[Application of vascular replacement technique with allogenic blood vessel in radical resection for pancreatic carcinoma: a report of 33 cases].
Objective: To analyze the application of vascular replacement technique with allogenic blood vessel in radical resection for pancreatic carcinoma. Methods: The clinical data of 33 patients with vascular invasion of pancreatic carcinoma who underwent radical resection from April 2013 to April 2017 in Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital were retrospectively analyzed. There were 14 males and 19 females with age of (62.5±10.6)years(ranging from 35 to 78 years). Vascular replacement technique with allogenic blood vessel was used on all patients who underwent radical resection for pancreatic carcinoma. The operation procedure was made according to the specific location of the carcinoma, and the allogenic blood vessel was selected according to the type of vascular invasion. The matching vessel was selected for replacement to the patient who was invaded only one vessel. And the "Y" type of iliac vein was selected for replacement to the patient who was invaded the confluence of portal vein, splenic vein and superior mesenteric vein. After the operation, the patients were followed up by telephone and outpatient review. Results: All of 33 patients were successfully completed the operations. There were 28 patients underwent pancreaticoduodenectomy with vascular replacement, and 5 patients underwent total pancreatectomy with vascular replacement. All the patients were confirmed pancreatic carcinoma and R0 resection according to the postoperative pathology. There were 16 patients with the carcinoma invasion the confluence of portal vein, splenic vein and superior mesenteric vein, 12 patients with the carcinoma invasion the superior mesenteric vein, and 5 patients with the carcinoma invasion the portal vein. There was no perioperative death in this group and no complications related to allogenic blood vessel. The incidence of postoperative complications was 18.2% (6/33), and the incidence of pancreatic fistula was 6.1% (2/33), all of which were biochemical fistula. There were 32 patients were followed up, and the follow-up rate was 96.9%. The median survival time was 14.6 months. The half-year, 1-year and 2-year survival rates were 75.6%, 37.6% and 27.4%. Conclusion: The application of vascular replacement technique with allogenic blood vessel for pancreatic carcinoma has a great significance for improving the R0 resection rate and the prognosis of patients.


Frequency of patient-physician contact and patient outcomes in hemodialysis care.
There is little evidence supporting the widespread belief that regular patient-physician contact in chronic disease management leads to better patient outcomes. The objective of this study was to examine the relationship of the frequency of patient-physician contact with several patient outcomes in a prospective cohort study begun in 1995 of incident hemodialysis patients treated at 75 US dialysis clinics. Average frequency of patient-physician contact at each clinic was determined by clinic survey (low, monthly or less frequent; intermediate, between monthly and weekly; high, more than weekly). The authors used logistic, Poisson, and Cox proportional hazards regression analyses to assess the relationship between contact and satisfaction, quality of life, patient adherence, hospitalizations, and mortality. Of 735 hemodialysis patients, 14.3% were treated at clinics with high frequency of contact, 65.2% intermediate, and 20.5% low. Patients treated at clinics reporting less frequent physician contact had lower odds of rating the frequency at which they saw a nephrologist excellent (low: adjusted OR = 0.39, 95% CI, 0.23-0.67; intermediate: adjusted OR = 0.57, 95% CI, 0.37-0.87; reference, high) and greater odds of nonadherence (low: adjusted OR = 2.89, 95% CI, 1.01-8.29; intermediate: adjusted OR = 1.58, 95% CI, 0.78-3.19). However, patient survival did not vary by frequency of physician contact (low: adjusted RH = 0.87, 95% CI, 0.53-1.44; intermediate: adjusted RH = 1.33, 95% CI, 0.82-2.13), nor did patients' overall ratings of care, hospitalization rates, or quality of life measures. Although less frequent patient-physician contact was associated with lower patient satisfaction with that contact and patient nonadherence, it was not associated with several other outcomes of care. Future studies are needed to assess the individual frequency and nature of physician contact over time, including total time spent with the patient and quality of the interaction, to guide the provision of patient-centered and cost-effective care.


Temporal properties of visual motion signals for the initiation of smooth pursuit eye movements in monkeys.
1. Our goal was to assess whether visual motion signals related to changes in image velocity contribute to pursuit eye movements. We recorded the smooth eye movements evoked by ramp target motion at constant speed. In two different kinds of stimuli, the onset of target motion provided either an abrupt, step change in target velocity or a smooth target acceleration that lasted 125 ms followed by prolonged target motion at constant velocity. We measured the eye acceleration in the first 100 ms of pursuit. Because of the 100-ms latency from the onset of visual stimuli to the onset of smooth eye movement, the eye acceleration in this 100-ms interval provides an estimate of the open-loop response of the visuomotor pathways that drive pursuit. 2. For steps of target velocity, eye acceleration in the first 100 ms of pursuit depended on the "motion onset delay," defined as the interval between the appearance of the target and the onset of motion. If the motion onset delay was > 100 ms, then the initial eye movement consisted of separable early and late phases of eye acceleration. The early phase dominated eye acceleration in the interval from 0 to 40 ms after pursuit onset and was relatively insensitive to image speed. The late phase dominated eye acceleration in the interval 40-100 ms after the onset of pursuit and had an amplitude that was proportional to image speed. If there was no delay between the appearance of the target and the onset of its motion, then the early component was not seen, and eye acceleration was related to target speed throughout the first 100 ms of pursuit. 3. For step changes of target velocity, the relationship between eye acceleration in the first 40 ms of pursuit and target velocity saturated at target speeds > 10 degrees /s. In contrast, the relationship was nearly linear when eye acceleration was measured in the interval 40-100 ms after the onset of pursuit. We suggest that the first 40 ms of pursuit are driven by a transient visual motion input that is related to the onset of target motion (motion onset transient component) and that the next 60 ms are driven by a sustained visual motion input (image velocity component). 4. When the target accelerated smoothly for 125 ms before moving at constant speed, the initiation of pursuit resembled that evoked by steps of target velocity. However, the latency of pursuit was consistently longer for smooth target accelerations than for steps of target velocity.(ABSTRACT TRUNCATED AT 400 WORDS)


Mouse model of hypersensitivity pneumonitis after inhalation exposure to different microbial antigens associated with organic dusts.
The aim of this study was to reproduce in laboratory conditions hypersensitivity pneumonitis (HP) pathogenesis in a new animal model predictive of the human response, and to select the microbial antigen associated with organic dust that exerts the strongest pathogenic effect on the respiratory organ. To achieve this goal, mice of the strain C57BL/6J prone to fibrosis were exposed for 1 hour daily up to 28 days to the inhalation of aerosols of each of the 5 microbial components of organic dusts whose conjunction with the occurrence of HP has been confirmed by numerous authors: Pantoea agglomerans saline extract (SE), P. agglomerans microvesicle-bound endotoxin, Saccharopolyspora rectivirgula SE, Aspergillus fumigatus SE, saline extract of dust from a grain sample overgrown with S. rectivirgula and Thermoactinomyces vulgaris, and a saline solvent (PBS) was used as a control. Exposure of the animals to organic dust components was conducted using a novel inhalation challenge set. Lung samples were collected from untreated mice and from mice exposed for 7 and 28 days, and examined by digitalized histopathology and biochemistry for the presence of inflammatory changes and fibrosis. P. agglomerans SE appeared to be the sole antigen which evoked a statistically significant fibrosis and a significant increase of hydroxyproline in the lungs of mice exposed for 28 days to this extract, both compared to the mice untreated and to those exposed to the solvent. P. agglomerans SE also evoked the strongest and statistically significant inflammatory response in the lungs of the mice, both after 7 and 28 days of exposure. After 7 days, significant inflammatory changes were also found in mice exposed to A. fumigatus SE, and after 28 days in mice exposed to all antigens. In conclusion, our results allow us to define a useful animal model of HP which can be a supplement for now commonly used bleomycin model. This model should comprise: present set of instruments for inhalation, mice of the line C57BL/6J and the saline extract of P. agglomerans as the antigen. For a better understanding of the presented results, a detailed study covering immunological investigations, focused on the mechanism of antigen action, are needed.


Leukodepleted Packed Red Blood Cells Transfusion in Patients Undergoing Major Cardiovascular Surgical Procedure: Systematic Review and Meta-Analysis.
Leukocytes contained in the allogeneic packed red blood cell (PRBC) are the cause of certain adverse reactions associated with blood transfusion. Leukoreduction consists of eliminating leukocytes in all blood products below the established safety levels for any patient type. In this systematic review, we appraise the clinical effectiveness of allogeneic leukodepleted (LD) PRBC transfusion for preventing infections and death in patients undergoing major cardiovascular surgical procedures. We searched randomized controlled trials (RCT), enrolling patients undergoing a major cardiovascular surgical procedure and transfused with LD-PRBC. Data were extracted, and risk of bias was assessed according to Cochrane guidelines. In addition, trial sequential analysis (TSA) was used to assess the need of conducting additional trials. Quality of the evidence was assessed using the GRADE approach. Seven studies met the eligibility criteria. Quality of the evidence was rated as moderate for both outcomes. The risk ratio for death from any cause comparing the LD-PRBC versus non-LD-PRBC group was 0.69 (CI 95% = 0.53 to 0.90; I 2 = 0%). The risk ratio for infection in the same comparison groups was 0.77 (CI 95% = 0.66 to 0.91; I 2 = 0%). TSA showed a conclusive result in this outcome. We found evidence that supports the routine use of leukodepletion in patients undergoing a major cardiovascular surgical procedure requiring PRBC transfusion to prevent death and infection. In the case of infection, the evidence should be considered sufficient and conclusive and hence indicated that further trials would not be required.


Enhanced secretion of Escherichia coli beta-lactamase by a spontaneous erythromycin-resistant mutant of Bacillus subtilis.
An extracellular-protease-deficient mutant, ME142, was isolated from Bacillus subtilis as a spontaneous erythromycin-resistant (Eryr) clone. This mutant showed conditional sporulation and only sporulated normally in the absence of erythromycin. In the presence of the antibiotic, sporulation was greatly reduced. Production of extracellular proteases by ME142 also exhibited conditional deficiency, possibly due to pleiotropic effects of the sporulation deficiency. The production of protease was 2-10% that of the wild-type level in the presence of erythromycin. ME142 showed poor competence for transformation even in the absence of erythromycin; however, derivatives of ME142 were isolated which had the same Eryr phenotype but which exhibited normal competence. One such mutant, ME162, was used as a host for the secretion of Escherichia coli beta-lactamase. The amount of beta-lactamase in the culture supernatants of ME162 increased significantly when the cells were cultured with erythromycin, suggesting that proteolysis of the beta-lactamase in the supernatants of ME162 was greatly reduced as compared to that in the supernatants of the wild-type strain.


Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury.
Dehydroepiandrosterone (DHEA) is an endogenous steroid that blocks carcinogenesis, retards aging, and exerts antiproliferative properties. In vitro, it is a potent inhibitor of glucose-6-phosphate dehydrogenase, the first committed step of the pentose phosphate pathway. In man, serum levels of DHEA and its sulfate peak in early adulthood and drop markedly with age. Epidemiologic evidence indicates that low levels of DHEA or its sulfate conjugate are linked to an increased risk of developing cancer or of death from cardiovascular disease. Like cancer, atherosclerosis is a proliferative process characterized by both initiation and promotion phases. This similarity provided a framework in which to study the antiatherogenic effects of DHEA. Rabbits were randomly assigned to four groups. Two groups of rabbits received aortic endothelial injury by balloon catheter and were fed a 2% cholesterol diet for 12 wk. DHEA, 0.5%, was incorporated into the diet of one group receiving the 2% cholesterol diet and endothelial injury and also into the diet of one of the control groups. Animals were killed after 12 wk and aortas, hearts, and livers were studied. Plasma samples were analyzed for total cholesterol, VLDL, LDL, HDL, triglycerides, DHEA, and DHEA-sulfate levels. The atherogenic insult resulted in severe atherosclerosis in animals not treated with DHEA. In those receiving DHEA there was an almost 50% reduction in plaque size (P = 0.006), inversely related to the serum level of DHEA attained. Fatty infiltration of the heart and liver were also markedly reduced. These beneficial actions were not attributable to differences in body weight gain, food intake, total plasma cholesterol or distribution of cholesterol among the VLDL, LDL, or HDL fractions. The results show that high levels of plasma DHEA inhibit the development of atherosclerosis and they provide an important experimental link to the epidemiologic studies correlating low DHEA-sulfate plasma levels with an enhanced risk of cardiovascular mortality.


[Hypovitaminosis D in pediatric patients on renal replacement therapy].
Hypovitaminosis D has a high prevalence among patients with chronic kidney disease (CKD). To determine the prevalence of 25 hydroxy vitamin D (25(OH) D) insufficiency and deficiency in pediatric patients on dialysis and kidney transplantation. Serum calcium and phosphorus, parathormone (PTH), alkaline phosphatases and 25 (OH)D were measured in 13 children on hemodialysis (HD), 18 on peritoneal dialysis (PD) and 53 that received an allograft (Tx), aged 9.8 ± 4.6 years (51% females). Fifty four percent of patients had height Z score less than -1.88. Patients on HD had the lowest values. The average time of replacement therapy was 2.9 ± 2.8 years. Mean 25(OH)D levels in all was 18.7 ± 10.7ng/ml (HD: 21 ± 16.8, PD: 18.9 ± 8.5, Tx: 18.1 ± 9.72 ng/ml). Eighty eight percent of patients had levels below 30 ng/ml. Mean of serum calcium was 9.5 ± 0.64 mg/dl, serum phosphorus 5.03 ± 1.02 mg/dl, calcium-phosphorus product 48 ± 11.8 mg/dl and alkaline phosphatases 300.5 ± 171.3 IU/L. Average PTH values in dialyzed and Tx patients were 724.6 ± 640.5 and 107.7 ± 56.2 pg/ml, respectively (p < 0.001). A positive correlation between 25 (OH) D and calcium levels among PD patients was observed (r = 0.490, p = 0.04). Hypovitaminosis D is highly prevalent among children on renal substitution therapy, regardless of the type of therapy used and the stage of renal failure.


Critical Role for the Extended N Terminus of Chlamydial MreB in Directing Its Membrane Association and Potential Interaction with Divisome Proteins.
Chlamydiae lack the conserved central coordinator protein of cell division FtsZ, a tubulin-like homolog. Current evidence indicates that Chlamydia uses the actin-like homolog, MreB, to substitute for the role of FtsZ in a polarized division mechanism. Interestingly, we observed MreB as a ring at the septum in dividing cells of Chlamydia We hypothesize that MreB, to substitute for FtsZ in Chlamydia, must possess unique properties compared to canonical MreB orthologs. Sequence differences between chlamydial MreB and orthologs in other bacteria revealed that chlamydial MreB possesses an extended N-terminal region, harboring predicted amphipathicity, as well as the conserved amphipathic helix found in other bacterial MreBs. The conserved amphipathic helix-directed green fluorescent protein (GFP) to label the membrane uniformly in Escherichia coli but the extended N-terminal region did not. However, the extended N-terminal region together with the conserved amphipathic region directed GFP to restrict the membrane label to the cell poles. In Chlamydia, the extended N-terminal region was sufficient to direct GFP to the membrane, and this localization was independent of an association with endogenous MreB. Importantly, mutating the extended N-terminal region to reduce its amphipathicity resulted in the accumulation of GFP in the cytosol of the chlamydiae and not in the membrane. The N-terminal domain of MreB was not required for homotypic interactions but was necessary for interactions with cell division components RodZ and FtsK. Our data provide mechanistic support for chlamydial MreB to serve as a substitute for FtsZ by forming a ringlike structure at the site of polarized division.IMPORTANCEChlamydia trachomatis is an obligate intracellular pathogen, causing sexually transmitted diseases and trachoma. The study of chlamydial physiology is important for developing novel therapeutic strategies for these diseases. Chlamydiae divide by a unique MreB-dependent polarized cell division process. In this study, we investigated unique properties of chlamydial MreB and observed that chlamydial species harbor an extended N-terminal region possessing amphipathicity. MreB formed a ring at the septum, like FtsZ in Escherichia coli, and its localization was dependent upon the amphipathic nature of its extended N terminus. Furthermore, this region is crucial for the interaction of MreB with cell division proteins. Given these results, chlamydial MreB likely functions at the septum as a scaffold for divisome proteins to regulate cell division in this organism.


Nasal interfaces for neonatal resuscitation.
The Neonatal Task Force of the International Liaison Committee on Resuscitation (ILCOR) makes practice recommendations for the care of newborn infants in the delivery room (DR). ILCOR recommends that all infants who are gasping, apnoeic, or bradycardic (heart rate < 100 per minute) should be given positive pressure ventilation (PPV) with a manual ventilation device (T-piece, self-inflating bag, or flow-inflating bag) via an interface. The most commonly used interface is a face mask that encircles the infant's nose and mouth. However, gas leak and airway obstruction are common during face mask PPV. Nasal interfaces (single and binasal prongs (long or short), or nasal masks) and laryngeal mask airways (LMAs) may also be used to deliver PPV to newborns in the DR, and may be more effective than face masks. To determine whether newborn infants receiving PPV in the delivery room with a nasal interface compared to a face mask, laryngeal mask airway (LMA), or another type of nasal interface have reduced mortality and morbidity. To assess whether safety and efficacy of the nasal interface differs according to gestational age or ventilation device. Searches were conducted in September 2022 in CENTRAL, MEDLINE, Embase, Epistemonikos, and two trial registries. We searched conference abstracts and checked the reference lists of included trials and related systematic reviews identified through the search. We included randomised controlled trials (RCTs) and quasi-RCT's that compared the use of nasal interfaces to other interfaces (face masks, LMAs, or one nasal interface to another) to deliver PPV to newborn infants in the DR. Each review author independently evaluated the search results against the selection criteria, screened retrieved records, extracted data, and appraised the risk of bias. If they were study authors, they did not participate in the selection, risk of bias assessment, or data extraction related to the study. In such instances, the study was independently assessed by other review authors. We contacted trial investigators to obtain additional information. We completed data analysis according to the standards of Cochrane Neonatal, using risk ratio (RR) and 95% confidence Intervals (CI) to measure the effect of the different interfaces. We used fixed-effect models and the GRADE approach to assess the certainty of the evidence. We included five trials, in which 1406 infants participated. They were conducted in 13 neonatal centres across Europe and Australia. Each of these trials compared a nasal interface to a face mask for the delivery of respiratory support to newborn infants in the DR. Potential sources of bias were a lack of blinding to treatment allocation of the caregivers and investigators in all trials. The evidence suggests that resuscitation with a nasal interface in the DR, compared with a face mask, may have little to no effect on reducing death before discharge (typical risk ratio (RR) 0.72, 95% CI 0.47 to 1.13; 3 studies, 1124 infants; low-certainty evidence). Resuscitation with a nasal interface may reduce the rate of intubation in the DR, but the evidence is very uncertain (RR 0.68, 95% CI 0.54 to 0.85; 5 studies, 1406 infants; very low-certainty evidence). The evidence is very uncertain for the rate of intubation within 24 hours of birth (RR 0.97, 95% CI 0.85 to 1.09; 3 studies, 749 infants; very low-certainty evidence), endotracheal intubation outside the DR during hospitalisation (RR 1.15, 95% CI 0.93 to 1.42; 1 study, 144 infants; very low-certainty evidence) and cranial ultrasound abnormalities (intraventricular haemorrhage (IVH) grade ≥ 3, or periventricular leukomalacia; RR 0.94, 95% CI 0.55 to 1.61; 3 studies, 749 infants; very low-certainty evidence). Resuscitation with a nasal interface in the DR, compared with a face mask, may have little to no effect on the incidence of air leaks (RR 1.09, 95% CI 0.85 to 1.09; 2 studies, 507 infants; low-certainty evidence), or the need for supplemental oxygen at 36 weeks' corrected gestational age (RR 1.06, 95% CI 0.8 to 1.40; 2 studies, 507 infants; low-certainty evidence). We identified one ongoing study, which compares a nasal mask to a face mask to deliver PPV to infants in the DR. We did not identify any completed trials that compared nasal interfaces to LMAs or one nasal interface to another. Nasal interfaces were found to offer comparable efficacy to face masks (low- to very low-certainty evidence), supporting resuscitation guidelines that state that nasal interfaces are a comparable alternative to face masks for providing respiratory support in the DR. Resuscitation with a nasal interface may reduce the rate of intubation in the DR when compared with a face mask. However, the evidence is very uncertain. This uncertainty is attributed to the use of a new ventilation system in the nasal interface group in two of the five trials. As such, it is not possible to differentiate separate, specific effects related to the ventilation device or to the interface in these studies.


Active and passive smoking and the risk of subarachnoid hemorrhage: an international population-based case-control study.
This study was undertaken to better clarify the risks associated with cigarette smoking and subarachnoid hemorrhage (SAH). The study included 432 incident cases of SAH frequency matched to 473 community SAH-free controls to determine dose-dependent associations of active and passive smoking (at home) and smoking cessation with SAH. Compared with never smokers not exposed to passive smoking, the adjusted odds ratio for SAH among current smokers was 5.0 (95% confidence interval [CI], 3.1 to 8.1); for past smokers, 1.2 (95% CI, 0.8 to 2.0); and for passive smokers, 0.9 (95% CI, 0.6 to 1.5). Current and lifetime exposures showed a clear dose-dependent effect, and risks appeared more prominent in women and for aneurysmal SAH. Approximately 1 in 3 cases of SAH could be attributed to current smoking, but risks decline quickly after smoking cessation, even among heavy smokers. A strong positive association was found between cigarette smoking and SAH, especially for aneurysmal SAH and women, which is virtually eliminated within a few years of smoking cessation. Large opportunities exist for preventing SAH through smoking avoidance and cessation programs.


Categorisation of culturable bioaerosols in a fruit juice manufacturing facility.
Bioaerosols are defined as aerosols that comprise particles of biological origin or activity that may affect living organisms through infectivity, allergenicity, toxicity, or through pharmacological or other processes. Interest in bioaerosol exposure has increased over the last few decades. Exposure to bioaerosols may cause three major problems in the food industry, namely: (i) contamination of food (spoilage); (ii) allergic reactions in individual consumers; or (iii) infection by means of pathogenic microorganisms present in the aerosol. The aim of this study was to characterise the culturable fraction of bioaerosols in the production environment of a fruit juice manufacturing facility and categorise isolates as harmful, innocuous or potentially beneficial to the industry, personnel and environment. Active sampling was used to collect representative samples of five areas in the facility during peak and off-peak seasons. Areas included the entrance, preparation and mixing area, between production lines, bottle dispersion and filling stations. Microbes were isolated and identified using 16S, 26S or ITS amplicon sequencing. High microbial counts and species diversity were detected in the facility. 239 bacteria, 41 yeasts and 43 moulds were isolated from the air in the production environment. Isolates were categorised into three main groups, namely 27 innocuous, 26 useful and 39 harmful bioaerosols. Harmful bioaerosols belonging to the genera Staphylococcus, Pseudomonas, Penicillium and Candida were present. Although innocuous and useful bioaerosols do not negatively influence human health their presence act as an indicator that an ideal environment exists for possible harmful bioaerosols to emerge.


[Quality management within the competence network of paediatric oncology and haematology].
The competence network paediatric oncology and haematology aims at improving the structure of paediatric oncology and haematology as a whole focussing in particular on the quality of clinical trials and study centres. This implicates the following measures: (1) Employment of research and trial assistants in order to improve the quality of documentation and study management in the participating hospitals. (2) Building up of an Internet portal to provide medical information for non-professionals, for patients and their families as well as for health professionals. (3) The project "Study Assistance" supports study centers during the process of writing and examining new treatment protocols so that they are in compliance with the Good Clinical Practice criteria, formal criteria and statutory provisions. It presently works on a structural standardisation of study protocols and case record forms in order to improve their usability. In addition, the working group "Quality Assurance in GPOH Study Centres" is engaged in developing a quality management system for study centers.


Reactive oxygen species and the Antarctic macroalgal wound response.
Reactive oxygen species (ROS) are commonly produced by algal, vascular plant, and animal cells involved in the innate immune response as cellular signals promoting defense and healing and/or as a direct defense against invading pathogens. The production of reactive species in macroalgae upon injury, however, is largely uncharacterized. In this study, we surveyed 13 species of macroalgae from the Western Antarctic Peninsula and show that the release of strong oxidants is common after macroalgal wounding. Most species released strong oxidants within 1 min of wounding and/or showed cellular accumulation of strong oxidants over an hour post-wounding. Exogenous catalase was used to show that hydrogen peroxide was a component of immediate oxidant release in one of five species, but was not responsible for the entire oxidative wound response as is common in vascular plants. The other component(s) of the oxidant cocktail released upon wounding are unknown. We were unable to detect protein nitration in extracts of four oxidant-producing species flash frozen 30 s after wounding, but a role for reactive nitrogen species such as peroxynitrite cannot be completely ruled out. Two species showed evidence for the production of a catalase-activated oxidant, a mechanism previously known only from the laboratory and from the synthetic drug isoniazid used to kill the human pathogen Mycobacterium tuberculosis. The rhodophyte Palmaria decipiens, which released strong oxidants after wounding, also produced strong oxidants upon grazing by a sympatric amphipod, suggesting that oxidants are involved in the response to grazing.


miRNAs: Key Players in Neurodegenerative Disorders and Epilepsy.
MicroRNAs (miRNAs) are endogenous, ∼22 nucleotide, non-coding RNA molecules that function as post-transcriptional regulators of gene expression. miRNA dysregulation has been observed in cancer and in neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases, amyotrophic lateral sclerosis, and the neurological disorder, epilepsy. Neuronal degradation and death are important hallmarks of neurodegenerative disorders. Additionally, abnormalities in metabolism, synapsis and axonal transport have been associated with Alzheimer's disease, Parkinson's disease, and frontotemporal dementia. A number of recently published studies have demonstrated the importance of miRNAs in the nervous system and have contributed to the growing body of evidence on miRNA dysregulation in neurological disorders. Knowledge of the expressions and activities of such miRNAs may aid in the development of novel therapeutics. In this review, we discuss the significance of miRNA dysregulation in the development of neurodegenerative disorders and the use of miRNAs as targets for therapeutic intervention.


The immunoregulatory landscape of human tuberculosis granulomas.
Tuberculosis (TB) in humans is characterized by formation of immune-rich granulomas in infected tissues, the architecture and composition of which are thought to affect disease outcome. However, our understanding of the spatial relationships that control human granulomas is limited. Here, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) to image 37 proteins in tissues from patients with active TB. We constructed a comprehensive atlas that maps 19 cell subsets across 8 spatial microenvironments. This atlas shows an IFN-γ-depleted microenvironment enriched for TGF-β, regulatory T cells and IDO1+ PD-L1+ myeloid cells. In a further transcriptomic meta-analysis of peripheral blood from patients with TB, immunoregulatory trends mirror those identified by granuloma imaging. Notably, PD-L1 expression is associated with progression to active TB and treatment response. These data indicate that in TB granulomas, there are local spatially coordinated immunoregulatory programs with systemic manifestations that define active TB.


Aggregation, adsorption, and surface properties of multiply end-functionalized polystyrenes.
The properties of polystyrene blends containing deuteriopolystyrene, multiply end-functionalized with C8F17 fluorocarbon groups, are strikingly analogous to those of surfactants in solution. These materials, denoted FxdPSy, where x is the number of fluorocarbon groups and y is the molecular weight of the dPS chain in kg/mol, were blended with unfunctionalized polystyrene, hPS. Nuclear reaction analysis experiments show that FxdPSy polymers adsorb spontaneously to solution and blend surfaces, resulting in a reduction in surface energy inferred from contact angle analysis. Aggregation of functionalized polymers in the bulk was found to be sensitive to FxdPSy structure and closely related to surface properties. At low concentrations, the functionalized polymers are freely dispersed in the hPS matrix, and in this range, the surface excess concentration grows sharply with increasing bulk concentration. At higher concentrations, surface excess concentrations and contact angles reach a plateau, small-angle neutron scattering data indicate small micellar aggregates of six to seven F2dPS10 polymer chains and much larger aggregates of F4dPS10. Whereas F2dPS10 aggregates are miscible with the hPS matrix, F4dPS10 forms a separate phase of multilamellar vesicles. Using neutron reflectometry (NR), we found that the extent of the adsorbed layer was approximately half the lamellar spacing of the multilamellar vesicles. NR data were fitted using an error function profile to describe the concentration profile of the adsorbed layer, and reasonable agreement was found with concentration profiles predicted by the SCFT model. The thermodynamic sticking energy of the fluorocarbon-functionalized polymer chains to the blend surface increases from 5.3kBT for x = 2 to 6.6kBT for x = 4 but appears to be somewhat dependent upon the blend concentration.


Relation of maternal hypertension with infant growth in a prospective birth cohort: the ABCD study.
The aim of this study was to investigate the assumed positive association of pre-existent and pregnancy-induced hypertension with the offspring's weight and length gain in the first 14 months of life. We studied 3994 pregnant women and their offspring in a prospective community-based cohort study, starting between 2003 and 2004 (Amsterdam Born Children and their Development, ABCD study). Questionnaires obtaining information about hypertension during pregnancy were completed, and this was complemented with additional information from the obstetric caregiver. Anthropometry of the offspring was followed during the first 14 months of life. Main outcome measures were presence or absence of growth acceleration in weight or length (normal: ΔSDS ⩽ 0.67 v. growth acceleration: ΔSDS > 0.67). The relation between hypertension during pregnancy and weight and length gain was addressed by logistic regression analyses. We found that pre-existent hypertension was related to growth acceleration in weight and length. After correction for birth weight and pregnancy duration, the effect remained significant for growth acceleration in weight (OR 1.89; 95% CI 1.21-2.97; P < 0.01). Pregnancy-induced hypertension showed similar results, although correction for birth weight and pregnancy duration rendered the associations non-significant. In conclusion, infants of women with pre-existent hypertension during pregnancy more frequently have growth acceleration in weight and length, and yet the mechanisms acting on postnatal growth appear to be different.


Factors influencing catheter-related infections in the Dutch multicenter study on high-dose chemotherapy followed by peripheral SCT in high-risk breast cancer patients.
Neutropenia following high-dose chemotherapy leads to a high incidence of infectious complications, of which central venous catheter-related infections predominate. Catheter-related infections and associated risk factors in 392 patients participating in a randomized adjuvant breast cancer trial and assigned to receive high-dose chemotherapy and peripheral stem-cell reinfusion were evaluated. Median catheter dwell time was 25 days (range 1-141). Catheter-related infections were seen in 28.3% of patients (11 infections per 1000 catheter-days). Coagulase-negative staphylococci were found in 104 of 186 positive blood cultures (56%). No systemic fungal infections occurred. Cox regression analysis showed that duration of neutropenia >10 days (P=0.04), using the catheter for both stem-cell apheresis and high-dose chemotherapy (P= <0.01), and use of total parenteral nutrition (TPN, P=0.04) were predictive for catheter-related infections. In conclusion, a high incidence of catheter-related infections after high-dose chemotherapy was seen related to duration of neutropenia, use of the catheter for both stem-cell apheresis and high-dose chemotherapy, and use of TPN. Selective use and choice of catheters could lead to a substantial reduction of catheter-related infectious complications.


Bimanual phacoemulsification for subluxated cataractous lens.
Bimanual phacoemulsification has been established as a safe and efficacious means of nuclear emulsification in the past. This case report presents the use of this technique in a man in his early forties, who had subluxated cataractous lenses in both eyes. The technique allowed for effective nuclear emulsification within a closed chamber, providing better control over intraocular events. The report emphasizes the safety and effectiveness of bimanual phacoemulsification in cataract extraction, even in challenging cases like a subluxated lens.


Animal health and welfare planning improves udder health and cleanliness but not leg health in Austrian dairy herds.
Animal health and welfare planning is considered an important tool for herd management; however, its effectiveness is less well known. The aim of this study was to conduct animal health and welfare planning on 34 Austrian dairy farms and to evaluate changes in health and welfare after 1 yr. After an initial assessment using the Welfare Quality protocol (Welfare Quality Consortium, Lelystad, the Netherlands), results were reported back to the farmers. Health and welfare area(s) in which both the farmer and the researcher regarded improvement as important were discussed. Management practices and husbandry measures were chosen according to the respective farm situation. One year after interventions had been initiated, farms were reassessed, and the degree of implementation of improvement measures was recorded. The average implementation rate was 57% and thus relatively high when compared with other studies. High degrees of implementation were achieved related to cleanliness and udder health, at 77 and 63%, respectively. Intervention measures addressing udder health were mostly easy to incorporate in the daily routine and led to a reduced somatic cell score, whereas this score increased in herds without implementation of measures. The decrease in cows with dirty teats was more pronounced when measures were implemented compared with control farms. The implementation rate regarding leg health (46%) was comparably low in the present study, and leg health did not improve even when measures were implemented. Lying comfort, social behavior, and human-animal relationship did not require interventions and were therefore seldom chosen by farmers as part of health and welfare plans. In conclusion, the structured, participatory process of animal health and welfare planning appears to be a promising way to improve at least some animal health and welfare issues.


Large air pressure changes triggered by P-SV ground motion in a cave in northern Taiwan.
Acoustic-gravity waves are generally considered to be one of the major factors that drive changes of the total electron content in the ionosphere. However, causal mechanisms of couplings between sources in the lithosphere and responses in the atmosphere and the ionosphere are not fully understood, yet. A barometer in the cave of the SBCB station records an unusual phenomenon of larger amplitudes in air pressure changes inside than those at the Xinwu station (outside). Accordingly, the comparison between the recorded data at the SBCB and Xinwu station can drive investigations of potential sources of the unusual phenomenon. Analytical results of phase angle differences reveal that the air pressure outside the cave at the Xinwu station often leads air pressure changes inside at the SBCB station at relatively low frequency bands. In contrast, the larger pressure changes at frequencies > ~ 5 × 10-4 Hz inside the cave at the SBCB station lead smaller changes outside at the Xinwu station. To expose causal mechanisms of the unusual phenomenon, continuous seismic waveforms are further conducted for examination. When the horizontal and vertical ground velocities of ground vibrations yield a difference in the phase angle close to 90°, coherence values between the air pressure changes and ground vibrations become large. This suggests that the pressure-shear vertical ground vibrations can drive air pressure changes. Meanwhile, the results shed light on investigating the existence of acoustic waves near the Earth's surface using a partially confined space underground due to that the assumptions of the waves can propagate upward into the atmosphere driving changes in the ionosphere.


[History of anaesthesia in Belgium].
Man has for a long time searched means of fighting pain, by administration of plant extracts such as poppy seed, jimson weed, henbane, mandrake and alcohol. These substances were given in the form of cataplasms, potions or clysters. Somniferous sponges, applied on the face, were known since Antiquity and have been in use in some countries up to the 13th century. Surgery and pain were inseparable till mid 19th century. Indications for surgery were few, even though some patients could benefit from these sedative drugs. The anesthetic properties of ether and nitrous oxide (laughing gas), known since the 18th century, were only recognized in the 19th century. William Morton, a dentist, was the first to successfully provide general anesthesia with ether in 1846 in Boston. News spread to England shortly afterwards. On the European continent, the first use of ether was due to 2 Belgian surgeons. Next came chloroform as novel anesthetic. They were administered via either a gauze or a mask by the general practitioner, a medical student or a nurse. Unlike England, the use of these drugs for obstetrical anesthesia (called anesthesia "a la reine", alluding to Queen Victoria who benefited from chloroform during childbirth) was never very popular in Belgium. Since the years 1880, the use of cocaine, then of novocaine allowed to perform local anesthesia, then local nerve blocks and spinal anesthesia, installed by the surgeon prior to operating. Since then, surgery experienced rapid progress, Belgium included. During the 1914-1918 first World War, these advances saved many human lives. When general anesthesia was necessary, it was cared for by another physician or a nurse. The interwar period did not see significant advances in anesthesia, except in intravenous anesthesia with barbiturates, appeared in the late 1930's. Intra- and postoperative complications were frequent. Apart from sulfonamides, antibiotics were non-existent. During the war 1940-45, there was no progress in anesthesia and surgery in Belgium. After the Liberation, Belgian doctors specifically trained in anesthesia by the British army, or elsewhere in non-occupied countries, will form the core of a new specialty, "anesthesiology-reanimation", who will fight to be recognized as a specialty in itself in Belgium. It will beneficiate from--and largely contribute to--the technical and scientific advances in the medical field. Initially based on clinical symptoms, monitoring and care of operated patients, during and after operation, will beneficiate from modern monitoring and other technical apparatus, which will allow the most audacious surgical technical performances in all domains. Postoperative and intensive care units will appear in the years 1960's. Nowadays, anesthesiologists work in all hospital settings, and also organize One-day clinics and Pain clinics. In Belgium, the quality of the clinical and scientific training of anesthesiologists is widely acknowledged, as well as clinical and experimental research.


Genetically Determined Response to Artemisinin Treatment in Western Kenyan Plasmodium falciparum Parasites.
Genetically determined artemisinin resistance in Plasmodium falciparum has been described in Southeast Asia. The relevance of recently described Kelch 13-propeller mutations for artemisinin resistance in Sub-Saharan Africa parasites is still unknown. Southeast Asia parasites have low genetic diversity compared to Sub-Saharan Africa, where parasites are highly genetically diverse. This study attempted to elucidate whether genetics provides a basis for discovering molecular markers in response to artemisinin drug treatment in P. falciparum in Kenya. The genetic diversity of parasites collected pre- and post- introduction of artemisinin combination therapy (ACT) in western Kenya was determined. A panel of 12 microsatellites and 91 single nucleotide polymorphisms (SNPs) distributed across the P. falciparum genome were genotyped. Parasite clearance rates were obtained for the post-ACT parasites. The 12 microsatellites were highly polymorphic with post-ACT parasites being significantly more diverse compared to pre-ACT (p < 0.0001). The median clearance half-life was 2.55 hours for the post-ACT parasites. Based on SNP analysis, 15 of 90 post-ACT parasites were single-clone infections. Analysis revealed 3 SNPs that might have some causal association with parasite clearance rates. Further, genetic analysis using Bayesian tree revealed parasites with similar clearance phenotypes were more closely genetically related. With further studies, SNPs described here and genetically determined response to artemisinin treatment might be useful in tracking artemisinin resistance in Kenya.


A method for accurate determination of terminal sequences of viral genomic RNA.
A combination of ligation-anchored PCR and anchored cDNA cloning techniques were used to clone the termini of the saguaro cactus virus (SCV) RNA genome. The terminal sequences of the viral genome were subsequently determined from the clones. The 5' terminus was cloned by ligation-anchored PCR, whereas the 3' terminus was obtained by a technique we term anchored cDNA cloning. In anchored cDNA cloning, an anchor oligonucleotide was prepared by phosphorylation at the 5' end, followed by addition of a dideoxynucleotide at the 3' end to block the free hydroxyl group. The 5' end of the anchor was subsequently ligated to the 3' end of SCV RNA. The anchor-ligated, chimerical viral RNA was then reverse-transcribed into cDNA using a primer complementary to the anchor. The cDNA containing the complete 3'-terminal sequence was converted into ds-cDNA, cloned, and sequenced. Two restriction sites, one within the viral sequence and one within the primer sequence, were used to facilitate cloning. The combination of these techniques proved to be an easy and accurate way to determine the terminal sequences of SCV RNA genome and should be applicable to any other RNA molecules with unknown terminal sequences.


Refractory CD20 Positive Cellular Rejection in Living Kidney Transplant: A Case Report and Review of Literature.
Transplant is the optimal therapy for patients with end-stage renal disease. Acute cellular rejection refractory to treatment remains a major risk factor for graft loss and poor outcomes. In this study, we describe a 39-year-old man who received a living-related kidney transplant. Two days after transplant, the patient displayed acute deterioration of graft function. Conventional anti-rejection therapy was initiated, but graft function did not improve. Biopsy revealed acute cellular rejection (grade IIA), and C4d and HLA antibodies were negative. Immunohistochemistry phenotyping revealed clusters of CD20-positive lymphocytes, with 80% being CD3 positive. Rituximab was prescribed, and graft function improved dramatically. After 1 week, a second graft biopsy was done due to lagging of graft function, shown by serum creatinine of 2.1 mg/dL. Biopsy revealed regenerating acute tubular necrosis with disappearance of the CD20-positive lymphocyte cluster infiltrates. Two year, after transplant, the patient's graft function maintained stable. Phenotyping of the cellular infiltrate is important as it may lead to a proper selection of immunosuppression and consequent improvement of graft outcome.


Soft tissue correction of a single-tooth pontic space: a comparative quantitative volume assessment.
Various augmentation procedures are recommended for the correction of localized alveolar ridge defects. However, no study has quantitatively evaluated the results of these procedures to date. This study compared 2 soft tissue augmentation surgeries commonly used to alter contours of single-tooth pontic space by quantifying 3-dimensional volume changes with the optical projection Moiré method at 1 and 3.5 months after surgery. Twenty-four patients required surgery. Each patient had a localized alveolar ridge defect, corresponding to a mesial-distal width of 1 single tooth. The defect of 12 patients was corrected with a subepithelial connective tissue graft; the remaining 12 patients were treated by receiving a free full-thickness gingival graft, which included epithelium and connective tissue with fatty tissue. Six unoperated defects of 6 patients formed the control group. For each defect, an impression was made before treatment, at 1 and 3.5 months after surgery to measure the volume changes on the dental casts with a validated projection Moiré system. Volume change was assessed relative to the preoperative dimension at the buccal and crestal aspects of the single-tooth pontic space. At 3.5 months postsurgery, mean volumetric gain for the connective tissue group with 159 mm(3) (SD +/- 80) was significantly greater (P =.027) than for free full-thickness gingival graft group with 104 mm(3) (SD +/- 31). The applied projection Moiré method proved its applicability in assessing 3-dimensional volume changes of pontic spaces with a single-tooth width. Volumetric assessment after 1 and 3.5 months revealed significantly greater volume gain with the subepithelial connective tissue graft in comparison to the free full-thickness gingival graft.


Cash transfer and microfinance interventions for tuberculosis control: review of the impact evidence and policy implications.
To quantify the impact of cash transfer and microfinance interventions on a selected list of tuberculosis (TB) risk factors and assess their potential role in supporting TB control. Published and unpublished references identified from clinical and social electronic databases, grey literature and web sites. Eligible interventions had to be conducted in middle- or low-income countries and document an impact evaluation on any of the following outcomes: 1) TB or other respiratory infections; 2) household socio-economic position; and 3) factors mediating the association between low household socio-economic position and TB, including inadequate health-seeking behaviours, food insecurity and biological TB risk factors such as human immunodeficiency virus (HIV) and adult malnutrition. Interventions targeting special populations were excluded. Fifteen cash transfer schemes (four unconditional and 11 conditional) and seven microfinance programmes met the eligibility criteria. No intervention addressed TB or any other respiratory infection. Of 11 cash transfer and four microfinance interventions, respectively seven and four reported a positive impact on indicators of economic well-being. A positive impact on household food security was documented in respectively eight of nine and three of five cash transfer and microfinance interventions. Improved health care access was documented respectively in 10 of 12 cash transfer and four of five microfinance interventions. The only intervention evaluating impact on HIV incidence was a microfinance project that found no effect. No cash transfer or microfinance interventions had an impact on adult malnutrition. Cash transfer and microfinance interventions can positively impact TB risk factors. Evaluation studies are urgently needed to assess the impact of these social protection interventions on actual TB indicators.


CircRPN2 Inhibits Aerobic Glycolysis and Metastasis in Hepatocellular Carcinoma.
Although circular RNAs (circRNA) are known to modulate tumor initiation and progression, their role in hepatocellular carcinoma (HCC) metastasis remains poorly understood. Here, three metastasis-associated circRNAs identified in a previous circRNA-sequencing study were screened and validated in two HCC cohorts. CircRPN2 was downregulated in highly metastatic HCC cell lines and HCC tissues with metastasis. Patients with HCC with lower circRPN2 levels displayed shorter overall survival and higher rates of cumulative recurrence. Mechanistic studies in vitro and in vivo revealed that circRPN2 binds to enolase 1 (ENO1) and accelerates its degradation to promote glycolytic reprogramming through the AKT/mTOR pathway, thereby inhibiting HCC metastasis. CircRPN2 also acted as a competing endogenous RNA for miR-183-5p, which increases forkhead box protein O1 (FOXO1) expression to suppress glucose metabolism and tumor progression. In clinical samples, circRPN2 expression negatively correlated with ENO1 and positively correlated with FOXO1, and expression of circRPN2, either alone or in combination with ENO1 and FOXO1, was a novel indicator of HCC prognosis. These data support a model wherein circRPN2 inhibits HCC aerobic glycolysis and metastasis via acceleration of ENO1 degradation and regulation of the miR-183-5p/FOXO1 axis, suggesting that circRPN2 represents a possible therapeutic target in HCC. The circRNA circRPN2 is a potential prognostic biomarker and therapeutic target in hepatocellular carcinoma that suppresses aerobic glycolysis and metastasis.


Modulation of antibody affinity by an engineered amino acid substitution.
The crystal model of the complex of the somatically mutated anti-p-azophenylarsonate (Ars) Ab 36-71 F(ab) with phenylarsonate reveals that six residues (Asn35, Trp47, Tyr50, Ser99, and Tyr106 in the H chain and Arg96 in the L chain) contact hapten. Further study of this model suggested that H chain Phe108, which forms the base of the combining cavity, also affects Ars binding. We predicted that Trp with a bulkier aromatic side chain might be accommodated in this position and increase Ars affinity. The substitution of Phe by Trp using in vitro mutagenesis at position 108 enhanced affinity 10-fold in the germline-encoded Ab 36-65. However, the same mutation in Ab 36-71 abolished the binding. Phe108 was then mutated to different amino acids in both Abs. The results indicated that except for the Trp substitution in 36-65, all other substitutions at position 108 decrease or abolish Ars binding in both Abs. It was shown previously that the 200-fold difference in affinity between 36-65 and 36-71 could be reproduced by changing only three VH amino acids. Because the mutation of Phe108 to Trp has never been observed during in vivo affinity maturation, we constructed mutants of 36-65 in which Trp108 was combined with one or more of the "favorable" mutations of 36-71, to determine whether the mutations were additive. The results indicate that it is possible to maintain an affinity significantly higher than wild-type by such combined mutations. Thus, the failure to observe Trp108 in vivo is not due to structural idiosyncrasy, but may simply be due to codon usage at Phe108 in the germline sequence. Such limited "adaptability" of a germline sequence indicates that it is possible to achieve higher affinity Abs through protein engineering via routes that are constrained during in vivo selection.


Caulis Spatholobi extracts inhibit osteosarcoma growth and metastasis through suppression of CXCR4/PI3K/AKT signaling.
The therapeutic potential of Caulis Spatholobi (CS) extracts against various cancers has been well documented, yet its impact and mechanism in osteosarcoma (OS) remain unexplored. This study aims to elucidate the effects of CS extracts on the growth and metastasis of OS, along with its underlying molecular mechanism. The impact of CS extracts on the proliferative potential of two OS cell lines (Saos-2 and U2OS) was assessed using MTT and colony-formation assays. Additionally, the migratory and invasive capacities of OS cells were investigated through Transwell assays. The modulation of CXCR4 expression by CS extracts was evaluated using qRT-PCR and Western blotting. Furthermore, the influence of CS extracts on the activation of PI3K/Akt signaling was determined through Western blotting. CS extracts exhibited a dose- and time-dependent inhibition of proliferation and colony formation in OS cells. Notably, CXCR4 expression was prominently observed in Saos-2 and U2OS, and treatment with CS extracts led to a dose-dependently reduction in CXCR4 levels. Silencing CXCR4 or inhibiting its function diminished the migratory and invasive capacities of OS cells. Conversely, the CS extracts induced suppression of OS cell migration and invasion was counteracted by CXCR4 overexpression. Mechanistically, CS extracts repressed PI3K/AKT signaling in OS cells by downregulating CXCR4 expression. CS extracts mitigate the CXCR4/PI3K/AKT signaling-mediated growth and metastasis capacities of OS cells, thus might play an anti-tumor role in OS.


Obesity and risk of new-onset atrial fibrillation after cardiac surgery.
New-onset postoperative atrial fibrillation (AF) is a common complication of cardiac surgery that has substantial effects on outcomes. In the general (nonsurgical) adult population, AF has been linked to increasing obesity, which correlates with left atrial enlargement. It is not known whether postoperative AF is similarly linked to obesity. This was a retrospective analysis of the incidence of AF in terms of body mass index (BMI). A total of 8051 consecutive cardiac surgery patients (1994 to 2004; mean age 64 [SD 11] years; 5372 men [67%]) who were free of any history of preoperative AF or flutter were included in the analysis. This series included 3164 obese patients (39%; median age 62 years) and 4887 nonobese patients (61%; median age 66 years), who were further divided on the basis of BMI (kg/m2) into 6 groups: BMI <22 kg/m2, 22< or =BMI< or =25 kg/m2 (normal), 25<BMI> or =30 kg/m2 (overweight), 30<BMI > or =35 kg/m2 (obese I), 35<BMI> or =40 kg/m2 (obese II), and BMI >40 kg/m2 (obese III). Unadjusted AF incidence was similar in obese and nonobese patients (n=742 [23.5%] versus n=1068 [21.9%], respectively; P=0.099). Covariate-adjusted ORs for AF were systematically greater for larger patients than for patients in the normal group (adjusted OR [95% CI]=1.18 [1.00 to 1.40], 1.36 [1.14 to 1.63], 1.69 [1.35 to 2.11], and 2.39 [1.81 to 3.17] for overweight, obese I, obese II, and obese III, respectively). Other AF predictors included age (adjusted OR=1.52 [95% CI 1.46 to 1.58] per 10 years), mitral valve surgery (adjusted OR=2.42 [95% CI 1.92 to 3.06]), aortic valve surgery (adjusted OR=1.79 [95% CI 1.45 to 2.22]), chronic obstructive pulmonary disease (adjusted OR=1.28 [95% CI 1.12 to 1.46]), male gender (adjusted OR=1.24 [95% CI 1.10 to 1.40]), preoperative beta-blocker use (adjusted OR=1.17 [95% CI 1.05 to 1.32]), vascular disease (adjusted OR=1.18 [95% CI 1.05 to 1.32]), white race (adjusted OR=1.33 [95% CI 1.07 to 1.66]), history of arrhythmia other than AF/flutter (adjusted OR=0.80 [95% CI 0.68 to 0.96]), ejection fraction <40% (adjusted OR=1.16 [95% CI 1.03 to 1.31]), left main disease (adjusted OR=1.15 [95% CI 1.00 to 1.32]), and off-pump surgery (adjusted OR=0.61 [95% CI 0.44 to 0.83]). The obesity-AF association was confirmed in 4 1-to-1 propensity-matched obese versus nonobese comparisons and in 2 separate derivation/validation subcohort analyses. Obesity is an important determinant of new-onset AF after cardiac surgery. Future postoperative AF risk models should incorporate BMI or obesity levels. Studies examining the efficacy of AF-minimizing prophylactic interventions in high-BMI patients, particularly in the elderly, may be warranted.


Appendiceal carcinoid in a pediatric patient with Peutz-Jeghers syndrome: A case report and comprehensive literature review.
Peutz-Jeghers syndrome (PJS), a rare autosomal dominant disorder, is characterized by mucocutaneous pigmentations, hamartomatous polyps in the gastrointestinal tract, and a high risk of developing various malignancies. To the best of our knowledge, only 1 case of appendiceal carcinoid associated with PJS has been previously reported in the pediatric population. We report a 7-year-old girl who was admitted for severe, intermittent abdominal pain and cramps, nausea, and vomiting. Multiple brown melanotic macules on the lips, buccal mucosa, and the tongue were noted. A plain abdominal X-ray in a standing position revealed dilated intestinal loops with multiple air-fluid levels. A computed tomography scan of the abdomen showing a "coffee bean" appearance of the jejunal loop with a transition point to the duodenal loop. Axial-contrast-enhanced computed tomography scan of the abdomen showing dilated jejunum loops, filled with fluid with the swirled appearance of mesentery typical for volvulus. The diagnosis of PJS was based on clinical findings along with the histopathologic confirmation of the hamartomatous polyps. An emergency laparotomy was performed, revealing a jejunojejunal intussusception starting 40 cm from the duodenojejunal flexure. Jejunotomy revealed that a lead-point intussusception was a necrotic hamartomatous polyp. After resecting the involved jejunal necrotic segment, including the polyp, end-to-end jejuno-jejunal anastomosis was performed. Further exploration revealed the presence of a jejunal mass 80 cm from the duodenojejunal flexure identified as another hamartomatous pedunculated polyp. The polyp was resected, and the enterotomy was then closed transversely. The grossly normal appendix was also removed. Clinical findings along with the histopathologically confirmed hamartomatous polyps were consistent with PJS. An appendiceal carcinoid (well-differentiated neuroendocrine tumor, European Neuroendocrine Tumor Society stage pT2) was incidentally detected during histological examination of the appendix. The patient and parents were counseled accordingly, focusing on active surveillance and control of symptoms. Two additional hamartomatous polyps (gastric and jejunal) were detected endoscopically and resected in the fourth postoperative week. A regular, 1-year follow-up and surveillance revealed no complications or recurrences. Unusual neoplasms can occasionally be encountered in well-defined syndromes such as PJS. Therefore, active follow-up and surveillance are mandatory for all patients with PJS.


The Influence of Hazelnut Skin Addition on Quality Properties and Antioxidant Activity of Functional Yogurt.
There is an increasing interest in applying fruit-processing wastes as functional food ingredients. Hazelnut skin, an interesting and innovative ingredient has recently been evaluated as one of the richest edible sources of polyphenolic compounds. This study aimed to evaluate the use of hazelnut skin as a functional additive in yogurt and to determine the effect of various percentages (2%, 3%, and 4%) of hazelnut skin on the physicochemical, microbiological, rheological, biochemical, and sensorial properties of yogurt. The results showed that the addition of hazelnut skin significantly increased total solids from 16.5% to 17.7% and fat content from 3.45% to 4.60% and decreased titratable acidity by up to 36%. The enrichment with hazelnut skin also improved the viability of yogurt bacteria, water holding capacity (WHC), and antioxidant activity of yogurts. Better results for WHC and antioxidant values were found in yogurt enriched with 4% hazelnut skin. Total phenolic content and Fe2+ chelating activity of yogurts increased with the increasing hazelnut skin ratio. However, yogurts with hazelnut skin had low instrumental texture parameters and apparent viscosity values. On the other hand, acceptable sensorial properties similar to control yogurts increase the consumption potential of yogurts enriched with hazelnut skin.


Nested sampling for materials: the case of hard spheres.
The recently introduced nested sampling algorithm allows the direct and efficient calculation of the partition function of atomistic systems. We demonstrate its applicability to condensed phase systems with periodic boundary conditions by studying the three-dimensional hard-sphere model. Having obtained the partition function, we show how easy it is to calculate the compressibility and the free energy as functions of the packing fraction and local order, verifying that the transition to crystallinity has a very small barrier, and that the entropic contribution of jammed states to the free energy is negligible for packing fractions above the phase transition. We quantify the previously proposed schematic phase diagram and estimate the extent of the region of jammed states. We find that within our samples, the maximally random jammed configuration is surprisingly disordered.


VeChat: correcting errors in long reads using variation graphs.
Error correction is the canonical first step in long-read sequencing data analysis. Current self-correction methods, however, are affected by consensus sequence induced biases that mask true variants in haplotypes of lower frequency showing in mixed samples. Unlike consensus sequence templates, graph-based reference systems are not affected by such biases, so do not mistakenly mask true variants as errors. We present VeChat, as an approach to implement this idea: VeChat is based on variation graphs, as a popular type of data structure for pangenome reference systems. Extensive benchmarking experiments demonstrate that long reads corrected by VeChat contain 4 to 15 (Pacific Biosciences) and 1 to 10 times (Oxford Nanopore Technologies) less errors than when being corrected by state of the art approaches. Further, using VeChat prior to long-read assembly significantly improves the haplotype awareness of the assemblies. VeChat is an easy-to-use open-source tool and publicly available at https://github.com/HaploKit/vechat .


ALK alteration is a frequent event in aggressive breast cancers.
Breast cancer is the most common female malignancy worldwide and, despite improvements in treatment modalities, there are increased chances of recurrence and metastasis in a substantial number of cases and it remains one of the major causes of mortality among female cancer patients. Anaplastic lymphoma kinase (ALK) gene has been found to be altered in several solid and hematologic tumors. We aimed to comprehensively study the prevalence of ALK expression, and changes in copy number and translocation in a large cohort of breast cancer cases in a Middle Eastern population. ALK protein expression was investigated by immunohistochemistry and numerical and structural variations of the ALK gene were analyzed by fluorescence in situ hybridization (FISH) in a tissue microarray format in a cohort of more than 1000 Middle Eastern breast cancers. The data were correlated with clinicopathologic parameters and other important molecular biomarkers. Immunohistochemical analysis showed ALK overexpression in 36.0 % of the breast cancer patients and gene amplification was present in 13.3 % of cases, seen by FISH analyses. ALK overexpression was significantly associated with ALK gene amplification (p = 0.0031). ALK-overexpressing tumors showed significant association with high-grade tumors (p = 0.0039), ductal histologic subtype (p = 0.0076), triple-negative phenotype (p = 0.0034), and high Ki-67 (p = 0.0001) and p-AKT (p <0.0001). Immunohistochemical analysis showed ALK is overexpressed in a substantial proportion of breast cancers and possibly plays a significant role in the aggressive behavior of this cancer. Gene amplification is hypothesized to be a possible cause for a significant proportion of this overexpression. Based on these findings, a potential role for an ALK inhibitor, as a therapeutic agent targeting aggressive subtypes of breast cancer, merits further investigation.


Influence of mental health professionals' attitudes and personality traits on decision-making around coercion: Results from an experimental quantitative survey using case vignettes.
Research on coercion in mental healthcare has recently shifted to the investigation of subjective aspects, both on the side of the people with mental disorders affected and the staff members involved. In this context, the role of personality traits and attitudes of staff members in decision-making around coercion is increasingly being assessed. This study aimed to examine the role of staff attitudes towards coercion and staff members' personality traits in decision-making around coercion in an experimental setting. We assessed the attitudes towards coercion and (general) personality traits of mental health professionals in psychiatric hospitals with a quantitative survey. Furthermore, we developed case vignettes representing cases in a 'grey zone' and included them in the survey to assess staff members' decisions about coercion in specific situations. A general approving attitude towards coercion significantly influenced decisions around coercion in individual cases-resulting in a more likely approval of applying coercion in the cases described in the vignettes. Personality traits did not seem to be relevant in this regard. Strategies to reduce coercion in mental healthcare institutions should focus more on the role of staff attitudes and encourage staff members to reflect on them critically.


Spatial and seasonal variability of photosynthetic parameters and their relationship to leaf nitrogen in a deciduous forest.
We used gas exchange techniques to estimate maximum rate of carboxylation (V(cmax)), a measure of photosynthetic capacity, in the understory and upper crown of a closed deciduous forest over two seasons. There was extensive variability in photosynthetic capacity as a result of vertical canopy position, species type, leaf age and drought. Photosynthetic capacity was greater in oaks than in maples and greater in the overstory than in the understory. Parameter V(cmax) was maximal early in the season but declined slowly throughout most of the summer, and then more rapidly during senescence. There was also an apparent decline during drought in some trees. Variability in V(cmax) as a result of species or vertical canopy gradients was described well by changes in leaf nitrogen per unit area (N(a)). However, temporal changes in V(cmax) were often poorly correlated with leaf nitrogen, especially in spring and summer and during drought. This poor correlation may be the result of a seasonally dependent fractional allocation of leaf nitrogen to Rubisco; however, we could not discount Rubisco inactivation, patchy stomatal closure or changes in mesophyll resistance. Consequently, when a single annual regression equation of V(cmax) versus N(a) was used for this site, there were substantial errors in the temporal patterns in V(cmax) that will inevitably result in modeling errors.


Ocular pathological changes in hamsters experimentally infected with Schistosoma mansoni.
Ocular lesions have been reported in patients with schistosomiasis; however, the problem with studying schistosomal infection of the human eye is that biopsies are almost impossible to take, and histopathological examination of suspicious lesions can only be undertaken post-mortem or after enucleation. This work aimed to study the possible effects and pathogenesis of schistosomiasis on the eye. This study involved 55 hamsters; five hamsters remained non-infected and the remaining 50 hamsters were infected with Schistosoma mansoni cercariae. Infected hamsters were sacrificed on weeks 8, 12, 16 and 20 post-infection (pi). Eye sections were prepared and stained for histopathological and immunohistochemical studies. Histopathological changes detected in hamsters infected after 16 and 20 weeks included looseness and oedema of the innermost retinal layers together with hyperplastic polypoid growth. Neither eggs nor granulomata were detected in eye sections throughout the experimental period. Deposition of S. mansoni antigen was revealed in 35% of infected hamsters. Later, on weeks 16 and 20 pi, moderate subepithelial conjuctival deposits and marked subchoroidal and scleral deposition were detected. In conclusion, the deposition of schistosomal antigen and immune complexes may play a pivotal role in the ocular changes that occur in schistosomiasis, even in the absence of detectable Schistosoma eggs. Schistosomiasis should be suspected in cases with unexplained ophthalmological findings, especially in endemic areas.


Difficulties in Conducting Long Term Follow Ups in Psychotherapy Research-Issues in the Literature and Data From a Randomized Therapy Comparison Study for Posttraumatic Stress Disorder.
Studies of psychotherapy for posttraumatic stress disorder (PTSD) typically encompass short follow-up periods, leading to a dearth of information on the long-term course of symptoms after treatment. We summarize existing long-term follow-up studies and highlight the issues making such research difficult. In this context, we report on a 2-year follow-up on a randomized treatment study comparing dialogical exposure therapy and cognitive processing therapy for adults with PTSD after type I trauma. Many of the problems connected to long-term follow-up also pertained to this study. Attrition was high, and the recruited sample was not representative of the study completers. Gains made during therapy were mostly stable, with no significant differences between interventions. At least for an originally successful subset of patients, the gains made during both treatments in our study tended to stay stable 2 years after the end of treatment.


Pain and opioid prescriptions vary by procedure after breast surgery.
With the opioid epidemic in the United States, evaluating opioid prescribing patterns is essential. We evaluated opioids prescribed at discharge following breast surgery and their association with patient factors and pain scores. We retrospectively identified adult patients who underwent a mastectomy for cancer at Mayo Clinic sites from January 2010 to December 2016. Pain scores and prescription data were compared across operations and patient factors by univariate and multivariable analyses. Of 4021 patients, 3782 (94.1%) received an opioid prescription. Median oral milligram morphine equivalents (MME) were similar across all site-specific procedure groups (medians ranging from 225 to 375) while pain scores ranged from 1 to 4. Patients undergoing bilateral mastectomy (BM) and immediate breast reconstruction (IBR) reported the greatest pain scores. Pain scores did not vary with age or diagnosis for patients undergoing unilateral mastectomy or BM with lymph node surgery and IBR procedures. On multivariable analysis, variables associated with a MME discharge prescription >Q4 values included age, body mass index, site, year, inpatient status, and pain before discharge >3. Patient-reported pain following breast surgery varied by procedure, while MMEs prescribed remained similar. This suggests current opioid prescribing does not reflect intensity of pain and requires further research to optimize discharge opioid prescribing practices.


Xenopus transcription factor IIIA binds to the flanking regions of the 5 S RNA gene intragenic control region in a unique and highly ordered state.
The interaction of Xenopus transcription factor IIIA (TFIIIA) with the intragenic control region (ICR) of the 5 S RNA gene was studied by footprinting techniques under conditions which elicited a unique DNase I digestion pattern. Although a typical full footprint at the ICR was apparent at a 5 nM TFIIIA concentration, higher concentrations (greater than or equal to 50 nM) resulted in a decrease in the size of the footprint (on the 5' side of the ICR) concomitant with the appearance of an alternating protection pattern (APP) located both in the 3'- and 5'-flanking regions of the ICR with a periodicity of approximately 10 base pairs. This periodicity indicates that TFIIIA binding occurs on only one side of the DNA helix. The minimum size of the highly ordered and apparently cooperative APP effect was determined to be at least 250 base pairs in length and could be abolished through competition with nonspecific DNA. However, binding of TFIIIA to nonspecific DNA alone was not sufficient to generate the APP effect at any of the TFIIIA concentrations studied. Removal of the C-terminal domain of the protein by either tryptic or papain digestion resulted in the abolition of the APP effect at all concentrations studied, indicating the necessity of the protein-protein interactions for this effect. A nucleation site, most likely at or near the ICR, is proposed to exist through which TFIIIA specifically interacts and orients the binding of additional protein molecules in a cooperative and highly ordered manner to the flanking DNA sequences on either side of the ICR. The APP effect near the ICR may play a role in the initiation and stabilization of 5 S RNA gene transcription.


[Treatment of neoplastic hypercalcemia].
Hypercalcemia (HC) is a frequent complication of tumoral disease which should always be treated, tumor therapy being the best treatment. Occasionally, it can prove to be a medical emergency and should be treated without delay, especially where high risk patients are concerned. Sometimes, the treatment is not successful due to the fact that the drugs used in acute crises, although effective, have high toxicity; meanwhile, the drugs used for chronic HC lack the desired level of effectiveness and, in addition, tolerance problems are also implicated. In this paper, we consider the therapeutic schedule, based on physiopathologic mechanisms; and, the various drugs presently being used are reviewed. The therapeutic attitude to be followed during HC is indicated.


The conversion of exogenous retinol and related compounds into retinyl phosphate mannose by adult Brugia pahangi in vitro.
Adult Brugia pahangi took up and incorporated beta-carotene and free retinol in vitro. The uptake of retinol was 50 times greater than that of beta-carotene under similar incubation conditions. beta-Carotene was almost entirely metabolized, primarily to retinol. The metabolism of retinol by B. pahangi in vitro was less extensive, with a variety of retinoids tentatively identified, including retinyl phosphate (Ret-P), retinyl phosphate mannose (Ret-P-Man) and anhydroretinol as minor metabolites. B. pahangi microsomes were also shown to biosynthesize Ret-P-Man from exogenous Ret-P and GDP-mannose, but not from endogenous lipid acceptors alone. In this circumstance an unidentified lipid appeared to be mannosylated by B. pahangi. The rate of mannose transfer to exogenous Ret-P by B. pahangi microsomes was 150 pmol X min -1. (mg of protein) -1. Ret-P-Man synthetase activity from both B. pahangi and rat liver microsomes had an absolute requirement for bovine serum albumin and MnCl2, and occurred in the absence of detergent. The results suggest a biochemical role for vitamin A in B. pahangi, possibly in filarial glycoprotein synthesis.


Depression, anxiety, and quality of life in patients with obstructive hypertrophic cardiomyopathy three months after alcohol septal ablation.
Patients with obstructive hypertrophic cardiomyopathy are presumed to have poor quality of life (QOL) and distress related to their cardiac symptoms and functional limitations. Alcohol septal ablation (ASA) is designed to improve heart function and reduce cardiac symptoms. The purpose of this study was to examine psychosocial factors and QOL in patients with obstructive hypertrophic cardiomyopathy before and 3 months after ASA. Twenty-two adult participants (mean age 57 +/- 14 years, 59% women, 100% Caucasian, 67% married) were recruited during their initial evaluations or scheduled index hospitalizations for ASA. Psychosocial and medical measures were collected before and 3 months after ASA. The results indicated that before ASA, 57% of patients reported clinically relevant levels of depression (Center for Epidemiologic Studies Depression Scale score >16), symptoms of anxiety, and reduced QOL. Repeated-measures analyses of variance revealed that ASA is an effective procedure in reducing disease severity (i.e., peak left ventricular outflow tract gradient, septal thickness, posterior wall thickness) (p = 0.001 to 0.05), depression (p = 0.005), and anxiety (p = 0.029) and improving cardiac-specific QOL (p < 0.001) and generic physical health-related QOL (p = 0.009). Changes in satisfaction with life, optimism, and generic mental health-related QOL were not significant (p = 0.143 to 0.899). In conclusion, significant psychological distress and compromised well-being were present in this sample of pre-ASA patients with obstructive hypertrophic cardiomyopathy. After ASA, significant reductions in psychological distress and improvements in well-being and echocardiographic parameters indicating disease severity were demonstrated. These results suggest that patients perceived broad health benefits from ASA in short-term follow-up.


Phlebotomy for obtaining platelet-rich fibrin autograft in children for pediatric dental procedures: Parental views, understanding, and acceptance.
The negative perception of parents toward invasive dental procedures has always created a barrier in delivering successful treatment to pediatric patients. Surprisingly, little is known about the perspective of parents and the impact of demographic and psychological factors guiding their decision. To evaluate the acceptability of phlebotomy for obtaining platelet-rich fibrin (PRF) to be used in pediatric endodontic procedures among parents of children. A cross-sectional study design was used for the survey. The design involved interviewing the parents of children aged 3 to 14 years, who fulfilled the inclusion criteria and were indicated for regenerative pulp therapy using PRF. The sample included one hundred and fifty shortlisted parents who were made to answer questionnaires on sociodemographic data and psychological variables. A single pediatric dentist educated the parents individually on the procedure, risks, and benefits of PRF, following which parental consent and views were recorded in the developed performa. Consent of 63.3% was recorded at the end of the study. Parenting pattern and parental dental anxiety were found to have significant correlation with the treatment acceptance. It is the responsibility of the pediatric dentist to communicate the treatment strategies in a manner that is acceptable to the parents for which a thorough knowledge about parental factors is necessary. This study helps in identifying such factors and highlights the importance of demonstration aids in parental education and motivation.


Strong Expansion of Human Regulatory T Cells for Adoptive Cell Therapy Results in Epigenetic Changes Which May Impact Their Survival and Function.
Adoptive transfer of regulatory T cells (Treg) is a promising new therapeutic option to treat detrimental inflammatory conditions after transplantation and during autoimmune disease. To reach sufficient cell yield for treatment, ex vivo isolated autologous or allogenic Tregs need to be expanded extensively in vitro during manufacturing of the Treg product. However, repetitive cycles of restimulation and prolonged culture have been shown to impact T cell phenotypes, functionality and fitness. It is therefore critical to scrutinize the molecular changes which occur during T cell product generation, and reexamine current manufacturing practices. We performed genome-wide DNA methylation profiling of cells throughout the manufacturing process of a polyclonal Treg product that has proven safety and hints of therapeutic efficacy in kidney transplant patients. We found progressive DNA methylation changes over the duration of culture, which were donor-independent and reproducible between manufacturing runs. Differentially methylated regions (DMRs) in the final products were significantly enriched at promoters and enhancers of genes implicated in T cell activation. Additionally, significant hypomethylation did also occur in promoters of genes implicated in functional exhaustion in conventional T cells, some of which, however, have been reported to strengthen immunosuppressive effector function in Tregs. At the same time, a set of reported Treg-specific demethylated regions increased methylation levels with culture, indicating a possible destabilization of Treg identity during manufacturing, which was independent of the purity of the starting material. Together, our results indicate that the repetitive TCR-mediated stimulation lead to epigenetic changes that might impact functionality of Treg products in multiple ways, by possibly shifting to an effector Treg phenotype with enhanced functional activity or by risking destabilization of Treg identity and impaired TCR activation. Our analyses also illustrate the value of epigenetic profiling for the evaluation of T cell product manufacturing pipelines, which might open new avenues for the improvement of current adoptive Treg therapies with relevance for conventional effector T cell products.


Exposure to Kynurenic Acid during Adolescence Increases Sign-Tracking and Impairs Long-Term Potentiation in Adulthood.
Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and α7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with L-kynurenine (L-KYN), the precursor of KYNA. As adults, the rats were tested drug-free in an autoshaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing) when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value) as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP). Rats treated with L-KYN exhibited no LTP after a burst of high-frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during adolescence.


Soluble Epoxide Hydrolase Inhibitor Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Improves Survival in Mice.
Acute lung injury (ALI) is characterized by rapid alveolar injury, vascular leakage, lung inflammation, neutrophil accumulation, and induced cytokines production leading to lung edema. The mortality rate of patients suffering from ALI remains high. Epoxyeicosatrienoic acids (EETs) are cytochrome P450-dependent derivatives of polyunsaturated fatty acid with antihypertensive, profibrinolytic, and anti-inflammatory functions. EETs are rapidly hydrated by soluble epoxide hydrolase (sEH) to their less potent diols. The aim of this study was to investigate the role of sEH inhibitor trifluoromethoxyphenyl propionylpiperidin urea (TPPU) and EETs in lipopolysaccharide (LPS)-induced ALI of mice. Our studies revealed that inhibition of sEH with TPPU attenuated the morphological changes in mice, decreased the neutrophil infiltration to the lung, pro-inflammatory cytokine levels (IL-1β and TNF-α) in serum and bronchoalveolar lavage fluid (BALF), and alveolar capillary leakage (lung wet/dry ratio and total protein concentration in BALF). TPPU improved the survival rate of LPS-induced ALI. In addition, in vitro experiments revealed that both TPPU and EETs (11,12-EET and 14,15-EET) suppressed the expression of IL-1β and TNF-α, and LDH release in RAW264.7 cells. These results indicate that EETs play a role in dampening LPS-induced acute lung inflammation, and suggest that sEH could be a valuable candidate for the treatment of ALI.


The potential of Pseudozyma yeastlike epiphytes for the production of heterologous recombinant proteins.
Although Basidiomycetes represent the most evolved class of fungi, they have been neglected with regard to recombinant gene expression. In this work, basidiomycetous yeasts belonging to Pseudozyma spp. were studied with respect to their amenability to heterologous protein production. Single plasmid or cotransformation experiments routinely afforded 100 to 200 independent transformants for the two tested species of Pseudozyma. Green fluorescent protein (GFP) was expressed in the correctly folded conformation, as demonstrated by fluorescence microscopy, and hen egg white lysozyme (HEWL) was expressed in its active form, as revealed by its lytic activity on Micrococcus lysodeikticus cells. Protease analysis established that Pseudozyma spp. contained equivalent or less extracellular protease activity than yeasts and far less protease activity than ascomycetous filamentous fungi in similar culture conditions. This proteolytic activity was inhibited by over 97% with a combination of PMSF and Pepstatin A. N-glycosylation patterns of native Pseudozyma flocculosa secreted proteins were comprised of one or a few short glycan chains that possess a classic eukaryotic structure typical of higher fungi and animal cells. This is the first report of a Basidiomycete that possesses multiple intrinsic characteristics necessary for use as a heterologous gene expression system.


[Laryngopharyngeal reflux and larynx-related symptoms].
Chronic hoarseness, globus sensation or mucous obstruction are among a wide range of symptoms possibly related to laryngopharyngeal reflux (LPR). A selective literature research was carried out using PubMed, in which original articles and reviews in German and English were included. Altogether, 2541 articles were found. Despite the large number of publications, there are still open questions regarding aspects of LPR. It can be assumed that refluxate reaching the larynx can damage it. Due to the fact that the symptoms possibly related to LPR can, however, be linked to other causes, a careful consideration of the patient's medical history is of the utmost importance, followed by mandatory laryngoscopy. Diagnostic procedures, such as the trial administration of proton pump inhibitors (PPI) or long-term pH measurement should be used selectively. Depending on the individual symptoms, breathing or voice therapy and/or PPI therapy might be useful. Lifestyle changes including dietary measures should also be contemplated.


[Measurement of mitochondrial transmembrane electric potential using the fluorescent probe DSM].
The measurement of transmembrane electric potential of rat liver mitochondria was performed with fluorescent probe DSM. In the incubation medium with succinate the electric potential was -190 +/- 5 mV. Complete uncoupling caused by CCCP in the concentration 0.5 microM decreased the potential to -142 +/- 3 mV. In the partial uncoupling with a half of the mentioned CCCP concentration the potential was -158 +/- 6 mV. DSM influence on oxidation and phosphorylation was not detected.


A genetic algorithm to find optimal reading test word subsets for estimating full-scale IQ.
In clinical neuropsychology the cognitive abilities of neurological patients are commonly estimated using well-established paper-based tests. Typically, scores on some tests remain relatively well preserved, whilst others exhibit a significant and disproportionate decline. Scores on those tests that measure preserved cognitive functions (so-called 'hold' tests) may be used to estimate premorbid abilities, including scores in non-hold tests that would have been expected prior to the onset of cognitive impairment. Many hold tests entail word reading, with each word being graded as correctly or incorrectly pronounced. Inevitably, such tests are likely to contain words that provide little or no diagnostic power (i.e., can be eliminated without negatively affecting prediction accuracy). In this paper, a genetic algorithm is developed and demonstrated, using n = 92 neurologically healthy participants, to identify optimal word subsets from the National Adult Reading Test that minimize the mean error in predicting the most widely used clinical measure of IQ and cognitive ability, the Wechsler Adult Intelligence Scale Fourth Edition IQ. In addition to requiring only 17-20 of the original 50 words (suggesting that this test could be revised to be up to 66% shorter) and minimizing mean prediction error, the algorithm increases the proportion of the variance in the predicted variable explained in comparison to using all words (from r2 = 0.46 to r2 = 0.61). In a clinical setting this would improve estimates of premorbid cognitive function and, if an abbreviated revision to this test were to be adopted, reduce the arduousness of the test for patients. The proposed method is evaluated with jackknifing and leave one out cross validation. The general approach may be used to optimize the relationship between any two psychological tests by finding the question subset in one test that minimizes the prediction error in a second test by training the genetic algorithm using data collected from participants upon whom both tests have been administered. This approach may also be used to develop new predictive tests, since it provides a method to identify an optimal subset of a set of candidate questions (for which empirical data have been collected) that maximizes prediction accuracy and the proportion of variance in the predicted variable that can be explained.


Redistribution of synaptic efficacy: a mechanism to generate infinite synaptic input diversity from a homogeneous population of neurons without changing absolute synaptic efficacies.
Changing the reliability of neurotransmitter release results in a change in the efficacy of low frequency synaptic transmission and in the rate of high frequency synaptic depression thus it can not cause an uniform change in strength of synapses and instead results in a change in the dynamics of synaptic transmission referred to as 'redistribution of synaptic efficacy' (RSE). Since the change in synaptic transmission associated with RSE depends on the history of action potential activity it is concluded that RSE serves as a mechanism to generate a potentially infinite diversity of synaptic input.


Longitudinal study of the effects of teat condition on the risk of new intramammary infections in dairy cows.
Machine milking-induced alterations of teat tissue may impair local defense mechanisms and increase the risk of new intramammary infections. The objective of the current study was to assess the influence of short-term and long-term alterations of teat tissue and infectious status of the udder quarter on the risk of naturally occurring new intramammary infections, inflammatory responses, and mastitis. Short-term and long-term changes in teat condition of right udder quarters of 135 cows of a commercial dairy farm in Saxony-Anhalt, Germany, were recorded monthly for 10 mo using simple classification schemes. Quarter milk samples were collected from all examined quarters at each farm visit. Bacteriological culture results and somatic cell counts of quarter milk samples were used to determine new inflammatory responses (increase from ≤100,000 cells/mL to >100,000 cells/mL between 2 samples), new infections (detection of a pathogen from a quarter that was free of the same pathogen at the preceding sampling), and new mastitis (combination of new inflammatory response and new infection). Separate Poisson mixed models for new inflammatory responses, new infections, and new mastitis caused by specific pathogens or groups of pathogens (contagious, environmental, major, minor, or any) were used to estimate risk ratios and 95% confidence intervals. Data preparation and parameter estimation were performed using the open source statistical analysis software R. We observed no effect of any variable describing teat condition on the risk of new intramammary infections, inflammatory responses, or mastitis. Intramammary infections of the same udder quarter in the preceding month did not affect risk either.