of the land ambulance crew. The χ(2) test was used to calculate p values; with significance adjusted to account for multiple testing. There were 2203 helicopter activations analysed: MOI 18.9% (n=417), INT 62.4% (n=1375) and REQ 18.7% (n=411). Appropriate dispatch rates were MOI 58.7% (245/417), INT 69.7% (959/1375) and REQ 72.2% (297/411). INT and REQ were both significantly more accurate than MOI (p<0.0001). There was no significant difference in accuracy between INT and REQ (p=0.36). Combining MOI and INT remotely identified 80.2% of patients, with an overtriage rate of 32.8%. Mean time to dispatch (in minutes) was MOI 4, INT 8 and REQ 21. Telephone interrogation of the caller by a flight paramedic is as accurate as ground ambulance crew requests, and both are significantly better than MOI in identifying serious injury. Overtriage remains an issue with all methods.


Gingival enlargement as an early diagnostic indicator in therapy-related acute myeloid leukemia: A rare case report and review of literature.
Treatment for Hodgkin's lymphoma (HL) has resulted in excellent survival rates but is associated with increased risks of secondary therapy-related acute myeloid leukemia (t-AML). Gingival enlargement associated with bleeding and ulceration is the most common rapidly appearing oral manifestations of leukemic involvement. An 8 months pregnant patient reported with generalized gingival enlargement, with localized cyanotic and necrotic papillary areas. Co-relating the hematological report with the oral lesions and her past medical history of HL, a diagnosis of t-AML secondary to treatment for HL was made by the oncologist. As oral lesions are one of the initial manifestations of acute leukemia, they may serve as a significant diagnostic indicator for the dental surgeons and their important role in diagnosing and treating such cases. Furthermore, this case report highlights the serious complication of t-AML subsequent to HL treatment and the important role that a general and oral health care professional may play in diagnosing and treating such cases.


EGFR-binding peptide: a patent evaluation of WO2014002836.
Peptide ligands have many desirable features enabling them to act as drug molecules and are valuable in the drug discovery processes because of their fewer side effects and great potential to cure diseases. In this patent, three kinds of peptide ligands with 12-50 amino acid residues were identified by phase display technology. Some of them not only could be used as potential therapeutic agents for the treatment of EGFR-overexpressed cancers, but also show promising application in detecting cancer tissue or cancer cells that express the EGFR.


The long term efficacy of a hardjo-pomona vaccine in preventing leptospiruria in cattle exposed to natural challenge with Leptospira interrogans serovar hardjo.
The long term efficacy of a commercially prepared bivalent vaccine against Leptospira interrogans serovar hardjo and L. interrogans serovar pomona was evaluated in a group of 82 dairy heifers exposed to natural challenge with L. interrogans serovar hardjo for up to 55 weeks after calfhood vaccination. Nineteen heifers were vaccinated twice with a one-month interval, at calfhood (9 to 10 months). A further 18 heifers received a similar calfhood vaccination regimen plus a third injection at adulthood (22 to 23 months), while 19 heifers were vaccinated twice at adulthood only and finally 22 heifers were used as unvaccinated controls. At 55 weeks after calfhood vaccination and prior to adulthood vaccination, only 2.7% of the vaccinated heifers were found to have leptospiruria compared with 58.5% of the unvaccinated heifers (p less than 0.0001). Microscopic agglutination (MA) titres at the same time in the unvaccinated heifers ranged from 32 to 4096 while those vaccinated at calfhood ranged from 32 to 64. Adult vaccination of infected animals did not significantly reduce leptospiruria . Prior to adulthood vaccination, 9 of 19 heifers had leptospiruria , in comparison to 4 of 15 after adulthood vaccination. At the same sampling periods 15 of 22 controls had leptospiruria in comparison to 4 of 9 subsequently tested.


Psychoendocrine investigation in schizophrenia: relationship between pituitary-gonadal function and behavior.
The Authors examine possible connections between the schizophrenic syndrome and the hypothalamo-pituitary-gonadal system, assuming that hormonal impairments may correlate with the appearance and development of peculiar behavioral features. The hormonal status and the behavioral parameters have been examined before, during and after a psychopharmacological therapy, and a combination of a psychopharmacological-hormonal treatment. Data have been obtained in 12 male hebephrenic schizophrenics, aged 18-36 years, with onset of the disease between 12 months and 20 years before our experiments. The patients were treated for 30 days with Haloperidol (6 mg.i.m.p.d. to a total dose of 180 mg.) and then for 45 days with Haloperidol at the same dose in combination with Chorionic Gonadotrophin (5000 I.U.i.m. twice a week for a total dose of 60.000 I.U.). The following hormonal assays were performed: total urinary gonadotrophins, serum FSH and LH, total urinary 17 ketosteroids, total urinary estrogens, serum testosterone. The hormonal assays were performed twice prior to therapy, twice during the Haloperidol therapy (12th and 26th days) twice during the Haloperidol plus HCG therapy (20th and 40th day) and 1 month after the withdrawal of the therapy. The psychological-behavioral parameters were examined through the Wittenborn Rating Scale. The result obtained seem to reveal a stimulatory effect of the Haloperidol plus HCG therapy on the deficient hormonal status. Moreover, it is evident that a constant correlation exists between biochemical improvement and behavioral improvement, especially in regard to affectivity disorders, adjustment to reality, active behavior.


Impact of COVID-19 on the parent-nurse relationship in NICU: a phenomenological study of nurses lived experience.
During the Covid-19 pandemic, the family presence in hospital was reduced, or excluded, to limit the contagiousness, but that could impact negatively on the quality of communication, family education, and the best development outcome for the newborn. This study aims to explore and describe if and how the pandemic influenced the relationship and care provided to the family in NICU (Neonatal Intensive Care Unit). This is a descriptive qualitative study. The data were collected through a questionnaire and semi-structured interviews with 7 NICU nurses from different Italian Regions in the period June-August 2021, by snowball sampling. Thematic analysis by Braun and Clarke method was conducted. The data show an overview of the hospitals' choices about parents' access to NICUs, from total to partial closure. The thematic analysis revealed how some nurses have boycotted corporate choices in favor of child's and family's well-being, while others have consolidated the idea that NICUs must remain closed. Moreover, nurses report that they standardized their practice rather than individualize care. The Covid-19 limitations created many inconveniences and negatively impacted the quality of the care provided, as the safety of the discharge of these fragile patients. It is important to evaluate how this situation impacts long-term patient outcomes, but also how some organizational decisions influence the well-being of professionals, who facing difficult choices, during a health emergency. This study aims to give leadership data to understand the value that the family has in the care process in NICU and that parents cannot be considered "visitors".


Reversible phase separation of ESCRT protein ALIX through tyrosine phosphorylation.
Cytokinetic abscission, the last step of cell division, is regulated by the ESCRT machinery. In response to mitotic errors, ESCRT proteins, namely, ALIX, CHMP4B, and CHMP4C, accumulate in the cytosolic compartments termed "abscission checkpoint bodies" (ACBs) to delay abscission and prevent tumorigenesis. ALIX contributes to the biogenesis and stability of ACBs via an unknown mechanism. We show that ALIX phase separates into nondynamic condensates in vitro and in vivo, mediated by the amyloidogenic portion of its proline-rich domain. ALIX condensates confined CHMP4 paralogs in vitro. These condensates dissolved and reformed upon reversible tyrosine phosphorylation of ALIX, mediated by Src kinase and PTP1B, and sequestration of CHMP4C altered their Src-mediated dissolution. NMR analysis revealed how ALIX triggers the activation of CHMP4 proteins, which is required for successful abscission. These results implicate ALIX's phase separation in the modulation of ACBs. This study also highlights how posttranslational modifications can control protein phase separation.


Intrathyroidal metastasis of tonsillar squamous cell carcinoma masquerading as a primary thyroid tumor.
Intrathyroidal metastasis of tonsillar squamous cell carcinoma is rare. To date, only six cases have been reported in the literature. This case was unusual and presented with thyromegaly before the diagnosis of the primary tumor. A 55-year-old male patient was suspected to have a primary thyroid tumor with nodal metastasis. The thyroid gland was diffusely enlarged, with no discernible mass. Histologically, the thyroid parenchyma revealed extensive endolymphatic tumor emboli, which were positive for p40 and p16 in a background of chronic lymphocytic thyroiditis. Positron emission tomography-computed tomography revealed hypermetabolic activity in the right tonsillar region. Tonsillar biopsy revealed human papillomavirus-positive squamous cell carcinoma. The present case is the first reported case of intrathyroidal metastasis of tonsillar squamous cell carcinoma with an initial clinical presentation of thyroid enlargement before the primary tumor of tonsillar cancer was diagnosed.


Influence of mineral metabolism parameters on pulse pressure in healthy subjects.
The role of mineral metabolism in cardiovascular pathologies has been studied almost exclusively in chronic kidney disease patients. There are no studies that relate mineral metabolism to pulse pressure in healthy populations. 692 subjects were initially selected. After applying clinical exclusion criteria, 659 subjects were recruited. Creatinine clearance was then calculated to detect subjects with occult chronic kidney disease. Statistical analysis was applied to the remaining population after excluding subjects with occult chronic kidney disease (n = 466). Pulse pressure, creatinine clearance, calcium, phosphorus, intact parathormone, 25-hydroxivitamin D3 and Bsm I genotype of the vitamin D receptor were determined. Means and frequencies were compared by ANOVA and Chi-square, respectively. Multivariate analysis was applied to the whole population and then to Caucasians, Sub-Saharans, Caucasian men and Caucasian women separately. Pulse pressure (PP) was the dependent variable, and adjustments were made for clinical and laboratory data. The prevalence of occult chronic kidney disease was 32%. In subjects without kidney disease, phosphorus and vitamin D were independent predictors of elevated PP in Caucasian males whereas Bsm I genotype of the vitamin D was an independent predictor of elevated PP in the Caucasian population in both genders. No covariable showed relationship with PP in Sub-Saharan subjects. Mineral metabolism influences pulse pressure in Caucasian men.


Acute pancreatitis secondary to duodenoduodenal intussusception in duodenal adenoma.
Duodenoduodenal intussusception is a rare condition that is in general caused by a tumor. We describe duodenoduodenal intussusception secondary to a tubulovillous adenoma that caused acute pancreatitis in a 31-year-old female. We resected a duodenal tumor from the submucosal layer and then simply closed the duodenal wall. To the best of our knowledge, this is the first description of acute pancreatitis secondary to duodenoduodenal intussusception by tubulovillous adenoma in the second part of the duodenum in an adult.


Mechanism of ribonucleic acid chain initiation. 1. A non-steady-state study of ribonucleic acid synthesis without enzyme turnover.
A non-steady-state kinetic method has been developed to observe the initiation of long RNA chains by Escherichia coli RNA polymerase without the enzyme turnover. This method was used to determine the order of binding of the first two nucleotides to the enzyme in RNA synthesis with the first two nucleotides to the enzyme in RNA synthesis with poly(dA-dT) as the template. It was shown that initiator [ATP, uridyly(3'-5')adenosine, or adenyly(3'-5')uridylyl-(3'-5')adenosine] binds first to the enzyme-template complex, followed by UTP binding. The concentration dependence of UTP incorporation into the initiation complex suggests that more than one UTP molecule may bind to the enzyme-DNA complex during the initiation process. Comparison of the kinetic parameters derived from these studies with those obtained under steady-state conditions indicates that the steps involving binding of initiator or UTP during initiation cannot be rate limiting in the poly(dA-dT)-directed RNA synthesis. The non-steady-state technique also provides a method for active-site titration of RNA polymerase. The results show that only 36 +/- 9% of the enzyme molecules are active in a RNA polymerase preparation of high purity and specific activity. In addition, the minimal length of poly(dA-dT) involved in RNA synthesis by one RNA polymerase molecule was estimated to be approximately 500 base pairs.


Postprandial Levels of Branch Chained and Aromatic Amino Acids Associate with Fasting Glycaemia.
High fasting plasma concentrations of isoleucine, phenylalanine, and tyrosine have been associated with increased risk of hyperglycaemia and incidence of type 2 diabetes. Whether these associations are diet or metabolism driven is unknown. We examined how the dietary protein source affects the postprandial circulating profile of these three diabetes associated amino acids (DMAAs) and tested whether the postprandial DMAA profiles are associated with fasting glycaemia. We used a crossover design with twenty-one healthy individuals and four different isocaloric test meals, containing proteins from different dietary sources (dairy, fish, meat, and plants). Analysis of the postprandial DMAAs concentrations was performed using targeted mass spectrometry. A DMAA score was defined as the sum of all the three amino acid concentrations. The postprandial area under the curve (AUC) of all the three amino acids and the DMAA score was significantly greater after intake of the meal with dairy protein compared to intake of the three other meals. The postprandial AUC for the DMAA score and all the three amino acids strongly associated with fasting glucose level and insulin resistance. This indicates the importance of the postprandial kinetics and metabolism of DMAAs in understanding the overall association between DMAAs and glycaemia.


Effect of Jian-Pi-Zhi-Dong Decoction on striatal glutamate and γ-aminobutyric acid levels detected using microdialysis in a rat model of Tourette syndrome.
Jian-Pi-Zhi-Dong Decoction (JPZDD) is a dedicated treatment of Tourette syndrome (TS). The balance of neurotransmitters in the cortico-striato-pallido-thalamo-cortical network is crucial to the occurrence of TS and related to its severity. This study evaluated the effect of JPZDD on glutamate (Glu) and γ-aminobutyric acid (GABA) and their receptors in a TS rat model. Rats were divided into four groups (n=12 each). TS was induced in three of the groups by injecting them with 3,3'-iminodipropionitrile for 7 consecutive days. Two model groups were treated with tiapride (Tia) or JPZDD, while the control and the remaining model group were gavaged with saline. Behavior was assessed by stereotypic score and autonomic activity. Striatal Glu and GABA contents were detected using microdialysis. Expressions of N-methyl-D-aspartate receptor 1 and GABAA receptor (GABAAR) were observed using Western blot and real-time polymerase chain reaction. Tia and JPZDD groups had decreased stereotypy compared with model rats; however, the JPZDD group showed a larger decrease in stereotypy than the Tia group at a 4-week time point. In a spontaneous activity test, the total distance of the JPZDD and Tia groups was significantly decreased compared with the model group. The Glu levels of the model group were higher than the control group and decreased with Tia or JPZDD treatment. The GABA level was higher in the model group than the control group. Expressions of GABAAR protein in the model group were higher than in the control group. Treatment with Tia or JPZDD reduced the expression of GABAAR protein. In the case of the mRNA expression, only Tia reduced the expression of N-methyl-D-aspartate receptor 1, compared with the model group. JPZDD could alleviate impairments in behavior and dysfunctional signaling by downregulating GABAAR in the striatum. We suggest that this acts to maintain the balance of Glu and GABA.


Zeitgeber hierarchy in humans: resetting the circadian phase positions of blind people using melatonin.
Four blind individuals who were thought to be entrained at an abnormal circadian phase position were reset to a more normal phase using exogenous melatonin administration. In one instance, circadian phase was shifted later. A fifth subject who was thought to be entrained was monitored over four years and eventually was shown to have a circadian period different from 24 h. These findings have implications for treating circadian phase abnormalities in the blind, for distinguishing between abnormally entrained and free-running blind individuals, and for informing the debate over zeitgeber hierarchy in humans.


Esthetic rehabilitation of anterior teeth with molar-incisor hypomineralization and dental fluorosis: a case report.
This case report describes the treatment of a patient who had molar-incisor hypomineralization associated with dental fluorosis, a diagnosis established through a comprehensive review of the clinical record, an intraoral clinical examination, and assessment of photographic records. First, dental hypersensitivity was treated with fluoride varnish, which was applied separately to each dental quadrant. Subsequently, the functional and esthetic reconstruction of the permanent maxillary central incisors was completed in a single session through the placement of direct composite resin veneers. After the treatment, the patient was reexamined monthly for 12 months to evaluate the durability of the restorations. At the 12-month follow-up, no fractures or pigmentations were observed, and only a slight loss of brightness of the restorations was noted. The dental hypersensitivity had been eliminated. When an adhesive restorative technique with composite resin is well executed, it is possible to obtain satisfactory and long-lasting esthetics and relief of painful symptoms.


Arabidopsis RAP2.2: an ethylene response transcription factor that is important for hypoxia survival.
Arabidopsis (Arabidopsis thaliana) RAP2.2 (At3g14230) is an APETALA2/ethylene response factor-type transcription factor that belongs to the same subfamily as the rice (Oryza sativa) submergence tolerance gene SUB1A. RAP2.2 is expressed at constitutively high levels in the roots and at lower levels in the shoots, where it is induced by darkness. Effector studies and analysis of ethylene signal transduction mutants indicate that RAP2.2 is induced in shoots by ethylene and functions in an ethylene-controlled signal transduction pathway. Overexpression of RAP2.2 resulted in improved plant survival under hypoxia (low-oxygen) stress, whereas lines containing T-DNA knockouts of the gene had poorer survival rates than the wild type. This indicates that RAP2.2 is important in a plant's ability to resist hypoxia stress. Observation of the expression pattern of 32 low-oxygen and ethylene-associated genes showed that RAP2.2 affects only part of the low-oxygen response, particularly the induction of genes encoding sugar metabolism and fermentation pathway enzymes, as well as ethylene biosynthesis genes. Our results provide a new insight on the regulation of gene expression under low-oxygen conditions. Lighting plays an important regulatory role and is intertwined with hypoxia conditions; both stimuli may act collaboratively to regulate the hypoxic response.


Senescence of Pancreas in Middle-Aged Rats with Normal Vascular Function.
BACKGROUND In organ transplantation, particularly pancreas transplantation, donor age is a determinant factor for graft survival. Physiological aging is crucial in the progressive deterioration of organs in adulthood. We compared the senescence and function features of pancreas and vascular tissues in young rats and middle-aged rats. MATERIAL AND METHODS Islet morphology and the area of cells secreting insulin or glucagon was investigated using immunohistology in young rats (12 weeks) and middle-aged rats (52 weeks) (n=8). Senescence markers, oxidative stress (ROS), and tissue factor (TF) were measured in the rat pancreases. Circulating microparticles (MPs) were measured as surrogates of vascular cell injury. Vascular function was studied in mesenteric arterial rings. RESULTS Larger islets were twice as frequent in young rats versus middle-aged rats. In middle-aged rats there was a significant decrease of the β-cells/islet area ratio. Western blot analysis showed an increased expression of p53, p21, and p16 senescence markers (2-, 7- and 3-fold respectively) with no modification in caspase-3 activation. A 30% decrease of endothelial nitric oxide synthase (eNOS) was observed together with a 4-fold increase in TF expression. ROS formation increased significantly (2-fold) in middle-aged rats and their main source, determined by pharmacological inhibition, was NADPH oxidase and uncoupled nitric-oxide (NO) synthase. No sign of vascular injury (microparticles) or dysfunction was evidenced. CONCLUSIONS Modification in islet morphology and function were detected in middle-aged rats before any measurement of macro-vascular dysfunction. The data indicate a pancreatic senescence in the process of aging associated with uncontrolled accumulation of oxidative species that suggests a determining role of donor age in transplantation.


Environmental variation and experience-related differences in the demography of the long-lived black-browed albatross.
1. It has been largely demonstrated that demographic performances of animals increase with age or experience as a result of an improvement of foraging skills, an increasing reproductive effort or a selection process. However, little is known about the age or experience-related response of populations to environmental variations. Theoretical studies consider that age-related variations of the performances are greater under more restricting conditions, but this has rarely been tested. 2. We tested this hypothesis on a long-lived species, black browed albatross Thalassarche melanophrys Temminck, using a long-term capture-mark-recapture data set. We investigated the responses of a population to climate, by studying the effects of climatic factors and breeding experience on survival and breeding success. 3. First-time breeders appear to be poorer performers compared with experienced adults, with lower reproductive success and lower survival. In addition, interannual variations of demographic traits were partly explained by climatic indices, reflecting environmental variations. The survival probability of black-browed albatrosses varied with experience and climate, and differences being greater under harsh conditions. By contrast, the reproductive success of inexperienced individuals was affected by climatic fluctuations in the same way as the experienced ones. 4. First breeding event acts as a strong selective process on the highly heterogeneous class of inexperienced individuals, suggesting the increase in survival and breeding success with experience may mainly reflect a reduction in the heterogeneity among individual qualities.


Boundary-Spanning Care: Reducing Psychiatric Rehospitalization and Self-Injury in a Jail Population.
Individuals with serious mental illness detained in jail may require frequent psychiatric hospitalization due to the destabilizing nature of the jail environment. This study examined the impact of a pilot treatment program involving continuity of patient care across jail and hospital settings aimed at reducing hospitalizations and negative health outcomes for a population of high-risk, incarcerated individuals with mental illness. This study examined rate ratios of psychiatric hospitalizations, injuries, and suicide watches, comparing 15 patients in the treatment program to themselves pretreatment and to a control group of 15 frequently rehospitalized patients. Patients in treatment experienced significant decreases in overall hospitalizations ( p < .001), 15-day rehospitalizations ( p < .002), and suicide watches in jail ( p < .02), compared to themselves pretreatment. A boundary-spanning treatment program lowered hospitalization rates and need for suicide watch for a small, yet clinically complicated and challenging group of patients.


Norwegian-grown Jerusalem artichoke (Helianthus tuberosus L.): morphology and content of sugars and fructo-oligosaccharides in stems and tubers.
Two field trials growing Jerusalem artichoke (Helianthus tuberosus L.) are discussed. Twenty genetic variants were compared in order to find genotypes suitable for Norwegian production. A second trial investigated the above-ground part of early and late variants. The highest yield (28.7 t ha(-1)) and highest amount of tubers per plant was obtained in early variants, e.g. the white Tysnes gave 1.72 kg tubers plant(-1). Early variants had a markedly lower portion of smooth tubers. Late variants gave the most preferable tuber shape, but low yield. Only a weak correlation was found between dry matter content and total content of fructo-oligosaccharides (FOS) (r = 0.255) in the tubers. The mean content of FOS including sucrose through all variants was found to be 116 g kg(-1) fresh weight (FW) or 550 g kg(-1) dry weight (DW). The average chain length of FOS in the tubers was found to be DP3.9. There was no difference in tuber FOS content between early and late variants. The highest above-ground amount biomass was found for the late variants when harvested in September. The content of soluble carbohydrates was found to be highest in stalks in August (sucrose and FOS major compounds). Early variants give the highest tuber yield under Norwegian growing conditions. Late variants give highest above-ground biomass.


Comparison of Biological Responses of Polymers Based on Imine and Disulfide Backbones for siRNA Delivery.
To achieve a successful delivery of siRNA by carriers in vivo, the degradation of polymers in response to tiny intracellular changes should be seriously considered. In addition, the balance between degradation and stability of polymers is another key point for high performance of carriers. In this study, imine and disulfide linkages, which are sensitive to pH changes and redox environment, respectively, were constructed as the main backbone of polymers to deliver siRNA at the intracellular and animal level. Comparisons were made between performances of these two different polymers. Both of the polymers synthesized here have good ability to condense siRNA. However, polyplexes formed by the imine backbone-based polymer (TPSP) showed a larger particle size and a higher zeta potential than that of the disulfide backbone-based polymer (DTDPS). Although both TPSP and DTDPS could deliver the target siRNA into 7721 cells, polyplexes formed by TPSP showed a higher silence efficiency in vitro and accomplished more accumulation in tumors. In conclusion, we believe TPSP is superior to be used for siRNA delivery and promises a potential for widespread use.


The effect of culture medium composition and incubation time on synthesis of gibberellin-like substances by bacteria isolated from the roots of pine seedlings (Pinus silvestris L.).
It was found that synthesis of gibberellin-like substances by ten strains of Coryneform bacteria isolated from the roots of pine seedlings depended on both the composition of the medium and incubation time. More of these substances were produced in mineral medium with glucose in complex medium with casamino acids and yeast extract. Most gibberellin-like substances were found in 7 or 14-day old cultures. Culture supernatant fluids of most of the bacteria tested contained several gibberellin-like substances which on chromatograms run with the solvent system benzene, acetic acid (10:3, v/v) were located at Rf 0.0-0.3; 0.4-0.6 and 0.8-1.0.